AUTOIMMUNE ORIGIN OF SARCOIDOSIS: DETERMINATION OF SPECIFIC IMMUNE COMPLEXES IN PATIENTS WITH RESPIRATORY SARCOIDOSIS

The etiology of sarcoidosis is not completely understood. A hypothesis exists about the relationship between sarcoidosis and a complex of pathological autoimmune reactions that occur under the influence of triggering factors. In this study, specific immune complexes in the blood plasma of patients have been determined, which can indirectly reveal the causes of the disease.

The study included 33 patients with lung sarcoidosis (I group), compared to 24 healthy donors who served as a control group (II group). The patients underwent standard examination. Their blood plasma was investigated by the dynamic light scattering method with addition of tuberculosis antigens (ESAT-6/SFP-10) and “lung healthy tissue extract”. Statistical analysis was performed using the Statistica 7.0 program. Test results were considered significant at p < 0.05.

Аccording to the data obtained, addition of ESAT-6/SFP-10 to patient’s blood plasma almost did not lead to the formation of immune complexes in most samples. Meanwhile, development of such complexes after addition of “lung tissue extract” was revealed in all the patients. The immune complexes were not detected in any donor from control group after stimulation with both kinds of antigens (p < 0.01).

The data on distinct formation of immune complexes with the addition of “lung healthy tissue extract” in patients with lung sarcoidosis may be considered an indirect evidence for occurrence of autoimmune reaction under the influence of some pathogenic factors. Absence of de novo immune complex formation after addition of tuberculosis antigens (ESAT-6/SFP-10) makes it unlikely any direct effects of tuberculosis bacteria upon development of sarcoidosis.

1. Belokurov M.A., Chernokhayeva I.V., Zinserling V.A., Dvorakovskaya I.V., Novitskaya Т.А., Mazitova F.M., Karev V.E., Pavlova M.V., Archakova L.I., Kozak A.R. The case of differential diagnosis of tuberculosis with other lung diseases. Meditsinskiy alyans = Medical Alliance, SPb., 2015, no. 4, pp. 99-109.(In Russ.)

2. Vizel A.A., Vizel I.Yu. Sarcoidosis in oral presentations and publications of annual conference of American thoracic society (ATS 2016). Rossiyskiy meditsinskiy zhurnal = Medical Journal of the Russian Federation, 2017, no. 3, pp. 206-210.(In Russ.)

3. Vizel I.Yu., Vizel A.A. Sarcoidosis on the road to understanding. Medical Alliance, 2013, no. 3, pp. 73-78. (In Russ.)

4. Vizel I.Yu., Vizel A.A. Dynamics of clinical, radiation and functional parameters in the treatment of patients with sarcoidosis. Klinicheskaya meditsina = Clinical Medicine (Russian Journal), 2017, Vol. 95, no. 1, pp. 60-65.(In Russ.)

5. Disseminated lung diseases. Ed. by M.M. Ilkovich]. Moscow: GEOTAR-Media, 2011. 480 p.

6. Ershov G.A., Churilov L.P. About the possibility of autoimmune nature of sarcoidosis: what autoantigens are involved and why? Klinicheskaya patofiziologiya = Clinical Pathophysiology, 2017, no. 3, pp. 77-82. (In Russ.)

7. Korablev P.V., Landa S.B, Semenova E.V., Filatov M.V. Dynamic light scattering – a simple and sensitive method to determine the occurrence of immune complexes in biological fluids. Biopreparaty = Biopreparation, 2015, no. 54, pp. 53-58.(In Russ.)

8. Landa S.B., Filatov M.V., Arutyunyan A.V., Varfolomeeva E.V. Study of plasma megamolecular complexation by laser correlation spectroscopy. Klinicheskaya Laboratornaya Diagnostika = Russian Clinical Laboratory Diagnostics, 2008, no. 4, pp. 37-41.(In Russ.)

9. Zinserling V.A., Starshinova A.A., Karev V.E., Novitskaya T.A., Mazitova F.M., Belokurov M.A., Vasiliev I.V., Pavlova M.V., Kozak A.R. Granulomatous inflammation of Mycoplasma and Chlamydia etiology. Zhurnal infektologii = Journal of Infectology, 2015, Vol. 7, no. 4, pp. 5-9.(In Russ.)

10. Bindoli S., Dagan A., Torres-Ruiz J.J., Perricone C., Bizjak M., Doria A., Shoenfeld Y. Sarcoidosis and аutoimmunity: from genetic background to environmental factors. Isr. Med. Assoc. J., 2016, Vol. 18, no. 3-4, pp. 197-202.

11. Dubaniewicz A. Mycobacterium tuberculosis heat shock proteins and autoimmunity in sarcoidosis. Autoimmun. Rev., 2010, Vol. 9, no. 6, pp. 419-424.

12. Ferrara G., Valentini D., Rao M., Wahlstrom J., Grunewald J., Larsson L.-O., Brighenti S., Dodoo E., Zumla A., Maeurer M. Humoral immune profiling of mycobacterial antigen recognition in sarcoidosis and Lofgren’s syndrome using high-content peptide microarrays. Int. J. Infect. Dis., Vol. 56, pp. 167-175.

13. Goyal B., Sheikh J.A., Agarwal R., Verma I. Levels of circulating immune complexes containing Mycobacterium Tuberculosis-specific antigens in pulmonary tuberculosis and sarcoidosis patients. Indian J. Med. Microbiol., 2017, Vol. 35, pp. 290-292.

14. Gupta D., Agarwal R., Aggarwal A.N., Verma I. Immune responses to mycobacterial antigens in sarcoidosis: a systematic review. Indian J. Chest. Dis. Allied. Sci., 2011, Vol. 53, no. 1, pp. 41-49.

15. Gupta D., Agarwal R., Aggarwal A.N., Jindal S.K. Sarcoidosis and tuberculosis: the same disease with different manifestations or similar manifestations of different disorders. Curr. Opin. Pulm. Med., 2012, Vol. 18, no. 5, pp. 506-516.

16. Jamilloux Y., Valeyre D., Lortholary O., Bernard C., Kerever S., Lelievre L., Neel A., Broussolle C., Seve P. The spectrum of opportunistic diseases complicating sarcoidosis. Autoimmun. Rev., 2015, Vol. 14, no. 1, pp. 64-74.

17. Lebedev A.D., Ivanova M.A., Lomakin A.V., Noskin V.A. Heterodyne quasi-elastic light-scattering instrument for biomedical diagnostics. Appl. Opt., 1997, Vol. 36, no. 30, pp. 7518-7522.

18. Ohyama K., Kuroda N. Proteomic approaches to profiling the humoral immune response and identifying disease-associated antigens. Biol. Pharm. Bull., 2012, Vol. 35, no. 9, pp. 1409-1412.

19. Ohyama K., Ueki Y., Kawakami A., Kishikawa N., Tamai M., Osaki M., Kamihira S., Nakashima K., Kuroda N. Immune complexome analysis of serum and its application in screening for immune complex antigens in rheumatoid arthritis. Clin Chem., 2011, Vol. 57, no. 6, pp. 905-909.

20. Shoenfield Y., Agmon-Levin N. “ASIA” – autoimmune/inflammatory syndrome induced by adjuvants. J. Autoimmun., 2011, Vol. 36, no. 1, pp. 4-8.