Objectives:

SummaryThe aim of this study is to evaluate the humoral autoimmune response in the experimental model of systemic sclerosis (SSc) induced by human type V collagen (huCol V). New Zealand rabbits were immunized with huCol V in Freund's complete adjuvant (FCA) and boosted twice with 15 days intervals with huCol V in Freund's incomplete adjuvant. Control groups included animals injected only with FCA or bovine serum albumin. Bleeding was done at days 0, 30, 75 and 120. Tissue specimens were obtained for histopathological investigation. Serological analysis included detection of antibodies against huCol V and anti-topoisomerase I (AntiScl70) by enzyme-linked immunosorbent assay, antinuclear antibodies (ANA) by indirect immunofluorescence, and rheumatoid factor (RF) by a latex agglutination test. Target antigens were characterized by immunoblot. Histological analysis revealed extracellular matrix remodeling with fibrosis and vasculitis. Anti-Scl70 and ANA were detected as early as 30 days in all huCol V animals. The universal ANA staining pattern was Golgi-like. This serum reactivity was not abolished by previous absorption with huCol V. Characterization of the target antigen by immunoblot revealed two major protein fractions of 175 000 and 220 000 MW. Similarly to ANA, there was a gradual increase of reactivity throughout the immunization and also it was not abolished by preincubation of serum samples with huCol V. RF testing was negative in hyperimmune sera. Conclusion: The production of autoantibodies, including anti-Scl70, a serological marker for SSc associated with histopathological alterations, validates huCol V induced-experimental model and brings out its potential for understanding the pathophysiology of SSc.

Antibody to Epstein-Barr virus (EBV) early antigen diffuse (anti-EA-D) is associated with viral replication. However, their possible associations with clinical/therapeutic features in primary Sjögren's syndrome (pSS) were not established. We evaluated 100 pSS patients (American-European Criteria) and 89 age/gender/ethnicity-matched healthy controls. Disease activity was measured by EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Antibodies to EBV (anti-VCA IgG/IgM, anti-EBNA-1 IgG, anti-EA-D IgG) were determined by ELISA. Patients and controls had comparable frequencies and mean levels of anti-VCA IgG (90 vs. 86.5 %, p = 0.501; 2.6 ± 1.1 vs. 2.5 ± 1.1 AU/mL, p = 0.737) and anti-EBNA-1 IgG (92 vs. 94.4 %, p = 0.576; 141.3 ± 69.8 vs. 135.6 ± 67.5 RU/mL, p = 0.464). Anti-VCA IgM was negative in all cases. Noteworthy, higher frequency and increased mean levels of anti-EA-D were observed in patients than controls (36 vs. 4.5 %, p < 0.0001; 38.6 ± 57.4 vs. 7.9 ± 26.3 RU/mL, p < 0.0001). Further analysis of patients with (n = 36) and without (n = 64) anti-EA-D revealed comparable age/gender/ethnicity (p ≥ 0.551), current prednisone dose (4.8 ± 6.9 vs. 5.1 ± 10.4 mg/day, p = 0.319), and current uses of prednisone (52.8 vs. 37.5 %, p = 0.148) and immunosuppressants (44.4 vs. 31.3 %, p = 0.201). ESSDAI values were comparable (p = 0.102), but joint activity was more frequent (25 vs. 9.4 %, p = 0.045) in anti-EA-D positive patients. Anti-EA-D antibodies were not associated with anti-Ro/SSA (p = 1.000), anti-La/SSB (p = 0.652), rheumatoid factor (p = 1.000), anti-α-fodrin (p = 0.390) or antiphospholipid antibodies (p = 0.573), not suggesting cross-reactivity. The higher anti-EA-D frequency associated with joint activity raises the possibility that a subclinical EBV reactivation may trigger or perpetuate the articular involvement in pSS.

Objectives To evaluate immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in systemic autoimmune myopathies (SAMs) and the possible influence of baseline disease parameters, comorbidities, and therapy on immune response. Methods This prospective controlled study included 53 patients with SAMs and 106 non-immunocompromised control group (CTRL). All participants received two doses of the Sinovac-CoronaVac vaccine (28-day interval). Immunogenicity was assessed by anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC), anti-S1/S2 IgG geometric mean titer (GMT), factor increase GMT (FI-GMT), neutralizing antibodies (NAb) positivity, and median neutralizing activity after each vaccine dose (D0 and D28) and six weeks after the second dose (D69). Participants with pre-vaccination positive IgG serology and/or NAb and those with RT-PCR confirmed COVID-19 during the protocol were excluded from immunogenicity analysis. Results Patients and CTRL had comparable sex (P&gt;0.99) and age (P=0.90). Immunogenicity of 37 patients and 79 CTRL naïve participants revealed at D69, a moderate but significantly lower SC (64.9% vs. 91.1%, P&lt;0.001), GMT [7.9 (95%CI 4.7-13.2) vs. 24.7 (95%CI 30.0-30.5) UA/mL, P&lt;0.001] and frequency of NAb (51.4% vs. 77.2%, P&lt;0.001) in SAMs compared to CTRL. Median neutralizing activity was comparable in both groups [57.2% (IQR 43.4-83.4) vs. 63.0% (IQR 40.3-80.7), P=0.808]. Immunosuppressives were less frequently used among NAb+ patients vs. NAb- patients (73.7% vs. 100%, P=0.046). Type of SAMs, disease status, other drugs or comorbidities did not influence immunogenicity. Vaccine-related adverse events were mild with similar frequencies in patients and CTRL (P&gt;0.05). Conclusion Sinovac-CoronaVac is safe and has a moderate short-term immunogenicity in SAMs, but reduced compared to CTRL. We further identified that immunosuppression is associated with diminished NAb positivity. CLINICAL TRIAL REGISTRATION NUMBER #NCT04754698

Our aim was to study skin remodeling and autoantibody production in an experimental model of scleroderma (SSc), following nasal tolerance with human type V collagen (Col V). Female New Zealand rabbits (n = 12) were immunized with two doses of 1 mg/ml of Col V in complete Freund's adjuvant and additional two boosters in incomplete Freund's adjuvant to induce SSc. After 150 days, half of these immunized rabbits were submitted to type V collagen-induced tolerance receiving a daily nasal administration of 25 mug of Col V. Control animals (n = 6) were only submitted to type V collagen-induced tolerance. Serial skin biopsies were performed on days 0, 150 and 210, and stained with H&E, Masson's trichrome and Picrosirius for morphological and morphometric analysis. Types I, III and V collagen were identified by immunofluorescence. The animals' serum samples were collected to determine anti types I, III, IV and V collagen and antinuclear antibodies (ANA). Skin biopsies from immunized animals confirmed SSc morphology as previously described, such as progressive decrease of papillary dermis, appendages atrophy, increased type I, III and V collagen deposition. Rabbits with Col V-induced nasal tolerance showed reduction of skin involvement, with significant decrease of collagen amount. Humoral immune response did not change with nasal tolerance. Collagen V nasal tolerance promotes regression of skin remodeling process in an experimental model of SSc. We suggest that nasal tolerance with type V collagen can be a promising therapeutic option to treat scleroderma patients.

No abstract

Objective. Metabolic syndrome (MetS) is highly prevalent in rheumatic diseases and is recognized as a new independent cardiovascular risk factor. This study was undertaken to determine the clinical significance of MetS in patients with primary antiphospholipid syndrome (APS). Methods. Seventy-one primary APS patients and 73 age-and sex-matched healthy controls were included. Serum samples were tested for lipid profile, Lp(a), glucose, insulin, thyroid-stimulating hormone, free T4, erythrocyte sedimentation rate, C-reactive protein level, and uric acid. MetS was defined by the International Diabetes Federation criteria, and insulin resistance was established using the homeostasis model assessment index. Results. The prevalence of MetS was 33.8%, and further comparison between primary APS patients with and withoutMetS revealed that the former had a higher frequency of arterial events (79.2% versus 42.6%; P ‫؍‬ 0.003), angina (29.2% versus 2.1%; P ‫؍‬ 0.002), and positive lupus anticoagulant antibody (95.8% versus 76.6%; P ‫؍‬ 0.049). In addition, primary APS patients with MetS, as expected, had a higher prevalence of cardiovascular risk factors. On multivariate analysis, only MetS was independently associated with arterial events in primary APS. Conclusion. Coexistence of primary APS and MetS seems to identify a subgroup of patients with higher risk of arterial events, suggesting that MetS may aggravate existing endothelial abnormalities of primary APS.

The objective of this study is to determine if digital vasculitis (DV), a clinical manifestation with a high systemic lupus erythematosus disease activity index (SLEDAI) score, is associated with lupus severity. DV and other clinical manifestations defined according to the SLEDAI were evaluated in 168 consecutive patients with systemic lupus erythematosus (SLE). Two groups were defined according to presence (DV+, n = 27) or absence of DV (DV-, n = 141) at the time of evaluation. The exclusion criterion was the presence of antiphospholipid syndrome (Sapporo's criteria). The two groups were comparable with regard to age (P = 0.09), gender (P = 1.00), white race (P = 0.81), and disease duration (P = 0.78). Compared to the DV- group, the DV+ group had a significantly higher frequency of mucocutaneous manifestations (66.7 vs. 39.0%, P = 0.01), haematological abnormalities (22.2 vs. 6.4%, P = 0.02) and constitutional symptoms (11.1 vs. 0.7%, P = 0.01). Renal and neurological involvements were similar in both groups (P = 0.57 and P = 1.00, respectively). The evaluation of each SLEDAI parameter confirmed that the DV+ group had higher frequencies of mild manifestations, such as new rash (P = 0.02), alopecia (P = 0.02), oral ulcers (P = 0.045), fever (P = 0.01) and leucopenia (P = 0.005). In contrast, both groups had similarly increased anti-dsDNA (P = 0.78) and decreased complement levels (P = 0.29). In conclusion, DV in patients with SLE identifies a subgroup of a mild disease. The high 'weighted' index attributed to this alteration in the SLEDAI score should therefore be revised.