**2. Autoantibodies in RA**

diabetes and systemic lupus erythemathosus (SLE). Similarly, autoantibodies are also found in other diseases, where although they may play a minor pathogenic role, but can be used as

Furthermore, in addition to T cells and autoantibodies, cytokines also play a pivotal role in development of the autoimmune response. Proinflammatory cytokines have significant involvement in autoimmune associated damage. This chapter aims to discuss the involve-

Immune system has the capacity to mount an immune response against virtually all foreign molecules as well as self. However, several mechanisms exist within the human system that prevent or subdue the response to self-antigens. The immune system has developed a series of checks and balances that enable it to distinguish dangerous signals from harmless ones and allow it to respond to foreign or non-self-antigens. When these mechanisms undergo a breakdown or are overridden, a response directed against self-antigen can occur, resulting in

RA is a complex chronic disease, primarily affects the lining of the synovial joints and can cause progressive disability, premature death, and socioeconomic burdens. The clinical manifestations of symmetrical joint involvement include arthralgia, swelling, redness, and even

Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases. RA is more frequent in females as compared to males [10]. Organ specific autoimmune diseases involve single or multiple autoantigens. In RA, presence of various autoantibodies such as RF and ACPA, and anti-cartilage type II antibodies in serum

The pathological hallmarks of synovitis in rheumatoid arthritis include the proliferation of resident synovial fibroblasts, new blood vessel formation and the recruitment of a wide range of leukocytes including B and T lymphocytes, monocytes/macrophages and mast cells; in turn this leads to synovial hypertrophy and the invasion of cartilage and bone by activated inflammatory tissue. Cytokines are fundamental orchestrators of the development and maintenance of this lesion [12]. RA disorder is a multifactorial disorder other than autoantibodies there are many other important factors involved such as proinflammatory cytokines such as TNF-α, IL-6 and IL-1 are key mediators of cell migration and inflammation in RA [13]. Cartilage degradation in RA occurs when TNF-α, IL-1 and IL-6 activate synoviocytes, resulting in the secretion of matrix metalloproteinases (MMPs), cathepsins and mast cell proteinases into the synovial fluid [14, 15]. Cytokines also activate chondrocytes, leading to the direct release of

Although the availability of advanced drugs and treatment regimes, however the complete remission of the disease is still not achieved. This chapter shed light on the complex network of the autoantibodies and proinflammatory cytokines as immune responses in the RA disease

pathogenesis and the development of bio-therapeutics used in RA disorder.

ment of autoantibodies and cytokines in the pathogenesis of RA.

autoimmune reactions and/or autoimmune diseases [8].

and synovial fluid have long been associated with RA severity [11].

valuable diagnostic markers [1–7].

102 Autoantibodies and Cytokines

limiting the range of motion [9].

additional MMPs into the cartilage [14, 15].

Several studies have been demonstrated that levels of disease-related biomarkers (such as RF and antibodies to citrullinated protein antigen, as well as secretory phospholipase A2, C-reactive protein (CRP), glycated HSA, and multiple cytokines/chemokines) may be elevated prior to the onset of symptomatic rheumatoid arthritis [16–24].

These findings suggest that there is a substantial "preclinical" period of RA, during which detectable immunologic and inflammatory changes are occurring that are related to disease development. These increased levels of RA related autoantibodies in preclinical RA may be highly specific for early RA detection [18, 19]. There is a great hope that these autoantibodies may be used to predict which currently asymptomatic individuals are at sufficiently high risk for future RA that they may be targeted with preventive therapies.
