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This study tested the hypothesis that a more senescent immune system would predict a worse outcome in older patients hospitalized for community-acquired pneumonia (CAP). CAP has long been responsible for high rates of mortality and readmissions among older people. Although immunosenescence is a key factor in the increased susceptibility to infections, there are no related biomarkers currently available in clinical practice. In this context, the aim of this prospective study was to identify immunosenescence-related biomarkers to predict outcomes in patients older than 65 years hospitalized for CAP. We evaluated 97 patients admitted to our hospital for CAP in 2019 and 2020. All patients were followed for 1 year. Our findings showed that elevated levels of early differentiated CD28+ CD27+ T cells at admission were associated with better short (2 months) and long-term (1 year) outcomes in terms of mortality and readmissions. Early differentiated CD28+ CD27+ CD4+ T cell counts were even better long-term predictors. In conclusion, early differentiated CD28+ CD27+ T cells could be useful biomarkers to identify high-risk older patients with CAP, helping clinicians with risk stratification and follow-up.

Lleixa and Caballero-avila et al. report that antibodies targeting the flotillin-1/2 complex are present in a subgroup of patients with multiple sclerosis. Further studies are needed to understand the clinical and pathological relevance of anti-flotillin-1/2 autoantibodies in multiple sclerosis. Multiple sclerosis is a tissue-specific autoimmune disease of the central nervous system in which the antigen(s) remains elusive. Antibodies targeting the flotillin-1/2 complex have been described in 1-2% of the patients in a recent study. Other candidate antigens as anoctamin-2 or neurofascin-155 have been previously described in multiple sclerosis patients, although their clinical relevance remains uncertain. Our study aims to analyse the frequency and clinical relevance of antibodies against neurofascin-155, anoctamin-2 and flotillin-1/2 complex in multiple sclerosis. Serum (n = 252) and CSF (n = 50) samples from 282 multiple sclerosis patients were included in the study. The control group was composed of 260 serum samples (71 healthy donors and 189 with other neuroinflammatory disorders). Anti-flotillin-1/2, anti-anoctamin-2 and anti-neurofascin-155 antibodies were tested by cell-based assays using transfected cells. We identified six multiple sclerosis patients with antibodies against the flotillin-1/2 complex (2.1%) and one multiple sclerosis patient with antibodies against anoctamin-2 (0.35%). All multiple sclerosis patients were negative for anti-neurofascin-155 antibodies. Three of the anti-flotillin-1/2 positive patients showed anti-flotillin-1/2 positivity in other serum samples extracted at different moments of their disease. Immunoglobulin G subclasses of anti-flotillin-1/2 antibodies were predominantly one and three. We confirm that antibodies targeting the flotillin-1/2 complex are present in a subgroup of patients with multiple sclerosis. Further studies are needed to understand the clinical and pathological relevance of anti-flotillin-1/2 autoantibodies in multiple sclerosis.

The use of artificial diets for rearing natural enemies is an expensive technique with negative implications in the development of parasitoids. The aim of this study was to determine the effects on the development of the parasitoid Chelonus insularis Cresson (Hymenoptera: Braconidae) using as the host Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) larvae reared on castor bean (Ricinus communis L.) and maize (Zea mays L.) leaves. Twenty-five egg masses of S. frugiperda were exposed to adult parasitoids of C. insularis. One hundred twenty-three larvae were fed with castor bean leaves and 309 larvae with maize. Survival of S. frugiperda larvae and emergence of healthy adults of C. insularis were recorded. Durations of the developmental stages, weight per parasitoid, length of the radial cell, and total length of the forewing also were recorded. No significant differences were determined between the two host plants with respect to survival of S. frugiperda larvae or the emergence of healthy adults of C. insularis. Durations of the developmental stages of the parasitoid were longer on castor bean leaves than on maize. The length of the radial cell and the total length of the forewing were greater on parasitoids that emerged from castor bean-reared larvae than those reared on maize for both females and males. The weight per parasitoid did not differ. Chelonus insularis can be maintained in S. frugiperda larvae reared on castor and maize leaves but, based on these results, the use of castor bean leaves favors the size of the parasitoid.

Resistance to Spodoptera frugiperda (Lepidoptera: Noctuidae) damage has been documented in some Mexican maize races and teosintes. There are approximately 31 races of native maize and three races of teosinte in Oaxaca state, but little is known about their resistance to insect damage. This study compared the development and fecundity of S. frugiperda fed on native maize and the teosinte Zea luxurians, from Oaxaca, Mexico. No significant differences were determined in the development parameters of males and females according to the host plant types, except the pupal weight of males, which was higher on teosinte (0.189 g) than on native maize (0.174 g). Duration from hatching to adult emergence was 28.96 to 30.17 d on native maize and 28.51 to 30.34 d on teosinte. Females emerged before males in both host plant types. The sex ratio was approximately 0.5 for both sexes. Larval weight was higher on teosinte (0.451 to 0.459 g) than on native maize (0.442 to 0.454 g). According to the fecundity parameters, no significant differences in the duration of oviposition, the number of eggs per egg mass, eggs per female, and eggs per host plant types were determined. Fitness Index was positively correlated with the pupal weight of both sexes and the fecundity parameters of S. frugiperda females. Our results demonstrated that larval feeding on native maize and teosinte did not affect the development parameters and fecundity of S. frugiperda. Constitutive defenses in native maize leaves were similar to those of teosinte.

Multiple sclerosis (MS) is a tissue-specific autoimmune disease of the central nervous system in which the antigen(s) remains elusive. Antibodies targeting the flotillin-1/2 (FLOT–1/2) complex have been described in 1-2% of the patients in a recent study. Other candidate antigens as anoctamin-2 (ANO2) or neurofascin-155 (NF155) have been previously described in MS patients, although their clinical relevance remains uncertain. Our study aims to analyse the frequency and clinical relevance of antibodies against NF155, ANO2 and the FLOT-1/2 complex in MS.Serum (n=252) and CSF (n=50) samples from 282 MS patients were included in the study. The control group was composed of 260 serum samples (71 healthy donors and 189 with other neuroinflammatory disorders). Anti-FLOT1/2, anti-ANO2 and anti-NF155 antibodies were tested by cell-based assays using transfected-HEK293 cells. We identified 6 MS patients with antibodies against the FLOT-1/2 complex (2.1%) and 1 MS patient with antibodies against ANO2 (0.35%). All MS patients were negative for anti-NF155 antibodies. Three of the anti-FLOT1/2 positive patients showed anti-FLOT-1/2 positivity in other serum samples extracted at different moments of their disease. IgG subclasses of anti-FLOT-1/2 antibodies were predominantly IgG1 and IgG3.We confirm that antibodies targeting the Flotillin-1/2 complex are present in a subgroup of patients with MS. Further studies are needed to understand the clinical and pathological relevance of anti-FLOT-1/2 autoantibodies in MS.

Previous studies have described the clinical, serological and pathological features of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and antibodies directed against the paranodal proteins neurofascin-155, contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), or nodal forms of neurofascin. Such antibodies are useful for diagnosis and potentially treatment selection. However, antibodies targeting Caspr1 only or the Caspr1/CNTN1 complex have been reported in few patients with CIDP. Moreover, it is unclear if these patients belong to the same pathophysiological subgroup. Using cell-based assays in routine clinical testing, we identified sera from patients with CIDP showing strong membrane reactivity when both CNTN1 and Caspr1 were co-transfected (but not when CNTN1 was transfected alone). Fifteen patients (10 male; aged between 40 and 75) with antibodies targeting Caspr1/CNTN1 co-transfected cells were enrolled for characterization. The prevalence of anti-Caspr1/CNTN1 antibodies was 1.9% (1/52) in the Sant Pau CIDP cohort, and 4.3% (1/23) in a German cohort of acute-onset CIDP. All patients fulfilled European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite diagnostic criteria for CIDP. Seven (47%) were initially diagnosed with Guillain-Barré syndrome due to an acute-subacute onset. Six (40%) patients had cranial nerve involvement, eight (53%) reported neuropathic pain and 12 (80%) ataxia. Axonal involvement and acute denervation were frequent in electrophysiological studies. Complete response to intravenous immunoglobulin was not observed, while most (90%) responded well to rituximab. Enzyme-linked immunosorbent assay (ELISA) and teased nerve fibre immunohistochemistry confirmed reactivity against the paranodal Caspr1/CNTN1 complex. Weaker reactivity against Caspr1 transfected alone was also detected in 10/15 (67%). Sera from 13 of these patients were available for testing by ELISA. All 13 samples reacted against Caspr1 by ELISA and this reactivity was enhanced when CNTN1 was added to the Caspr1 ELISA. IgG subclasses were also investigated by ELISA. IgG4 was the predominant subclass in 10 patients, while IgG3 was predominant in other three patients. In conclusion, patients with antibodies to the Caspr1/CNTN1 complex display similar serological and clinical features and constitute a single subgroup within the CIDP syndrome. These antibodies likely target Caspr1 primarily and are detected with Caspr1-only ELISA, but reactivity is optimal when CNTN1 is added to Caspr1 in cell-based assays and ELISA.

This study tested the hypothesis that a more senescent immune system would predict a worse outcome in older patients hospitalized for community-acquired pneumonia (CAP). CAP has long been responsible for high rates of mortality and readmissions among older people. Although immunosenescence is a key factor in the increased susceptibility to infections, there are no related biomarkers currently available in clinical practice. In this context, the aim of this prospective study was to identify immunosenescence-related biomarkers to predict outcomes in patients older than 65 years hospitalized for CAP. We evaluated 97 patients admitted to our hospital for CAP in 2019 and 2020. All patients were followed for 1 year. Our findings showed that elevated levels of early differentiated CD28

Studies on the cessation of face mask use after a COVID-19 vaccine in patients with diabetes are not available, despite their greater predisposition to complications. We estimated the prevalence of cessation of face mask use after receiving the COVID-19 vaccine in patients with diabetes and identified which factor was most strongly associated with non-use. This was a cross-sectional study in patients with diabetes 18–70 years with at least one dose of vaccine against COVID-19 (n = 288). Participants were asked to respond face-to-face to a questionnaire in a primary care center. Descriptive statistics, chi-square tests, and multivariate binary logistic regression were used for analyzing the association between vulnerability, benefits, barriers, self-efficacy, vaccine expectations (independent variables), and cessation of use (dependent variable), controlling for sociodemographic, smoking, medical, vaccine, and COVID-19 history. The prevalence of cessation of face masks was 25.3% (95% CI 20.2, 30.5). Not feeling vulnerable to hospitalization increased the odds of non-use (adjusted OR = 3.3, 95% CI 1.2, 8.6), while perceiving benefits did the opposite (adjusted OR = 0.4, 95% CI 0.2, 0.9). The prevalence was low, and only two factors were associated with the cessation of face mask use after COVID-19 vaccination in patients with type 2 diabetes.

Altres ajuts: Bristol Myers Squibb; Fondo de Investigaciones Sanitarias (FIS); Program for the Stabilization of Investigators of the Direcció d'Estrategia i Coordinació del Departament de Salut, Generalitat de Catalunya; Immunology Program of Universitat Autònoma de Barcelona (UAB). Immune-related adverse events (irAEs) are unpredictable autoimmune-like toxicities induced by immune checkpoint inhibitors (ICI). irAEs are a consequence of a breakdown in self-tolerance. ICIs can induce autoantibody formation, and the presence of antinuclear autoantibodies (ANAs) has been reported in patients who developed irAEs. Our goal was to compare ANA patterns by indirect immunofluorescence at different timepoints before (baseline) and after the initiation of ICI treatment and to analyze the role of ANA pattern changes as predictors of irAEs. This is a 2-year-follow-up prospective study of 152 consecutive patients with solid tumors treated with anti-PD-(L)1 blockade agents. They were included from September 2018 until March 2020 in the Hospital de la Santa Creu I Sant Pau (Barcelona, Spain). We grouped patients into three groups: ANA de novo (patients who showed new ANA patterns at any time after ICI initiation), ANA (ANA positive at baseline without changes in the ANA patterns after initiation of treatment) and non-ANA (ANA negative at baseline and after ICI initiation). We did not find any association between the appearance of ANAs and irAE rates or the number and types of irAEs. However, patients in the ANA de novo group showed higher severe irAE rates (grade ≥ 3) than the other groups. Additionally, in most of the patients with severe irAEs (83.3%), changes in ANA patterns preceded irAE onset. In conclusion, we found ANA induction during ICI therapies in 22 patients and our results suggest that the appearance of ANAs may predict the severity of the irAE.

Background and ObjectivesTo study the clinical and laboratory features of antineurofascin-155 (NF155)–positive autoimmune nodopathy (AN).MethodsPatients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up.ResultsForty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2–4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = −0.88, p < 0.001) and with maximum I-RODS achieved (r = −0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients.DiscussionAnti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases.Classification of EvidenceThis study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

Micronutrient deficiencies are common among bariatric patients; this study aimed to determine whether a cognitive dissonance-based virtual program improved adherence to multivitamin use in bariatric patients from northern Mexico.A randomized controlled trial of the supplementation strategy was conducted over three months. The participants were randomized to an intervention or waitlisted control group and received two psycho-educative and four cognitive dissonance virtual sessions. Multiple linear regression was used to determine standardized estimates of associations between the intervention and dependent variables. Two path analyses were evaluated considering baseline and post-test measurements.Intervention was associated with higher concentrations of Hb (β=0.758, p0.001), vitamin D (β=0.577, p0.001), iron (β=0.523, p0.001), folate (β=0.494, p0.01), calcium (β=0.452, p0.01), higher adherence (β=0.467, p0.001), and level of knowledge (β=0.298, p0.05.The dissonance-based intervention potentiated the level of supplementation adherence. A higher level of adherence was reflected in micronutrient concentrations, thus providing confirmation of intervention. Thus, support is found for a multidisciplinary clinical practice that enhances nutrition status after bariatric surgery for obesity.

Most studies focus on damage caused by beetle larvae to various crops; however, little is known about the association of adults with wild and ornamental species, their food preferences, and plant-beetle relationships. Therefore, the objective of this work was to report new host plants and floral associations for four species of Cetoniinae and Rutelinae beetles (Coleoptera: Scarabaeidae) and to provide a checklist of Scarabaeidae from San Andres Huayapam, Oaxaca, Mexico. The checklist had 15 species grouped into 12 genera, nine tribes, and four subfamilies. Twelve species had new locality records, of which one was the first accurate distribution record for the State of Oaxaca.

Hypogammaglobulinemia in the first months after allogeneic hematopoietic stem cell transplantation (HSCT) is common in paediatric patients. During this phase, replacement therapy with human immunoglobulin must be administered parenterally to prevent infections. In some cases, this hypogammaglobulinemia persists over time, which forces further treatment when the patient is usually no longer a carrier of a central line, making them ideal candidates for subcutaneous replacement therapy. There is little published literature describing the use of this method in paediatric patients undergoing HSCT, widely described in replacement treatment in children with primary immunodeficiencies with very good results.An observational, descriptive, longitudinal and retrospective study is carried out. During the years 2008-2019, we evaluated all paediatric patients undergoing HSCT in our center with persistent chronic hypogammaglobulinemia (for over a year). The treatment phase with intravenous immunoglobulin (Privigen®) and the first four years of treatment with subcutaneous immunoglobulin (Hizentra®) are evaluated using a questionnaire.During the years 2008-2019, 175 patients underwent HSCT, 143 (82%) of whom exceeded three months after transplantation. Three (2%) of them had persistent hypogammaglobulinemia. All three share factors described in the literature involved in immune reconstitution. After analysing the questionnaire, it is observed that switching from intravenous to subcutaneous gammaglobulin has involved a great improvement in their quality of life.The origin of chronic hypogammaglobulinemia in our patients shows different factors and cannot be attributed to a single cause. Due to the limited number of patients no conclusions can be drawn at the population level. We have been able to observe that replacement treatment with Hizentra 20% has been as effective as the intravenous administration without evidence of an increase in bacterial infections. Furthermore, it has also led to an improvement in quality of life and increased comfort, as the patients themselves have stated.

Despite the importance of maize (Zea mays L.) worldwide and multiple records of arthropods in the crop, only the United States, Mexico, and Peru register Lepidoptera from the family Hesperiidae as phytophagous on maize. For this reason, it is important to document for Mexico the presence of Hesperiidae species in maize. The work was done in the State of Oaxaca at the towns of Santa Cruz Xoxocotlan, Santiago Apostol, Coatecas Altas, and Villa de Zaachila in the Central Valley region; and at La Cofradia and Santa Lucia Miahuatlan in the Sierra Sur region. Maize landrace crops of Bolita, Conical-Chalqueno, Zapalote Chico, and teosinte Zea luxurians (Durieu y Asch.) Bird were sampled. Larvae obtained in the field were fed until becoming adult butterflies. Four species of Hesperiidae were identified: Ancyloxypha arene (W. H. Edwards), Lerema accius (J. E. Smith), L. liris Evans, and Naevolus orius Mabille. For the first time, maize landraces were documented as food for larvae of L. liris and N. orius.

Background: Different classification criteria for systemic lupus erythematosus (SLE) have been launched over the years. Our aim was to evaluate the performance of the EULAR/ACR-2019, SLICC-2012 and ACR-1997 classification criteria in a cohort of SLE patients with longstanding disease. Methods: Descriptive observational study in 79 patients with established and longstanding SLE. The three classification criteria sets were applied to those patients. Results: Of the 79 patients, 70 were women (88.6%), with a mean age of 51.8 ± 14 years and a mean disease duration of 15.2 ± 11.5 years. The sensitivity of the different criteria were: 51.9%, 87.3% and 86.1% for ACR-1997, SLICC-2012 and EULAR/ACR-2019, respectively. In total, 68 out of 79 patients (53.7%) met all three classification criteria, 11.4% did not meet any classification criteria and were characterized by low SLEDAI (0.6 ± 0.9), low SLICC/ACR Damage Index (0.88 ± 0.56) and fulfilling only skin domains, antiphospholipid antibodies or hypocomplementemia. To fulfill EULAR/ACR-2019 criteria was associated with low complement levels (p &lt, 0.04), high anti-dsDNA levels (p &lt, 0.001), presence of lupus nephritis III-IV (p &lt, 0.05) and arthritis (p &lt, 0.001). Conclusion: The EULAR/ACR-2019 classification criteria showed high sensitivity, similar to SLICC-2012, in SLE patients with longstanding disease. Patients with serological, articular or renal involvement are more likely to fulfill SLICC-2012 or EULAR/ACR-2019 criteria.

Background Guillain-Barre syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barre syndrome. Methods Autoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed. Results None of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factors. Conclusion Our study confirms that (1) GBS patients display a heterogeneous repertoire of autoantibodies targeting nerve cells and structures; (2) gangliosides are the most frequent antigens in GBS patients and have a prognostic value; (3) further antigen-discovery experiments may elucidate other potential antigens in GBS.

Vitiligo pathophysiology is mediated by antigen-specific cytotoxic T cells. Environmental stressors cause susceptible melanocytes to secrete damage-associated molecular patterns (DAMPs). DAMPs are recognized by receptors such as the endocytic low-density-lipoprotein receptor-related-protein (LRP1/CD91), expressed in antigen presenting cells, which activate self-reactive CD8+ T cells, leading to melanocyte destruction. Within this response, interferon-gamma triggers production of cytokine CXCL10, recruiting more activated T cells causing further melanocytic damage. We hypothesized that expression of LRP1/CD91 was higher in vitiligo patients compared to non-vitiligo individuals. And further that levels/expression of CXCL10 in plasma were linked to disease severity. We enrolled forty individuals in this study: 18 patients with vitiligo and 22 healthy volunteers. We assessed LRP1/CD91 expression and plasma CXCL10 in patients with vitiligo and healthy volunteers. Additionally, vitiligo patients received combined treatment for 16-weeks following which the said parameters were reassessed. Vitiligo Area Scoring Index were calculated before and after treatment for these patients. Analysis of LRP1/CD91 MFI values in monocytes from vitiligo patients showed high surface levels of LRP1/CD91 than from healthy volunteers (10.50±0.77 vs 6.55±0.77 MFI units, p

Guzmán-Vásquez, Héctor Miguel, Martínez-Martínez, Laura (2020): New Distribution Record for Phyllophaga latipes (Bates, 1888) with a Key to the Species of the Subgenus Chlaenobia from Oaxaca, Mexico (Coleoptera: Scarabaeidae). The Coleopterists Bulletin 74 (3): 576-580, DOI: 10.1649/0010-065X-74.3.576, URL: http://dx.doi.org/10.1649/0010-065x-74.3.576

Resumen. Se documenta por primera vez la presencia de larvas de Toxomerus politus depredando huevos de Spodoptera frugiperda colocados en hojas de maiz en Oaxaca, Mexico.

ObjectiveTo describe the clinical, serologic and histologic features of a cohort of patients with brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc) and unravel disease-specific pathophysiologic mechanisms occurring in these patients.MethodsWe reviewed clinical, immunologic, muscle MRI, nailfold videocapillaroscopy, muscle biopsy, and response to treatment data from 8 patients with BCIM-SSc. We compared cytokine profiles between patients with BCIM-SSc and SSc without muscle involvement and controls. We analyzed the effect of the deregulated cytokines in vitro (fibroblasts, endothelial cells, and muscle cells) and in vivo.ResultsAll patients with BCIM-SSc presented with muscle weakness involving cervical and proximal muscles of the upper limbs plus Raynaud syndrome, telangiectasia and/or sclerodactilia, hypotonia of the esophagus, and interstitial lung disease. Immunosuppressive treatment stopped the progression of the disease. Muscle biopsy showed pathologic changes including the presence of necrotic fibers, fibrosis, and reduced capillary number and size. Cytokines involved in inflammation, angiogenesis, and fibrosis were deregulated. Thrombospondin-1 (TSP-1), which participates in all these 3 processes, was upregulated in patients with BCIM-SSc. In vitro, TSP-1 and serum of patients with BCIM-SSc promoted proliferation and upregulation of collagen, fibronectin, and transforming growth factor beta in fibroblasts. TSP-1 disrupted vascular network, decreased muscle differentiation, and promoted hypotrophic myotubes. In vivo, TSP-1 increased fibrotic tissue and profibrotic macrophage infiltration in the muscle.ConclusionsPatients with SSc may present with a clinically and pathologically distinct myopathy. A prompt and correct diagnosis has important implications for treatment. Finally, TSP-1 may participate in the pathologic changes observed in muscle.

Background: The LRP1 (CR9) domain and, in particular, the sequence Gly1127-Cys1140 (P3) plays a critical role in the binding and internalization of aggregated LDL (agLDL). We aimed to evaluate whether immunization with P3 reduces high-fat diet (HFD)-induced atherosclerosis. Methods: Female New Zealand White (NZW) rabbits were immunized with a primary injection and four reminder doses (R1-R4) of IrP (irrelevant peptide) or P3 conjugated to the carrier. IrP and P3-immunized rabbits were randomly divided into a normal diet group and a HFD-fed group. Anti-P3 antibody levels were determined by ELISA. Lipoprotein profile, circulating and tissue lipids, and vascular pro-inflammatory mediators were determined using standardized methods while atherosclerosis was determined by confocal microscopy studies and non-invasive imaging (PET/CT and Doppler ultrasonography). Studies treating human macrophages (hMΦ) and coronary vascular smooth muscle cells (hcVSMC) with rabbit serums were performed to ascertain the potential impact of anti-P3 Abs on the functionality of these crucial cells. Results: P3 immunization specifically induced the production of anti-P3 antibodies (Abs) and did not alter the lipoprotein profile. HFD strongly induced cholesteryl ester (CE) accumulation in the aorta of both the control and IrP groups, and their serum dose-dependently raised the intracellular CE of hMΦ and hcVSMC, promoting TNFR1 and phospho-NF-kB (p65) overexpression. These HFD pro-inflammatory effects were dramatically decreased in the aorta of P3-immunized rabbits and in hMΦ and hcVSMC exposed to the P3 rabbit serums. Microscopy studies revealed that P3 immunization reduced the percentage of lipids, macrophages, and SMCs in the arterial intima, as well as the atherosclerotic extent and lesion area in the aorta. PET/CT and Doppler ultrasonography studies showed that the average standardized uptake value (SUVmean) of the aorta and the arterial resistance index (ARI) of the carotids were more upregulated by HFD in the control and IrP groups than the P3 group. Conclusions: P3 immunization counteracts HFD-induced fatty streak formation in rabbits. The specific blockade of the LRP1 (CR9) domain with Anti-P3 Abs dramatically reduces HFD-induced intracellular CE loading and harmful coupling to pro-inflammatory signaling in the vasculature.

Background: Minor salivary gland biopsy (MSGB) is the most important diagnostic test of Sjogren’s Syndrome (SS). It demonstrates the presence of the inflammatory infiltration in the most affected site. It’s possible role as a biomarker in the disease is still unknown. The Inmunology Department of our center conducts a detailed analysis of the MSGB about the leukocyte infiltration and quantifies number of each cell. Objectives: To describe the inmunologic features of the MSGB and carry out an association analysis with clinical variables Methods: Clinical variables, ESSDAI index at the moment of diagnosis and laboratory parameters were recorded. As from the MSGB, number of infiltration focus (1, 2 or several), big infiltrations (>100 cells), number of B and T cells, CD4/CD8 ratio and presence of isolated lymphocyte were collected. Categorical variables were described as frequencies and analysed using Fisher exact test. T student and Wilcoxon Rank Sum Test were used for comparison of means (μ). Results: In 2017, a total of 104 MSGB were carried out in our center. Among them 58 were diagnosed as SS by medical and ACR/EULAR 2016 criteria. Finally 41 patients with SS and abnormal MSGB result were included for this study. Biopsy: Patients with active disease (ESSDAI≥2) had greater amount of cells (μ 159 cells vs 509 cells; p=0,055) as well as those with extraglandular disease (μ 160 vs 488; p=0.08). Patients with active disease also had larger number of infiltration focus (p= 0.062). The presence of isolated CD8+ T cells was observed in 13 patients and they had lesser cells (μ 136 vs 381; p=0.35). In those samples with predominance of T cells over B cells had larger number of infiltrate focus (7/20; 35% vs 12/21; 57.14%; p=0.155). No association with disease activity or extraglandular manifestation was found. Extraglandular manifestation and disease activity: 18 patients had extraglandular disease. Moderate or severe ESSDAI activity was found in 14 of these patients (34.2%, p=0.00). The biopsy of patients with extraglandular disease had larger amount of cells (μ 200 vs 145; p=0.01). Patients with active disease had more infiltratre focus (6/22 vs 11/19; p=0.047). Disease evolution time was similar with a mean duration of 8-9 years in both groups. Corticosteroids: There were 3 patients with active steroid treatment (≥prednisone 10mg/d) at the moment of the biopsy. All 3 of them had >1 focus in the sample and 2 of them had large infiltrate with >150 cells. Eight of them had received steroids in the last 5 years, 6 of them had large infiltate with >150 cells and 4 had >1 infiltrate focus in the biopsy. A study with more sample should be carried out to study the influence of steroids in the biopsy results. Conclusion: Patients with extraglandular disease have larger amount of cells in the composition of infiltration. Those with more disease activity had more number of infiltration focus. In 14 patients specific antibodies and antinuclear antibodies were negative. In these patients the biopsy is the most useful diagnostic test. Possible association of those variables that were statistically not signifcant should not be ruled out due to the small sample size of the study. Disclosure of Interests: HYE SANG PARK: None declared, LAURA MARTINEZ-MARTINEZ: None declared, Berta Magallares: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000 USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, Cesar Diaz-Torne: None declared, Ana Laiz Consultant for: Lilly, Novartis, AbbVvie, MSD, UCB and Janssen, Speakers bureau: Lilly, Novartis, Abvvie, MSD, UCB and Janssen, Patricia Moya: None declared, Ana Milena Millan Arciniegas: None declared, Andrea Garcia-Guillen: None declared, Sycille Jeria: None declared, DAVID LOBO: None declared, Susana P. Fernandez-Sanchez: None declared, CONXITA PITARCH: None declared, MANEL RIERA: None declared, MARIA CARMEN HERNANDEZ LAFUENTE: None declared, Candido Juarez: None declared, Hector Corominas: None declared

Background: The antibody against the transcriptional intermediate factor 1γ (Anti-TIF1γ or anti-p155), is considered specific for dermatomyositis (DM) and its a marker of cancer risk. Our center carries out the determination of anti-TIF1γ by a homemade immunoblot (IB) technique with a 155 kDa TIF1γ human recombinant protein (OriGene). Currently there is a commercial technique of IB to detect TIF1γ (Euroimmun), however, commercial kits sometimes elaborate antigens without using whole protein structure. To date, there are no studies that study the agreement between the commercial kit and homemades IB. Objectives: 1-To compare the commercial IB results of anti-TIF1γ with homemade IB. 2-To describe and compare the clinical characteristics of the patients analyzed by both techniques. METHODS: Observational retrospective study that included adult patients with some determination of anti-TIF1γ antibodies since 2014 in two tertiary-level university hospitals. We collected demographic and clinical data of all patients. Taking into account their diagnoses we grouped them into: Cancer associated Myositis (CAM), DM without cancer, Systemic autoimmune Diseases (SAD) non-DM and other diagnoses. Subsequently, the clinical agreement with the IB results of anti-TIF1γ performed by commercial (cIB) and homemade (hIB) technique were analyzed. A p value RESULTS: 48 patients were recruited (77.1% women). 13 had diagnosis of CAM, 19 of DM without cancer, 7 of other non-DM EAS, and 9 had other diagnoses. Of all DM (CAM and DM without cancer), 12 were positive for both techniques. 5 presented discordant results (4 hIB positive with negative cIB and 1 cIB positive with negative hIB). 15 DM were negative for the two techniques, of which 8/15 had other antibodies associated with autoimmune Myopathy (3 NXP-2, 1 Mi2, 1 MDA5, 1 SAE, 1 Jo1 and 1 Ro52). When we analyzed patients with CAM with both techniques, 10/13 presented positive hIB vs 8/13 cIB positive. DM without cancer, 6/19 had positive hIB vs 5/19 cIB positive. The sensitivity and specificity of each test was evaluated in CAM and DM without cancer, being 61.5% and 73.7% respectively for cIB (p = 0.071), compared to 76.9% and 68.4% for hIB (p = 0.029). In non-DM SAD group, 1 patient had positive determination for both techniques, 3 had positive cIB with negative hIB, and 3 cIB negative with positive hIB. We also found other antibodies in 6/7 patients with non-DM SAD. The 9 patients with other diagnoses were: 1 positive for both techniques and 8 positive for cIB and negative for hIB. CONCLUSIONS: Homemade IB with 155 kDa recombinant protein was superior to cIB to detect TIFγ in our serie of patients with CAM. This could have clinical implications in screening and early detection of neoplasia that affect false negative by cIB. A positive cIB in patients not suspected as a SAD were negative for hIB in the major part of cases. It would be recommended to check the commercial IB using homemade IB, due to its known clinical-therapeutic implications. Disclosure of interests: Ana Milena Millan arciniegas: None declared, M. ANGELES MARTINEZ: None declared, aNAIS MARISCAL: None declared, aNDRES BAUCELLS: None declared, Leticia alserawan: None declared, Ernesto Trallero: None declared, Cesar Diaz-Torne: None declared, ana Laiz Consultant for: Lilly, Novartis, abbVvie, MSD, UCB and Janssen, Speakers bureau: Lilly, Novartis, abvvie, MSD, UCB and Janssen, Berta Magallares: None declared, Patricia Moya: None declared, HyeSang Park: None declared, andrea Garcia-Guillen: None declared, Sycille Jeria: None declared, DAVID LOBO: None declared, albert Gil: None declared, Coral Gozalvez: None declared, Susana P. Fernandez-Sanchez: None declared, Laura Martinez-Martinez: None declared, Esther Moga: None declared, Hector Corominas: None declared, Candido Juarez: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, albert Selva-O’Callaghan: None declared

Background:Currently, there are no biomarkers to predict respiratory worsening in patients with Coronavirus infectious disease, 2019 (COVID- 19) pneumonia.Objectives:We aimed to determine the prognostic value of Krebs von de Lungen-6 circulating serum levels (sKL-6) predicting COVID- 19 evolving trends.Methods:We prospectively analyzed the clinical and laboratory characteristics of 375 COVID- 19 patients with mild lung disease on admission. sKL-6 was obtained in all patients at baseline and compared among patients with respiratory worsening.Results:45.1% of patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were higher in patients who had respiratory worsening (median [IQR] 303 [209-449] vs. 285.5 [15.8-5724], P=0.068). The best sKL-6 cut-off point was 408 U/mL (area under the curve 0.55; 33% sensitivity, 79% specificity). Independent predictors of respiratory worsening were sKL-6 serum levels, age >51 years, time hospitalized, and dyspnea on admission. Patients with baseline sKL-6 ≥ 408 U/mL had a 39% higher risk of developing respiratory aggravation seven days after admission. In patients with serial determinations, sKL-6 was also higher in those who subsequently worsened (median [IQR] 330 [219-460] vs 290.5 [193-396]; pConclusion:sKL-6 has a low sensibility to predict respiratory worsening in patients with mild COVID-19 pneumonia. Baseline sKL-6 ≥ 408 U/mL is associated to a higher risk of respiratory worsening. sKL-6 levels are not useful as a screening tool to stratify patients on admission but further research is needed to investigate if serial determinations of sKL-6 may be of prognostic use.References:[1]Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. 5.[2]Tian W, Jiang W, Yao J, Nicholson CJ, Li RH, Sigurslid HH, et al. Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis. J Med Virol. 2020.[3]Wang D, Li R, Wang J, Jiang Q, Gao C, Yang J, et al. Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study. BMC Infect Dis. 2020;20(1):519.Disclosure of Interests:None declared.

Background and objective Statin-associated autoimmune myopathy (SAAM) with anti-HMGCR antibodies has recently been described. Several specific immunoassays are in use to detect HMGCR antibodies. In the course of systematic autoantibody screening we recognized a new distinct IFL staining pattern on rat liver sections that regularly coincided with anti-HMGCR antibodies. In this study we investigated whether this new IFL pattern is specifically associated to statin-associated autoimmune myopathy and corresponds to anti-HMGCR antibodies. Patients and methods Twenty-three patients positive for anti-HMGCR antibodies (14 diagnosed with SAAM) were investigated for anti-HMGCR antibodies by two ELISA assays and confirmed by immmunoblot. HMGCR associated liver IFL pattern (HALIP) was detected by indirect IFL and the reactivity against HMGCR was confirmed by immunoabsorption using purified human HMGCR antigen. 90 patients with other autoimmune diseases and 45 non-autoimmune statin treated patients were studied as controls. Results 21 out of 23 (91%) anti-HMGCR positive patients were HALIP positive. The staining was completely and specifically removed by immunoabsorption with human purified HMGCR. None of the control sera from autoimmune patients or non-autoimmune statin treated subjects was positive for HALIP. Statistical concordance between HALIP and anti-HMGCR antibody specific tests was 98.7%, kappa 0.95. Conclusions A new and distinct IFL staining pattern (HALIP) is associated to HMGCR associated myopathy. Absorption and concordance studies indicate that the antigen recognized in the liver by HALIP is HMGCR or a closely related protein. Awareness of this new pattern can help to detect HMGCR autoantibodies in statin treated patients tested for autoimmune serology.

Background:Positivity of dense fine speckles antibodies (anti-DFS70) has been associated with antinuclear antibodies positivity in people with no evidence of systemic autoimmune disease. They could be useful to distinguish patients with these characteristics that do not meet diagnostic and/or classifying criteria for any systemic autoimmune disease (SAD).Objectives:To evaluate the use of anti- DFS70 in patients with suspicion of SAD.Methods:A cross-sectional observational study was conducted at 2 tertiary-level hospitals. We included a cohort of patients visited in the last year by either rheumatology or other specialties, under suspicion of SAD, in which the IgG isotype anti-DFS70 was obtained by recombination with the Euroline Immunoblot of Euroimmun. Demographic, clinical and immunological variables were collected.Results:102 patients (78% women) were included, median age of 49 years old. The descriptive statistics are summarized in Table 1. All patients had ANA titters > 1/80. 37% were positive for anti-DFS70, with homogeneous, speckled and other patterns in 36%, 72% and 15% respectively.74% were visited by rheumatologists under the suspicion of systemic lupus erythematosus (SLE) in 27%, other SAD 25%, arthralgia 36% and fibromyalgia 12%. 13% presented high DNA titters, low C3/C4 levels in 14% and 9%. SLE’s symptoms were: arthritis 21%, arthralgia 41%, cutaneous 20% and oral ulcers 8%. Anti-DFS70(+) was related to the speckled pattern in 46% compared to other patterns (p=0,009), which had a negative association with anti-DFS70(p=0,003). Regarding the diagnoses, there was a negative association with SLE, other SAD and other rheumatologic diagnoses in 88%, 75% and 55% respectively(p=0,006). Anti-DFS70(-) was associated with oral ulcers (p=0,024), decreased C3/C4 levels (p=0,007/p=0,018), psoriatic arthritis (p=0,024) and cutaneous lupus (p=0,008), but not with drug-induced SLE (p=0,48) or lupus nephritis (p=0,067). There was no statistical significance between anti-DFS70(+) and arthralgia or fibromyalgia, but these patients don’t have a SAD diagnosis.Table 1.RHEUMATOLOGY(n=75)OTHER SPECIALTIES(n=27)antiDFS70(+)n=25(100%)antiDFS70(-)n=50(100%)antiDFS70(+)n=13(100%)antiDFS70(-)n=14(100%)Women20(80)43(86)8(62)9(64)Age years (ED)47,1(±20,1)50,4(±15,5)45,1(±26,7)54,7(±15,6)ANAHomogeneous8(32)23(46)2(15)4(29)PatternSpeckled22(88)*30(60)12(92)9(64)IIFOther010(20)1(8)4(29)Final diagnosisArthralgia12(48)15(30)SpecialityFibromyalgia3(12)6(12)Dermatology4(31)7(49)Drug-induced SLE2(8)2(4)Gastroenterology3(23)3(21)SLE3(12)17(34)*Hematology1(8)2(14)Cutaneous lupus08(16)*Other5(38)2(14)PsA06(12)*Other6(25)16(32)SLEArthritis3(12)13(26)Arthralgia13(52)18(36)Cutaneous3(12)12(24)Oral ulcers0(0)6(12)*Leukopenia0(0)4(8)Thrombocytopenia0(0)1(2)Fever1(4)1(2)Pleuritis0(0)1(2)Pericarditis0(0)1(2)Nephritis0(0)4(8)Myositis1(4)0(0)ANA (antinuclear antibody), IIF (indirect immunofluorescence), SLE (systemic lupus erythematosus), PsA (psoriatic arthritis), *pConclusion:Our results suggest that patients with suspicion of SAD, especially SLE, presented a greater proportion of negative anti-DFS70 compared to other diagnoses, including SAD, along with a decrease in complement levels and the presence of oral ulcers, being useful at the initial study of these patients. More studies are needed to characterize this association.Disclosure of Interests:Jose Luis TANDAIPAN JAIME: None declared, Berta Magallares: None declared, Julia Bernardez: None declared, ELENA RIERA ALONSO: None declared, FRANCISCO PUJALTE: None declared, Laura Martínez-Martínez: None declared, ANDRES BAUCELLS: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Hector Corominas: None declared, Silvia Martinez Pardo: None declared

BACKGROUND: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. OBJECTIVE: We sought to investigate the incidence of gene mosaicism in patients with PIDs. METHODS: The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. RESULTS: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate-to-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. CONCLUSION: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:143 issue:1 pages:359-368 ispartof: location:United States status: published

Background Serum Calprotectin is a new biomarker of clinical activity in Rheumatology, especially in Juvenile Idiopathic Arthritis (JIA) Objectives To assess the use of serum Calprotectin in paediatric patients with inflammatory/Rheumatic diseases in clinical practice Methods We retrospectively collected Demographic and Clinical data from patients of our Paediatric Rheumatology Clinic, in which serum Calprotectin levels were determined. The determination of serum Calprotectin was carried out using the ELISA technique. Diagnostic and Inflammatory activity data were also collected: RCP, ESR and Clinical Assessment of the patients Results We present 28 patients, 61% females, with an average age of 11 (3–23 years) The diagnoses were as follows: 16 JIA (57% of the total), of which 8 were of the Oligoarticular type, 3 were Polyarticular, 3 were Arthritis related to Enthesitis, 1 was Psoriatic and 1 Systemic. Other diagnoses were: Behcet,1 Autoinflammatory Diseases: 4 (2 ADA2 Deficit, 1 Familial Mediterranean Fever, 1 PFAPA) and 7 patients had suspected rheumatological/inflammatory diseases in study 17 patients were considered clinically inactive, 6 with inflammatory activity and 3 doubtful at the time of blood test. The mean values of Calprotectin, RCP and ESR can be seen in Table 1. Calprotectin was statistically correlated with Clinical Activity (p=0.018), however, neither ESR (p=0.539) nor RCP (p=0.059) did, although in RCP there was a clinical trend, (ANOVA) Calprotectin, RCP and ESR were negative in 91%, 80% and 76% respectively of Inactive patients; and positive in 43%, 100% and 33% of the Active ones The analysis of the ROC curves in our sample showed that the value that allows to discriminate between active and non-active disease with a Sensitivity of 80% and a Specificity of 69% is 2’07 µg/mL Serum Calprotectin was 2 points higher in the group of patients with Autoinflammatory diseases than in the group of JIA, with a mean of 4.91 compared to 2.90 (p=0.002). However, since it is a retrospective study, we must bear in mind that this can be influenced by the reasons for the test request, being in the group of Autoinflammatory Disease the suspicion of active disease, and in the AIJ simply monitoring or assessment of treatment optimisation. It should be noted that, in the patients in diagnostic process that did not present any rheumatological disease (final diagnoses of: arthralgias in 3 cases and glomerulonephritis not associated to rheumatologic/autoimmune disease in 1), serum Calprotectine did not exceed in any case the 1.15 µg/mL Conclusions Serum Calprotectin is emerging as a useful marker, not only in the field of JIA, but also in other diagnostic groups such as Autoinflammatory Diseases. Prospective and larger studies are needed to determine its role Disclosure of Interest None declared

Background Serum Calprotectin (MPR8/MPR14) is a promising biomarker in the management of juvenile idiopathic arthritis (JIA), mainly as a predictor of flare, especially in treatment de-escalation Objectives To describe the evolution of serum Calprotectin in patients with JIA, their clinical evolution and its impact on therapeutic decisions Methods Demographic, clinical and inflammatory activity data (RCP and ESR) were retrospectively collected in patients with JIA of any subtype in whom serum Calprotectin had been determined at least once Results We present the data of 15 children, 7 with Oligoarticular subtype JIA, 1 Systemic, 3 Polyarticular, 1 Psoriasic and 3 Enthesitis Related Arthritis (ERA) The average age was 11 years, 66% female. The characteristics of each patient can be seen in table 1, together with the first determination of serum Calprotectin, CRP and ESR. It also shows the physiscan’s decision, and the outcome, obtained from the assessment in the next visit Considering the cutoff point of serum Calprotectin in our sample of: 2.2 µg/mL (80% sensitivity and 69% specificity), 9 of 15 patients presented high values, 2 of them presented a flare (1 Oligo and 1 Poly), both had maintained the same treatment, because they were considered inactive. There were no flares in patients with negative Calprotectin The evolution of serum Calprotectin, together with the clinical decisions (based on clinical and analytical assessment) are described in table 1 In most of stable patients in whom serum calprotectin was high, it was decided not to lower treatment, and only in one case it was de-escalated. There were no flares in any of them Conclusions Serum Calprotectin is a useful biomarker in routine clinical practice, together with other markers such as CRP and ESR, and our clinical judgment, it helps us to make therapeutic decisions Disclosure of Interest None declared

Gain-of-function STAT1 mutations have recently been associated with autosomal dominant chronic mucocutaneous candidiasis (CMC). The purpose of this study was to characterize the three members of a non-consanguineous family, the father and his two sons, who presented with recurrent oral thrush and ocular candidiasis since early childhood. The three patients had reduced levels of IL-17-producing T cells. This reduction affected specifically IL-17 + IFN-γ − T cells, because the levels of IL-17 + IFN-γ + T cells were similar to controls. We found that PBMC (peripheral blood mononuclear cells) from the patients did not respond to Candida albicans ex vivo . Moreover, after polyclonal activation, patients’ PBMC produced lower levels of IL-17 and IL-6 and higher levels of IL-4 than healthy controls. Genetic analyses showed that the three patients were heterozygous for a new mutation in STAT1 (c.894A > C, p.K298N) that affects a highly conserved residue of the coiled-coil domain of STAT1. STAT1 phosphorylation levels were significantly higher in patients’ cells than in healthy controls, both in basal conditions and after IFN-γ stimulation, suggesting a permanent activation of STAT1. Cells from the patients also presented increased IFN-γ-mediated responses measured as MIG and IP-10 production. In conclusion, we report a novel gain-of-function mutation in the coiled-coil domain of STAT1, which increases STAT1 phosphorylation and impairs IL-17-mediated immunity. The mutation is responsible for CMC in this family with autosomal dominant inheritance of the disease.

The aim of this study was to determine the possibility of using formulations of entomopathogenic nematodes in two soil moisture conditions for effective control of larvae of white grub, Phyllophaga vetula (Horn) (Coleoptera: Melolonthidae). Mortality of P. vetula larvae was compared using Steinernema glaseri Steiner, Heterorhabditis bacteriophora Poinar, and Steinernema feltiae Filipjev in three forms of application (formulated in cadavers of Galleria mellonella L. larvae, bentonite pellet, and aqueous suspension) and two soil moisture conditions (moderate,11.8%, and high, 20.5%). The difference among treatments was very significant: S. glaseri was the most effective nematode, killing 75% of larvae when applied in aqueous suspension with moderate moisture. Next most effective was S. glaseri in cadavers with the same moisture conditions that killed 55%. The nematodes H. bacteriophora and S. feltiae applied in all three forms (aqueous medium, infected cadaver, and bentonite pellet) and with the tw...

Background The aim of the research is to study the human leukocyte antigen (HLA) class II allele frequencies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with anti-neurofascin 155 (NF155) antibodies. Methods Thirteen anti-NF155+ and 35 anti-NF155 negative (anti-NF155neg) CIDP patients were included in a case-control study. The frequencies of the DRB1 HLA allele were analyzed in all patients while DQ frequencies were only studied in patients sharing the DRB1*15 allele. In silico HLA-peptide binding and NF155 antigenicity, predictions were performed to analyze overlap between presented peptides and antigenic regions. Results DRB1*15 alleles (DRB1*15:01 and DRB1*15:02) were present in 10 out of 13 anti-NF155+ CIDP patients and in only 5 out of 35 anti-NF155neg CIDP patients (77 vs 14%; OR = 20, CI = 4.035 to 99.13). DRB1*15 alleles appeared also in significantly higher proportions in anti-NF155+ CIDP than in normal population (77 vs 17%; OR = 16.9, CI = 4.434 to 57.30). Seven anti-NF155+ CIDP patients (53%) and 5 anti-NF155neg CIDP patients had the DRB1*15:01 allele (OR = 7, p = 0.009), while 3 anti-NF155+ CIDP patients and none of the anti-NF155neg CIDP patients had the DRB1*15:02 allele (OR = 23.6, p = 0.016). In silico analysis of the NF155 peptides binding to DRB1*15 alleles showed significant overlap in the peptides presented by the 15:01 and 15:02 alleles, suggesting functional homology. Conclusions DRB1*15 alleles are the first strong risk factor associated to a CIDP subset, providing additional evidence that anti-NF155+ CIDP patients constitute a differentiated disease within the CIDP syndrome. Electronic supplementary material The online version of this article (10.1186/s12974-017-0996-1) contains supplementary material, which is available to authorized users.

Introduction: Interstitial pneumonia with autoimmune features (IPAF) was recently defined to gather interstitial lung diseases (ILD) having suggestive features of a systemic autoimmune process without meeting conventional criteria for a defined connective tissue disease (CTD). Sjogren’s syndrome (SS) frequently involves the respiratory system but as symptoms are unspecific could be under recognized. Objective: Describe the results of Minor salivary gland biopsy (MSGB) in patients with IPAF criteria and possible SS. Methods: Retrospective study including all ILD patients with IPAF and possible SS, evaluated since 2013, which underwent MSGB. Clinical, laboratory and histological data were collected. MSGB was considered positive when 1 or more focus score >50 lymphocytes/4mm3 were founded, except in patients under immunosuppressive treatment, in which the threshold was established in 20-50 lymphocytes/4mm3. Results: Twenty-three patients were included. Median age (±SD) was 74± 8years and 52% were females. Overall, nine MSBG (39%) were considered positive and the diagnosis of SS was confirmed. In those patients, sicca syndrome was present in 6(66%), positive Schirmer in 5(43%) and ANA>1:320 in 3(33%). The median FVC (% predicted) was 78±15%. Non specific interstitial pattern 4(44%) and usual interstitial pattern 4(44%) were the most common radiological findings. In 6 of those patients (67%) the results of MSBG conditioned therapeutic changes. No complications of the MSBG were reported. Conclusions: MSGB could be considered a useful diagnostic tool in patients with IPAF and possible SS. This data should be confirmed in a larger prospective IPAF cohort.

Çalışmada 35 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır. Background: Gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) cause susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life-threatening. Hematopoietic stem cell transplantation (HSCT) has been used in some patients with more severe symptoms to treat and cure the disorder. However, the outcome of HSCT for this disorder is not well established. Objective: We sought to aggregate the worldwide experience of HSCT in patients with GOF-STAT1 mutations and to assess outcomes, including donor engraftment, overall survival, graft-versus-host disease, and transplant-related complications. Methods: Data were collected from an international cohort of 15 patients with GOF-STAT1 mutations who had undergone HSCT-using a variety of conditioning regimens and donor sources. Retrospective data collection allowed the outcome of transplantation to be assessed. In vitro functional testing was performed to confirm that each of the identified STAT1 variants was in fact a GOF mutation. Results: Primary donor engraftment in this cohort of 15 patients with GOF-STAT1 mutations was 74%, and overall survival was only 40%. Secondary graft failure was common (50%), and posttransplantation event-free survival was poor (10% by 100 days). Asubset of patients had hemophagocytic lymphohistiocytosis before transplant, contributing to their poor outcomes. Conclusion: Our data indicate that HSCT for patients with GOF-STAT1 mutations is curative but has significant risk of secondary graft failure and death. United States Department of Health & Human Services National Institutes of Health(NIH) - USA (R13 AI094943) Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science (16H05355) Japan Agency for Medical Research and Development (AMED) Jeffrey Modell Foundation United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Allergy & Infectious Diseases (NIAID) (R13AI094943) ReumaFonds (LLP-10)