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2. Evidence for charge-based mimicry in anti dsDNA antibody generation

Author

Bruschi, M, Angeletti, A, Kajana, X, Moroni, G, Sinico, R, Fredi, M, Vaglio, A, Cavagna, L, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Negrini, S, Bui, F, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Verrina, E, Franceschini, F, Ravelli, A, Prunotto, M, Meroni, P, Ghiggeri, G, Bruschi, Maurizio, Angeletti, Andrea, Kajana, Xhuliana, Moroni, Gabriella, Sinico, Renato Alberto, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe Alvise, Esposito, Pasquale, Negrini, Simone, Bui, Federica, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisani, Isabella, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Verrina, Enrico, Franceschini, Franco, Ravelli, Angelo, Prunotto, Marco, Meroni, Pier Luigi, Ghiggeri, Gian Marco, Bruschi, M, Angeletti, A, Kajana, X, Moroni, G, Sinico, R, Fredi, M, Vaglio, A, Cavagna, L, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Negrini, S, Bui, F, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Verrina, E, Franceschini, F, Ravelli, A, Prunotto, M, Meroni, P, Ghiggeri, G, Bruschi, Maurizio, Angeletti, Andrea, Kajana, Xhuliana, Moroni, Gabriella, Sinico, Renato Alberto, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe Alvise, Esposito, Pasquale, Negrini, Simone, Bui, Federica, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisani, Isabella, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Verrina, Enrico, Franceschini, Franco, Ravelli, Angelo, Prunotto, Marco, Meroni, Pier Luigi, and Ghiggeri, Gian Marco

Abstract

Mechanisms for the generation of anti-dsDNA autoantibodies are still not completely elucidated. One theory states that dsDNA interacts for mimicry with antibodies raised versus other antigens but molecular features for mimicry are unknown. Here we show that, at physiological acid-base balance, anti-Annexin A1 binds IgG2 dsDNA in a competitive and dose-dependent way with Annexin A1 and that the competition between the two molecules is null at pH 9. On the other hand, these findings also show that dsDNA and Annexin A1 interact with their respective antibodies on a strictly pH-dependent basis: in both cases, the binding was minimal at pH 4 and maximal at pH9-10. The anionic charge of dsDNA is mainly conferred by the numerous phosphatidic residues. The epitope binding site of Annexin A1 for anti-Annexin A1 IgG2 was here characterized as a string of 34 amino acids at the NH2 terminus, 10 of which are anionic. Circulating levels of anti-dsDNA and anti-Annexin A1 IgG2 antibodies were strongly correlated in patients with systemic lupus erythematosus (n 496) and lupus nephritis (n 425) stratified for age, sex, etc. These results show that dsDNA competes with Annexin A1 for the binding with anti-Annexin A1 IgG2 on a dose and charged mediated base, being able to display an inhibition up to 75%. This study provides the first demonstration that dsDNA may interact with antibodies raised versus other anionic molecules (anti-Annexin A1 IgG2) because of charge mimicry and this interaction may contribute to anti-dsDNA antibodies generation.

Published
2022

3. Clinical and histological findings at second but not at first kidney biopsy predict end-stage kidney disease in a large multicentric cohort of patients with active lupus nephritis

Author

Gatto, M, Radice, F, Saccon, F, Calatroni, M, Frontini, G, Trezzi, B, Zen, M, Ghirardello, A, Tamborini, F, Binda, V, L'Imperio, V, Doria, A, Vaglio, A, Sinico, R, Moroni, G, Iaccarino, L, Gatto, Mariele, Radice, Francesca, Saccon, Francesca, Calatroni, Marta, Frontini, Giulia, Trezzi, Barbara, Zen, Margherita, Ghirardello, Anna, Tamborini, Francesco, Binda, Valentina, L'Imperio, Vincenzo, Doria, Andrea, Vaglio, Augusto, Sinico, Renato Alberto, Moroni, Gabriella, Iaccarino, Luca, Gatto, M, Radice, F, Saccon, F, Calatroni, M, Frontini, G, Trezzi, B, Zen, M, Ghirardello, A, Tamborini, F, Binda, V, L'Imperio, V, Doria, A, Vaglio, A, Sinico, R, Moroni, G, Iaccarino, L, Gatto, Mariele, Radice, Francesca, Saccon, Francesca, Calatroni, Marta, Frontini, Giulia, Trezzi, Barbara, Zen, Margherita, Ghirardello, Anna, Tamborini, Francesco, Binda, Valentina, L'Imperio, Vincenzo, Doria, Andrea, Vaglio, Augusto, Sinico, Renato Alberto, Moroni, Gabriella, and Iaccarino, Luca

Abstract

Objective To investigate second kidney biopsy as predictor of end-stage kidney disease (ESKD) in active lupus nephritis (LN). Methods Patients with biopsy-proven LN (International Society of Nephrology/Renal Pathology Society 2003) who had undergone a second kidney biopsy between January 1990 and December 2018 were included. Clinical and histological findings at first and at second biopsy were analysed with Cox proportional hazard models to predict ESKD, defined as start of kidney replacement therapy. Survival curves were calculated with Kaplan-Meier method. Results Ninety-two patients with LN were included, 87% females, mean follow-up 17.9±10.1 years. Reasons for second kidney biopsy encompassed nephritic flares (n=28, 30.4%), proteinuric flares (n=46, 50%) or lack of renal response (n=18, 19.5%). Class switch from first biopsy occurred in 50.5% of cases, mainly from non-proliferative towards proliferative classes. Class IV remained stable in over 50% of cases. Twenty-five patients (27.2%) developed ESKD, mostly belonging to the nephritic flare group (17/28, 60.7%). Independent predictors of ESKD at second biopsy were activity index (AI; (HR 95% CI) 1.20 (1.03 to 1.41), p=0.022), chronicity index (CI; 1.41 (1.09 to 1.82), p=0.008) and 24h-proteinuria (1.22 (1.04 to 1.42), p=0.013). AI≥2 (log-rank p=0.031), CI >4 (log-rank p=0.001) or proteinuria ≥3.5 g/day (log-rank=0.009) identified thresholds for higher ESKD risk. In a subgroup analysis, glomerular activity and tubular chronicity mostly accounted for AI and CI association with ESKD. No histological or laboratory predictors emerged at first biopsy (95% CI): AI: 0.88 to 1.19; CI: 0.66 to 1.20; proteinuria 0.85 to 1.08. Conclusions Findings at second but not at first kidney biopsy in patients with persistently active or relapsing LN inform about ESKD development in a long-term follow-up.

Published
2022

4. Análisis de polimorfismo de nucleótido simple en el gen FASN y su relación con características de producción en pollos

Author

MARRUBE, G., ROZEN, F.M.B., PINTO, G.B., FASSA, V., PACIENZA, N., DEMARCO, A.N, ROMANO, E.G., FAIN BINDA, V, CANET, Z., and MELO, J.E

Subjects
broilers, productive traits, FASN gene polymorphism., Agriculture, Agriculture (General), S1-972
Abstract

The purpose of this work is to evaluate possible associations between a Single Nucleotide Polymorphism(SNP) of FASN gene and each of the following productive traits: Feed Intake (FI), Weight Gain (WG) and FinalBody Weight (FBW). At the National Institute of Agricultural Technology (INTA), 229 chickens were organizedand bred in full sib and paternal half sib families, these birds were caged individually with water and fed withpellet ad libitum. Body weight was recorded at 54 days old and then individual feed intake and weight were determined weekly during 21 days. FASN gene genotypes were identified by PCR amplification and digested by endonuclease Hae III. Phenotypical data were analyzed independently by ANOVA with a random Model.The SNP evaluated in this work has not been demonstrated as affecting the considered traits.

Published
2013

5. Factors Associated With Real-Life Functioning in Persons With Schizophrenia in a 4-Year Follow-up Study of the Italian Network for Research on Psychoses

Author

Mucci, A., Galderisi, S., Gibertoni, D., Rossi, A., Rocca, P., Bertolino, A., Aguglia, E., Amore, M., Bellomo, A., Biondi, M., Blasi, G., Brasso, C., Bucci, P., Carpiniello, B., Cuomo, A., Dell'Osso, L., Giordano, G. M., Marchesi, C., Monteleone, P., Niolu, C., Oldani, L., Pettorruso, M., Pompili, M., Roncone, R., Rossi, R., Tenconi, E., Vita, A., Zeppegno, P., Maj, M., Piegari, G., Aiello, C., Brando, F., Giuliani, L., Palumbo, D., Coccia, C., Papalino, M., Calia, V., Romano, R., Barlati, S., Deste, G., Valsecchi, P., Pinna, F., Lai, A., Lostia di Santa Sofia, S., Salvina Signorelli, M., Fusar Poli, L., Surace, T., Martinotti, G., Montemitro, C., Fraticelli, S., Altamura, M., Angelini, E., Elia, A., Calcagno, P., Belvederi Murri, M., Cattedra, S., Pacitti, F., Talevi, D., Socci, V., Giusti, L., Salza, A., Mammarella, S., de Bartolomeis, A., Favaro, A., Collantoni, E., Meneguzzo, P., Tonna, M., Ossola, P., Gerra, M. L., Gramaglia, C., Binda, V., Gambaro, E., Carmassi, C., Carpita, B., Cremone, I. M., Corrivetti, G., Cascino, G., Del Buono, G., Brugnoli, R., Comparelli, A., Corigliano, V., Buzzanca, A., Gerardi, N., Frascarelli, M., Fagiolini, A., Goracci, A., Bolognesi, S., Siracusano, A., Di Lorenzo, G., Ribolsi, M., Montemagni, C., Riccardi, C., Del Favero, E., Mucci, A., Galderisi, S., Gibertoni, D., Rossi, A., Rocca, P., Bertolino, A., Aguglia, E., Amore, M., Bellomo, A., Biondi, M., Blasi, G., Brasso, C., Bucci, P., Carpiniello, B., Cuomo, A., Dell'Osso, L., Giordano, G. M., Marchesi, C., Monteleone, P., Niolu, C., Oldani, L., Pettorruso, M., Pompili, M., Roncone, R., Rossi, R., Tenconi, E., Vita, A., Zeppegno, P., Maj, M., Mucci A., Galderisi S., Gibertoni D., Rossi A., Rocca P., Bertolino A., Aguglia E., Amore M., Bellomo A., Biondi M., Blasi G., Brasso C., Bucci P., Carpiniello B., Cuomo A., Dell'Osso L., Giordano G.M., Marchesi C., Monteleone P., Niolu C., Oldani L., Pettorruso M., Pompili M., Roncone R., Rossi R., Tenconi E., Vita A., Zeppegno P., and Maj M.

Subjects
Adult, Hospitals, Psychiatric, Male, Mental Health Services, Social Cognition, Apathy, Psychological intervention, Relapse prevention, schizophrenia, functioning, psychopatology, Structural equation modeling, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, Cognitive Dysfunction, Female, Follow-Up Studies, Independent Living, Italy, Middle Aged, Psychotic Disorders, Schizophrenia, Functional Status, Original Investigation, business.industry, Mental health, Hospitals, Cognitive training, 030227 psychiatry, Psychiatry and Mental health, Settore MED/25, schizophrenia, real-life functioning, SEM, Psychiatric, Work Skills, business, Psychosocial, 030217 neurology & neurosurgery, Psychopathology, Clinical psychology
Abstract

Importance: The goal of schizophrenia treatment has shifted from symptom reduction and relapse prevention to functional recovery; however, recovery rates remain low. Prospective identification of variables associated with real-life functioning domains is essential for personalized and integrated treatment programs. Objective: To assess whether baseline illness-related variables, personal resources, and context-related factors are associated with work skills, interpersonal relationships, and everyday life skills at 4-year follow-up. Design, Setting, and Participants: This multicenter prospective cohort study was conducted across 24 Italian university psychiatric clinics or mental health departments in which 921 patients enrolled in a cross-sectional study were contacted after 4 years for reassessment. Recruitment of community-dwelling, clinically stable persons with schizophrenia was conducted from March 2016 to December 2017, and data were analyzed from January to May 2020. Main Outcomes and Measures: Psychopathology, social and nonsocial cognition, functional capacity, personal resources, and context-related factors were assessed, with real-life functioning as the main outcome. Structural equation modeling, multiple regression analyses, and latent change score modeling were used to identify variables that were associated with real-life functioning domains at follow-up and with changes from baseline in these domains. Results: In total, 618 participants (427 male [69.1%]; mean [SD] age, 45.1 [10.5] years) were included. Five baseline variables were directly associated with real-life functioning at follow-up: neurocognition with everyday life (β, 0.274; 95% CI, 0.207-0.341; P

Published
2021

6. Simple parameters from complete blood count predict in-hospital mortality in covid-19

Author

Bellan, M., Azzolina, D., Hayden, E., Gaidano, G., Pirisi, M., Acquaviva, A., Aimaretti, G., Valletti, P. A., Angilletta, R., Arioli, R., Avanzi, G. C., Avino, G., Balbo, P. E., Baldon, G., Baorda, F., Barbero, E., Baricich, A., Barini, M., Barone-Adesi, F., Battistini, S., Beltrame, M., Bertoli, M., Bertolin, S., Bertolotti, M., Betti, M., Bobbio, F., Boffano, P., Boglione, L., Borre, S., Brucoli, M., Calzaducca, E., Cammarata, E., Cantaluppi, V., Cantello, R., Capponi, A., Carriero, A., Casciaro, G. F., Castello, L. M., Ceruti, F., Chichino, G., Chirico, E., Cisari, C., Cittone, M. G., Colombo, C., Comi, C., Croce, E., Daffara, T., Danna, P., Corte, F. D., de Vecchi, S., Dianzani, U., Benedetto, D. D., Esposto, E., Faggiano, F., Falaschi, Z., Ferrante, D., Ferrero, A., Gagliardi, I., Galbiati, A., Gallo, S., Garavelli, P. L., Gardino, C. A., Garzaro, M., Gastaldello, M. L., Gavelli, F., Gennari, A., Giacomini, G. M., Giacone, I., Via, V. G., Giolitti, F., Gironi, L. C., Gramaglia, C., Grisafi, L., Inserra, I., Invernizzi, M., Krengli, M., Labella, E., Landi, I. C., Landi, R., Leone, I., Lio, V., Lorenzini, L., Maconi, A., Malerba, M., Manfredi, G. F., Martelli, M., Marzari, L., Marzullo, P., Mennuni, M., Montabone, C., Morosini, U., Mussa, M., Nerici, I., Nuzzo, A., Olivieri, C., Padelli, S. A., Panella, M., Parisini, A., Pasche, A., Patrucco, F., Patti, G., Pau, A., Pedrinelli, A. R., Percivale, I., Ragazzoni, L., Re, R., Rigamonti, C., Rizzi, E., Rognoni, A., Roveta, A., Salamina, L., Santagostino, M., Saraceno, M., Savoia, P., Sciarra, M., Schimmenti, A., Scotti, L., Spinoni, E., Smirne, C., Tarantino, V., Tillio, P. A., Tonello, S., Vaschetto, R., Vassia, V., Zagaria, D., Zavattaro, E., Zeppegno, P., Zottarelli, F., Sainaghi, P. P., Aiosa, G., Airoldi, A., Barco, A., Bargiacchi, O., Bazzano, S., Berni, P., Bianchi, B., Bianco, S., Biffi, S., Binda, V., Bolgeo, T., Bolla, C., Bonato, V., Bonizzoni, G., Bragantini, A., Brustia, D., Bullara, V., Burlone, M., Brustia, F., Caccia, S., Calareso, A., Cammarota, G., Cancelliere, L., Carbone, R., Cassinari, A., Ceriani, E., Cena, T., Clivati, E., Collimedaglia, L., Colombatto, A., Cornella, C., Costanzo, M., Croce, A., de Benedittis, C., Delorenzi, S., Dionisio, R., Donato, P., Esposito, M., Fangazio, S., Feggi, A., Ferrillo, S., Foci, V., Fra, G. P., Gaggino, C., Gambaro, E., Gattoni, E., Gattoni, L., Giacchero, F., Gianfreda, R., Giubertoni, A., Grecu, L., Grossi, F., Guglielmetti, G., Guido, S., Iannantuoni, G., Ingrao, S., Jona, A., Lazzarich, E., Lissandrin, R., Maduli, E., Magne, F., Mantia, E., Marangon, D., Massara, M., Matino, E., Mauri, M. G., Menegatti, M., Moglia, R., Molinari, R., Morelli, S., Morlino, P., Naldi, P., Nebbiolo, C., Omodeo, P., Palmieri, D., Panero, A., Parodi, M., Pedrazzoli, R., Pelazza, C., Penpa, S., Perucca, R., Pirovano, A., Pittau, S., Pochetti, P., Poletti, F., Polla, B., Prandi, P., Prodam, F., Prosperini, P., Puma, A., Quaglia, M., Raie, A., Rapetti, R., Ravera, S., Re, A., Reale, M., Rossati, A., Rossi, M., Rossi, P., Rostagno, R., Salomoni, G., Sama, M. T., Sarchi, E., Sarcoli, M., Sarda, C., Sguazzotti, I., Soddu, D., Sola, D., Stobbione, P., Todoerti, M., Vallese, G. C., Varrasi, C., Veia, A., Vignazia, G. L., Zanotti, I., Zecca, E., Zichittella, D., Zisa, G., and Zoppis, E.

Subjects
Adult, Male, medicine.medical_specialty, Medicine (General), Multivariate analysis, Article Subject, Clinical Decision Rules, COVID-19, Prognosis, Blood Cell Count, Hospital Mortality, Severity of Illness Index, Clinical Biochemistry, Asymptomatic, Severity of Illness Index, NO, R5-920, Internal medicine, Clinical Decision Rules, Severity of illness, Genetics, 80 and over, Medicine, Humans, Hospital Mortality, Molecular Biology, Aged, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, business.industry, Biochemistry (medical), Complete blood count, COVID-19, Retrospective cohort study, Red blood cell distribution width, General Medicine, Odds ratio, Middle Aged, Prognosis, Female, Italy, Multivariate Analysis, Blood Cell Count, Cohort, medicine.symptom, business, Research Article
Abstract

Introduction. The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. Materials and Methods. In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. Results. At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p < 0.001 ), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006 ), and platelet count ( χ 2 5.39; p = 0.02 ), along with age ( χ 2 87.6; p < 0.001 ) and gender ( χ 2 17.3; p < 0.001 ), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality OR = 3.40 (2.40-4.82), while the OR for a RDW > 13.7 % was 4.09 (2.87-5.83); a platelet count > 166,000 /μL was, conversely, protective (OR: 0.45 (0.32-0.63)). Conclusion. Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.

Published
2021

7. Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (Part 2): prospective study

Author

Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, Maurizio, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe A, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, d'Alessandro, Matteo, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Prunotto, Marco, Verrina, Enrico, Angeletti, Andrea, Ravelli, Angelo, Ghiggeri, Gian Marco, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, Maurizio, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe A, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, d'Alessandro, Matteo, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Prunotto, Marco, Verrina, Enrico, Angeletti, Andrea, Ravelli, Angelo, and Ghiggeri, Gian Marco

Abstract

Objectives: Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. Methods: Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques. Results: LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months. Conclusions: Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN. Trial registration: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).

Published
2021

8. Second wave antibodies in autoimmune renal diseases: The case of lupus nephritis

Author

Angeletti, A, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Ravelli, A, Ghiggeri, G, Angeletti, Andrea, Bruschi, Maurizio, Moroni, Gabriela, Sinico, Renato, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, d'Alessandro, Matteo, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Prunotto, Marco, Verrina, Enrico, Ravelli, Angelo, Ghiggeri, Gian Marco, Angeletti, A, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Ravelli, A, Ghiggeri, G, Angeletti, Andrea, Bruschi, Maurizio, Moroni, Gabriela, Sinico, Renato, Franceschini, Franco, Fredi, Micaela, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello, Manfredi, Angelo, Ramirez, Giuseppe, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, d'Alessandro, Matteo, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Volpi, Stefano, Mosca, Marta, Tincani, Angela, Candiano, Giovanni, Prunotto, Marco, Verrina, Enrico, Ravelli, Angelo, and Ghiggeri, Gian Marco

Abstract

Clinical Trial registry name and registration number: Zeus study, NCT02403115

Published
2021

9. Serum IgG2 antibody multicomposition in systemic lupus erythematosus and lupus nephritis (Part 1): cross-sectional analysis

Author

Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Volpi, S, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, Maurizio, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela&nbsp, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello&nbsp, Manfredi, Angelo, Ramirez, Giuseppe A, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Mosca, Marta, Tincani, Angela&nbsp, Candiano, Giovanni, Prunotto, Marco, Volpi, Stefano, Verrina, Enrico, Angeletti, Andrea, Ravelli, Angelo, Ghiggeri, Gian Marco, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Volpi, S, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, Maurizio, Moroni, Gabriella, Sinico, Renato Alberto, Franceschini, Franco, Fredi, Micaela&nbsp, Vaglio, Augusto, Cavagna, Lorenzo, Petretto, Andrea, Pratesi, Federico, Migliorini, Paola, Locatelli, Francesco, Pazzola, Giulia, Pesce, Giampaola, Bagnasco, Marcello&nbsp, Manfredi, Angelo, Ramirez, Giuseppe A, Esposito, Pasquale, Murdaca, Giuseppe, Negrini, Simone, Cipriani, Leda, Trezzi, Barbara, Emmi, Giacomo, Cavazzana, Ilaria, Binda, Valentina, Fenaroli, Paride, Pisani, Isabella, Garibotto, Giacomo, Montecucco, Carlomaurizio, Santoro, Domenico, Scolari, Francesco, Mosca, Marta, Tincani, Angela&nbsp, Candiano, Giovanni, Prunotto, Marco, Volpi, Stefano, Verrina, Enrico, Angeletti, Andrea, Ravelli, Angelo, and Ghiggeri, Gian Marco

Abstract

Objectives: Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. Methods: A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques. Results: The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low-medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0-12 months), and high levels at T0-1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions. Conclusion: Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients. Trial registration: The Zeus study was registered at https://clinicaltrials.gov, NCT02403115.

Published
2021

11. Serum IgG2 antibody multi composition in systemic lupus erythematosus and in lupus nephritis

Author

Bruschi, M, Moroni, G, Sinico, Ra, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, Ga, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Angeletti, A, Ravelli, A, and Ghiggeri, Gm.

Published
2020

12. Kidney Involvement

Author

Sinico, R, Pagni, F, L’Imperio, V, Binda, V, Fabbrini, P, Pieruzzi, F, Moroni, G, Sinico, Renato Alberto, Pagni, Fabio, L’Imperio, Vincenzo, Binda, Valentina, Fabbrini, Paolo, Pieruzzi, Federico, Moroni, Gabriella, Sinico, R, Pagni, F, L’Imperio, V, Binda, V, Fabbrini, P, Pieruzzi, F, Moroni, G, Sinico, Renato Alberto, Pagni, Fabio, L’Imperio, Vincenzo, Binda, Valentina, Fabbrini, Paolo, Pieruzzi, Federico, and Moroni, Gabriella

Abstract

Renal involvement is a frequent and severe complication of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV). It is generally characterized by a pauci-immune necrotizing and crescentic glomerulonephritis with a very rapid decline of renal function (rapidly progressive glomerulonephritis). Even though there are no qualitative differences in glomerular lesions in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), chronic damage is usually higher in MPA (and/or P-ANCA-positive patients) than in GPA (and/or CANCA-positive patients). If untreated, necrotizing and crescentic glomerulonephritis has an unfavorable course leading in a few weeks or months to end-stage renal disease (ESRD). Serum creatinine at diagnosis, sclerotic lesions, and the number of normal glomeruli at kidney biopsy are the best predictors of renal outcome. Corticosteroids and cyclophosphamide or rituximab (with the addition of plasma exchange in the most severe cases) are the cornerstone of induction treatment of ANCA-associated renal vasculitis, followed by azathioprine (or methotrexate, mycophenolate, rituximab) for maintenance. Despite significant improvement in patient outcomes over the past decades, AAV still results in ESRD in a quarter of patients over 5 years. Relapse rates are significantly lower in patients on chronic dialysis. Patient survival on regular replacement treatment (RRT) does not differ between AAV and matched nondiabetic patients, while it is lower than that of glomerulonephritis. Patients with AAV who undergo kidney transplantation have a mortality not different from the matched control group of primary glomerulonephritides, and favorable transplant survival is similar to that of the matched control groups.

Published
2020

13. Lack of EULAR/ERA-EDTA response at 1 year predicts poor long-term renal outcome in patients with lupus nephritis

Author

Moroni, G, Gatto, M, Tamborini, F, Quaglini, S, Radice, F, Saccon, F, Frontini, G, Alberici, F, Sacchi, L, Binda, V, Trezzi, B, Vaglio, A, Messa, P, Sinico, R, Doria, A, Moroni, Gabriella, Gatto, Mariele, Tamborini, Francesco, Quaglini, Silvana, Radice, Francesca, Saccon, Francesca, Frontini, Giulia, Alberici, Federico, Sacchi, Lucia, Binda, Valentina, Trezzi, Barbara, Vaglio, Augusto, Messa, Piergiorgio, Sinico, Renato Alberto, Doria, Andrea, Moroni, G, Gatto, M, Tamborini, F, Quaglini, S, Radice, F, Saccon, F, Frontini, G, Alberici, F, Sacchi, L, Binda, V, Trezzi, B, Vaglio, A, Messa, P, Sinico, R, Doria, A, Moroni, Gabriella, Gatto, Mariele, Tamborini, Francesco, Quaglini, Silvana, Radice, Francesca, Saccon, Francesca, Frontini, Giulia, Alberici, Federico, Sacchi, Lucia, Binda, Valentina, Trezzi, Barbara, Vaglio, Augusto, Messa, Piergiorgio, Sinico, Renato Alberto, and Doria, Andrea

Abstract

Objectives Short-term predictive endpoints of chronic kidney disease (CKD) are needed in lupus nephritis (LN). We tested response to therapy at 1 year. Methods We considered patients with LN who underwent renal biopsy followed by induction therapy between January 1970 and December 2016. LN was assessed using the International Society of Nephrology/Renal Pathology Society (2003) criteria and the National Institute of Health (NIH) activity and chronicity index. The renal outcome was CKD. Response was defined according to EULAR/European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations: complete: proteinuria <0.5 g/24 hours, (near) normal estimated glomerular filtration rate (eGFR); partial: ≥50% proteinuria reduction to subnephrotic levels, (near) normal eGFR; and no response: all the other cases. Logistic regression analysis was employed for 12-month response and Cox regression for CKD prediction. Results We studied 381 patients (90.5% Caucasians). After 12-month therapy, 58%, 26% and 16% of patients achieved complete, partial and no response, respectively, according to EULAR/ERA-EDTA. During a median follow-up of 10.7 (IQR: 4.97-18.80) years, 53 patients developed CKD. At 15 years, CKD-free survival rate was 95.2%, 87.6% and 55.4% in patients with complete, partial and no response at 12 months, respectively (p<0.0001). CKD-free survival rates did not differ between complete and partial responders (p=0.067). Serum creatinine (HR: 1.485, 95% CI 1.276 to 1.625), eGFR (HR 0.967, 95% CI 0.957 to 0.977) and proteinuria at 12 months (HR 1.234, 95% CI 1.111 to 1.379) were associated with CKD, yet no reliable cut-offs were identified on the receiver operating characteristic curve. In multivariable analysis, no EULAR/ERA-EDTA response at 12 months (HR 5.165, 95% CI 2.770 to 7.628), low C4 (HR 1.053, 95% CI 1.019 to 1.089) and persistent arterial hypertension (HR 3.154, 95% CI 1.500 to 4.547) inde

Published
2020

14. Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient)

Author

Binda, V, Trezzi, B, Del Papa, N, Beretta, L, Frontini, G, Porata, G, Fabbrini, P, Pozzi, M, Messa, P, Sinico, R, Moroni, G, Binda, Valentina, Trezzi, Barbara, Del Papa, Nicoletta, Beretta, Lorenzo, Frontini, Giulia, Porata, Giulia, Fabbrini, Paolo, Pozzi, Maria Rosa, Messa, Piergiorgio, Sinico, Renato Alberto, Moroni, Gabriella, Binda, V, Trezzi, B, Del Papa, N, Beretta, L, Frontini, G, Porata, G, Fabbrini, P, Pozzi, M, Messa, P, Sinico, R, Moroni, G, Binda, Valentina, Trezzi, Barbara, Del Papa, Nicoletta, Beretta, Lorenzo, Frontini, Giulia, Porata, Giulia, Fabbrini, Paolo, Pozzi, Maria Rosa, Messa, Piergiorgio, Sinico, Renato Alberto, and Moroni, Gabriella

Abstract

Background: Belimumab (Benlysta) is currently approved for the treatment of active Lupus despite standard therapy. Few data are available on the efficacy of this drug in lupus nephritis (LN). Methods: 17 LN female followed in two Nephrology Italian Unit received belimumab for a median period of 36 months (range 6–42 months). The indications were: arthralgia in 3 patients, cutaneous manifestations in 2, residual proteinuria in 8, and the need to reduce steroids for severe side effects in 4. Of interest, 1 patient started therapy during Peritoneal Dialysis and continued after kidney transplantation due to non-responsive arthralgias. Results: Arthralgia and skin manifestations resolved in all patients. Proteinuria normalized in three patients and stabilized in all but one of the others. Steroids were indefinitely stopped in six patients (35%) and reduced to around 40% of the basal dosage in the other patients. During belimumab therapy, three extrarenal and one renal SLE flares were diagnosed accounting for a rate of renal flares of 0.02/patient/year. No major adverse events leading to therapy withdrawal occurred. Clinical case: Arthralgia resolved, immunological parameters improved and prednisone could be reduced within few months in the patient who started belimumab during peritoneal dialysis. After kidney transplantation belimumab was stopped but due to arthralgias unresponsive to standard immunosuppressive therapy it was restarted with success. Conclusions: Belimumab allows the achievement of complete response together with the withdrawal or the reduction of corticosteroids in almost all our patients. Of interest its satisfactory use in a patient in peritoneal dialysis and after kidney transplantation.

Published
2020

15. CLINICAL FEATURES AND RENAL PROGNOSIS IN LUPUS NEPHRITIS PATIENTS UNDERGOING A REPEATED BIOPSY: RESULTS OF 103 RE-BIOPSIES IN 438 PATIENTS

Author

Gatto, M, Saccon, F, Radice, F, Vercelloni, P, Sinico, R, Frontini, G, Binda, V, Messa, P, Alberici, F, Moroni, G, Doria ., A, M. Gatto, F. Saccon, F. Radice, P. G. Vercelloni, R. A. Sinico, G. Frontini, V. Binda, P. Messa, F. Alberici, G. Moroni, A. Doria ., Gatto, M, Saccon, F, Radice, F, Vercelloni, P, Sinico, R, Frontini, G, Binda, V, Messa, P, Alberici, F, Moroni, G, Doria ., A, M. Gatto, F. Saccon, F. Radice, P. G. Vercelloni, R. A. Sinico, G. Frontini, V. Binda, P. Messa, F. Alberici, G. Moroni, and A. Doria .

Abstract

Background: Indications to repeat renal biopsy (RB) in lupus nephritis (LN) are not unanimously acknowledged. Objectives: To evaluate the renal outcome of patients with LN undergoing a second RB. Methods: We retrospectively analyzed prospectively collected data of patients with LN followed up in four Italian referral centres for systemic lupus eryhtematosus. Serological and clinical information were retrieved according to a shared database. RB were classified according to ISN/RPS 2003 classification; chronicity (CI) and activity indexes (AI) were defined according to Austin et al. The primary renal outcome was renal failure, defined as serum creatinine (SCr)>1.0mg/dL with eGFR<60ml/min. Non-parametric tests were used for statistics. Patients repeating RB due to renal remission were excluded from the analysis. Results: Four-hundred and thirty-eight patients were recruited. One-hundred and three patients repeated RB after 6.1±4.7 (mean± SD) years from the first due to: protocol biopsy due to renal remission (Group 1, n=8); proteinuric flare (Group 2, n=51); worsened renal function (Group 3, n=26); partial renal response (Group 4 n=18). Patients undergoing a second RB were younger (p<0.001), had lower serum C3 at LN diagnosis (p<0.001) and displayed more frequently class IV and higher AI at first RB (p=0.0038 and p=0.043, respectively). At the end of follow-up, patients who repeated RB had more frequently renal failure (p=0.003). At the second RB, the histological class was unchanged in 55% of patients. CI increased at second RB compared to the first (3.6±2.4 vs.1.7±1.7; p<0.001). Overall, 26 out of 103 patients (25%) developed renal failure: 0 from group 1, 10 from group 2, 14 from group 3, 2 from group 4 (p<0.001). Uncontrolled hypertension at LN diagnosis, increased SCr and increased proteinuria at second RB predicted renal failure (Table). Conclusion: Patients undergoing a repeated RB had more aggressive clinical and histological features already

Published
2020

16. Primer análisis de restos óseos humanos del Sitio PP9.I

Author

González Baroni, Lucía G., Binda, V. R., Castellanos, M. C., Haros, M. C., Colaneri, M. G., and Babot, María del Pilar

Subjects
Ciencias Naturales, Antropología, Anthropology, GN1-890, Physical anthropology. Somatology, GN49-298
Abstract

La recuperación de restos óseos humanos provenientes de un entierro secundario del sitio Punta de la Peña 9, sector I, motivó la necesidad de efectuar un primer análisis bioantropológico de los mismos. Estos corresponden a ocupaciones agropastoriles anteriores a los 830 años AP que fechan carbones suprayacentes. El material recuperado, fragmentado y en regular estado de conservación, fue objeto de una inspección macroscópica, seguida de un análisis morfológico y métrico destinado a estimar MNI, edad, sexo, estado sanitario y presencia, o no, de deformación cefálica artificial. Los resultados alcanzados son: 2 individuos, uno de probable sexo femenino (el otro no determinado), de edad entre 20 y 40 años, sin señales de violencia evidentes, y con una asimetría de la sutura sagital y espina frontal, desplazadas hacia la izquierda del individuo. Se encuentra en proceso una segunda etapa de aná- lisis que permita completar o complementar los aspectos arriba mencionados incluyendo el estudio del contexto de depositación.

Published
2007

20. Can we withdraw immunosuppressants in patients with lupus nephritis in remission? An expert debate

Author

Moroni, G. Gatto, M. Raffiotta, F. Binda, V. Frangou, E. Lightstone, L. Boumpas, D.T.

Abstract

Lupus nephritis (LN) treatment requires an initial intensive period of therapy followed by a long-term maintenance treatment in order to stabilize disease control and eventually reach renal remission. In this section, Authors discuss the feasibility of safely lowering and even suspending maintenance therapy in LN patients having entered remission, highlighting hurdles in predicting the depth and durability of disease quiescence together with the need for minimizing potentially toxic therapies. Even though no firm conclusions can still be drawn, the treating physician has to find the wise balance between disease control and treatment-related drawbacks by following patients closely and recognizing as early as possible the ones who are likely to reach a deep and durable renal remission; there is consensus that is these are the only patients in whom a potential safe complete withdrawal can be foreseen so far. © 2017

Published
2018

22. Sporadic pemphigus foliaceus and class II human leucocyte antigen allele associations in the white British and Indo‐Asian populations in the UK.

Author

Saha, M., Harman, K., Mortimer, N. J., Binda, V., Black, M. M., Kondeatis, E., Vaughan, R., and Groves, R. W.

Abstract

Summary: Background: Pemphigus foliaceus (PF) has both genetic and environmental susceptibility factors. Current data on human leucocyte antigen (HLA) in patients with sporadic PF are limited. Aim: To better define the distribution of HLA alleles in patients with PF in the UK. Methods: We recruited 36 patients [26 of white British (WB) descent, 10 of Indo‐Asian (IA) descent] with PF who were living in the UK and 159 ethnically matched normal controls, and analysed their class II HLA DRB1 and DQB1 allele distribution. Results: There was an increased frequency of DRB1*1404 in association with DQB1*0503 in IA patients with PF. The DRB1*04 allele group as a whole had an increased frequency (P < 0.001) in the WB patient group compared with controls. The alleles contributing to this significance were DRB1*0401 (P = 0.03) and DRB1*0404 (P < 0.01). Conclusion: This is the largest HLA association study in sporadic PF from the UK to date. There appears to be a difference in PF susceptibility alleles between WB and IA patients, highlighting the importance of racial variation in genetic susceptibility to disease development. [ABSTRACT FROM AUTHOR]

Published
2019
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23. Anger Expression, Impulsivity And Expressed Emotion: a Comparison Between Patients With Eating Disorder And Schizophrenia

Author

Gambaro, E., primary, Gramaglia, C., additional, Cenci, D., additional, Delicato, C., additional, Lombardi, A., additional, Rizza, C., additional, Girardi, L., additional, Binda, V., additional, Chieppa, N., additional, Prosperini, P., additional, Bert, F., additional, Siliquini, R., additional, and Zeppegno, P., additional

Published
2016
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25. PP.39.13

Author

Alfieri, C., primary, Regalia, A., additional, Meneghini, M., additional, Gandolfo, M.T., additional, Binda, V., additional, Cresseri, D., additional, Campise, M.R., additional, Croci, M.D., additional, and Messa, P., additional

Published
2015
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28. Feeling Through the Body: Alexithymia and Eating Disorders

Author

Lombardi, A., primary, Gambaro, E., additional, Prosperini, P., additional, Antona, M., additional, Delicato, C., additional, Feggi, A., additional, Rizza, M.C., additional, Palazzolo, A., additional, Binda, V., additional, Chieppa, N., additional, Do, F., additional, Gramaglia, C., additional, and Zeppegno, P., additional

Published
2015
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29. Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey

Author

Ballerini, Andrea, Boccalon, Roberto M., Boncompagni, Giancarlo, Casacchia, Massimo, Margari, Francesco, Minervini, Lina, Righi, Roberto, Russo, Federico, Salteri, Andrea, Frediani, Sonia, Rossi, Andrea, Scatigna, Marco, Barale, F., Bonzano, A., Scioli, R., Bellomo, A., De Giorgi, A., Cammeo, C., Cao, A., Zara, B., Conforti, I., Chillemi, C., Dagnino, L., Ponzoni, M., Della Pietra, F., Benettazzo, M., Esposito, V., Sposito, M., Fato, M., Signorello, G., Fiorenzoni, S., Singali, A., Margari, F., Sicolo, M., Martino, C., Leria, G., Tavoaccini, L., Nigro, G., Russo, V., La Roere, R., Righi, R., Mazzo, M., Rocchetti, R., De Martiis, L., Rodighiero, S., Morello, M., Vescera, M., Pisciotti, D. G., Villari, V., Barzegna, G., Annicchiarico, V., Cosmai, M. G., Rossi, G., Baraldi, E. C., Casacchia, M., Ruggiero, D., Galimberti, P., Fellini, F. A., Francobandiera, G., Gaspari, D., Turati, D., Matacchieri, B., Moscati, G., Mautone, A., DEL CASALE, Monia, Mellado, C., Scaramelli, B., Flilippo, A., Miccichè, M., Minervini, I., Banzato, C., Orengo, S., Alisio, G., Picci, R. L., Venturello, S., D'Aloise, A., Vaira, F., Boccalon, R. M., Cavrini, L., Cogrossi, S., Prato, K., Cremonese, C., Menardi, A., Parisi, M., Mentastro, C., Prosperini, P., Binda, V., Romano, G., Materzanini, A., Crudele, A., Stella, Giuseppe, Petio, C., Fuà, B., Laich, L., Miori, M., Salteri, A., Catania, G., Achena, M., Fara, F. M., Padoani, W., Compagno, S., Pecchioli, S., Moretti, S., Bacchi, L., Vicari, E., Arvizzigno, C., Minunni, P., Rossi, E., Zaiti, M. F., Boncompagni, G., Selleri, M. S., Minnai, G. P., Loche, A. P., Russo, FRANCESCA PAOLA, Antonucci, Annapaola, Chiurco, L., Amendola, R., De Giovanni, M. G., Martano, A., Borsetti, G., Santone, G., Pettolino, A. R., Lisanti, F., Parodi, A., Ciammella, L., Botto, G., Gillotta, S., Florio, G., Fiore, F., Santangelo, E., Fucci, G., Ricci, M., Ciaramella, A., Della Porta, A., Sittinieri, M., D'Asta, L., Triolo, S., Spatola, A., Frediani, S., Rossi, A., Macchi, S., Giovannini, L., Germani, S., Fabbri, Luigi, Fiori, G., Sala, S., Sgarbi, S., Simoni, L., and Zanoli, M.

Subjects
life habits and psychiatric diagnoses, Polypharmacy, Pediatrics, medicine.medical_specialty, business.industry, lcsh:RC435-571, psychiatric emergency, epidemiology, risk factors, medicine.disease, Psychiatry and Mental health, Epidemiology of child psychiatric disorders, Schizophrenia, lcsh:Psychiatry, Epidemiology, medicine, Observational study, Medical prescription, Primary Research, business, Psychiatry, Geriatric psychiatry, Depression (differential diagnoses)
Abstract

Background The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications. Methods A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period. Results Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay. Conclusion Results confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.

Published
2007

30. Primer análisis de restos óseos humanos del Sitio PP9.I : Estructura I - Antofagasta de la Sierra, Catamarca

Author

González Baroni, Lucía G., Binda, V. R., Castellanos, María Cecilia, Haros, M. C., Colaneri, M. G., and Babot, María del Pilar

Subjects
Antropología, bones, bioantropología, osteoarchaelogy, Ciencias Naturales, Catamarca (Argentina), Arqueología
Abstract

La recuperación de restos óseos humanos provenientes de un entierro secundario del sitio Punta de la Peña 9, sector I, motivó la necesidad de efectuar un primer análisis bioantropológico de los mismos. Estos corresponden a ocupaciones agropastoriles anteriores a los 830 años AP que fechan carbones suprayacentes. El material recuperado, fragmentado y en regular estado de conservación, fue objeto de una inspección macroscópica, seguida de un análisis morfológico y métrico destinado a estimar MNI, edad, sexo, estado sanitario y presencia, o no, de deformación cefálica artificial. Los resultados alcanzados son: 2 individuos, uno de probable sexo femenino (el otro no determinado), de edad entre 20 y 40 años, sin señales de violencia evidentes, y con una asimetría de la sutura sagital y espina frontal, desplazadas hacia la izquierda del individuo. Se encuentra en proceso una segunda etapa de aná- lisis que permita completar o complementar los aspectos arriba mencionados incluyendo el estudio del contexto de depositación., Sesión de pósters., Asociación de Antropología Biológica de la República Argentina (AABRA)

Published
2007

31. Primary and secondary glomerulonephritis II

Author

Valdivia Vega, R. P., primary, Perez Carlos, J., additional, LI, X., additional, Xu, X., additional, Zhang, W., additional, Ren, H., additional, Chen, N., additional, Yorioka, N., additional, Doi, T., additional, Hirashio, S., additional, Arita, M., additional, Hirabayashi, A., additional, Tilkiyan, E., additional, Chonova, E., additional, Ronchev, Y., additional, Kumchev, E., additional, Giamalis, P., additional, Spartalis, M., additional, Stangou, M., additional, Tsouchnikas, I., additional, Moysiades, D., additional, Dimopoulou, D., additional, Garyfalos, A., additional, Efstratiadis, G., additional, Memmos, D., additional, Schonermarck, U., additional, Eichhorn, P., additional, Sitter, T., additional, Wendler, T., additional, Vielhauer, V., additional, Lederer, S., additional, Fechner, K., additional, Fischereder, M., additional, Bantis, C., additional, Heering, P., additional, Kouri, N.-M., additional, Schwandt, C., additional, Kuhr, N., additional, Ivens, K., additional, Rump, L.-C., additional, Matta, V., additional, Melis, P., additional, Conti, M., additional, Cao, R., additional, Binda, V., additional, Altieri, P., additional, Asunis, A. M., additional, Catani, W., additional, Floris, M., additional, Angioi, A., additional, Congia, M., additional, Cucca, F., additional, Minerba, L., additional, Peri, M., additional, Pani, A., additional, Beck, L. H., additional, Fervenza, F. C., additional, Bomback, A. S., additional, Ayalon, R., additional, Irazabal, M. V., additional, Eirin, A., additional, Cattran, D. C., additional, Appel, G. B., additional, Salant, D. J., additional, Santoro, D., additional, Postorino, A., additional, Costantino, G., additional, Bellinghieri, G., additional, Savica, V., additional, Weiner, M., additional, Goh, S. M., additional, Mohammad, A., additional, Eriksson, P., additional, Westman, K., additional, Selga, D., additional, Salama, A., additional, Segelmark, M., additional, Chocova, Z., additional, Hruskova, Z., additional, Mareckova, H., additional, Svobodova, B., additional, Jancova, E., additional, Bednarova, V., additional, Rysava, R., additional, Tesar, V., additional, Hanzal, V., additional, Zamboch, K., additional, Grussmannova, M., additional, Svojanovsky, J., additional, Klaboch, J., additional, Kubisova, M., additional, Sevcik, J., additional, Olsanska, R., additional, Sobotkova, M., additional, Becvar, R., additional, Nemec, P., additional, Kodeda, M., additional, Jilek, D., additional, Hussain, M., additional, Dhaygude, A., additional, Cartery, C., additional, Huart, A., additional, Plaisier, E., additional, Bongard, V., additional, Montastruc, F., additional, Ronco, P., additional, Pourrat, J., additional, Chauveau, D., additional, Prasad, N., additional, Gurjar, D., additional, Bhadauria, D., additional, Sharma, R. K., additional, Gupta, A., additional, Kaul, A., additional, Jain, M., additional, Venning, M., additional, Brown, N., additional, Bruce, I., additional, Noor, S., additional, Bekker, P., additional, Potarca, A., additional, Dairaghi, D., additional, Miao, S., additional, Powers, J. P., additional, Jaen, J. C., additional, Schall, T. J., additional, Kalavrizioti, D., additional, Gerolymos, M., additional, Komninakis, D., additional, Rodi, M., additional, Mouzaki, A., additional, Kalliakmani, P., additional, Goumenos, D., additional, Choi, B. S., additional, Park, C. W., additional, Kim, Y.-S., additional, Yang, C. W., additional, Sun, I. O., additional, Qin, W., additional, Xie, L., additional, Tan, C., additional, Mian, W., additional, Fu, P., additional, Kaminskyy, V., additional, Hao, X., additional, Wang, W., additional, Cengiz, C., additional, Nur, C., additional, Nurdan, Y., additional, Selman, G., additional, Pinar, T., additional, Mehmet, T., additional, Lale, S., additional, Caliskan, S., additional, Shinzawa, M., additional, Yamamoto, R., additional, Nagasawa, Y., additional, Oseto, S., additional, Mori, D., additional, Niihata, K., additional, Fukunaga, M., additional, Yamauchi, A., additional, Tsubakihara, Y., additional, Rakugi, H., additional, Isaka, Y., additional, Chen, J.-S., additional, Lin, Y.-F., additional, Lin, W.-Y., additional, Shu, K.-H., additional, Chen, H.-H., additional, Wu, C.-J., additional, Yang, C.-S., additional, Tseng, T.-L., additional, Zaza, G., additional, Bernich, P., additional, Lupo, A., additional, Panizo, N., additional, Rivera, F., additional, Lopez Gomez, J. M., additional, Regn, S. R. o. G., additional, Ceresini, G., additional, Vaglio, A., additional, Urban, M. L., additional, Corradi, D., additional, Usberti, E., additional, Palmisano, A., additional, Buzio, C., additional, Zineb, H., additional, Ramdani, B., additional, Marques, L. P. J., additional, Rioja, L. D. S., additional, Rocco, R., additional, Nery, A. C. F., additional, Novaes, B. C., additional, Bridoux, F., additional, Sicard, A., additional, Labatut, D., additional, Touchard, G., additional, Sarkozy, C., additional, Vanhille, P., additional, Callard, P., additional, Essig, M., additional, Provot, F., additional, Nony, A., additional, Karras, A., additional, Agustin, C. P., additional, M Belen, H. R., additional, Carmen, C. P., additional, Eliana, O., additional, Elisa, P., additional, Luis, P., additional, Alberto, M.-C., additional, Javier, N., additional, Isabel, F., additional, Atzeni, A., additional, Fois, A., additional, Piras, D., additional, Maxia, S., additional, Sau, G., additional, Pili, G., additional, Porcu, M., additional, Derudas, D., additional, Angelucci, E., additional, Ledda, A., additional, La Nasa, G., additional, Ossareh, S., additional, Asgari, M., additional, Savaj, S., additional, Ataipour, Y., additional, Abdi, E., additional, Malakoutian, T., additional, Rajaa, R., additional, Berkchi, F. Z., additional, Haffane, L., additional, Squalli, Z., additional, Rouass, L., additional, Al Hamany, Z., additional, Ezzaitouni, F., additional, Benamar, L., additional, Bayahya, R., additional, Ouzeddoun, N., additional, Gao-Yuan, H., additional, Yao, X., additional, Xin, C., additional, Zhen, C., additional, Yong-Chun, G., additional, Qing-Wen, W., additional, Hui-Ping, C., additional, Da-XI, J., additional, De-Hua, G., additional, Wei-Xin, H., additional, Zhi-Hong, L., additional, Fatima Zahra, B., additional, Laila, H., additional, Zoubair, S., additional, Naima, O., additional, Smykal-Jankowiak, K., additional, Niemir, Z., additional, Polcyn-Adamczak, M., additional, Szramka-Pawlak, B., additional, Zaba, R., additional, Zhang, C., additional, MA, Y., additional, Shen, P., additional, Ouyang, Y., additional, Pan, X., additional, Wang, Z., additional, Feng, X., additional, and Ni, L., additional

Published
2012
Full Text
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32. AKI - Clinical

Author

Gok Oguz, E., primary, Olmaz, R., additional, Turgutalp, K., additional, Muslu, N., additional, Sungur, M. A., additional, Kiykim, A., additional, Van Biesen, W., additional, Vanmassenhove, J., additional, Glorieux, G., additional, Vanholder, R., additional, Chew, S., additional, Forster, K., additional, Kaufeld, T., additional, Kielstein, J., additional, Schilling, T., additional, Haverich, A., additional, Haller, H., additional, Schmidt, B., additional, Hu, P., additional, Liang, X., additional, Chen, Y., additional, LI, R., additional, Jiang, F., additional, LI, Z., additional, Shi, W., additional, Lim, C. C. W., additional, Chia, C. M. L., additional, Tan, A. K., additional, Tan, C. S., additional, Ng, R., additional, Subramani, S., additional, Perez de Jose, A., additional, Bernis Carro, C., additional, Madero Jarabo, R., additional, Bustamante, J., additional, Sanchez Tomero, J. A., additional, Chung, W., additional, Ro, H., additional, Chang, J. H., additional, Lee, H. H., additional, Jung, J. Y., additional, Fazzari, L., additional, Giuliani, A., additional, Scrivano, J., additional, Pettorini, L., additional, Benedetto, U., additional, Luciani, R., additional, Roscitano, A., additional, Napoletano, A., additional, Coclite, D., additional, Cordova, E., additional, Punzo, G., additional, Sinatra, R., additional, Mene, P., additional, Pirozzi, N., additional, Shavit, L., additional, Manilov, R., additional, Algur, N., additional, Wiener-Well, Y., additional, Slotki, I., additional, Pipili, C., additional, Vrettou, C. S., additional, Avrami, K., additional, Economidou, F., additional, Glynos, K., additional, Ioannidou, S., additional, Markaki, V., additional, Douka, E., additional, Nanas, S., additional, De Pascalis, A., additional, Cofano, P., additional, Proia, S., additional, Valletta, A., additional, Vitale, O., additional, Russo, F., additional, Buongiorno, E., additional, Filiopoulos, V., additional, Biblaki, D., additional, Lazarou, D., additional, Chrysis, D., additional, Fatourou, M., additional, Lafoyianni, S., additional, Vlassopoulos, D., additional, Zakiyanov, O., additional, Kriha, V., additional, Vachek, J., additional, Svarcova, J., additional, Zima, T., additional, Tesar, V., additional, Kalousova, M., additional, Kaushik, M., additional, Ronco, C., additional, Cruz, D., additional, Zhang, L., additional, Zhang, W., additional, Chen, N., additional, Ejaz, A. A., additional, Kambhampati, G., additional, Ejaz, N., additional, Dass, B., additional, Lapsia, V., additional, Arif, A. A., additional, Asmar, A., additional, Shimada, M., additional, Alsabbagh, M., additional, Aiyer, R., additional, Johnson, R., additional, Chen, T.-H., additional, Chang, C.-H., additional, Chang, M.-Y., additional, Tian, Y.-C., additional, Hung, C.-C., additional, Fang, J.-T., additional, Yang, C.-W., additional, Chen, Y.-C., additional, Cantaluppi, V., additional, Quercia, A. D., additional, Figliolini, F., additional, Giacalone, S., additional, Pacitti, A., additional, Gai, M., additional, Guarena, C., additional, Leonardi, G., additional, Biancone, L., additional, Camussi, G., additional, Segoloni, G. P., additional, De Cal, M., additional, Lentini, P., additional, Clementi, A., additional, Virzi, G. M., additional, Scalzotto, E., additional, Lacquaniti, A., additional, Donato, V., additional, Fazio, M. R., additional, Lucisano, S., additional, Cernaro, V., additional, Lupica, R., additional, Buemi, M., additional, Helvaci, I., additional, Anik, E., additional, Wani, M., additional, Wani, D. I., additional, Bhat, D. M. A., additional, Banday, D. K., additional, Najar, D. M. S., additional, Reshi, D. A. R., additional, Palla, D. N. A., additional, Iglesias, P., additional, Olea, T., additional, Vega-Cabrera, C., additional, Heras, M., additional, Bajo, M. A., additional, Del Peso, G., additional, Arias, M. J., additional, Selgas, R., additional, Diez, J. J., additional, Daher, E., additional, Costa, P. L., additional, Pereira, E. N. S., additional, Santos, R. D. P., additional, Abreu, K. L., additional, Silva Junior, G., additional, Pereira, E. D. B., additional, Raimundo, M., additional, Crichton, S., additional, Syed, Y., additional, Martin, J., additional, Whiteley, C., additional, Bennett, D., additional, Ostermann, M., additional, Gjyzari, A., additional, Thereska, N., additional, Koroshi, A., additional, Barbullushi, M., additional, Kodra, S., additional, Idrizi, A., additional, Strakosha, A., additional, Petrela, E., additional, Lemmich Smith, J., additional, Klimenko, A., additional, Tuykhmenev, E., additional, Villevalde, S., additional, Kobalava, Z., additional, Avdoshina, S., additional, Tyukhmenev, E., additional, Efremovtseva, M., additional, Hayashi, H., additional, Suzuki, S., additional, Kataoka, K., additional, Kondoh, Y., additional, Taniguchi, H., additional, Sugiyama, D., additional, Nishimura, K., additional, Sato, W., additional, Maruyama, S., additional, Matsuo, S., additional, Yuzawa, Y., additional, Geraldine, D., additional, Muriel, F., additional, Alexandre, H., additional, Eric, R., additional, Fu, P., additional, Pozzato, M., additional, Ferrari, F., additional, Cecere, P., additional, Mesiano, P., additional, Vallero, A., additional, Livigni, S., additional, Quarello, F., additional, Hudier, L., additional, Decaux, O., additional, Haddj-Elmrabet, A., additional, Mandart, L., additional, Lino-Daniel, M., additional, Bridoux, F., additional, Renaudineau, E., additional, Sawadogo, T., additional, Le Pogamp, P., additional, Vigneau, C., additional, Famee, D., additional, Koo, H. M., additional, Oh, H. J., additional, Han, S. H., additional, Choi, K. H., additional, Kang, S.-W., additional, Mehdi, M., additional, Nicolas, M., additional, Mariat, C., additional, Shah, P., additional, Kute, V. B., additional, Vanikar, A., additional, Gumber, M., additional, Patel, H., additional, Trivedi, H., additional, Manetos, C., additional, Poulaki, S., additional, Tripodaki, E.-S., additional, Papastylianou, A., additional, Routsi, C., additional, Uchida, K., additional, Kensuke, U., additional, Yamagata, K., additional, Saitou, C., additional, Okada, M., additional, Chita, G., additional, Davies, M., additional, Veriawa, Y., additional, Naicker, S., additional, Mukhopadhyay, P., additional, Mukherjee, D., additional, Mishra, R., additional, Kar, M., additional, Zickler, D., additional, Wesselmann, H., additional, Schindler, R., additional, Gutierrez*, E., additional, Egido, J., additional, Rubio-Navarro, A., additional, Buendia, I., additional, Blanco-Colio, L. M., additional, Toldos, O., additional, Manzarbeitia, F., additional, De Lorenzo, A., additional, Sanchez, R., additional, Praga^, M., additional, Moreno^, J. A., additional, Kim, M. Y., additional, Kang, N. R., additional, Jang, H. R., additional, Lee, J. E., additional, Huh, W., additional, Kim, Y.-G., additional, Kim, D. J., additional, Hong, S.-C., additional, Kim, J.-S., additional, Oh, H. Y., additional, Okamoto, T., additional, Kamata, K., additional, Naito, S., additional, Tazaki, H., additional, Kan, S., additional, Anne-Kathrin, L.-G., additional, Matthias, K., additional, Speer, T., additional, Andreas, L., additional, Heinrich, G., additional, Thomas, V., additional, Poppleton, A., additional, Danilo, F., additional, Lai, C.-F., additional, Wu, V.-C., additional, Shiao, C.-C., additional, Huang, T.-M., additional, Wu, K.-D., additional, Bedford, M., additional, Farmer, C., additional, Irving, J., additional, Stevens, P., additional, Patera, F., additional, Mattozzi, F., additional, Battistoni, S., additional, Fagugli, R. M., additional, Park, M. Y., additional, Choi, S. J., additional, Kim, J. G., additional, Hwang, S. D., additional, Xie, H., additional, Chen, H., additional, Xu, S., additional, He, Q., additional, Liu, J., additional, Hu, W., additional, Liu, Z., additional, Dalboni, M., additional, Blaya, R., additional, Quinto, B. M., additional, Narciso, R., additional, Oliveira, M., additional, Monte, J., additional, Durao, M., additional, Cendoroglo, M., additional, Batista, M., additional, Hanemann, A. L., additional, Liborio, A., additional, Martins, A., additional, Pinheiro, M. C. C., additional, Meneses, G., additional, De Paula Pessoa, R., additional, Sousa, M., additional, Bezerra, F. S. M., additional, Albuquerque, P. L. M. M., additional, Lima, J. B., additional, Lima, C. B., additional, Veras, M. D. S. B., additional, Nemoto Matsui, T., additional, Totoli, C., additional, Cruz Andreoli, M. C., additional, Vilela Coelho, M. P., additional, Guimaraes de Souza, N. K., additional, Ammirati, A. L., additional, De Carvalho Barreto, F., additional, Ferraz Neto, B.-H., additional, Fortunato Cardoso Dos Santos, B., additional, Abraham, A., additional, Abraham, G., additional, Mathew, M., additional, Duarte, P. M. A., additional, Duarte, F. B., additional, Barros, E. M., additional, Castro, F. Q. S., additional, Palomba, H., additional, Castro, I., additional, Sousa, S. R., additional, Jesus, A. N., additional, Romano, T., additional, Burdmann, E., additional, Yu, L., additional, Kwon, S. H., additional, You, J. Y., additional, Hyun, Y. K., additional, Woo, S. A., additional, Jeon, J. S., additional, Noh, H. J., additional, Han, D. C., additional, Tozija, L., additional, Petronievic, Z., additional, Selim, G., additional, Nikolov, I., additional, Stojceva-Taneva, O., additional, Cakalaroski, K., additional, Lukasz, A., additional, Beneke, J., additional, Menne, J., additional, Schiffer, M., additional, Polanco, N., additional, Hernandez, E., additional, Gutierrez, E., additional, Gutierrez Millet, V., additional, Gonzalez Monte, E., additional, Morales, E., additional, Praga, M., additional, Francisco Javier, L., additional, Nuria, G.-F., additional, Jose Maria, M.-G., additional, Bes Rastrollo, M., additional, Angioi, A., additional, Conti, M., additional, Cao, R., additional, Atzeni, A., additional, Pili, G., additional, Matta, V., additional, Murgia, E., additional, Melis, P., additional, Binda, V., additional, Pani, A., additional, Thome*, F., additional, Leusin, F., additional, Barros, E., additional, Morsch, C., additional, Balbinotto, A., additional, Pilla, C., additional, Premru, V., additional, Buturovic-Ponikvar, J., additional, Ponikvar, R., additional, Marn-Pernat, A., additional, Knap, B., additional, Kovac, J., additional, Gubensek, J., additional, Kersnic, B., additional, Krnjak, L., additional, Prezelj, M., additional, Granatova, J., additional, Havrda, M., additional, Hruskova, Z., additional, Kratka, K., additional, Remes, O., additional, Mokrejsova, M., additional, Bolkova, M., additional, Lanska, V., additional, Rychlik, I., additional, Uniacke, M. D., additional, Lewis, R. J., additional, Harris, S., additional, Roderick, P., additional, Martin, N., additional, Ulrich, K., additional, Jan, B., additional, Jorn, B., additional, Reinhard, B., additional, Jan, K., additional, Hermann, H., additional, Meyer Tobias, F., additional, Leyla, R., additional, Schmidt Bernhard, M. W., additional, Harald, S., additional, Jurgen, S., additional, Tanja, K., additional, Mario, S., additional, Sang Hi, E., additional, Claus, M., additional, Frank, V., additional, Aleksej, S., additional, Sengul, S., additional, Robert, S., additional, Karin, W., additional, Feikah, G., additional, Menne Tobias, F., additional, Meyer Tobias, N., additional, Beutel, G., additional, Fleig, S., additional, Steinhoff, J., additional, Meyer, T., additional, Hafer, C., additional, Bramstedt, J., additional, Busch, V., additional, Vischedyk, M., additional, Kuhlmann, U., additional, Ries, W., additional, Mitzner, S., additional, Mees, S., additional, Stracke, S., additional, Nurnberger, J., additional, Gerke, P., additional, Wiesner, M., additional, Sucke, B., additional, Abu-Tair, M., additional, Kribben, A., additional, Klause, N., additional, Merkel, F., additional, Schnatter, S., additional, Dorresteijn, E., additional, Samuelsson, O., additional, Brunkhorst, R., additional, Stec-Hus Registry, G., additional, Reising, A., additional, Bange, F.-C., additional, Hiss, M., additional, Vetter, F., additional, Bode-Boger, S. M., additional, Martens-Lobenhoffer, J., additional, Schmidt, B. M. W., additional, Kielstein, J. T., additional, Shin, H. S., additional, Jung, Y. S., additional, and Rim, H., additional

Published
2012
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33. [Use of first and second generation antidepressants. A clinical study]

Author

Bogetto F, Binda V, Giuseppe Maina, Passera R, Pastore G, Torta R, and Ravizza L

Subjects
Male, Depression, Humans, Female, Antidepressive Agents, Drug Utilization
Abstract

The study assesses the quantitative percentage use of second generation antidepressants (non-tricyclics or modified tricyclics) in clinical psychiatric practice in comparison with first generation products. The study was conducted on patients presenting in the surgery and psychiatric ward of Novara and in Turin Psychiatric Clinic in an-June 1987 and covers all patients receiving antidepressant drugs. For each individual given thymoanaleptic drugs, the type used and the reasons for its selection were examined as well as the combined use of antidepressants with other psychotherapeutic drugs. The data show that second generation antidepressants have come to play a major therapeutic role, though further research is needed to define their specific use and as far as possible to eliminate their use as a "vicarious" substitute for traditional drugs.

Published
1990

37. Serum IgG2 antibody multicomposition in systemic lupus erythematosus and lupus nephritis (Part 1): cross-sectional analysis

Author

Simone Negrini, Paola Migliorini, Angelo Ravelli, Marcello Bagnasco, Marta Mosca, Andrea Angeletti, Giampaola Pesce, Carlomaurizio Montecucco, Augusto Vaglio, Gabriella Moroni, Francesco Locatelli, Paride Fenaroli, Giacomo Emmi, Barbara Trezzi, Ilaria Cavazzana, Isabella Pisani, Giuseppe A. Ramirez, Valentina Binda, Maurizio Bruschi, Angela Tincani, Lorenzo Cavagna, Renato Alberto Sinico, Enrico Verrina, Francesco Scolari, Stefano Volpi, Leda Cipriani, Franco Franceschini, Gian Marco Ghiggeri, Pasquale Esposito, Giuseppe Murdaca, Federico Pratesi, Giovanni Candiano, Micaela Fredi, Andrea Petretto, Marco Prunotto, Giacomo Garibotto, Angelo A. Manfredi, Giulia Pazzola, Domenico Santoro, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Volpi, S, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, M., Moroni, G., Sinico, R. A., Franceschini, F., Fredi, M., Vaglio, A., Cavagna, L., Petretto, A., Pratesi, F., Migliorini, P., Locatelli, F., Pazzola, G., Pesce, G., Bagnasco, M., Manfredi, A., Ramirez, G. A., Esposito, P., Murdaca, G., Negrini, S., Cipriani, L., Trezzi, B., Emmi, G., Cavazzana, I., Binda, V., Fenaroli, P., Pisani, I., Garibotto, G., Montecucco, C., Santoro, D., Scolari, F., Mosca, M., Tincani, A., Candiano, G., Prunotto, M., Volpi, S., Verrina, E., Angeletti, A., Ravelli, A., and Ghiggeri, G. M.

Subjects
Male, 0301 basic medicine, Cross-sectional study, Lupus nephritis, SLE, Gastroenterology, LN, Arthritis, Rheumatoid, Histones, 0302 clinical medicine, immune system diseases, Antibody Specificity, anti-C1q antibodie, Lupus Erythematosus, Systemic, Pharmacology (medical), skin and connective tissue diseases, Annexin A1, anti-ENO1 antibodie, biology, Radioimmunoassay, Clinical Science, Middle Aged, Antiphospholipid Syndrome, Lupus Nephritis, Isotype, anti-C1q antibodies, anti-ENO1 antibodies, anti-Histone 2A antibodies, biomarkers, Adolescent, Adult, Antibodies, Antinuclear, Biomarkers, Tumor, Complement C1q, Cross-Sectional Studies, DNA, DNA-Binding Proteins, Female, Humans, Immunoglobulin G, Nucleosomes, Phosphopyruvate Hydratase, Tumor Suppressor Proteins, Undifferentiated Connective Tissue Diseases, Young Adult, biomarker, Antibody, medicine.medical_specialty, anti-Histone 2A antibodie, 03 medical and health sciences, Rheumatology, Antigen, Internal medicine, medicine, 030203 arthritis & rheumatology, business.industry, Anti-dsDNA antibodies, medicine.disease, 030104 developmental biology, biology.protein, Complication, business
Abstract

Objectives Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. Methods A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques. Results The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low–medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0–12 months), and high levels at T0–1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions. Conclusion Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients. Trial registration The Zeus study was registered at https://clinicaltrials.gov, NCT02403115.

Published
2021

38. Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (Part 2): prospective study

Author

Paride Fenaroli, Enrico Verrina, Paola Migliorini, Renato Alberto Sinico, Leda Cipriani, Angelo A. Manfredi, Francesco Locatelli, Marta Mosca, Federico Pratesi, Angelo Ravelli, Marcello Bagnasco, Augusto Vaglio, Giulia Pazzola, Micaela Fredi, Andrea Petretto, Carlomaurizio Montecucco, Barbara Trezzi, Franco Franceschini, Valentina Binda, Domenico Santoro, Giacomo Garibotto, Giovanni Candiano, Marco Prunotto, Francesco Scolari, Giuseppe A. Ramirez, Giacomo Emmi, Matteo D'Alessandro, Isabella Pisani, Andrea Angeletti, Giampaola Pesce, Simone Negrini, Pasquale Esposito, Giuseppe Murdaca, Angela Tincani, Gabriella Moroni, Gian Marco Ghiggeri, Ilaria Cavazzana, Stefano Volpi, Maurizio Bruschi, Lorenzo Cavagna, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Angeletti, A, Ravelli, A, Ghiggeri, G, Bruschi, M., Moroni, G., Sinico, R. A., Franceschini, F., Fredi, M., Vaglio, A., Cavagna, L., Petretto, A., Pratesi, F., Migliorini, P., Locatelli, F., Pazzola, G., Pesce, G., Bagnasco, M., Manfredi, A., Ramirez, G. A., Esposito, P., Murdaca, G., Negrini, S., Cipriani, L., Trezzi, B., Emmi, G., Cavazzana, I., Binda, V., D'Alessandro, M., Fenaroli, P., Pisani, I., Garibotto, G., Montecucco, C., Santoro, D., Scolari, F., Volpi, S., Mosca, M., Tincani, A., Candiano, G., Prunotto, M., Verrina, E., Angeletti, A., Ravelli, A., and Ghiggeri, G. M.

Subjects
0301 basic medicine, Male, Anti-nuclear antibody, Lupus nephritis, lupus nephriti, Gastroenterology, Histones, 0302 clinical medicine, systemic lupus erythematosus, anti-C1q antibodie, Lupus Erythematosus, Systemic, Pharmacology (medical), Prospective Studies, Prospective cohort study, AcademicSubjects/MED00360, Annexin A1, anti-ENO1 antibodie, education.field_of_study, Keywords: anti-C1q antibodies, anti-ENO1 antibodies, anti-Histone 2A antibodies, biomarkers, lupus nephritis, Proteinuria, biology, anti-C1q antibodies, Adult, Antibodies, Antinuclear, Autoantibodies, Biomarkers, Tumor, Complement C1q, DNA, DNA-Binding Proteins, Disease Progression, Female, Humans, Immunoglobulin G, Lupus Nephritis, Middle Aged, Nucleosomes, Phosphopyruvate Hydratase, Tumor Suppressor Proteins, Clinical Science, biomarker, medicine.symptom, medicine.medical_specialty, anti-Histone 2A antibodie, Population, Renal function, systemic lupus erythematosu, 03 medical and health sciences, Rheumatology, Internal medicine, medicine, education, 030203 arthritis & rheumatology, business.industry, Anti-dsDNA antibodies, Autoantibody, medicine.disease, 030104 developmental biology, biology.protein, business
Abstract

Objectives Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. Methods Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques. Results LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months. Conclusions Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN. Trial registration The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).

Published
2021

39. Evidence for charge-based mimicry in anti dsDNA antibody generation

Author

Maurizio Bruschi, Andrea Angeletti, Xhuliana Kajana, Gabriella Moroni, Renato Alberto Sinico, Micaela Fredi, Augusto Vaglio, Lorenzo Cavagna, Federico Pratesi, Paola Migliorini, Francesco Locatelli, Giulia Pazzola, Giampaola Pesce, Marcello Bagnasco, Angelo Manfredi, Giuseppe Alvise Ramirez, Pasquale Esposito, Simone Negrini, Federica Bui, Barbara Trezzi, Giacomo Emmi, Ilaria Cavazzana, Valentina Binda, Paride Fenaroli, Isabella Pisani, Carlomaurizio Montecucco, Domenico Santoro, Francesco Scolari, Stefano Volpi, Marta Mosca, Angela Tincani, Giovanni Candiano, Enrico Verrina, Franco Franceschini, Angelo Ravelli, Marco Prunotto, Pier Luigi Meroni, Gian Marco Ghiggeri, Bruschi, M, Angeletti, A, Kajana, X, Moroni, G, Sinico, R, Fredi, M, Vaglio, A, Cavagna, L, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Negrini, S, Bui, F, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, Fenaroli, P, Pisani, I, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Verrina, E, Franceschini, F, Ravelli, A, Prunotto, M, Meroni, P, and Ghiggeri, G

Subjects
Immunology, IgG2, DNA, anti-dsDNA antibodie, Lupus Nephritis, Anionic epitope, Antibodies, Antinuclear, Immunoglobulin G, Immunology and Allergy, Humans, Lupus Erythematosus, Systemic, Mimicry, anti-Annexin A1 antibodie, Isotype, Autoantibodies, Annexin A1
Abstract

Mechanisms for the generation of anti-dsDNA autoantibodies are still not completely elucidated. One theory states that dsDNA interacts for mimicry with antibodies raised versus other antigens but molecular features for mimicry are unknown. Here we show that, at physiological acid-base balance, anti-Annexin A1 binds IgG2 dsDNA in a competitive and dose-dependent way with Annexin A1 and that the competition between the two molecules is null at pH 9. On the other hand, these findings also show that dsDNA and Annexin A1 interact with their respective antibodies on a strictly pH-dependent basis: in both cases, the binding was minimal at pH 4 and maximal at pH9-10. The anionic charge of dsDNA is mainly conferred by the numerous phosphatidic residues. The epitope binding site of Annexin A1 for anti-Annexin A1 IgG2 was here characterized as a string of 34 amino acids at the NH2 terminus, 10 of which are anionic. Circulating levels of anti-dsDNA and anti-Annexin A1 IgG2 antibodies were strongly correlated in patients with systemic lupus erythematosus (n 496) and lupus nephritis (n 425) stratified for age, sex, etc. These results show that dsDNA competes with Annexin A1 for the binding with anti-Annexin A1 IgG2 on a dose and charged mediated base, being able to display an inhibition up to 75%. This study provides the first demonstration that dsDNA may interact with antibodies raised versus other anionic molecules (anti-Annexin A1 IgG2) because of charge mimicry and this interaction may contribute to anti-dsDNA antibodies generation.

Published
2022

40. Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient)

Author

Piergiorgio Messa, Maria Rosa Pozzi, Nicoletta Del Papa, Giulia Porata, Giulia Frontini, Gabriella Moroni, Paolo Fabbrini, Barbara Trezzi, Renato Alberto Sinico, Valentina Binda, Lorenzo Beretta, Binda, V, Trezzi, B, Del Papa, N, Beretta, L, Frontini, G, Porata, G, Fabbrini, P, Pozzi, M, Messa, P, Sinico, R, and Moroni, G

Subjects
Nephrology, medicine.medical_specialty, medicine.medical_treatment, SLE, 030232 urology & nephrology, Lupus nephritis, Systemic lupus erythematosu, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Peritoneal dialysis, Kidney transplantation, 03 medical and health sciences, Systemic lupus erythematosus, 0302 clinical medicine, Renal Dialysis, Prednisone, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, Glucocorticoids, Dialysis, business.industry, Lupus nephriti, medicine.disease, Lupus Nephritis, Belimumab, Treatment Outcome, Female, business, Immunosuppressive Agents, medicine.drug
Abstract

Background: Belimumab (Benlysta) is currently approved for the treatment of active Lupus despite standard therapy. Few data are available on the efficacy of this drug in lupus nephritis (LN). Methods: 17 LN female followed in two Nephrology Italian Unit received belimumab for a median period of 36 months (range 6–42 months). The indications were: arthralgia in 3 patients, cutaneous manifestations in 2, residual proteinuria in 8, and the need to reduce steroids for severe side effects in 4. Of interest, 1 patient started therapy during Peritoneal Dialysis and continued after kidney transplantation due to non-responsive arthralgias. Results: Arthralgia and skin manifestations resolved in all patients. Proteinuria normalized in three patients and stabilized in all but one of the others. Steroids were indefinitely stopped in six patients (35%) and reduced to around 40% of the basal dosage in the other patients. During belimumab therapy, three extrarenal and one renal SLE flares were diagnosed accounting for a rate of renal flares of 0.02/patient/year. No major adverse events leading to therapy withdrawal occurred. Clinical case: Arthralgia resolved, immunological parameters improved and prednisone could be reduced within few months in the patient who started belimumab during peritoneal dialysis. After kidney transplantation belimumab was stopped but due to arthralgias unresponsive to standard immunosuppressive therapy it was restarted with success. Conclusions: Belimumab allows the achievement of complete response together with the withdrawal or the reduction of corticosteroids in almost all our patients. Of interest its satisfactory use in a patient in peritoneal dialysis and after kidney transplantation.

Published
2020

41. Clinical and histological findings at second but not at first kidney biopsy predict end-stage kidney disease in a large multicentric cohort of patients with active lupus nephritis

Author

Mariele Gatto, Francesca Radice, Francesca Saccon, Marta Calatroni, Giulia Frontini, Barbara Trezzi, Margherita Zen, Anna Ghirardello, Francesco Tamborini, Valentina Binda, Vincenzo L'Imperio, Andrea Doria, Augusto Vaglio, Renato Alberto Sinico, Gabriella Moroni, Luca Iaccarino, Gatto, M, Radice, F, Saccon, F, Calatroni, M, Frontini, G, Trezzi, B, Zen, M, Ghirardello, A, Tamborini, F, Binda, V, L'Imperio, V, Doria, A, Vaglio, A, Sinico, R, Moroni, G, and Iaccarino, L

Subjects
Inflammation, Male, Lupus Erythematosus, Biopsy, Immunology, Systemic, General Medicine, Lupus Nephriti, Kidney, Lupus Nephritis, Kidney Failure, Proteinuria, Lupus Erythematosus, Systemic, Female, Humans, Retrospective Studies, Kidney Failure, Chronic, Chronic
Abstract

ObjectiveTo investigate second kidney biopsy as predictor of end-stage kidney disease (ESKD) in active lupus nephritis (LN).MethodsPatients with biopsy-proven LN (International Society of Nephrology/Renal Pathology Society 2003) who had undergone a second kidney biopsy between January 1990 and December 2018 were included. Clinical and histological findings at first and at second biopsy were analysed with Cox proportional hazard models to predict ESKD, defined as start of kidney replacement therapy. Survival curves were calculated with Kaplan-Meier method.ResultsNinety-two patients with LN were included, 87% females, mean follow-up 17.9±10.1 years. Reasons for second kidney biopsy encompassed nephritic flares (n=28, 30.4%), proteinuric flares (n=46, 50%) or lack of renal response (n=18, 19.5%). Class switch from first biopsy occurred in 50.5% of cases, mainly from non-proliferative towards proliferative classes. Class IV remained stable in over 50% of cases. Twenty-five patients (27.2%) developed ESKD, mostly belonging to the nephritic flare group (17/28, 60.7%). Independent predictors of ESKD at second biopsy were activity index (AI; (HR 95% CI) 1.20 (1.03 to 1.41), p=0.022), chronicity index (CI; 1.41 (1.09 to 1.82), p=0.008) and 24h-proteinuria (1.22 (1.04 to 1.42), p=0.013). AI≥2 (log-rank p=0.031), CI >4 (log-rank p=0.001) or proteinuria ≥3.5 g/day (log-rank=0.009) identified thresholds for higher ESKD risk. In a subgroup analysis, glomerular activity and tubular chronicity mostly accounted for AI and CI association with ESKD. No histological or laboratory predictors emerged at first biopsy (95% CI): AI: 0.88 to 1.19; CI: 0.66 to 1.20; proteinuria 0.85 to 1.08.ConclusionsFindings at second but not at first kidney biopsy in patients with persistently active or relapsing LN inform about ESKD development in a long-term follow-up.

Published
2022

42. Second Wave Antibodies in Autoimmune Renal Diseases: The Case of Lupus Nephritis

Author

Ilaria Cavazzana, Renato Alberto Sinico, Francesco Locatelli, Francesco Scolari, Leda Cipriani, Angelo Ravelli, Andrea Angeletti, Giampaola Pesce, Marta Mosca, Federico Pratesi, Giulia Pazzola, Simone Negrini, Enrico Verrina, Micaela Fredi, Domenico Santoro, Valentina Binda, Marco Prunotto, Andrea Petretto, Carlomaurizio Montecucco, Giacomo Garibotto, Marcello Bagnasco, Pasquale Esposito, Paride Fenaroli, Paola Migliorini, Gabriella Moroni, Matteo D'Alessandro, Giuseppe Murdaca, Franco Franceschini, Angelo A. Manfredi, Gian Marco Ghiggeri, Angela Tincani, Giacomo Emmi, Maurizio Bruschi, Isabella Pisani, Lorenzo Cavagna, Giuseppe A. Ramirez, Stefano Volpi, Giovanni Candiano, Augusto Vaglio, Barbara Trezzi, Angeletti, A, Bruschi, M, Moroni, G, Sinico, R, Franceschini, F, Fredi, M, Vaglio, A, Cavagna, L, Petretto, A, Pratesi, F, Migliorini, P, Locatelli, F, Pazzola, G, Pesce, G, Bagnasco, M, Manfredi, A, Ramirez, G, Esposito, P, Murdaca, G, Negrini, S, Cipriani, L, Trezzi, B, Emmi, G, Cavazzana, I, Binda, V, D'Alessandro, M, Fenaroli, P, Pisani, I, Garibotto, G, Montecucco, C, Santoro, D, Scolari, F, Volpi, S, Mosca, M, Tincani, A, Candiano, G, Prunotto, M, Verrina, E, Ravelli, A, and Ghiggeri, G

Subjects
medicine.medical_specialty, clinical trial, glomerulonephritis, lupus nephritis, rheumatology, systemic lupus erythematosus, biology, business.industry, Lupus nephritis, Autoantibody, Glomerulonephritis, General Medicine, medicine.disease, Rheumatology, Research Letters, Clinical trial, Nephrology, Internal medicine, Lupus Nephritis, autoantibodies, second wave, Immunology, medicine, biology.protein, Antibody, business
Abstract

Clinical Trial registry name and registration number: Zeus study, NCT02403115

Published
2021

43. CLINICAL FEATURES AND RENAL PROGNOSIS IN LUPUS NEPHRITIS PATIENTS UNDERGOING A REPEATED BIOPSY: RESULTS OF 103 RE-BIOPSIES IN 438 PATIENTS

Author

M. Gatto, F. Saccon, F. Radice, P. G. Vercelloni, R. A. Sinico, G. Frontini, V. Binda, P. Messa, F. Alberici, G. Moroni, A. Doria ., Gatto, M, Saccon, F, Radice, F, Vercelloni, P, Sinico, R, Frontini, G, Binda, V, Messa, P, Alberici, F, Moroni, G, and Doria ., A

Subjects
lupus nephritis. repeated kidney biopsy, prognosis
Abstract

Background: Indications to repeat renal biopsy (RB) in lupus nephritis (LN) are not unanimously acknowledged. Objectives: To evaluate the renal outcome of patients with LN undergoing a second RB. Methods: We retrospectively analyzed prospectively collected data of patients with LN followed up in four Italian referral centres for systemic lupus eryhtematosus. Serological and clinical information were retrieved according to a shared database. RB were classified according to ISN/RPS 2003 classification; chronicity (CI) and activity indexes (AI) were defined according to Austin et al. The primary renal outcome was renal failure, defined as serum creatinine (SCr)>1.0mg/dL with eGFR

Published
2020

44. Lack of EULAR/ERA-EDTA response at 1 year predicts poor long-term renal outcome in patients with lupus nephritis

Author

Francesco Tamborini, Federico Alberici, Piergiorgio Messa, Augusto Vaglio, Mariele Gatto, Francesca Radice, Giulia Frontini, Lucia Sacchi, Gabriella Moroni, Andrea Doria, Barbara Trezzi, Valentina Binda, Silvana Quaglini, Renato Alberto Sinico, Francesca Saccon, Moroni, G, Gatto, M, Tamborini, F, Quaglini, S, Radice, F, Saccon, F, Frontini, G, Alberici, F, Sacchi, L, Binda, V, Trezzi, B, Vaglio, A, Messa, P, Sinico, R, and Doria, A

Subjects
Adult, Male, Nephrology, medicine.medical_specialty, arterial hypertension, lupus nephritis, systemic lupus erythematosus, medicine.medical_treatment, Immunology, Lupus nephritis, systemic lupus erythematosu, Kidney Function Tests, lupus nephriti, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Internal medicine, medicine, Humans, Immunology and Allergy, Renal Insufficiency, Chronic, Survival rate, Dialysis, medicine.diagnostic_test, business.industry, Middle Aged, Prognosis, medicine.disease, Treatment Outcome, Renal pathology, Female, Renal biopsy, business, Rheumatism, Kidney disease
Abstract

ObjectivesShort-term predictive endpoints of chronic kidney disease (CKD) are needed in lupus nephritis (LN). We tested response to therapy at 1 year.MethodsWe considered patients with LN who underwent renal biopsy followed by induction therapy between January 1970 and December 2016. LN was assessed using the International Society of Nephrology/Renal Pathology Society (2003) criteria and the National Institute of Health (NIH) activity and chronicity index. The renal outcome was CKD. Response was defined according to EULAR/European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations:complete:proteinuria partial:≥50% proteinuria reduction to subnephrotic levels, (near) normal eGFR; andno response:all the other cases. Logistic regression analysis was employed for 12-month response and Cox regression for CKD prediction.ResultsWe studied 381 patients (90.5% Caucasians). After 12-month therapy, 58%, 26% and 16% of patients achieved complete, partial and no response, respectively, according to EULAR/ERA-EDTA. During a median follow-up of 10.7 (IQR: 4.97–18.80) years, 53 patients developed CKD. At 15 years, CKD-free survival rate was 95.2%, 87.6% and 55.4% in patients with complete, partial and no response at 12 months, respectively (pConclusionsLack of EULAR/ERA-EDTA response at 12 months predicts CKD.

Published
2020

45. Kidney Involvement

Author

Renato Alberto Sinico, Fabio Pagni, Vincenzo L’Imperio, Valentina Binda, Paolo Fabbrini, Federico Pieruzzi, Gabriella Moroni, Sinico, R, Pagni, F, L’Imperio, V, Binda, V, Fabbrini, P, Pieruzzi, F, and Moroni, G

Subjects
granulomatosis with polyangi- itis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), kidney involvement, rapidly progressive glomerulonephritis (RPGN)
Abstract

Renal involvement is a frequent and severe complication of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV). It is generally characterized by a pauci-immune necrotizing and crescentic glomerulonephritis with a very rapid decline of renal function (rapidly progressive glomerulonephritis). Even though there are no qualitative differences in glomerular lesions in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), chronic damage is usually higher in MPA (and/or P-ANCA-positive patients) than in GPA (and/or CANCA-positive patients). If untreated, necrotizing and crescentic glomerulonephritis has an unfavorable course leading in a few weeks or months to end-stage renal disease (ESRD). Serum creatinine at diagnosis, sclerotic lesions, and the number of normal glomeruli at kidney biopsy are the best predictors of renal outcome. Corticosteroids and cyclophosphamide or rituximab (with the addition of plasma exchange in the most severe cases) are the cornerstone of induction treatment of ANCA-associated renal vasculitis, followed by azathioprine (or methotrexate, mycophenolate, rituximab) for maintenance. Despite significant improvement in patient outcomes over the past decades, AAV still results in ESRD in a quarter of patients over 5 years. Relapse rates are significantly lower in patients on chronic dialysis. Patient survival on regular replacement treatment (RRT) does not differ between AAV and matched nondiabetic patients, while it is lower than that of glomerulonephritis. Patients with AAV who undergo kidney transplantation have a mortality not different from the matched control group of primary glomerulonephritides, and favorable transplant survival is similar to that of the matched control groups.

Published
2019

46. Using autologous umbilical cord blood and placental cells for hypoxic-ischemic encephalopathy: an exploratory safety and feasibility study.

Author

Solana C, Balanian N, Machado S, Binda V, Kuperman S, Gamba C, and Roca V

Abstract

Introduction. Hypoxic-ischemic encephalopathy (HIE) caused by lack of oxygen and perfusion to the brain can lead to acute neurological damage in newborns. Therapeutic hypothermia (TH) is the most effective and safest treatment. However, mortality remains high with numerous long-term sequelae. Cellular therapies, particularly umbilical cord blood (UCB), are being studied as alternative therapies. The aim of this study is to assess the feasibility and safety of combining autologous cord blood cell infusion with moderate hypothermia. Population and methods. Twelve infants of 36 weeks gestational age or older, diagnosed with moderate or severe HIE and with umbilical cord blood (UCB) collected were included. UCB was volume-reduced, and up to four doses were obtained. These doses were infused within the first 72 postnatal hours. Time to the first infusion and possible adverse reactions to the infusion were evaluated. Results. Between 2014 and 2019, 12 infants were included in the protocol (TH + UCB), 9 with a diagnosis of moderate HIE and 3 with severe HIE. In all cases, at least one dose of UCB was obtained for infusion. In all cases, the first dose was infused within 24 hours in every case, and no adverse reactions attributable to the infusion were observed. Conclusions. The collection, processing, and infusion of fresh autologous umbilical cord blood for use in newborns with HIE are feasible and safe under our conditions., (Sociedad Argentina de Pediatría.)

Published
2024
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47. A critical view on autoantibodies in lupus nephritis: Concrete knowledge based on evidence.

Author

Bruschi M, Angeletti A, Prunotto M, Meroni PL, Ghiggeri GM, Moroni G, Sinico RA, Franceschini F, Fredi M, Vaglio A, Cavalli A, Scapozza L, Patel JJ, Tan JC, Lo KC, Cavagna L, Petretto A, Pratesi F, Migliorini P, Locatelli F, Pazzola G, Pesce G, Giannese D, Manfredi A, Ramirez GA, Esposito P, Murdaca G, Negrini S, Bui F, Trezzi B, Emmi G, Cavazzana I, Binda V, Fenaroli P, Pisan I, Montecucco C, Santoro D, Scolari F, Mescia F, Volpi S, Mosca M, Tincani A, Ravelli A, Murtas C, Candiano G, Caridi G, La Porta E, and Verrina E

Subjects
Humans, Animals, Antibodies, Antinuclear immunology, Antibodies, Antinuclear blood, Immunoglobulin G immunology, Immunoglobulin G blood, Autoantigens immunology, Lupus Nephritis immunology, Lupus Nephritis diagnosis, Autoantibodies immunology, Autoantibodies blood
Abstract

Deposition of autoantibodies in glomeruli is a key factor in the development of lupus nephritis (LN). For a long time, anti-dsDNA and anti-C1q antibodies were thought to be the main cause of the kidney damage. However, recent studies have shown that the list of autoantibidies that have renal tropism and deposit in the kidney in LN is increasing and the link between anti-dsDNA and renal pathology is weak due to potential confounders. Aspecific bindings of dsDNA with cationic antibodies and of anti-dsDNA with several renal antigens such as actinin, laminin, entactin, and annexinA2 raised doubts about the specific target of these antibodies in the kidney. Moreover, the isotype of anti-dsDNA in SLE and LN has never received adequate interest until the recent observation that IgG2 are preponderant over IgG1, IgG3 and IgG4. Based on the above background, recent studies investigated the involvement of anti-dsDNA IgG2 and of other antibodies in LN. It was concluded that circulating anti-dsDNA IgG2 levels do not distinguish between LN versus non-renal SLE, and, in patients with LN, their levels do not change over time. Circulating levels of other antibodies such as anti-ENO1 and anti-H2 IgG2 were, instead, higher in LN vs non-renal SLE at the time of diagnosis and decreased following therapies. Finally, new classes of renal antibodies that potentially modify the anti-inflammatory response in the kidney are emerging as new co-actors in the pathogenetic scenario. They have been defined as 'second wave antibodies' for the link with detoxifying mechanisms limiting the oxidative stress in glomeruli that are classically stimulated in a second phase of inflammation. These findings have important clinical implications that may modify the laboratory approach to LN. Serum levels of anti-ENO1 and anti-H2 IgG2 should be measured in the follow up of patients for designing the length of therapies and identify those patients who respond to treatments. Anti-SOD2 could help to monitor and potentiate the anti-inflammatory response in the kidney., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Published
2024
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48. Unraveling the Link between Interferon-α and Systemic Lupus Erythematosus: From the Molecular Mechanisms to Target Therapies.

Author

Infante B, Mercuri S, Dello Strologo A, Franzin R, Catalano V, Troise D, Cataldo E, Pontrelli P, Alfieri C, Binda V, Frontini G, Netti GS, Ranieri E, Gesualdo L, Castellano G, and Stallone G

Subjects
Humans, Interferon-alpha therapeutic use, Antigen-Antibody Complex, Antigens, Nuclear, Lupus Erythematosus, Systemic drug therapy, Lupus Erythematosus, Systemic genetics, Interferon Type I metabolism
Abstract

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease with a wide range of clinical expressions. The kidney is often affected, usually within 5 years of the onset of SLE, and lupus nephropathy (LN) carries a high risk for increased morbidity. The clinical heterogeneity of the disease is accompanied by complex disturbances affecting the immune system with inflammation and tissue damage due to loss of tolerance to nuclear antigens and the deposition of immune complexes in tissues. Several studies have reported that in human SLE, there is an important role of the Type-I-interferons (INF) system suggested by the upregulation of INF-inducible genes observed in serial gene expression microarray studies. This review aims to describe the transduction pathways of Type-I-interferons, in particular INFα, and its immune-regulatory function in the pathogenesis of SLE and, in particular, in LN. In addition, recent novelties concerning biologic therapy in LN will be discussed.

Published
2022
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49. Evidence for charge-based mimicry in anti dsDNA antibody generation.

Author

Bruschi M, Angeletti A, Kajana X, Moroni G, Sinico RA, Fredi M, Vaglio A, Cavagna L, Pratesi F, Migliorini P, Locatelli F, Pazzola G, Pesce G, Bagnasco M, Manfredi A, Ramirez GA, Esposito P, Negrini S, Bui F, Trezzi B, Emmi G, Cavazzana I, Binda V, Fenaroli P, Pisani I, Montecucco C, Santoro D, Scolari F, Volpi S, Mosca M, Tincani A, Candiano G, Verrina E, Franceschini F, Ravelli A, Prunotto M, Meroni PL, and Ghiggeri GM

Subjects
Humans, Antibodies, Antinuclear, Autoantibodies, Immunoglobulin G, DNA, Lupus Nephritis, Lupus Erythematosus, Systemic, Annexin A1 metabolism
Abstract

Mechanisms for the generation of anti-dsDNA autoantibodies are still not completely elucidated. One theory states that dsDNA interacts for mimicry with antibodies raised versus other antigens but molecular features for mimicry are unknown. Here we show that, at physiological acid-base balance, anti-Annexin A1 binds IgG2 dsDNA in a competitive and dose-dependent way with Annexin A1 and that the competition between the two molecules is null at pH 9. On the other hand, these findings also show that dsDNA and Annexin A1 interact with their respective antibodies on a strictly pH-dependent basis: in both cases, the binding was minimal at pH 4 and maximal at pH9-10. The anionic charge of dsDNA is mainly conferred by the numerous phosphatidic residues. The epitope binding site of Annexin A1 for anti-Annexin A1 IgG2 was here characterized as a string of 34 amino acids at the NH2 terminus, 10 of which are anionic. Circulating levels of anti-dsDNA and anti-Annexin A1 IgG2 antibodies were strongly correlated in patients with systemic lupus erythematosus (n 496) and lupus nephritis (n 425) stratified for age, sex, etc. These results show that dsDNA competes with Annexin A1 for the binding with anti-Annexin A1 IgG2 on a dose and charged mediated base, being able to display an inhibition up to 75%. This study provides the first demonstration that dsDNA may interact with antibodies raised versus other anionic molecules (anti-Annexin A1 IgG2) because of charge mimicry and this interaction may contribute to anti-dsDNA antibodies generation., Competing Interests: Declaration of competing interest Authors declair Non competing interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Published
2022
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50. A Group Videoconferencing Intervention (C@nnected) to Improve Maternal Sensitivity: Protocol for a Randomized Feasibility Trial.

Author

Binda V, Olhaberry M, Castañon C, Abarca C, and Caamaño C

Abstract

Background: Early childhood development is highly dependent on the sensitive care provided by caregivers, and interventions focused on supporting parents to improve their sensitivity have shown to be effective. The COVID-19 pandemic has had a significant impact on mental health, with pregnant women and mothers of infants being an especially vulnerable group and maternal sensitivity particularly affected. However, access to face-to-face interventions is restricted; thus, it is important to have remote interventions to support this group of mothers., Objective: The objective of this study is to evaluate the feasibility and acceptability of C@nnected, a group videoconferencing intervention to improve maternal sensitivity aimed at mother-infant dyads attending primary health care centers in vulnerable areas of Santiago, Chile., Methods: This is a randomized feasibility single-masked (outcome assessor) study with a qualitative component. It will involve a block randomization procedure to generate a 3:2 allocation ratio (with more people allocated to the intervention arm). The intervention consists of 4 group videoconferencing sessions adapted from a face-to-face intervention with proven effectiveness. The control group will receive treatment as usual, along with educational brochures. The feasibility and acceptability of this study will be quantitatively and qualitatively assessed. Changes in clinical outcomes relating to maternal sensitivity, depressive symptoms, postpartum maternal attachment, and infant socioemotional development will also be evaluated., Results: We finished adapting the face-to-face intervention to the videoconferencing format in July 2021. The study began recruitment in August 2021, and enrollment is expected to end in August 2022, with final study results expected in December 2022., Conclusions: This study will contribute evidence for the use of eHealth interventions to promote maternal sensitivity. It will also inform the design and implementation of a future randomized clinical trial., Trial Registration: ClinicalTrials.gov NCT04904861; https://clinicaltrials.gov/ct2/show/NCT04904861., International Registered Report Identifier (irrid): DERR1-10.2196/35881., (©Victoria Binda, Marcia Olhaberry, Carla Castañon, Constanza Abarca, Catalina Caamaño. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.08.2022.)

Published
2022
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