HLA-B27 did not protect against COVID-19 in patients with axial spondyloarthritis - data from the ReumaCov-Brasil Registry.

BACKGROUND: Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. AIM: To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. METHODS: The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. RESULTS: From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. CONCLUSIONS: No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. TRIAL REGISTRATION: This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials - REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Long-term persistence of anti-ß2 glycoprotein I in treated leprosy patients.

ß2 glycoprotein I (ß2GPI) is a phospholipid binding protein that plays an important role in endothelial stability, blood coagulation, clearance of apoptotic debris and other physiologic processes. Anti-ß2GPI antibodies occur in normal individuals and transiently during the course of infections, but are also associated with thrombotic events in autoimmune disease: the antiphospholipid syndrome (APS). A total of 31 out of 37 treated leprosy patients previously found to present high titers of IgM anti-ß2GPI and/or anticardiolipin antibodies (aCL) remained positive for IgM antiphospholipid antibodies (aPL), and exhibited high titers of anti-ß2GPI. The 37 patients were part of the 77 aPL-positive patients from a previous study that evaluated 158 leprosy patients. The median time elapsed between the first and second sample was 66 months. None of the 37 patients had any thrombotic event and 24 had a reactional state and were still requiring the use of prednisone, thalidomide or both. None of them fulfilled World Health Organization criteria for leprosy recurrence.

Effect of age at disease onset in the clinical profile of spondyloarthritis: a study of 1424 Brazilian patients.

OBJECTIVES: To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients. METHODS: A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 ± 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 151 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%). RESULTS: Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low back pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups. CONCLUSIONS: There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset ≤ 40 years and another favouring the peripheral manifestations in those with later disease onset.

Anti-ß2-glycoprotein I antibodies are highly prevalent in a large number of Brazilian leprosy patients.

OBJECTIVES: To determine the prevalence of anticardiolipin (aCL) and anti-ß2-glycoprotein I (anti-ß2GPI) antibodies in leprosy patients, during and after specific multidrug therapy (MDT), and to evaluate a possible association between these antibodies and some clinical characteristics of leprosy, including clinical forms, reactional episodes and treatment. METHODS: The study included 158 leprosy patients, 129 gender-and-age matched healthy individuals, and 38 women with primary antiphospholipid syndrome (APS). Clinical and demographic characteristic of leprosy patients were collected, and serum samples, obtained from all participants, were kept frozen at - 20°C. Antibodies were measured either by an in house-developed ELISA (aCL) or by a commercial ELISA (anti-ß2GPI). RESULTS AND CONCLUSIONS: Increased levels of aCL and anti-ß2GPI antibodies were found in leprosy patients and in the APS group, however, in contrast to APS, the predominant isotype in leprosy was IgM. The frequency of aCL and anti-ß2GPI antibodies was significantly higher in leprosy patients than in healthy individuals (15.8% vs. 3.1%; p>0.01; 46.2% vs. 9.4%, p>0.01), respectively. The lepromatous form predominated among aCL positive leprosy patients (p>0.01). There was no difference in aCL and anti-ß2GPI positivity between leprosy patients taking MDT and those completed MDT as cured. Furthermore the duration of discharged period (period between discharge from MDT and the realization of the study) had no effect on anti-ß2GPI positivity, and a slight increase in aCL positivity was observed in patients with longer follow up periods (p=0.04), suggesting that the presence of antiphospholipid antibodies (aPL) was not a transient phenomenon. Although aPL in leprosy were frequent and ß2GPI-dependent as those found in APS, IgM was the predominant isotype, and there was no association with thrombosis or other APS manifestations.

Autoantibodies in leprosy patients, with and without joint involvement, in the state of Amazonas / Autoanticorpos em pacientes com hanseníase, com e sem comprometimento articular, no Estado do Amazonas

OBJETIVOS: Determinar a frequência do fator reumatoide (FR-IgM), anticorpos antipeptídeos citrulinados cíclicos (anti-CCP), antinucleares (AAN), anticitoplasma de neutrófilos (ANCA), anticardiolipina (aCL) e anti-β2 glicoproteína I (anti-β2GPI) em pacientes com hanseníase, com e sem comprometimento articular, avaliando a possível associação entre estes autoanticorpos e as manifestações articulares, a forma clínica, a reação hansênica, o tratamento com poliquimioterapia (PQT) e a alta. PACIENTES E MÉTODOS: 158 pacientes com hanseníase foram distribuídos em dois grupos; 73 pacientes com (Grupo I) e 82 sem comprometimento articular (Grupo II). Compuseram o Grupo III 129 indivíduos saudáveis. MÉTODOS: aglutinação com partículas de látex para FR-IgM, imunofluorescência indireta para AAN e ANCA, e, ELISA para anti-CCP, aCL e anti-β2GPI. RESULTADOS: Dentre 158 pacientes com hanseníase, 56 apresentavam a forma virchowiana (VV). A frequência de anticorpos anti-CCP, FR e AAN nos Grupos I e II foi semelhante à do Grupo III. ANCA não foi detectado em nenhum dos grupos. Anticorpos aCL foram mais frequentes nos pacientes com hanseníase (Grupos I e II) que em controles sadios (15,8 por cento vs. 3,1 por cento; P < 0,001), não sendo observada diferença entre Grupos I e II (P = 0,67). Anticorpos anti-β2GPI também foram mais frequentes nos pacientes que nos controles (46,2 por cento vs. 9,4; P < 0,001), sem diferença significativa entre os Grupos I e II. Houve predomínio do isotipo IgM com relação ao IgG tanto para aCL (88 por cento vs. 16 por cento, P = 0,001), quanto para anti-β2GPI (97,3 por cento vs. 12,3 por cento, P < 0,001). Nenhum paciente apresentou manifestações sugestivas de trombose vascular. CONCLUSÃO: A frequência de anticorpos aCL e anti-β2GPI foi significativamente maior nos pacientes com hanseníase que nos controles saudáveis. Entretanto, a positividade dos demais autoanticorpos foi semelhante à dos controles. Não foi observada associação entre autoanticorpos...

OBJECTIVE: Determine the frequency of rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP), antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), anticardiolipin antibodies (aCL), and anti-β2 glycoprotein I antibodies (anti-β2GPI) in leprosy patients, with and without joint involvement, and to evaluate the possible association among those antibodies and articular manifestations, clinical type, reactional episodes, polychemotherapic treatment (PCT), and discharge from PCT. PATIENTS AND METHODS: One hundred and fifty-eight leprosy patients were divided in two groups of 73 patients (Group I) and 82 patients (Group II). Group III was composed of 129 healthy individuals. Methods: Semi-quantitative latex agglutination test for IgM-RF, indirect immunofluorescence for ANA and ANCA, and ELISA for anti-CCP, aCL, and anti-β2GPI. RESULTS: Fifty-six (35.4 percent) of 158 leprosy patients had lepromatous leprosy (LL). The frequency of anti-CCP, RF, and ANA antibodies in Groups I and II was similar to that of Group III. Antineutrophil cytoplasmic antibodies were not detected in any patient. Anticardiolipin antibodies were more frequent in leprosy patients (Groups I and II) than in control group (15.8 percent vs. 3.1 percent; P < 0.001), and differences between Groups I and II (P = 0.67) were not observed. Anti-β2GPI antibodies were also more common in leprosy patients than in control group (46.2 percent vs. 9.4 percent; P < 0.001), without differences between Groups I and II. A predominance of IgM isotype over IgG isotype was observed both for aCL (88 percent vs. 16 percent; P = 0.001) and anti-β2GPI (97.3 percent vs. 12.3 percent; P < 0.001). Patients did not present manifestations suggestive of vascular thrombosis. CONCLUSION: The frequency of aCL and anti-β2GPI antibodies was significantly increased in leprosy patients than in healthy individuals. However, positivity to other autoantibodies...

Leprosy-related joint involvement.

We estimate the prevalence and evaluate the clinical characteristics of leprosy related arthritis. One thousand, two hundred fifty-seven leprosy patients were attended at "Alfredo da Matta" outpatient clinic in the state of Amazonas, Brazil from July to October 2004. Among them, 115 patients were identified with articular pain and were referred for evaluation with rheumatologist. Blood samples were collected and radiological evaluation of the involved joints was performed. All patients with arthritis who continued to be followed up were reevaluated. One hundred fifteen leprosy patients (9.1%) were identified with articular involvement. The articular complaints were attributed to a defined rheumatic disease in 36 cases and excluded from further analysis. Twenty-four patients had arthralgia, and 55 (37 males and 18 females) had leprosy-related arthritis. The prevalence of arthritis was similar in both genders, and all patients with leprosy-related arthritis had lepromatous or borderline type. Most of patients had polyarticular and symmetrical arthritis and had completed the multidrug therapy and was under reaction treatment. The mean duration of articular symptoms at the time of study was 1.06 years (ranging from 5 days to 14 years). Ninety-one percent of patients with leprosy-related arthritis presented erythema nodosum leprosum or reversal reactions. Only five patients with arthritis had never presented reactions. Fifty percent of patients became asymptomatic during the mean 24 months of follow-up. Leprosy-related arthritis has a lower prevalence than previously reported. Most cases of leprosy-related arthritis were associated with reactional episodes, and in a large number of cases, the arthritis had a chronic course not responsive to the conventional therapy for reactions.

Anti-cyclic citrullinated peptide antibodies and rheumatoid factor in leprosy patients with articular involvement.

The objective of the present research was to evaluate the usefulness of anti-cyclic citrullinated peptide (anti-CCP) antibodies and the IgM rheumatoid factor (IgM RF) test for the differential diagnosis of leprosy with articular involvement and rheumatoid arthritis (RA). Anti-CCP antibodies and IgM RF were measured in the sera of 158 leprosy patients (76 with and 82 without articular involvement), 69 RA patients and 89 healthy controls. Leprosy diagnosis was performed according to Ridley and Jopling classification criteria and clinical and demographic characteristics of leprosy patients were collected by a standard questionnaire. Leprosy patients with any concomitant rheumatic disease were excluded. Serum samples were obtained from all participants and frozen at -20 degrees C. Measurement of anti-CCP antibodies and IgM RF were performed by ELISA, using a commercial second-generation kit, and the latex agglutination test, respectively. Anti-CCP antibodies and IgM RF were detected in low frequencies (2.6 and 1.3%, respectively) in leprosy patients and were not associated with articular involvement. Among healthy individuals both anti-CCP antibodies and IgM RF were each detected in 3.4% of the subjects. In contrast, in the RA group, anti-CCP antibodies were present in 81.2% and IgM RF in 62.3%. In the present study, both anti-CCP antibodies and IgM RF showed good positive predictive value for RA, helping to discriminate between RA and leprosy patients with articular involvement. However, anti-CCP antibodies were more specific for RA diagnosis in the population under study.

Anti-cyclic citrullinated peptide antibodies and rheumatoid factor in leprosy patients with articular involvement

The objective of the present research was to evaluate the usefulness of anti-cyclic citrullinated peptide (anti-CCP) antibodies and the IgM rheumatoid factor (IgM RF) test for the differential diagnosis of leprosy with articular involvement and rheumatoid arthritis (RA). Anti-CCP antibodies and IgM RF were measured in the sera of 158 leprosy patients (76 with and 82 without articular involvement), 69 RA patients and 89 healthy controls. Leprosy diagnosis was performed according to Ridley and Jopling classification criteria and clinical and demographic characteristics of leprosy patients were collected by a standard questionnaire. Leprosy patients with any concomitant rheumatic disease were excluded. Serum samples were obtained from all participants and frozen at _20°C. Measurement of anti-CCP antibodies and IgM RF were performed by ELISA, using a commercial second-generation kit, and the latex agglutination test, respectively. Anti-CCP antibodies and IgM RF were detected in low frequencies (2.6 and 1.3 percent, respectively) in leprosy patients and were not associated with articular involvement. Among healthy individuals both anti-CCP antibodies and IgM RF were each detected in 3.4 percent of the subjects. In contrast, in the RA group, anti-CCP antibodies were present in 81.2 percent and IgM RF in 62.3 percent. In the present study, both anti-CCP antibodies and IgM RF showed good positive predictive value for RA, helping to discriminate between RA and leprosy patients with articular involvement. However, anti-CCP antibodies were more specific for RA diagnosis in the population under study.