Rheumatoid arthritis (RA) is a chronic autoimmune disease. The pathophysiology of RA implicates several mediators such as nitric oxide (NO) and cytokines such as interleukin-6 (IL-6), which is deeply involved in the main characteristics of RA. Furthermore, all-trans retinoic acid (ATRA) is an active vitamin A derivative well-known to have diverse immunomodulatory actions. In our study, we investigated first, the ex vivo immunomodulatory potential of ATRA on NO pathway by peripheral blood mononuclear cells (PBMCs) from Algerian RA patients. Then, we assessed the possible regulatory effect of ATRA on NO production induced by IL-6. PBMCs isolated from active and inactive RA patients and healthy controls were cultured with different concentrations of IL-6 or/with ATRA. NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence test. Our results revealed a high NO production during active RA. We noticed that while IL-6 induced a high NO production and iNOS expression, ATRA downregulated both. ATRA also inhibited nuclear NF-κB translocation. Interestingly, it seems that NO production mediated by IL-6 on PBMCs of RA patients is downregulated by ATRA. Taken together, our results highlight the immunomodulatory effect of ATRA on NO pathway in RA patients and its possible role in regulating IL-6-mediated NO production. All these findings suggest its potential therapeutic role during RA.
Objectives:To identify factors predicting the progression of early inflammatory arthritis (EIA) to rheumatoid arthritis (RA)Methods:This was a prospective longitudinal study of inflammatory rheumatism that could not be classified according to defined rheumatism criteria. Demographic, biological, immunological and radiographic data were collected at the time of inclusion in the study. Disease activity as determined by the Disease Activity Score 28-CPR (DAS28-CPR: 4 variables), functional handicap as calculated by Heath Assessment Score (HAQ), and bone and joint damage as evaluated by Sharp-Van der Heijde (SVDH) score. ultrasound joint imaging were evaluated at the beginning of the study and then 1 year later. Logistic regression was performed to identify predictive factors for progression to RA.Results:One hundred seventy two patients were included (24 men, 148 women), with an mean age 43.13±14.07 years and an mean time to diagnosis 10.24±6.84 months The mean ESR was 46.81±31.16 mm/1st hour, and the mean CRP level was 22.84±39.8 mg/l. Rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs) were present in 48.8% and 53% of patients, respectively. The erosion, joint space narrowing, and total SVDH scores were 3.38±3.48, 5.08±3.32, and 5.95±4.94, respectively. One hundred sixty one patients were followed up for 12 months. Multivariate regression analysis showed that a DAS28-CRP level >5.2 (OR=28.6; CI95% 8.7-94.5), an RF level >60 IU/L (OR=11.2; CI95% 4.3-87.5), and an ACPA level >60 IU/L (OR=5.4; CI95% 1.9-15.3) were predictive for progression to RA.Conclusion:Our study suggests that clinical evaluation of EIA by DAS28-CRP from the time of diagnosis, as well as evaluating the presence of RA auto-antibodies, can predict progression to RA.Disclosure of Interests:None declared
Rheumatoid arthritis is the most frequent chronic inflammatory rheumatism. Its management, especially in the case of early inflammatory rheumatism should be immediate, if possible, during the first six months of the evolution of the disease and should be adapted to the potential evolution of rheumatism because it is a therapeutic emergency. Management was drastically improved by a better knowledge of pathophysiology (role of anti-CCP antibodies established), a new diagnostic approach (new 2010 ACR/EULAR criteria and new international recommendations), and new prognostic and therapeutic approaches (biologics).
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