Treatment with biological therapy is associated with faster recovery and lower frequency of treatment switch among rheumatic patients with Chikungunya fever.

BACKGROUND/OBJECTIVE: The effects of Chikungunya virus (CHIKV) infection on patients with rheumatic diseases have not been extensively studied. Our aim was to compare the clinical course of patients with rheumatoid arthritis and spondyloarthritis, categorized according to the use or not of biologic disease modifying anti-rheumatic drugs (bDMARDs), during and after infection by CHIKV. METHODS: Patients from a northeastern Brazilian city that suffered an epidemic outbreak of Chikungunya fever (CHIK) between Oct 2015 and Jul 2016, on regular follow-up in a longitudinal registry of rheumatic patients (BiobadaBrasil), were invited to participate. Participants underwent a standardized clinical interview and collection of blood sample for serological tests (IgM/IgG) for CHIKV. A positive IgG was considered evidence of previous CHIKV infection. RESULTS: 105 patients (84 with rheumatoid arthritis, 17 with ankylosing spondylitis, and 4 with psoriatic arthritis) were evaluated. Most patients (58, 55.2%) were on therapy with bDMARDs. The overall prevalence of seropositivity for CHIKV was 47.6% (39.7% in patients on bDMARDs and 57.4% in those exclusively on conventional synthetic (cs-) DMARDs (p = 0.070). Among seropositive patients, asymptomatic disease had similar frequency in those treated and not treated with bDMARDs (39.1% versus 33.3%, respectively; p = 0.670). However, patients exclusively on csDMARDs presented significantly higher prevalence of articular symptoms beyond 3 months and switched treatment more often than patients on bDMARDs (p < 0.05 for both comparisons). CONCLUSIONS: Among rheumatic patients with CHIK, those on bDMARDs had shorter persistence of articular symptoms and switched treatment scheme less often than patients exclusively treated with csDMARDs.

Atorvastatin inhibits IL-17A, TNF, IL-6, and IL-10 in PBMC cultures from patients with severe rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint damage, and it may present with comorbidities at the systemic level. The Th1/Th2/Th17 CD4+ lymphocyte imbalance produces inflammatory cytokines, which begin to act, injuring joint tissue. Atorvastatin is a cholesterol- lowering drug with a range of biological effects including anti-inflammatory potential. Patients with rheumatoid arthritis who used statins exhibited clinical improvement. However, the mechanism is not fully understood. Therefore, we aimed to evaluate the RA immunomodulatory activity of atorvastatin. METHODS: Peripheral blood mononuclear cells (PBMCs) of RA patients and healthy donors were exposed to atorvastatin in different concentrations following a cytotoxicity assay. Th1, Th2, and Th17 cytokines profiles were evaluated in the culture supernatant by cytometric bead array (CBA). Data were analyzed using the Wilcoxon test, and differences were considered significant when p < 0.05. RESULTS: Atorvastatin showed no toxicity at the tested doses in RA PBMC cultures, and at 10µM, it showed the most significant results, reducing IL-17A (p = 0.002), TNF (p = 0.002), and IL-6 (p = 0.008) supernatant levels. The outcomes also revealed that only patients with more severe disease activity and those sensitive to corticoid treatments were responders to atorvastatin in vitro. CONCLUSION: These findings suggest the potential immunomodulatory action of atorvastatin as a mechanism in rheumatoid arthritis treatment.

Sensitivity and specificity of Interleukin 29 in patients with rheumatoid arthritis and other rheumatic diseases.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and progressive inflammation that can cause a high degree of disability in affected individuals. Proinflammatory cytokines play central roles in the development of degradative and inflammatory responses in RA. IL-29 has been identified in RA and reported as a biomarker of the disease. OBJECTIVE: To analyze serum levels and accuracy of IL-29 in RA patients compared to healthy subjects and patients with other rheumatic diseases. METHODS: IL-29 serum levels were measured in 121 patients with RA, 53 patients with systemic lupus erythematosus (SLE), 60 patients with systemic sclerosis (SSc), 29 patients with fibromyalgia (FM), 50 patients with osteoarthritis (OA) and 68 healthy individuals as controls. IL-29 levels in serum were investigated by ELISA. Sensitivity, specificity and likelihood ratios (LR) for having RA were calculated. RESULTS: Serum levels of IL-29 were increased in RA patients 113.6 (IQR = 31.25-308.5) pg/ml compared to non-RA patients (SLE, SSc, OA, and FM) (31.25 pg/ml) and healthy controls (31.25 pg/ml, p < 0.001). The IL-29 cut-off values to distinguish patients with RA from non-RA patients were 61.11 pg/ml (sensitivity 57.02, specificity 92.71, LR: 7.82) and for all subjects 32.96 pg/ml (sensitivity 64.46, specificity 87.31, LR: 5.08). Additionally, IL-29 correlated negatively with age (r=-0189, p = 0.038) and disease duration (-0.192, p = 0.037). Interestingly, IL-29 correlated positively with neutrophil count in RA patients positive for rheumatoid factor (r = 0.259, p = 0.022). CONCLUSION: IL-29 is higher in the serum of patients with RA compared to non-RA subjects and may have potential for use as a biological marker.

Increased Serum Interleukin-9 Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Pathogenic Role or Just an Epiphenomenon?

The purpose of this paper was to evaluate the levels of IL-9 in patients with SLE and RA compared with controls and the association of IL-9 levels with clinical and laboratory parameters. IL-9 levels were assessed in 117 SLE patients, 67 RA patients, and 24 healthy controls by ELISA. Clinical and laboratory parameters were recorded. The IL-9 serum levels were significantly higher in RA patients (4,77 ± 3,618 pg/mL) and in SLE patients (12,26 ± 25,235 pg/mL) than in healthy individuals (1,22 ± 0,706 pg/mL) (p < 0,001). In SLE patients, there were no statistically significant associations or correlations between the levels of IL-9 and SLEDAI or other clinical and laboratorial parameters, with the exception of disease time, which showed a statistically significant negative correlation with IL-9 levels (r = -0,1948; p = 0,0378). In RA patients, no association or statistically significant correlation was observed with disease duration, DAS28, HAQ, rheumatoid factor positivity, or erosions on radiography. These data demonstrated increased serum levels of IL-9 in SLE and RA patients, but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target.

Synthesis of a novel thiazolidinedione and evaluation of its modulatory effect on IFN- γ , IL-6, IL-17A, and IL-22 production in PBMCs from rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is an autoimmune disease frequently characterized by chronic synovitis of multiple joints. The pathogenesis of RA is complex and involves many proinflammatory cytokines as Th17 related ones. PPAR γ is a nuclear receptor activator that represses proinflammatory gene expression. Thus, this work aimed to synthetize a new thiazolidinedione (TZD) analogue based on a well-known anti-inflammatory and PPAR γ agonist activity of this ring and evaluate its anti-inflammatory activity. After chemical structure confirmation, the compound named 5-(5-bromo-2-methoxy-benzylidene)-3-(2-nitro-benzyl)-thiazolidine-2,4-dione TM17 was submitted to cytokine releasing inhibition and PPAR γ genetic modulation assays. The new compound showed no toxicity on human and murine cells, decreasing IL-6 secretion by murine splenocytes and reducing IL-17A, IL-22, and IFN- γ expression in peripheral blood mononuclear cells from patients with RA. TM17 was more efficient in modulating the mRNA expression of PPAR γ than its well-used TZD agonist rosiglitazone. Surprisingly, TM17 was efficient on IL-17A and IFN- γ reduction, like the positive control methylprednisolone, and presented a better effect on IL-22 levels. In conclusion, PBMCs obtained from RA patients under TM17 treatment present a significant reduction in IL-17A, IL-22, and IFN- γ levels, but not IL-6 when compared with nontreated cells, as well as increase PPAR γ mRNA expression in absence of stimulus addressing it as a promising molecule in RA treatment.

PPARγ Agonists in Adaptive Immunity: What Do Immune Disorders and Their Models Have to Tell Us?

Adaptive immunity has evolved as a very powerful and highly specialized tool of host defense. Its classical protagonists are lymphocytes of the T- and B-cell lineage. Cytokines and chemokines play a key role as effector mechanisms of the adaptive immunity. Some autoimmune and inflammatory diseases are caused by disturbance of the adaptive immune system. Recent advances in understanding the pathogenesis of autoimmune diseases have led to research on new molecular and therapeutic targets. PPAR γ are members of the nuclear receptor superfamily and are transcription factors involved in lipid metabolism as well as innate and adaptive immunity. PPAR γ is activated by synthetic and endogenous ligands. Previous studies have shown that PPAR agonists regulate T-cell survival, activation and T helper cell differentiation into effector subsets: Th1, Th2, Th17, and Tregs. PPAR γ has also been associated with B cells. The present review addresses these issues by placing PPAR γ agonists in the context of adaptive immune responses and the relation of the activation of these receptors with the expression of cytokines involved in adaptive immunity.