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Background: Limited information is available on response to Covid-19 vaccines in autoimmune rheumatic disease patients(ARD) previously exposed to the SARS-CoV-2. We compared the dynamics of vaccine induced antibody production after immunization with CoronaVac in SARS-CoV-2 - seropositive ARD patients(ARD+) with two age/sex balanced groups: SARS-CoV-2 naive ARD patients(NAIVE-ARD) and SARS-CoV-2-seropositive control group(CTRL+). Methods: Participants of this phase 4 prospective controlled study were vaccinated with two doses of CoronaVac(28-days interval). Primary objective was immunogenicity dynamics evaluated by median neutralizing activity(NAb-activity)/anti-SARS-Cov-2 ln(IgG) titers[ln(IgG)] from D0-D28 and from D28-D69. Secondary objectives included safety and other immunogenicity parameters. Findings: Disease and therapy were similar in ARD+ and NAIVE-ARD groups(p>0·05). A comparable dynamics was observed for ARD+ and CTRL+ with a plateau increase occurring from D0-D28[ARD+, NAb-activity:59·1% to 81·8%, mean difference -12·1%,p=0·002 and anti-S1/S2-GMT:52·3 to 128·9, ln(IgG) mean difference -0·9,p 0·999) and anti-S1/S2-GMT(p 0·999 and D69:-12·3%,p=0·167/0·32%,p=0·258 with minor difference at D28:-13·6%, p=0·067/-0·45,p=0·006. Interpretation: ARD+ patients mount a robust plateau response after a single dose of inactivated SARS-CoV-2 vaccine, independent of pre-existing ARD/therapy, whereas NAIVE-ARD patients require the second dose to ensure a moderate antibody production. Our findings raise the possibility of a single dose regimen in ARD patients previously exposed to SARS-CoV-2.[clinicaltrials.gov#NCT04754698] Funding: FAPESP/CNPq/B3-Bolsa de Valores-Brasil. Declaration of Interest: The authors declare no competing interests. Ethical Approval: The protocol was approved by the National and Institutional Ethical Committee (CAAE: 42566621.0.0000.0068)

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CoronaVac, an inactivated SARS-CoV-2 vaccine, has been approved for emergency use in several countries. However, its immunogenicity in immunocompromised individuals has not been well established. We initiated a prospective phase 4 controlled trial (no. NCT04754698, CoronavRheum) in 910 adults with autoimmune rheumatic diseases (ARD) and 182 age- and sex-frequency-matched healthy adults (control group, CG), who received two doses of CoronaVac. The primary outcomes were reduction of ≥15% in both anti-SARS-CoV-2 IgG seroconversion (SC) and neutralizing antibody (NAb) positivity 6 weeks (day 69 (D69)) after the second dose in the ARD group compared with that in the CG. Secondary outcomes were IgG SC and NAb positivity at D28, IgG titers and neutralizing activity at D28 and D69 and vaccine safety. Prespecified endpoints were met, with lower anti-SARS-Cov-2 IgG SC (70.4 versus 95.5%, P < 0.001) and NAb positivity (56.3 versus 79.3%, P < 0.001) at D69 in the ARD group than in the CG. Moreover, IgG titers (12.1 versus 29.7, P < 0.001) and median neutralization activity (58.7 versus 64.5%, P = 0.013) were also lower at D69 in patients with ARD. At D28, patients with ARD presented with lower IgG frequency (18.7 versus 34.6%, P < 0.001) and NAb positivity (20.6 versus 36.3%, P < 0.001) than that of the CG. There were no moderate/severe adverse events. These data support the use of CoronaVac in patients with ARD, suggesting reduced but acceptable short-term immunogenicity. The trial is still ongoing to evaluate the long-term effectiveness/immunogenicity.

Background: People living with HIV (PLWH) may have a poor or delayed response to vaccines, mainly when CD4+ T cell counts are low. There are limited data concerning the safety and immunogenicity of COVID-19 vaccines in PLWH. Methods: This prospective controlled study evaluated the safety and immunogenicity of the SARS-CoV-2 inactivated vaccine CoronaVac in PLWH compared with controls with no known immunosuppression. Immunogenicity was assessed with SARS-CoV-2 IgG seroconversion (SC), neutralizing antibodies (NAb) activity, and factor increase in IgG geometric mean titers (FI-GMT). We also investigated if levels of CD4+ T cell counts (< or ≥500 cells/mm3) were associated with CoronaVac immunogenicity. Findings: 511 participants (215 PLWH and 296 controls) were eligible for the immunogenicity analysis. At vaccine completion (D69), although the percentage of participants with SC and NAb positivity was high for both PLWH and controls, it was somewhat lower in PLWH. CD4+ T cell was identified as a relevant factor for immunogenicity, with lower SC and NAb positivity in PLWH with CD4+ counts

ObjectivesThis study aimed to determine the prevalence of autoantibodies to cellular prion protein (PrP(C)) and its cognate ligand stress-inducible protein 1 (STI-1) in sera from patients with syst...

After publication of the original article [1], we were notified that there is a mistake in Fig. 2.

Background Primary Sjögren’s syndrome (pSS) is a systemic immune-mediated disease whose main characteristic is exocrine gland inflammation and, subsequent reduction in tear and saliva production. A delayed diagnosis is common due to the nonspecific clinical manifestations of disease. The aim of the present study was to develop recommendations for the diagnosis of glandular manifestations of pSS based on evidence and expert opinion. Main body of the abstract We conducted a systematic literature review to retrieve the best evidence available on the accuracy of diagnostic tests for pSS. We also held two in-person meetings with experts (rheumatologists, pathologists, ophthalmologists and dentists) to establish their level of agreement using the Delphi method. Ultimately, we generated 18 recommendations that aim to facilitate the diagnosis of the glandular manifestations of pSS. Conclusion The diagnosis of glandular manifestations of pSS is complex and multidisciplinary. It requires specific knowledge in the field of ophthalmology, immunology, pathology and imaging, making it compulsory for the rheumatologist to work with professionals from these different areas in order to improve accuracy and early diagnosis. Glandular dysfunction tests, ANA, RF, Anti-Ro, protein electrophoresis, urinalysis, blood count, C-Reactive protein, complement, testing for syphilis and viruses (HCV, HIV) and SGUS should be investigated when dryness or systemic manifestation are present. Minor salivary gland biopsy is recommended for all anti-Ro negative or incomplete criteria cases.

BackgroundType V collagen (Col V) has the potential to become an autoantigen and has been associated with the pathogenesis of systemic sclerosis (SSc). We characterized serological, functional, and histopathological features of the skin and lung in a novel SSc murine model induced by Col V immunization.MethodsFemale C57BL/6 mice (n = 19, IMU-COLV) were subcutaneously immunized with two doses of Col V (125 μg) emulsified in complete Freund adjuvant, followed by two intramuscular boosters. The control group (n = 19) did not receive Col V. After 120 days, we examined the respiratory mechanics, serum autoantibodies, and vascular manifestations of the mice. The skin and lung inflammatory processes and the collagen gene/protein expressions were analyzed.ResultsVascular manifestations were characterized by endothelial cell activity and apoptosis, as shown by the increased expression of VEGF, endothelin-1, and caspase-3 in endothelial cells. The IMU-COLV mice presented with increased tissue elastance and a nonspecific interstitial pneumonia (NSIP) histologic pattern in the lung, combined with the thickening of the small and medium intrapulmonary arteries, increased Col V fibers, and increased COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2 gene expression. The skin of the IMU-COLV mice showed thickness, epidermal rectification, decreased papillary dermis, atrophied appendages, and increased collagen, COL5A1, and COL5A2 gene expression. Anti-collagen III and IV and ANA antibodies were detected in the sera of the IMU-COLV mice.ConclusionWe demonstrated that cutaneous, vascular, and pulmonary remodeling are mimicked in the Col V-induced SSc mouse model, which thus represents a suitable preclinical model to study the mechanisms and therapeutic approaches for SSc.

Background Brazil faced a yellow fever(YF) outbreak in 2016–2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality. Objective This study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression. Methods and Results A total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3–1292.2) vs.731 (95%CI 593.6–900.2), p0.05). Conclusion Fractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(>80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas. Trial registration This clinical trial was registered with Clinicaltrials.gov (#NCT03430388)., Author summary Yellow fever is a viral hemorragic fever with high mortality rate and the vaccine is a remarkably successful way of preventing it. As a live attenuated virus vaccine, it is not recommended for rheumatic and other immunossupressed patients in general. However, in an outbreak scenario, the risk of dying of the disease can be higher than the risk of a vaccine serious adverse event. In 2018, the fractional-dose yellow fever vaccine was offered to the hospital employees and to the rheumatic patients without or with low immunossupression therapy in Hospital das Clinicas of University of São Paulo, during the yellow fever outbreak in São Paulo, Brazil. In order to optimize the yellow fever vaccine (YFV) supply, the fractional-dose (corresponding to one fifth) was adopted in the public vaccine campaign. This is the first study evaluating the primary vaccination with fractional-dose YFV in autoimmune rheumatic diseases(ARD) patients (n = 159) under low immunosuppression. Most vaccinated participants were able to produce enough neutralizing antibodies to be protected against yellow fever (seroconversion rate of 84% versus 96% in healthy controls). Neither activity of the rheumatic disease or serious adverse event was identified during the 30 days of followup after the vaccination.

Objective To assess the possible effect of therapy, disease subtype and severity on H1N1 immunogenicity in patients with SSc. Methods Ninety-two patients and 92 age- and gender-matched healthy controls received adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Blood samples were collected immediately before and 3 weeks after vaccination to evaluate antibody responses to the H1N1 virus. Efficacy was assessed by seroprotection (SP) and seroconversion (SC) rates and the factor increase in geometric mean antibody titre. Participants received a 21-day symptom diary card and were instructed to report local and systemic adverse events. Results SSc patients were predominantly females (91%) and 61% had limited SSc, 12% had severe skin involvement and 57.6% were on immunosuppressive (IS) therapy. SSc patients and controls presented comparable overall SP (P = 0.20) and SC (P = 0.61) rates. Further evaluation of the possible effect of disease and therapy revealed similar rates of SP and SC in patients with dcSSc vs lcSSc (SP P = 0.62 and SC P = 0.66), severe vs mild/moderate skin involvement (SP P = 1 and SC P = 0.45) and with vs without IS (SP P = 0.26 and SC P = 0.10). The frequency of mild local and minor systemic reactions was similar in patients with dcSSC vs lcSSc (P = 0.70 vs 0.32) and in those with and without severe skin involvement (P = 0.59 vs 0.28). Conclusion The non-adjuvanted influenza H1N1 virus vaccine proved to be safe and effective, independent of SSc clinical subtype, disease severity or therapy. These latter factors do not seem to contribute to mild adverse events observed in SSc. Our data support the annual influenza vaccination recommendation for these patients. Trial registration ClinicalTrials.gov (http://clinicaltrials.gov), NCT01151644.

Pode-se dizer que o lúpus eritematoso sistêmico (LES) é o protótipo das doenças inflamatórias crônicas sistêmicas. De fato, múltiplos sistemas orgânicos podem ser acometidos de forma simultânea ou evolutivamente, levando a um espectro muito amplo de apresentações clínicas, composto especialmente por manifestações decorrentes do envolvimento mucocutâneo (tais como fotossensibilidade, diferentes formas de erupções cutâneas, alopecia, úlceras de mucosas, lesões vasculíticas), poliartralgias/poliartrite, pleurite, pericardite, glomerulonefrite (hipertensão arterial sistêmica, hematúria microscópica, proteinúria, insuficiência renal aguda e crônica), alterações hematológicas (anemia, leucopenia, linfopenia, plaquetopenia) e acometimento do sistema nervoso central (que pode ocasionar convulsões, psicose, meningite asséptica, síndrome cerebral orgânica, etc.). Além disso, seu curso evolutivo é caracterizado pela alternância entre períodos de exacerbação (doença ativa) e remissão. A etiologia do LES ainda é desconhecida, mas a sua patogênese é sabidamente autoimune. Nesse aspecto, uma das características mais marcantes do LES e que reflete a ativação policlonal das células B observada nessa doença consiste na produção de múltiplos autoanticorpos circulantes, levando à formação de imunocomplexos, os quais, desencadeando o processo inflamatório, constituem uma importante causa de lesão orgânica no LES.

BACKGROUND/OBJECTIVE Our aim was to describe the short- and long-term outcome of peripheral neuropathy (PN) attributed exclusively to systemic lupus erythematosus (SLE). METHODS Systemic lupus erythematosus patients with defined PN (clinical and electroneuromyography) were retrospectively evaluated at onset, 1-year, and 5-year follow-up using a standardized electronic chart database that started in 2000. Exclusion criteria were comorbidities, drugs, and infections. Age-, sex-, and disease duration-matched SLE patients without PN were selected as controls. RESULTS Lupus PN was identified in 38 (1.8%) of 2074 patients, and almost two thirds had PN onset in the first 5 years of SLE (63.2%). Peripheral neuropathy SLE had higher frequencies of cutaneous vasculitis (50% vs 21.1%, p = 0.002), lymphopenia (60.5% vs 36.8%, p = 0.027), anti-Sm (52.6% vs 27.6%, p = 0.013), and higher SLEDAI-2K scores (11.5 ± 10.5 vs 4.9 ± 6.7, p < 0.001) compared with controls. The most common type was polyneuropathy (71.1%) with sensory-motor pattern (68.4%). At PN diagnosis, all patients received glucocorticoid and 97.4% started immunosuppressive therapy (50% intravenous cyclophosphamide, 42.1% azathioprine). After 1-year follow-up, 92.1% had a favorable outcome with complete (36.8%) or partial remission (55.2%), in parallel with a decrease in prednisone dose (48.3 ± 17.9 vs 15.3 ± 13.4 mg/d, p < 0.001), symptomatic therapy (57.9% vs 29.7%, p = 0.02), and SLEDAI-2K score (11.5 ± 10.5 vs 1.7 ± 3.7, p < 0.001). SLEDAI-2K scores were higher in patients who had PN onset with less than 1 year of SLE duration, compared with those with more than 5 years of disease (21.3 ± 9.1 vs 3.9 ± 5.3, p < 0.001). Early-PN-onset group had a better response to treatment (complete remission at 1-year follow-up 61.5% vs 25%, p = 0.039). At 5-year follow-up, 89.3% remained with complete/partial remission. CONCLUSIONS Peripheral neuropathy attributed to SLE itself is a rare manifestation with a bimodal pattern, characterized by a predominant early-onset group associated with high disease activity and a higher rate of complete remission, and a late-onset group with low disease activity and a partial therapy response.

Background: The V Brazilian Consensus for determination of autoantibodies against cellular constituents on HEp-2 cells, held in Brasilia (DF, Brazil) on August 27, 2016, discussed the harmonization between the Brazilian Consensus on ANA (BCA) guidelines and the International Consensus on ANA Patterns (ICAP) recommendations (www.anapatterns.org). Initial guidelines were formulated by the group of Brazilian experts with the purpose of guiding and enabling Brazilian clinical laboratories to adopt recommendations and to provide a common standard for national and international consensuses. Mainbody: Twenty Brazilian researchers and experts from universities and clinical laboratories representing the various geographical regions of the country participated in the meeting. Three main topics were discussed, namely the harmonization between the BCA guidelines and latest recommendations of the ICAP initiative, the adjustment of the terminology and report on HEp-2 patterns, and a reassessment of quality assurance parameters. For the three topics, our aim was to establish specific guidelines. All recommendations were based on consensus among participants. There was concrete progress in the adjustment of the BCA guidelines to match the ICAP guidelines. To a certain extent, this derives from the fact that ICAP recommendations were largely based on the algorithm and recommendations of the IV Brazilian ANA Consensus, as consistently recognized in the ICAP publications and presentations. However, although there is great overlap between the two Consensuses, there are some point divergences. These specific items were individually and extensively discussed, and it was acknowledged that in several points ICAP improved recommendations previously issued by the Brazilian ANA Consensus and these changes were readily implemented. Regarding some specific topics, the BCA panel of experts felt that the previously issued recommendations remained relevant and possibly will require further discussion with ICAP. The term anti-cell antibodies was adopted as the recommended designation, recognizing that the assay addresses antibodies against antigens in the nucleus and in other cell compartments. However, the acronym ANA HEp-2 was maintained due to historical and regulatory reasons. It was also signalized that the latest trend in ICAP is to adopt the term Indirect Immunofluorescent Assay on HEp-2 cell substrate (HEp-2 IIFA). In addition, the quality assurance strategies previously presented were ratified and emphasized. Conclusion: The V BCA edition was successful in establishing an overall harmonization with the ICAP recommendations for interpretation of the HEp-2 IIFA test, pinpointing the perspectives in filling the remaining gaps between both initiatives.

To assess the longitudinal production of anti-adalimumab antibody (AAA) and baseline risk factors for this antibody development in juvenile idiopathic arthritis (JIA) patients initiating adalimumab (ADA).Thirty consecutive JIA patients under ADA therapy were prospectively followed. JIA clinical/laboratorial/treatment data and sera for ADA and AAA assays (ELISA and bridging ELISA) were obtained at baseline (BL), 2 months (2M), 3 months (3M), 6 months (6M), 12 months (12M), and 24 months (24M). Patients with therapy failure requiring ADA withdrawn had their sera evaluated at their last medical visit prior to biologic switch (blinded to ADA and AAA levels).AAA was absent at BL, first detected at 2M after ADA initiation in 2/30 (7%) patients with a significant increase at 3M (10/29 (34%), p = 0.013) and no major change in 6M (11/30 (37%)) and 12M (9/26 (35%)). Of note, at 3M, AAA levels correlated negatively with ADA levels (r = - 0.781, p = 0.0001). Analysis of BL predictors revealed a significantly higher risk of developing AAA in patients with female gender (OR 21; 95% CI 1.08-406.57; p = 0.044), ESR30 mm/1st hour (OR 5.44; 95% CI 1.04-28.53; p = 0.045), and leflunomide use (OR 9.33; 95% CI 1.51-57.66; p = 0.016). In contrast, concomitant use of methotrexate was protective for AAA appearance (OR 0.08; 95% CI 0.01-0.53; p = 0.009). After 12M of ADA, 60% of AAA-positive patients required drug switch for drug failure compared with 15% in AAA-negative group (p = 0.03).This study provides novel evidence of AAA production kinetics demonstrating a timely significant increase starting at 3M and stable throughout 24M. We also identified female gender, increased ESR, and leflunomide use as relevant risk factors for AAA production at BL, whereas methotrexate was protective. Early systematic monitoring of AAA at 3M may, therefore, guide drug switching in these patients.Key Points• Anti-adalimumab antibodies (AAA) production kinetics demonstrated a timely significant increase starting at 3M in juvenile idiopathic arthritis (JIA) patients under adalimumab therapy• Female gender, increased ESR, and leflunomide use were identified as relevant risk factors for AAA production in JIA, whereas methotrexate was protective.

Background: Cyclic citrullinated peptides antibodies (anti-CCP) were described in primary Sjogren’s syndrome (pSS). However, its possible associations with joint erosions, synovitis and tenosynovitis on high resolution ultrasonography of hands and wrists (US) in pSS are uncertain. Objectives: To assess in pSS the US findings, and their possible associations with anti-CCP. Methods: We have evaluated 97 consecutive pSS patients (2016 ACR/EULAR Classification Criteria), of both sexes, aged 18-76 years, and without meeting the 1987 ACR classification criteria for rheumatoid arthritis (RA). Twenty RA patients (disease duration Results: Frequency of tenosynovitis on US was higher in the pSS group than in healthy controls (36.1 vs. 3.8%, p Conclusion: US detected higher frequencies of tenosynovitis and erosions in pSS patients than in healthy controls, and the numbers of synovitis and tenosynovitis correlated with ESSDAI, suggesting that US is an important tool for the evaluation of these patients. Moreover, grade 2/3 synovitis and moderate/large erosions appear to be relevant for the distinction between pSS and RA. The additional observation that erosions are associated with anti-CCP in pSS seems to characterize a subgroup of patients with a severe underlying mechanism of joint damage. Grant from FAPESP: 2015/03756-4. References: [1] Riente L, Scire CA, Delle Sedie A, et al. Ultrasound imaging for the rheumatologist. XXIII. Sonographic evaluation of hand joint involvement in primary Sjogren’s syndrome. Clin Exp Rheumatol. 2009;27(5):747-50. Disclosure of Interests: Lissiane Guedes: None declared, Elaine Leon: None declared, Margarete Vendramini: None declared, Tamyris Bocate: None declared, Karina Bonfiglioli Speakers bureau: Has received speaking fees from Roche, Pfizer, Bristol-Myers Squibb, Abbvie and Janssen., Eloisa Bonfa: None declared, Sandra Pasoto: None declared

Objectives To analyse the phenotype of patients with primary Sjogren syndrome (SjS) in whom a lymphoproliferative disease is diagnosed concomitantly. Methods By January 2019, The Big Data Sjogren Project included 11,420 consecutive patients with primary SjS recruited from 24 countries of the five continents. Results 117 (1%) patients were diagnosed with lymphoma and primary SjS synchronously. Age-gender adjusted multivariate analysis identified the following features associated with lymphoma (OR; CI95%): male gender (4.61; 2.88-7.18), White ethnicity (3.51; 1.78-7.91), abnormal oral tests (3.4; 1.38-10.88), positive biopsy (3.2; 1.3-10.17), positive RF (2.27; 1.48-3.53), hypocomplementemia (3.39; 2.06-5.54), and cryoglobulins (4.74; 2.57-8.38). Activity (score > 1) in the constitutional (2.97; 1.86-4.62), glandular (3.11; 2.1-4.57), cutaneous (2.17; 1.28-3.52), peripheral nerve (2.56; 1.4-4.41) and hematological (2.49; 1.64-3.75) ESSDAI domains was associated with lymphoma (frequencies summarized in the Figure). Conclusion Patients diagnosed concomitantly with primary SjS and lymphoma have a very specific, highly-active phenotype (men, White, severe oral involvement, cryoglobulinemic-related immunological markers, and high systemic activity). Disclosure of Interests: Soledad Retamozo: None declared, Nihan Acar-Denizli: None declared, Wan Fai Ng: None declared, Antonia Szanto: None declared, Astrid Rasmussen: None declared, Raphaele Seror Grant/research support from: Pfizer, Consultant for: Bristol-Myers Squibb, Pfizer, Amgen, Eli Lilly, Roche, Celgene, GlaxoSmithKline, MedImmune, Xiaomei Li: None declared, Chiara Baldini: None declared, Jacques-Eric Gottenberg Grant/research support from: Bristol-Myers Squibb, Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Lilly, Pfizer, Sanofi-Genzyme, UCB Pharma, Consultant for: Bristol-Myers Squibb, Eli Lilly, UCB, Sanofi-Genzyme, Pfizer, Pulukool Sandhya: None declared, Luca Quartuccio: None declared, Roberta Priori: None declared, Gabriela Hernandez-Molina: None declared, Berkan Armagan: None declared, Aike A. Kruize: None declared, Seung-Ki Kwok: None declared, Marika Kvarnstrom: None declared, Sonja Praprotnik: None declared, Damien Sene: None declared, Roser Solans-Laque: None declared, Maureen Rischmueller Consultant for: Abbvie, Bristol-Meyer-Squibb, Celgene, Glaxo Smith Kline, Hospira, Janssen Cilag, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Thomas Mandl: None declared, Yasunori Suzuki: None declared, David Isenberg: None declared, Valeria Valim: None declared, Agata Sebastian: None declared, Gunnel Nordmark: None declared, Hendrika Bootsma: None declared, Hideki Nakamura: None declared, Roberto Giacomelli Grant/research support from: Pfizer, Actelion, Speakers bureau: Actelion, Bristol-Myers Squibb, Merck Sharp & Dohme, Abbvie, Pfizer, Sobi, Roche, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche, Benedikt Hofauer Consultant for: Consultant for Galvani Bioelectronics for the area of sleep disorders., Michele Bombardieri Grant/research support from: Celgene, Consultant for: Medimmune, Virginia Fernandes Moca Trevisani: None declared, Daniel Hammenfors: None declared, Sandra Pasoto: None declared, Tamer A Gheita: None declared, Fabiola Atzeni: None declared, Jacques Morel: None declared, Cristina Vollenveider: None declared, Sandra Consani-Fernandez: None declared, Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma, Manuel Ramos-Casals: None declared, Pilar Brito-Zeron: None declared, Elena Bartoloni Bocci: None declared

African-Brazilians comprise a group of blacks and "pardos." As racial differences can be associated with distinct presentations, we evaluated the clinical and serological associations of African-Brazilians with systemic sclerosis (SSc).Sera from 260 adult SSc patients (203 whites and 57 African-Brazilians) were evaluated. Patients with overlap syndromes were excluded. Clinical and demographic data were obtained from an electronic register database. Laboratory analysis included the following: anti-CENP-A/CENP-B, Scl70, RNA polymerase III, Ku, fibrillarin, Th/To, PM-Scl75, and PM-Scl100 by line immunoassay and anti-nuclear antibodies (ANA) by indirect immunofluorescence (IIF) on HEp-2 cells.African-Brazilian SSc patients presented shorter disease duration (12.8 ± 6.5 vs. 15.9 ± 8.1 years, p = 0.009), higher frequency of nucleolar ANA pattern (28% vs. 13%, p = 0.008), and lower frequencies of centromeric ANA pattern (14% vs. 29%, p = 0.026) and CENP-B (18% vs. 34%, p = 0.017), as well as an association with severe interstitial lung disease (58% vs. 43%; p = 0.044). Further comparison of ethnic groups according to subsets revealed that diffuse SSc African-Brazilian patients presented higher frequency of pulmonary hypertension (p = 0.017), heart involvement (p = 0.037), nucleolar ANA pattern (p = 0.036), anti-fibrillarin antibodies (p = 0.037), and higher mortality (48% vs. 19%; p = 0.009). A different pattern was observed for the limited subset with solely a lower frequency of esophageal involvement (p = 0.050) and centromeric ANA pattern (p = 0.049). Survival analysis showed that African-Brazilians had a higher mortality, when adjusted for age, gender, and clinical subset (RR 2.06, CI 95% 1.10-3.83, p = 0.023).African-Brazilians have distinct characteristics according to clinical subset and an overall more severe SSc than whites, similar to the blacks from other countries.Key Points • African-Brazilian SSc patients were associated with severe interstitial lung disease and nucleolar ANA pattern when compared to white SSc patients. • When disease subsets were considered, African-Brazilian patients with diffuse SSc presented association with pulmonary hypertension, heart involvement, nucleolar ANA pattern, and anti-fibrillarin antibodies. • White SSc patients were associated with centromeric ANA pattern. • Survival analysis at 5, 10, 15, and 20 years, adjusted for age, gender, and disease subset, was significantly worse in African-Brazilian SSc patients.

OBJECTIVES To evaluate volumetric BMD (vBMD), microarchitecture and strength and vertebral fractures (VFs) in primary SS (pSS). METHODS We evaluated 71 female pSS patients and 71 gender-, age-, and race-matched controls. Clinical data including risk factors for osteoporosis (OP) and fractures were collected through a standardized protocol. Areal BMD and VFs were analysed by DXA. Bone microarchitecture, vBMD and bone strength were assessed by high-resolution peripheral quantitative CT (HR-pQCT), a non-invasive method. RESULTS pSS patients and controls were comparable for age, BMI, calcium intake, smoking, menopause, sedentary lifestyle and family history of fractures (P > 0.05). OP or low BMD for the patient's age (33.8 vs 5.6%; P < 0.0001) and VFs (19.7 vs 5.6%; P = 0.043) were more frequent in patients than controls. HR-pQCT showed deterioration of cortical and trabecular components and strength at the radius, and of cortical components and strength at the tibia (P < 0.05) in patients compared with controls. pSS patients and controls were also analysed by multivariate analysis adjusted for age, ethnicity, prednisone use, weight and height, which showed that the pSS group had lower values of cortical vBMD, cortical thickness and apparent modulus (P < 0.05) at the radius and cortical vBMD and apparent modulus (P < 0.05) at the tibia. Patients with VFs had more cortical bone deterioration (cortical vBMD/cortical thickness) at the tibia compared with patients without VFs (P < 0.05). CONCLUSIONS This study was the first to assess bone microarchitecture in pSS and demonstrated that cortical deterioration is the most important abnormality observed in pSS patients with VFs. This novel finding shows that this compartment contributes to vertebral fragility, suggesting that this non-invasive evaluation may be useful in the clinical practice.

Background and objective Primary Sjogren syndrome (pSS) is a systemic autoimmune rheumatic disease that particularly affects exocrine glands. Dry eye is one of the most important features of this syndrome, and a recent study reported reduced deoxyribonuclease I (DNase I) activity in the tear of patients with dry eye. We therefore postulated that patients with pSS might have antibodies targeting DNAse I. Methods We have evaluated in a cross-sectional study 85 patients with pSS (2002 American-European Consensus Group Criteria), 50 rheumatoid arthritis (RA) patients (1987 American College of Rheumatology Criteria) without sicca symptoms, and 88 healthy volunteers. IgG anti-DNase I was detected by enzyme-linked immunosorbent assay using as antigen bovine pancreas enzyme and confirmed by immunoblotting. Results Age and sex were alike in the 3 groups (p > 0.05). Anti-DNase I was detected in 43.5% of the pSS patients. In contrast, this reactivity was absent in all RA patients (p = 0.0001). Additional comparison of pSS patients with (n = 37) or without (n = 48) anti-DNase I showed that the former group had higher IgG serum levels (2293.2 ± 666.2 vs 1483.9 ± 384.6 mg/dL, p = 0.0001) and greater rate of non-drug-induced leukopenia (43% vs 19%, p = 0.02). A multivariate logistic regression analysis identified that only IgG levels were independently associated with anti-DNase I. Conclusions We describe a high frequency of anti-DNase I antibodies in pSS patients associated with higher serum IgG levels. The lack of this reactivity in RA patients without sicca symptoms suggests that this antibody may be helpful in the differential diagnosis of these diseases.

Influence of epidemiology and ethnicity on systemic expression of primary Sjogren syndrome in 9974 patients

Objectives To take a “high-definition” picture of the main features of primary Sjogren syndrome (SjS) following a worldwide data-sharing cooperative merging of international clinical SjS databases. Methods The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014 including leading clinical centres in SjS of the 5 continents that shared a harmonised data architecture and conducted cooperative online efforts to refine collected data of primary SjS patients fulfilling the 2002 classification criteria. Results By January 2018, the participant centres had included 10 475 patients from 22 countries, including 7637 (73%) patients from Europe, 1420 (14%) from America, 1186 (11%) from Asia, 167 (1.4%) from Australia and 65 (0.6%) from Africa. The cohort included 9781 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years. The frequencies of fulfilment of the 2002 criteria were 92% for dry eye, 94% for dry mouth, 83% for abnormal ocular tests, 82% for positive minor salivary gland biopsy, 78% for abnormal oral diagnostic tests and 76% for positive anti-Ro/La antibodies. The frequency of positive immunological markers at diagnosis was 79% for ANA, 73% for anti-Ro, 49% for RF, 45% for anti-La, 13% for low C3 levels, 14% for low C4 levels and 7% for cryoglobulins. Conclusions International data sharing-based projects merging disperse clinical registries may be essential tools to increase current knowledge and to improve patient care in specific systemic autoimmune diseases. Disclosure of Interest None declared

Objetivo: Esta revisão de literatura tem o propósito de oferecer aos cirurgiões-dentistas entendimento sobre os principais achados clínico-epidemiológicos da síndrome de Sjögren primária (SSp), bem como ressaltar os principais aspectos etiopatogênicos e histopatológicos da doença. Métodos: Buscou-se na base de dados Pubmed/Medline e ScienceDirect os descritores “síndrome de Sjögren”, “glândulas salivares”, “xerostomia”, “diagnóstico”, “glândula salivar menor”, “etiologia”, “biopsia” entre os anos de 1991 a 2017. Discussão: A SSp é uma exocrinopatia autoimune que tem como substrato, em especial, as glândulas lacrimais e salivares, culminando com os sintomas de xeroftalmia e xerostomia. Seu principal achado morfológico é a presença de agregados de leucócitos mononucleares ao redor dos ductos e ácinos. Outras manifestações sistêmicas podem estar presentes, acarretando considerável morbidade nos pacientes acometidos. Atualmente, foi publicado o mais novo conjunto de critérios diagnósticos da doença, sendo um marco histórico no diagnóstico precoce da enfermidade, fundamental para diminuir os altos números de subdiagnósticos e otimizar a conduta clínica. Conclusão: Esta revisão abordou os aspectos clínicos-epidemiológicos, histopatológicos e etiopatogênicos da SSp, objetivando melhor compreensão dessa doença multifatorial e, portanto, a necessidade de uma conduta multidisciplinar e do papel fundamental do cirurgião-dentista no manejo dos pacientes acometidos por essa síndrome. Objective: The aim of this present review is to provide dentists a better understanding of Primary Sjögren’s syndrome (SSp), clinical and epidemiological findings, also the etiopathogenic and histopathological features of the disease. Methods: The search was based on Pubmed/Medline and ScienceDirect database from 1991 to 2017. It was used keywords: “Sjögren’s syndrome”, “salivary gland”, “xerostomia”, “pathogenesis”, “diagnosis”, “minor salivary gland”, “ethiology”, “biopsy”. Discussion: Primary Sjögren’s syndrome (SSp) is an autoimmune exocrinopathy involving mainly the lacrimal and salivary glands, resulting in reduced secretory functions and classical sicca symptoms, such as dry eyes and dry mouth. The hallmark of the histopathological features is the presence of aggregates of mononuclear leukocytes surrounding ducts and acini. Others systemic manifestations can also be present, leading to considerable morbidity in the affected patients. The lastest diagnosis criteria of SSp was published in 2017, becoming a historical landmark in the early diagnosis of the disease, reducing the high number of underdiagnosis and improving therapeutic intervention. Conclusion: This review approached the clinical-epidemiological and histopathological features, and etiopathogenic factors of SSp, supporting a better comprehension of this multifactorial disease and needing a multidisciplinary approach and the role of the dentist in the clinical conduct of the patients affected by this syndrome.

Objectives To analyse the influence of geolocation on the clinical systemic presentation of primary Sjogren syndrome (SjS) at diagnosis. Methods The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014. Centres were classified by continent, with an additional north-south sub-classification according to latitude (>or or or Results The highest baseline ESSDAI scores were reported from Southern vs Northern countries in Europe (7.2 vs 4.6, p Conclusions This study provides the first evidence for a strong influence of geolocation on the systemic phenotype of primary SjS at diagnosis. Geographical determinants should be considered as key variables when systemic disease is scored. Disclosure of Interest None declared

The recommendations proposed by the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology for the treatment of Sjögren's syndrome were based on a systematic review of literature in Medline (PubMed) and the Cochrane databases until October 2014 and on expert opinion in the absence of studies on the subject. 131 articles classified according to Oxford & Grade were included. These recommendations were developed in order to guide the management and facilitate the access to treatment for those patients with an appropriate indication, considering the Brazilian socioeconomic context and pharmacological agents available in this country.

Objective To assess circulating follicular helper-like CD4+ T (cTfh-like) cells in systemic lupus erythematosus (SLE) and determine their relationship to disease activity.

Background Juvenile Sjogren9s syndrome (jSS) is a rare, poorly defined and possibly underdiagnosed condition. There is little information on the use of major salivary gland ultrasonography (SGUS) in this patient-group. Objectives To characterize symptoms and clinical findings of jSS and to investigate SGUS as a diagnostic tool. Methods Sixty-four patients were recruited from Brazil (n=40), Norway (n=11), the Netherlands (n=8) and Spain (n=5). All patients had disease onset at the age of 18 or younger. Clinical examination and sialometry was performed in 60/64 patients. Additional clinical information was obtained from the medical records and through patient interview. SGUS of the parotid and submandibular glands was performed in all patients using linear high-frequency transducers (6–15 MHz), by an expert in SGUS. Glandular homogeneity and presence of hypoechogenic areas were evaluated and glands characterized as normal or SS-like. Results The female:male ratio was 6:1. Mean age at diagnosis was 12.1 years (range 4–18), with first symptoms occurring at 10.3 years (range 1–17). Time from onset of symptoms until diagnosis was 1.6 years (range -2–8 years). Subjective oral and ocular symptoms were reported in 70% and 64% patients, respectively. Reduced secretion of tears was detected in 41% patients, and hyposalivation in 31% patients. Minor salivary gland lip biopsy had been performed and focus score determined in 34 patients; 28 biopsies (82%) had focus score ≥1. Serologically, 92% were positive for ANA, 73% were anti-Ro/SSA+, 38% were anti-La/SSB+, and 41% were RF+. Salivary gland enlargement had been experienced by 53% of the patients; one patient had also experienced lacrimal gland enlargement. Systemic manifestations at some time-point, was registered in 66% of the patients. Systemic treatment at inclusion was registered in 67% of the patients; previous systemic treatment was registered in 83%. Diagnostic criteria for primary Sjogren9s syndrome (pSS) was fulfilled by 34/64 patients (53%) and 39/64 patients (61%), AECG criteria and ACR/EULAR criteria, respectively. SGUS revealed SS-like changes in 37/64 patients (59%); interestingly, SS-like findings were observed in 22/23 patients in the European cohort, compared to 15/40 patients in the Brazilian cohort. Conclusions Common symptoms and findings in jSS include dry mouth, systemic manifestations and salivary gland enlargement, followed by reduced tear secretion and hyposalivation. Disclosure of Interest None declared

Baseline Essdai/ Das Scores In 8061 Patients With Primary Sjogren Syndrome : Characterization Of Systemic Disease

Objectives Baseline characterization of European patients diagnosed with primary Sjogren syndrome (SS) according to the 2002 AE criteria. Methods The Big Data Sjogren Project was formed in 2014 to take a “high-definition” picture of the main features of primary SS by merging international SS databases. International experts of the EULAR-SS Task Force were invited to participate. By January 2017, the database included 9302 consecutive patients recruited from 21 countries of the 5 continents. Results A total of 6586 (71%) patients were included from European countries. In comparison with non-European countries, European patients had a higher mean age (54 v 51yrs, p Conclusions European patients are diagnosed at older age, are more frequently men, and presented a lower frequency of anti-Ro/La antibodies and a higher frequency of immunological markers related to mixed cryoglobulinemia. Disclosure of Interest None declared

The aim of this longitudinal prospective study was to evaluate the effects of periodontal treatment on the clinical, microbiological and immunological periodontal parameters, and on the systemic activity (ESSDAI) and subjective (ESSPRI) indexes in patients with primary Sjögren’s Syndrome (pSS). Twenty-eight female patients were divided into four groups: pSS patients with or without chronic periodontitis (SCP, SC, respectively), and systemically healthy patients with or without chronic periodontitis (CP, C, respectively). Periodontal clinical examination and immunological and microbiological sample collection were performed at baseline, 30 and 90 days after nonsurgical periodontal treatment (NSPT). Levels of interleukin IL-1β, IL-8 and IL-10 in saliva and gingival crevicular fluid (GCF) were evaluated by ELISA, as well as the expression of Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans, (Aa) Tannerella forsythia (Tf), and Treponema denticola (Td), by qPCR. Systemic activity and pSS symptoms were evaluated by ESSDAI and ESSPRI. NSPT resulted in improved periodontal clinical parameters in both SCP and CP groups (p>0.05). Pg, Aa, and Tf levels decreased after NSPT only in CP patients (p

ObjectiveThe objectives of this paper are to objectively measure habitual physical activity levels in patients with primary Sjögren’s syndrome (pSS) with mild disease activity and to determine to which extent it may be associated with physical capacity and function and clinical features.MethodsIn this cross-sectional study, 29 women with pSS were objectively assessed for habitual physical activity levels (using accelerometry) and compared with 20 healthy women (CTRL) frequency-matched for physical activity levels, age, body mass index, and body fat percentage with regard to physical capacity and function, fatigue, depression, pain, and health-related quality of life.ResultspSS showed 8.5 min/day of moderate-to-vigorous physical activity (MVPA) when only MVPA accumulated in bouts ≥ 10 min was considered; when considering total MVPA (including bouts 2peak, lower muscle strength and function, higher fatigue, and poorer health-related quality of life when compared with CTRL ( p ConclusionWhen compared to physical activity-matched healthy controls, pSS patients showed reduced physical capacity and function, increased fatigue and pain, and reduced health-related quality of life. Except for aerobic conditioning, these differences were sustained when only more physically active participants were compared, indicating that minimum recommended levels of physical activity for the general population may not be sufficient to counteract pSS comorbidities.