Antibodies against Mycobacterial Antigens in the Synovial Fluid of Patients with Temporomandibular Disorders

Abstract

In the absence of active pulmonary disease, mycobacterial infection frequently causes arthritis and can be considered to initiate autoimmune diseases such as rheumatoid arthritis. Temporomandibular disorder (TMD) is a disease in which pain and impaired mandibular movement appear to arise directly from degenerative or inflammatory changes within the temporomandibular joint, but its precise pathogeny has not been elucidated. Here we examined whether mycobacterial infection is related to the pathology of TMD. The antibody levels against mycobacterial antigen in the synovial fluid (SF) of patients with TMD were assessed by enzyme-linked immunosorbent assay (ELISA). Six of 17 TMD patients (35%) were found to possess mycobacterial antigen-specific immunoglobulin (lg) G but not IgM, while the six healthy volunteers possessed neither. Western-blot analysis was used to isolate the reacted antigen, and the IgG reacted strongly to 44-kDa antigen. The first 14 N-terminal amino acid sequences were determined, and computer analysis revealed that it was homologous to translational elongation factor Tu (EF-Tu) of Mycobacterium tuberculosis, which was a major target antigen for these antibodies. The 44-kDa protein of Mycobacterium bovis BCG (BCG) was identical with the EF-Tu of M. tuberculosis. We cloned the gene encoding the EF-Tu of BCG by using the synthesized oligonucleotide primers by means of polymerase chain-reaction. The gene was expressed in Escherichia coli. The protein was purified, and the antibody levels against this recombinant protein in the SF of TMD patients were assessed by ELISA. Our findings suggest that some cases of TMD are concerned with the synovial IgG against the EF-Tu of M. tuberculosis, and that the existence of the antibody is a clinical indication of TMD.

Keywords

antibody synovial fluid TMD Mycobacterium bovis BCG EF-Tu.

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References

Anderton SM , van der Zee R. , Noordzij A. , van Eden W. (1994). Differential mycobacterial 65-kDa heat shock protein T cell epitope recognition after adjuvant arthritis-inducing or protective immunization protocols. J Immunol 152:3656-3664.

Billingham ME , Carney S. , Butler R. , Colston MJ (1990). A mycobacterial 65-kD heat shock protein induces antigen-specific suppression of adjuvant arthritis, but is not itself arthritogenic . J Exp Med 171:339-344.

Boog CJ , de Graeff-Meeder ER , Lucassen MA , van der Zee R. , Voorhorst-Ogink MM , van Kooten PJ , et al. (1992). Two monoclonal antibodies generated against human hsp60 show reactivity with synovial membranes of patients with juvenile chronic arthritis. J Exp Med 175:1805-1810.

Caplan HI , Benny RA (1978). Total osteolysis of the mandibular condyle in progressive systemic sclerosis. Oral Surg Oral Med Oral Pathol 46:362-366.

Carlin NI , Lofdahl S. , Magnusson M. (1992). Monoclonal antibodies specific for elongation factor Tu and complete nucleotide sequence of the tuf gene in Mycobacterium tuberculosis. Infect Immun 60:3136-3142.

Celis L. , Vandevyver C. , Geusens P. , Dequeker J. , Raus J. , Zhang J. (1997). Clonal expansion of mycobacterial heat-shock protein-reactive T lymphocytes in the synovial fluid and blood of rheumatoid arthritis patients . Arthritis Rheum 40:510-519.

Djavad N. , Bas S. , Shi X. , Schwager J. , Jeannet M. , Vischer T. , et al. (1996). Comparison of rheumatoid factors of rheumatoid arthritis patients, of individuals with mycobacterial infections and of normal controls: evidence for maturation in the absence of an autoimmune response . Eur J Immunol 26:2480-2486.

Hogervorst EJ , Wagenaar JP , Boog CJ , van der Zee R. , van Embden JD , van Eden W. (1992). Adjuvant arthritis and immunity to the mycobacterial 65 kDa heat shock protein. Int Immunol 4:719-727.

Holt I. , Cooper RG , Denton J. , Meager A. , Hopkins SJ (1992). Cytokine inter-relationships and their association with disease activity in arthritis. Br J Rheumatol 31:725-733.

10.

Israel HA (1989). Synovial fluid analysis. Oral Maxillofac Surg Clin North Am 1:85-92.

11.

Karlsson-Parra A. , Soderstrom K. , Ferm M. , Ivanyi J. , Kiessling R. , Klareskog L. (1990). Presence of human 65 kD heat shock protein (hsp) in inflamed joints and subcutaneous nodules of RA patients. Scand J Immunol 31:283-288.

12.

Karopoulos C. , Rowley MJ , Handley CJ , Strugnell RA (1995). Antibody reactivity to mycobacterial 65 kDa heat shock protein: relevance to autoimmunity. J Autoimmun 8:235-248.

13.

Kopp S. , Wenneberg B. , Clemensson E. (1983). Clinical, microscopical and biochemical investigation of synovial fluid from temporomandibular joints. Scand J Dent Res 91:33-41.

14.

Korszun A. , Papadopoulos E. , Demitrack M. , Engleberg C. , Crofford L. (1998). The relationship between temporomandibular disorders and stress-associated syndromes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86:416-420.

15.

Kubota E. , Imamura H. , Kubota T. , Shibata T. , Murakami K. (1997). Interleukin 1 beta and stromelysin (MMP3) activity of synovial fluid as possible markers of osteoarthritis in the temporomandibular joint. J Oral Maxillofac Surg 55:20-27.

16.

Kubota E. , Kubota T. , Matsumoto J. , Shibata T. , Murakami KI (1998). Synovial fluid cytokines and proteinases as markers of temporomandibular joint disease. J Oral Maxillofac Surg 56:192-198.

17.

Lanigan DT , Myall RW , West RA , McNeill RW (1979). Condylysis in a patient with a mixed collagen vascular disease. Oral Surg Oral Med Oral Pathol 48:198-204.

18.

Mousa HA (1998). Tuberculosis of bones and joints: diagnostic approaches . Int Orthop 22:245-246.

19.

Ogden GR (1986). Complete resorption of the mandibular condyles in rheumatoid arthritis. Br Dent J 160:95-97.

20.

Ramon Y. , Samra H. , Oberman M. (1987). Mandibular condylosis and apertognathia as presenting symptoms in progressive systemic sclerosis (scleroderma). Pattern of mandibular bony lesions and atrophy of masticatory muscles in PSS, presumably caused by affected muscular arteries. Oral Surg Oral Med Oral Pathol 63:269-274.

21.

Speculand B. , Goss AN ( 1985). Psychological factors in temporomandibular joint dysfunction pain. A review. Int J Oral Surg 14:131-137.

22.

Speculand B. , Hughes AO , Goss AN ( 1984). Role of recent stressful life events experience in the onset of TMJ dysfunction pain. Community Dent Oral Epidemiol 12:197-202.

23.

Suzuki Y. , Yoshinaga K. , Ono Y. , Nagata A. , Yamada T. (1987). Organization of rRNA genes in Mycobacterium bovis BCG. J Bacteriol 169:839-843.

24.

van Eden W. , Thole JE , van der Zee R. , Noordzij A. , van Embden JD , Hensen EJ , et al. (1988). Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature 331:171-173.

25.

Young CC , Bemlohr RW (1991). Elongation factor Tu is methylated in response to nutrient deprivation in Escherichia coli. J Bacteriol 173:3096-3100.

26.

Wexler GB , Steed PA (1998). Psychological factors and temporomandibular outcomes . Cranio 16:72-77.