Effect of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19

Abstract Objective: To investigate the effect of a single oral dose of 200,000 IU of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19. Methods: This is a post-hoc, exploratory analysis from a double-blind, placebo-controlled, randomized clinical trial performed in two centers in São Paulo, Brazil. Hospitalized patients with COVID-19 were randomly assigned to receive either vitamin D3 (n = 97) or placebo (n = 97). In this post-hoc analysis, the endpoints were titers and frequency of anti-β2-Glycoprotein-I (aβ2-GP) and Anticardiolipin (aCL) antibodies [Immunoglobulin G, M and A (IgG, IgM and IgA)]. Results: Overall mean (SD) age was 55.3 (13.9) years, Body Mass Index (BMI) was 32.2 (7.1 kg/m²), and 106 participants (54.6 %) were male. There was a significant group by time interaction (p = 0.046) for frequency of aCL IgG, with increased values from baseline to discharge in the placebo group [n (%), from 13 (13.4) to 25 (25.8)] compared to the vitamin D3 [from 25 (25.8) to 29 (29.9)]. However, the frequency of aCL IgG did not change between the groups on discharge. No significant differences between vitamin D3 and placebo groups were found for any other autoantibodies. Conclusion: These findings do not support the use of a single oral dose of 200,000 IU of vitamin D3 to modulate autoantibodies in hospitalized patients with moderate to severe COVID-19.

Cognitive dysfunction and serum levels of brain-derived neurotrophic factor (BDNF) in primary anti-phospholipid syndrome (PAPS).

OBJECTIVES: Cognitive dysfunction (CD) is a poorly understood non-stroke central neurological manifestation in anti-phospholipid syndrome (APS). Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in neural plasticity and could potentially be a biomarker of CD in primary APS (PAPS). The aim of the study is to assess CD in PAPS patients and to evaluate its association with clinical data, anti-phospholipid antibodies and serum BDNF levels. METHODS: This cross-sectional study compared 44 PAPS patients and 20 healthy controls matched for age, gender and education. PAPS patients and controls underwent a standardized cognitive examination. The demographic, clinical and laboratory characteristics of patients were recorded. Serum BDNF was measured by Enzyme Linked Immunosorbent. RESULTS: Fourteen (31.8%) of the 44 patients with PAPS had CD compared with only one (5%) healthy control (P =0.019). PAPS patients presented lower serum BDNF levels when compared with controls (P =0.007). Lower levels of BDNF were associated with CD in PAPS patients (P =0.032). In the univariate analysis, a positive association was found between CD and livedo reticularis, deep vein thrombosis, stroke, seizure, smoking as well as a negative association with Mini Mental State Examination and serum BDNF. According to multivariate analysis, the only independent predictor of CD in PAPS was stroke (OR 137.06; 95% CI: 4.73, 3974.32; P =0.004). CONCLUSIONS: CD is commonly reported in PAPS patients; however, its assessment lacks in standards and objective screening tests. The association between CD and low serum BDNF suggests that this neurotrophin can be a promising biomarker for PAPS cognitive impairment.

Anti-adalimumab antibodies kinetics: an early guide for juvenile idiopathic arthritis (JIA) switching.

OBJECTIVE: 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). METHOD: 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). RESULTS: 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), ESR > 30 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). CONCLUSIONS: 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.

Perfil demográfico, clínico e laboratorial de 100 pacientes com lúpus eritematoso sistêmico no Estado da Bahia / Demographic, clinical, and laboratory profile of 100 patients with systemic lupus erythematosus in the State of Bahia

Objetivos: Descrever as características demográficas, clínicas e laboratoriais de pacientes com LES em acompanhamento em serviço de referência no Estado da Bahia. Desenho do estudo: Descritivo, tipo corte transversal. Análise dos dados: Foram utilizados os testes do qui-quadrado e t de student para testar diferenças entre variáveis categóricas e contínuas, respectivamente. A comparação entre mais de duas médias foi feita através do teste F (ANOVA). Resultados: Cem pacientes, sendo 97 por cento mulheres, participaram do estudo. Entre esses, 62 eram mulatos, 22 brancos e 16 negros. A média de idade de ínicio da doença foi de 28,1 anos (7-55 anos). Comprometimentos das articulações e da pele foram as manifestações clínicas mais frequentes (97 e 87 por cento, respectivamente), seguidas pelas alterações hematológicas (57 por cento), renais (39 por cento), de serosas (27 por cento) e neurológicas (26 por cento). Houve maior frequência de nefropatia na raça branca. O FAN foi positivo em 100 por cento dos pacientes, anti-RNP em 34 por cento, anti-SSA em 20 por cento, anti-dsDNA em 17 pr cento, anti-Sm em 13 por cento e anti-SSB em 2 por cento. Anti-RNP foi mais frequente na raça negra. O anti-dsDNA apresentou associação com nefropatia, vasculites e eritema malar: e o anti RNP, associação com úlcera de mucosas e o anti-SSA com comprometimento mucocutâneo. Conclusão: O LES foi três vezes mais frequente entre as mulheres que na maioria dos relatos de literatura; as frequências dos comprometimentos clínicos foram semelhantes às das encontradas por outros autores; não houve predomínio da doença na raça negra; houve maior prevalência de nefropatia entre os pacientes brancos; o anti-RNP foi mais frequente entre os doentes negros e mulatos