Serum Autoantibodies in Primary Sjögren's Syndrome: Study of Clinical Associations and Possible Correlations with Antibodies to Viral Antigens (EBV and HTLV-1)

Abstract

Background: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized primarily by involvement of salivary and lacrimal glands, leading to sicca syndrome. Several organ systems may also be affected. Another striking feature is the production of multiple organ specific and non-organ specific circulating autoantibodies. Among these antibodies, we highlight the anti-Ro (SS-A)/ La (SS-B), present in 60-90% and 30-60% of patients with pSS, respectively, that are one of the classification criteria of this syndrome and indicate more severe disease. It is postulated that viral agents act as triggers for the onset of pSS in genetically predisposed individuals. Among these, the Epstein-Barr virus (EBV) has been the most involved. Antibodies directed to EBV antigens were detected in sera of patients with pSS, which could suggest prior infection and/or cross-reactivity. Subsequently, viral DNA was detected in epithelial cells of salivary glands from these patients, indicating latent infection. It is also interesting that was demonstrated molecular mimicry between EBV antigens and the protein Ro 60 kDa, an autoantigen with well established clinical relevance in pSS. The human T leukemia virus 1 (HTLV-1), although less studied, has also been implicated. But it is not known whether patients with pSS and antibodies reactive with EBV or HTLV-1 (antiviral antibodies) would have more severe disease and increased autoantibody production. Also unknown is the correlation between levels of different circulating autoantibodies and the degree of pSS activity, since only recently has published the first consensus on a score of disease activity. Objectives: 1) To determine the frequency of serum antibodies directed to EBV and HTLV-1 in patients with pSS compared with normal subjects and to study the possible correlations of these antibodies with clinical manifestations and autoantibody profile of these patients. 2) To evaluate the possible association between different organ specific and non-organ specific autoantibodies with various systemic affections of the pSS and with the score of disease activity. Methods: We will analyze 100 consecutive pSS patients according to international criteria (The American-European Consensus Group Criteria, 2002) of both sexes, 18-70 years old, and regularly followed in the Outpatient Unit of Sjögren's Syndrome (Rheumatology Division - HCFMUSP). Will be included as controls 100 healthy subjects without complaints of sicca syndrome and matched for sex, race, and age. Patients will be assessed using a standardized clinical protocol. Activity of disease will be evaluated according to the EULAR Sjögren's Syndrome Disease Activity Index. Will be collected serum samples from patients and normal individuals to detect antibodies to the EBV and HTLV-1 and autoantibodies. These determinations will be made through established techniques, including antinuclear antibodies (ANA), anti-RNP, anti-Ro and fractions of 52 kDa and 60 kDa, anti-La, rheumatoid factor, cryoglobulins, anti-alpha-fodrin, and antiphopholipid antibodies. Will be also analyzed marker antibodies of autoimmune associated diseases, anti-thyroperoxidase, anti-gastric parietal cell, anti-tissue transglutaminase, anti-mitochondria, anti-smooth muscle and anti-LKM1. In order to characterize disease activity will be measured serum levels of IgG and C3 and C4 complement fractions.