BACKGROUND: Tuberculosis is found everywhere in the world but it occupies a dominant position in underdeveloped countries. India has a large population of tubercular cases, both pulmonary and extra-pulmonary. Apart from the chronic nature of the disease, the waxy layer present on the bacteria is known to modulate the immune response of the host. In osteo-articular tuberculosis also these possibilities hold good. In addition, certain antigenic components released due to destruction of cartilages, synovial membrane and bony tissues in a host infected with Mycobacterium tuberculosis may lead to autoimmune antibody formation. To the best of our knowledge association of any form of tuberculosis with autoimmunity has not been looked in by workers so far. The present work was planned with an idea to elicit some data in osteoarticular tuberculosis, to find out whether tuberculosis may lead to any autoimmune disorder? Can rheumatoid arthritis be a result of tuberculosis infection? AIMS AND OBJECTIVES: The present study was undertaken to evaluate the autoimmune status in different groups of patients of osteoarticular tuberculosis and compare it with control subjects. MATERIAL AND METHODS: The study was conducted in Department of Orthopaedics, Pathology and Micro at Hind Institute of Medical Sciences, Barabanki, extending from 2010 to 2012. A total of 130 patients of osteoarticular tuberculosis attending the OPD of department and those admitted in ortho wards of hospital, were taken on random basis. Thirty healthy individuals were taken as controls, in which systemic infection and parasitic infestations were excluded. Patients were divided in two groups' viz. Group A (with active disease) and Group B (with healed disease). Each group was further divided into two sub-groups of synovial and non- synovial joint involvement. Thus there were four sub-groups which are as follows: Active disease of synovial joints (FS) : 36 patients Active disease of Non-synovial joints (FNS) : 31 patients Healed cases of synovial joint disease (HS) : 30 patients Healed cases of non-synovial joint disease (HNS) : 33 Patients 130 Patients Control cases : 30 Thus a total of 160 individuals were investigated. Routine haematological investigations, radiological investigations like Fluoroscopy chest/ x-ray Chest, X-ray of the affected parts were done. IMMUNOLOGICAL STUDIES: In all the cases and controls tissue non-specific and tissue specific autoantibodies were examined. The findings were recorded and data were analysed using suitable statistical techniques. Following auto antibodies were studied: A) Tissue Non-specific auto antibodies: a) Rheumatoid factor-Rose-Waaler test. b) Antinuclear antibody. B) Tissue specific auto-antibodies: a) Thyroid-Antithyroglobulin antibody. b) R.B.C.-Cold haem-agglutinating antibody. c) In addition as a parameter of in vivo immune reaction complement component 3 (C-3) level in serum was estimated. RESULTS AND DISSCUSSION: Sixty seven cases of active osteoarticular tuberculosis and 63 cases of healed osteoarticular tuberculosis and 30 healthy control subjects were examined in the present work for the prevalence of four types of auto-antibodies and level of complement 3 in their sera. The cases of active tuberculosis were divided into two groups depending on joints affected i.e. (i) Synovial and (ii) non-synovial. Similarly healed cases were also divided into two groups. Whereas, male patients were found in higher number with affection of synovial joints, female patients outnumbered the males in case of non-synovial joints (similar preponderance) of female patients in tuberculosis cases affecting non-synovial joints. In active disease affecting non-synovial joints 25.81% of patients were positive, whereas 30.30% of the healed cases of this category gave positive reaction to Rose-Waaler test. Healed patients were recalled after the mean period of 18.53 months of successful treatment. There was one patient who came 36 months after being healed and another patient came 16 months later both giving positive Rose-Waaler reaction. It appears that little percentage of cases of tuberculosis affecting non-synovial joints remained Rose-Waaler positive in 60 months after being healed. All the sera from control cases were negative but nine ( 25%) active synovial joint involvement and seven (22.58%) non-synovial joint cases were positive for anti-nuclear antibody. Amongst the healed patients ten cases (33.33%) of synovial joint involvement and six cases (18.18%) of non-synovial joint affection were also positive for anti-nuclear factor. Thus, the results of anti-nuclear antibody test not only showed its presence in patients with active osteoarticular tuberculosis but it was found even in cases that have been successfully treated and declared to be healed. It appears that the autoimmune antibody against nuclear antigen that is triggered by M. tuberculosis persists even after clinical cure. Serum of the same groups of patients and control subjects were examined for antibody to thyroglobulin. The control subjects six (20%) showed presence of antibody. Nine (25%), ten (33.33%), 13 (41.94%) and seven (21.21%) cases revealed antibody reactive to thyroglobulin amongst fresh synovial, healed synovial, fresh non-synovial and healed non-synovial cases, respectively. The prevalence of the antibody was significantly higher in fresh non-synovial cases only. In rest of the groups of the patients the prevalence of antibody was not significantly different from control subjects. But, while looking in the titre of positive cases it was found that amongst normal subjects four had a titre of 1: 8 and two reacted at 1: 16 dilution of the sera. In the study patients in active tuberculosis of synovial joints there was one patient who had anti-thyroglobulin antibody to attire of 1:256, rest of the patients in this group reacted at titre of 1: 16 or below. In healed synovial group there were two cases positive at 1:64 and another case at 1:128. In fresh nonsynovial, the anti-thyroglobulin antibody was either 1:8 or 1:16. Some range was also found in healed non-synovial cases. Cold haem-agglutinin in their sera, 08.33%, 10.0%, 6.45% and 24.24% cases in fresh synovial, healed non-synovial patients were positive, respectively. It appears that in certain percentage of active cases of tuberculosis of bones and joints cold haem-agglutinin appear in the blood which persists in a few cases even after healing. In all the study groups the mean levels of complement C3 were found to be significantly lower compared to that in the control subjects. Further, the mean complement levels in synovial or non-synovial cases were significantly lower corresponding to their healed groups. From the above results it appears that during the active phase of osteoarticular tuberculosis apart from autoimmune antibody, anti-mycobacterial antibody might also be involved in raising complement consumption in vivo, but in healed cases of tuberculosis the lower level of C3 found in study can only be explained by postulating continuation of autoimmune antibody formation leading to Ag-Ab reaction in vivo. CONCLUSION: Osteoarticular tuberculosis not only triggers formation of auto-antibodies, but once these auto-antibodies are formed, they appear to persist even when the patients, are healed of tuberculosis. As the present study is not a prospective one, definite conclusion on the responsibility of osteoarticular tuberculosis for autoimmune diseases cannot be drawn. Although there is very strong evidence available in results obtained in the present work, but perhaps a sustained examination with a long follow-up study with big number of patients will be necessary to clinch definitely the strong possibility of osteoarticular tuberculosis leads to autoimmune disorder.
