CHARACTERISTICS OF AUTOIMMUNE INFLAMMATION IN THE PATIENTS WITH LUNG TUBERCULOSIS

Tuberculosis is a granulomatous disease caused by Mycobacterium tuberculosis, being characterized by the development of caseous granulomas in various organs, mainly in lungs. M. tuberculosis is known to be a trigger for autoimmune inflammation, due to the possible mimicry of bacterial proteins as autoantigens. Recently, a significance of mesenchymal vimentin as an autoantigen in mycobacterial infections has been actively discussed. The aim of the present study was to determine autoantibodies for various vimentin modifications in the patients with tuberculosis.

The study was performed in 2014-2017 and included 28 patients with pulmonary tuberculosis (group I), 30 patients with nonspecific lung diseases (group II): 15 with granulomatous polyangiitis, and 15 with different alveolites. Control group consisted of healthy subjects (n = 40). Concentration of antibodies to mutated citrullinated vimentin (anti-MCV) was measured using ELISA (ORGENTEC, Germany). The patients with elevated anti-MCV levels were tested for antibodies to cyclic citrullinated peptide (anti-CCP) using ELISA technique (EUROIMMUN, Germany). Statistical analysis was carried out using GraphPad Prism 6 (GraphPad Software, USA), Statistica 10 (Statsoft, USA) using nonparametric analysis of samples with Mann-Whitney and Chi-square criteria, and Spearman method for correlation analysis. The differences were considered statistically significant at p < 0.05.

The anti-MCV concentrations were significantly higher in patients with tuberculosis (group I, 60.7% of cases, 17/28) than in group II, and control group (23.6 and 25.0% of cases, respectively). No statistically significant differences were revealed between the results of anti-MVC and anti-CCP levels in comparison group with the control group (p = 0.18).

High levels of anti-MCV antibodies in the patients with pulmonary tuberculosis reflect an opportunity of developing autoimmune process in the disease pathogenesis. Measurement of plasma anti-MCV antibody concentrations may be important for correction of the therapy, especially upon administration of immunosuppressive and hormonal corticosteroid drugs. It has been shown that anti-CCP are not characteristic to the lung diseases.

1. Phthisiatry. National clinical guidelines / ed. P.K. Yablonsky. Moscow: GEOTAR-Media, 2016. 240 p.

2. Arango M., Perricone C., Kivity S., Cipriano E., Ceccarelli F., Valesini G., Shoenfeld Y. HLA-DRB1 the notorious gene in the mosaic of autoimmunity. Immunol. Res., 2017, Vol. 65, no. 1, pp. 82-98.

3. Ang S.C., Moscovic E.A. Cross-reactive and species specific Mycobacterium tuberculosis antigens in the immunoprofile of Schaumann bodies: a major clue to the etiology of sarcoidosis. Histol. Histopathol., 1996, Vol. 11, no. 1, pp. 125-134.

4. Cain H., Kraus B. Immunofluorescence microscopic demonstration of vimentin filaments in asteroid bodies of sarcoidosis. A comparison with electron microscopic findings. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol., 1983, Vol. 42, no. 2, pp. 213-226.

5. Chen E.S., Wahlström J., Song Z., Willett M.H., Wikén M., Yung R.C., West E.E., McDyer J.F., Zhang Y., Eklund A., Grunewald J., Moller D.R. T Cell responses to mycobacterial catalase-peroxidase profile a pathogenic antigen in systemic sarcoidosis. J. Immunol., 2008, Vol. 181, no. 12, pp. 8784-8796.

6. Elkington P., Tebruegge M., Mansour S. Tuberculosis: an infection-initiated autoimmune disease? Trends Immunol., 2016, Vol. 37, no. 12, pp. 815-818.

7. Elkayam O., Caspi D., Lidgi M., Segal R. Auto-antibody profiles in patients with active pulmonary tuberculosis. Int. J. Tuberc. Lung Dis., 2007, Vol. 11, no. 3, pp. 306-310.

8. Ribeiro F.M., Goldenberg T. Mycobacteria and autoimmunity. Lupus, 2015, Vol. 24, pp. 374-381.

9. Fagan E.A., Moore-Gillon J.C., Turner-Warwick M. Multiorgan granulomas and mitochondrial antibodies. J. Med., 1983, Vol. 308, pp. 572-575.

10. Musaelyan A., Lapin S., Nazarov V., Tkachenko O., Gilburd B., Mazing A., Mikhailova L., Shoenfeld Y. Vimentin as antigenic target in autoimmunity: a comprehensive review. Autoimmun. Rev., 2018, Vol. 17, no. 9, pp. 926-934.

11. Samsonova M.V., Chernyaev A.L. Granulomatous lung diseases. Pulmonology, 2017, Vol. 27, no. 2, pp. 250-261.

12. Scadding JG. Mycobacterium tuberculosis in the aetiology of sarcoidosis. BMJ, 1960, Vol. 2, pp. 1617-1623.

13. Sester M., Kampmann B. What defines latent infection with Mycobacterium tuberculosis in patients with autoimmune diseases? Thorax, 2016, Vol. 71, pp. 64-72.

14. Shapira Y., Agmon-Levin N., Shoenfeld Y. Mycobacterium tuberculosis, autoimmunity, and vitamin D. Clin. Rev. Allerg. Immunol., 2010, Vol. 38, pp. 169-177.

15. Shoenfeld Y., Vilner Y., Coates A.R.M., Rauch J., Lavie G., Shaul D., Pinkhas J. Monoclonal anti-tuberculosis antibodies react with DNA, and monoclonal anti-DNA autoantibodies react with Mycobacterium tuberculosis. Clin. Exp. Immunol., 1986, Vol. 66, pp. 255-261.

16. Valesini G., Gerardi M.C., Iannuccelli C., Pacucci V.A., Pendolino M., Shoenfeld Y. Citrullination and autoimmunity. Autoimmun. Rev., 2015, Vol. 14, no. 6, pp. 490-497.