INSINUATIONS OF MULTIFACTORIAL AUTOIMMUNE DISORDERS AND THEIR INTERPLAY TO DEVELOP RHEUMATOID ARTHRITIS: FROM INFLAMMATION TO BONE DEFORMITY

Abstract

Background: Rheumatoid arthritis (RA) is a chronic and autoimmune disorder which leads to the disability, deformity of joints and even death. The particular reason of the disease is still unknown; but it has been confirmed that it is a multifactorial disease influenced by environmental and genetic factors. Destruction of the joint is associated with the immunological abnormalities and inflammatory mechanisms.

Objectives: The aim of this study is to determine the role of anti-oxidants, inflammatory cytokines and MMPs in the progression and aggregation of RA.

Methods: Blood samples of hundred male patients with rheumatoid arthritis were collected from University teaching hospital, The University of Lahore. Hundred age and sex matched blood samples from healthy volunteers were also collected as a control. Levels of MDA, NO, GSH, SOD and CAT were estimated spectrophotometrically while interleukins, TNF-α, MMP2,MMP3 and MMP9 were estimated by using a commercially available ELISA kit.

Results: The MDA levels in RA patients were elevated significantly as compared to control subjects (2.59±0.017 Vs 1.29±0.006 nmol/ml). The serum NO levels in these patients were recorded (18.58±4.160 μmol/L) as compared to normal subjects (9.28±1.22 μmol/L). However, the serum SOD, CAT, GSH and Vit E levels were measured in RA patients with the significant decrease values of 0.056±0.001 U/L, 0.99±0.015 U/L, 2.99±0.951 μmol/L and 1.95±0.019 μg/ml respectively. On the other hand, the levels of IL-1 (6.19±1.49 pg/ml), IL-6 (6.19±1.49 pg/ml), IL-15 (4.29±1.08 pg/ml) and TNF-α (31.25±1.99 pg/ml) were significantly increased in the patients with RA. Meanwhile, the increased serum MMP-2, MMP-9 and MMP-3 in these RA patients were recorded (96.58±6.59 ng/ml), (109.65±8.26 ng/ml) and (133.29±7.88 ng/ml) respectively against their control values 31.26±5.66 ng/ml, 36.29±4.16 ng/ml and 41.26±6.58 ng/ml. The levels of neutrophils were also increased in RA patients versus control (89.26±5.0 vs 51.66±3.66 μ/L). These values evidently points out the significant increase in oxidative stress and inflammation in bones, joints and cartilage that consequently leads to progression of RA.

Conclusions: Several lines of evidence suggest that decline in anti-oxidants activity triggers to enhance oxidative insult in RA patients. The macrophages in RA release wide range of inflammatory cytokines such as interleukins and tumor necrosis factor alpha. This enhances the expression of inflammatory mediators potentiating damage of bones and cartilage by stimulating various proteolytic enzymes including MMPs. These MMPs triggers the degradation of bone, cartilage by degrading several extracellular components such as proteoglycans, collagen matrix protein and also regulating other MMPs in the patients with RA.