The Indian Journal of Chest Diseases and Allied Sciences

Register      Login

VOLUME 53 , ISSUE 1 ( January-March, 2011 ) > List of Articles

REVIEW ARTICLE

Immune Responses to Mycobacterial Antigens in Sarcoidosis: A Systematic Review

D. Gupta, R. Agarwal, A.N. Aggarwal, Indu Verma

Keywords : Sarcoidosis, Mycobacterium tuberculosis, IGRA, T-cell responses, B-cell responses

Citation Information : Gupta D, Agarwal R, Aggarwal A, Verma I. Immune Responses to Mycobacterial Antigens in Sarcoidosis: A Systematic Review. Indian J Chest Dis Allied Sci 2011; 53 (1):41-50.

DOI: 10.5005/ijcdas-53-1-41

License: CC BY-NC 4.0

Published Online: 10-06-2022

Copyright Statement:  Copyright © 2011; The Author(s).


Abstract

From the time sarcoidosis has been described, there has always been a viewpoint that the disease is in some way related to tuberculosis (TB). Sarcoidosis is a granulomatous disease, which is likely a result of continued presentation of a poorly degradable antigen. Mycobacterium tuberculosis has been a very strong contender for this antigen. Besides the molecular studies demonstrating mycobacterial deoxyribonucleic acid (DNA) in the sarcoid tissue, assessment of immune responses against mycobacterial antigens provides a useful tool to study the role of mycobacteria in the pathogenesis of sarcoidosis. We reviewed the studies focussing on T-cell and B-cell responses to tubercular antigens in patients with sarcoidosis. Pooled data from various studies does provide a suggestive, though not unequivocal evidence in favour of mycobacteria as a cause of sarcoidosis. These findings not only reinforce the possible pathogenic role of mycobacterial antigens in sarcoidosis, but at the same time also limit the clinical utility of molecular and serological studies based on mycobacterial antigens in the differential diagnosis of TB from sarcoidosis, particularly in a country with high endemicity for TB.


PDF Share
  1. Perez RL, Rivera-Marrero CA, Roman J. Pulmonary granulomatous inflammation: from sarcoidosis to tuberculosis. Semin Respir Infect 2003;18:23-32.
  2. Newman LS. Aetiologies of sarcoidosis. Eur Respir Mon 2005;32:23-48.
  3. Thomeer M, Demedts M, Wuyts W. Epidemiology of sarcoidosis. Eur Respir Mon 2005;32:13-22.
  4. du Bois RM, Goh N, McGrath D, Cullinan P. Is there a role for microorganisms in the pathogenesis of sarcoidosis? J Intern Med 2003;253:4-17.
  5. Vidal S, de la Horra C, Martin J, Montes-Cano MA, Rodriguez E, Respaldiza N, et al. Pneumocystis jirovecii colonisation in patients with interstitial lung disease. Clin Microbiol Infect 2006;12:231-5.
  6. Drake WP, Newman LS. Mycobacterial antigens may be important in sarcoidosis pathogenesis. Curr Opin Pulm Med 2006;12:359-63.
  7. Ishige I, Eishi Y, Takemura T, Kobayashi I, Nakata K, Tanaka I, et al. Propionibacterium acnes is the most common bacterium commensal in peripheral lung tissue and mediastinal lymph nodes from subjects without sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2005;22:33-42.
  8. Oswald-Richter KA, Drake WP. The etiologic role of infectious antigens in sarcoidosis pathogenesis. Semin Respir Crit Care Med 2010;31:375-9.
  9. Sharma OP, Murray Kornfeld, American College of Chest Physicians, and sarcoidosis: a historical footnote: 2004 Murray Kornfeld Memorial Founders Lecture. Chest 2005; 128:1830-5.
  10. Gupta D, Agarwal R, Aggarwal AN, Jindal SK. Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis. Eur Respir J 2007;30:508-16.
  11. Mootha VK, Agarwal R, Aggarwal AN, Gupta D, Ahmed J, Verma I, et al. The sarcoid-tuberculosis link: evidence from a high TB prevalence country. J Infect 2010; 60:501-3.
  12. Kent DC, Houk VN, Elliott RC, Sokolowski JW Jr, Baker JH, Sorensen K. The definitive evaluation of sarcoidosis. Am Rev Respir Dis 1970;101:721-7.
  13. Hatzakis K, Siafakas NM, Bouros D. Miliary sarcoidosis following miliary tuberculosis. Respiration 2000;67:219-22.
  14. Vanek J, Schwarz J. Demonstration of acid-fast rods in sarcoidosis. Am Rev Respir Dis 1970;101:395-400.
  15. Cantwell AR Jr. Variably acid-fast bacteria in a case of systemic sarcoidosis and hypodermitis sclerodermiformis. Dermatologica 1981;163:239-48.
  16. Cantwell AR Jr. Histologic observations of variably acidfast pleomorphic bacteria in systemic sarcoidosis: a report of 3 cases. Growth 1982;46:113-25.
  17. Mitchell DN, Rees RJ. A transmissible agent from sarcoid tissue. Lancet 1969;2:81-4.
  18. Mitchell DN, Rees RJ. An attempt to demonstrate a transmissible agent from sarcoid material. Postgrad Med J 1970;46:510-4.
  19. Mitchell DN, Rees RJ, Goswami KK. Transmissible agents from human sarcoid and Crohn's disease tissues. Lancet 1976;2:761-5.
  20. Mitchell DN. The nature and physical characteristics of a transmissible agent from human sarcoid tissue. Ann N Y Acad Sci 1976;278:233-48.
  21. Almenoff PL, Johnson A, Lesser M, Mattman LH. Growth of acid fast L forms from the blood of patients with sarcoidosis. Thorax 1996;51:530-3.
  22. Song Z, Marzilli L, Greenlee BM, Chen ES, Silver RF, Askin FB, et al. Mycobacterial catalase-peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis. J Expir Med 2005;201:755-67.
  23. Rybicki BA, Hirst K, Iyengar SK, Barnard JG, Judson MA, Rose CS, et al. A sarcoidosis genetic linkage consortium: the sarcoidosis genetic analysis (SAGA) study. Sarcoidosis Vasc Diffuse Lung Dis 2005;22:115-22.
  24. Schurmann M. Genetics of sarcoidosis. Semin Respir Crit Care Med 2003;24:213-22.
  25. Hunninghake GW, Crystal RG. Pulmonary sarcoidosis: a disorder mediated by excess helper T-lymphocyte activity at sites of disease activity. N Engl J Med 1981;305:429-34.
  26. Semenzato G, Pezzutto A, Chilosi M, Pizzolo G. Redistribution of T lymphocytes in the lymph nodes of patients with sarcoidosis. N Engl J Med 1982;306:48-9.
  27. Grunewald J, Eklund A. Role of CD4+ T cells in sarcoidosis. Proc Am Thorac Soc 2007;4:461-4.
  28. Silver RF, Crystal RG, Moller DR. Limited heterogeneity of biased T-cell receptor V beta gene usage in lung but not blood T cells in active pulmonary sarcoidosis. Immunology 1996;88:516-23.
  29. Konishi K, Moller DR, Saltini C, Kirby M, Crystal RG. Spontaneous expression of the interleukin 2 receptor gene and presence of functional interleukin 2 receptors on T lymphocytes in the blood of individuals with active pulmonary sarcoidosis. J Clin Invest 1988;82:775-81.
  30. Robinson BW, McLemore TL, Crystal RG. Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis. J Clin Invest 1985;75:1488-95.
  31. Baughman RP, Strohofer SA, Buchsbaum J, Lower EE. Release of tumor necrosis factor by alveolar macrophages of patients with sarcoidosis. J Lab Clin Med 1990;115:36-42.
  32. Moller DR, Forman JD, Liu MC, Noble PW, Greenlee BM, Vyas P, et al. Enhanced expression of IL-12 associated with Th1 cytokine profiles in active pulmonary sarcoidosis. J Immunol 1996;156:4952-60.
  33. Agostini C, Trentin L, Facco M, Sancetta R, Cerutti A, Tassinari C, et al. Role of IL-15, IL-2, and their receptors in the development of T cell alveolitis in pulmonary sarcoidosis. J Immunol 1996;157:910-8.
  34. Kreipe H, Radzun HJ, Heidorn K, Barth J, Kiemle-Kallee J, Petermann W, et al. Proliferation, macrophage colony stimulating factor, and macrophage colony-stimulating factor-receptor expression of alveolar macrophages in active sarcoidosis. Lab Invest 1990;62:697-703.
  35. Pinkston P, Bitterman PB, Crystal RG. Spontaneous release of interleukin-2 by lung T lymphocytes in active pulmonary sarcoidosis. N Engl J Med 1983;308:793-800.
  36. Hunninghake GW, Bedell GN, Zavala DC, Monick M, Brady M. Role of interleukin-2 release by lung T-cells in active pulmonary sarcoidosis. Am Rev Respir Dis 1983;128:634-8.
  37. Agostini C, Adami F, Semenzato G. New pathogenetic insights into the sarcoid granuloma. Curr Opin Rheumatol 2000;12:71-6.
  38. Girgis RE, Basha MA, Maliarik M, Popovich J Jr, Iannuzzi MC. Cytokines in the bronchoalveolar lavage fluid of patients with active pulmonary sarcoidosis. Am J Respir Crit Care Med 1995;152:71-5.
  39. Shigehara K, Shijubo N, Ohmichi M, Takahashi R, Kon S, Okamura H, et al. IL-12 and IL-18 are increased and stimulate IFN-gamma production in sarcoid lungs. J Immunol 2001;166:642-9.
  40. Bingisser R, Speich R, Zollinger A, Russi E, Frei K. Interleukin-10 secretion by alveolar macrophages and monocytes in sarcoidosis. Respiration 2000;67:280-6.
  41. Berthet FX, Rasmussen PB, Rosenkrands I, Andersen P, Gicquel B. A Mycobacterium tuberculosis operon encoding ESAT-6 and a novel low-molecular-mass culture filtrate protein (CFP-10). Microbiology 1998;144:3195-203.
  42. Lalvani A, Nagvenkar P, Udwadia Z, Pathan AA, Wilkinson KA, Shastri JS, et al. Enumeration of T cells specific for RD1-encoded antigens suggests a high prevalence of latent Mycobacterium tuberculosis infection in healthy urban Indians. J Infect Dis 2001;183:469-77.
  43. Kunst H. Diagnosis of latent tuberculosis infection: the potential role of new technologies. Respir Med 2006; 100:2098-106.
  44. Dubaniewicz A, Trzonkowski P, Dubaniewicz-Wybieralska M, Singh M, Mysliwski A. Mycobacterial heat shock protein-induced blood T lymphocytes subsets and cytokine pattern: comparison of sarcoidosis with tuberculosis and healthy controls. Respirology 2007;12:346-54.
  45. Drake WP, Dhason MS, Nadaf M, Shepherd BE, Vadivelu S, Hajizadeh R, et al. Cellular recognition of Mycobacterium tuberculosis ESAT-6 and KatG peptides in systemic sarcoidosis. Infect Immun 2007;75:527-30.
  46. Carlisle J, Evans W, Hajizadeh R, Nadaf M, Shepherd B, Ott RD, et al. Multiple Mycobacterium antigens induce interferon-gamma production from sarcoidosis peripheral blood mononuclear cells. Clin Exp Immunol 2007;150:460-8.
  47. Launois P, DeLeys R, Niang MN, Drowart A, Andrien M, Dierckx P, et al. T-cell-epitope mapping of the major secreted mycobacterial antigen Ag85A in tuberculosis and leprosy. Infect Immun 1994;62:3679-87.
  48. Hajizadeh R, Sato H, Carlisle J, Nadaf MT, Evans W, Shepherd BE, et al. Mycobacterium tuberculosis antigen 85A induces Th-1 immune responses in systemic sarcoidosis. J Clin Immunol 2007;27:445-54.
  49. Allen SS, Evans W, Carlisle J, Hajizadeh R, Nadaf M, Shepherd BE, et al. Superoxide dismutase A antigens derived from molecular analysis of sarcoidosis granulomas elicit systemic Th-1 immune responses. Respir Res 2008;9:36.
  50. Chen ES, Wahlstrom J, Song Z, Willett MH, Wiken M, Yung RC, et al. T cell responses to mycobacterial catalaseperoxidase profile a pathogenic antigen in systemic sarcoidosis. J Immunol 2008;181:8784-96.
  51. Pathan AA, Wilkinson KA, Klenerman P, McShane H, Davidson RN, Pasvol G, et al. Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. J Immunol 2001;167:5217-25.
  52. Oswald-Richter KA, Culver DA, Hawkins C, Hajizadeh R, Abraham S, Shepherd BE, et al. Cellular responses to mycobacterial antigens are present in bronchoalveolar lavage fluid used in the diagnosis of sarcoidosis. Infect Immun 2009;77:3740-8.
  53. Andersen P. The T cell response to secreted antigens of Mycobacterium tuberculosis. Immunobiology 1994; 191: 537-47.
  54. Horster R, Kirsten D, Gaede KI, Jafari C, Strassburg A, Greinert U, et al. Antimycobacterial immune responses in patients with pulmonary sarcoidosis. Clin Respir J 2009; 3:229-38.
  55. Oswald-Richter K, Sato H, Hajizadeh R, Shepherd BE, Sidney J, Sette A, et al. Mycobacterial ESAT-6 and katG are recognized by sarcoidosis CD4+ T cells when presented by the American sarcoidosis susceptibility allele, DRB1*1101. J Clin Immunol 2010;30:157-66.
  56. Dubaniewicz A. Mycobacteriumtuberculosis heat shock proteins and autoimmunity in sarcoidosis. Autoimmun Rev 2010;9:419-24.
  57. Lecossier D, Valeyre D, Loiseau A, Cadranel J, Tazi A, Battesti JP, et al. Antigen-induced proliferative response of lavage and blood T lymphocytes: comparison of cells from normal subjects and patients with sarcoidosis. Am Rev Respir Dis 1991;144:861-8.
  58. Nishino K, Yoshida H, Yoshida O, Watanabe M, Fukushima A, Ueno H. Analysis of responses of peripheral blood lymphocytes from sarcoidosis patients to purified protein derivative. Jpn J Ophthalmol 2000;44:165-70.
  59. Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S, et al. The immune paradox of sarcoidosis and regulatory T cells. J Expir Med 2006;203:359-70.
  60. Hudspith BN, Flint KC, Geraint-James D, Brostoff J, Johnson NM. Lack of immune deficiency in sarcoidosis: compartmentalisation of the immune response. Thorax 1987;42:250-5.
  61. Mathew S, Bauer KL, Fischoeder A, Bhardwaj N, Oliver SJ. The anergic state in sarcoidosis is associated with diminished dendritic cell function. J Immunol 2008;181:746-55.
  62. Gupta D, Chetty M, Kumar N, Aggarwal AN, Jindal SK. Anergy to tuberculin in sarcoidosis is not influenced by high prevalence of tuberculin sensitivity in the population. Sarcoidosis Vasc Diffuse Lung Dis 2003;20:40-5.
  63. Hardy AB, Varma R, Collyns T, Moffitt SJ, Mullarkey C, Watson JP. Cost-effectiveness of the NICE guidelines for screening for latent tuberculosis infection: the QuantiFERONTB Gold IGRA alone is more cost-effective for immigrants from high burden countries. Thorax 2010; 65:178-80.
  64. Winje BA, Oftung F, Korsvold GE, Mannsaker T, Ly IN, Harstad I, et al. School based screening for tuberculosis infection in Norway: comparison of positive tuberculin skin test with interferon-gamma release assay. BMC Infect Dis 2008;8:140.
  65. Lee SS, Liu YC, Huang TS, Chen YS, Tsai HC, Wann SR, et al. Comparison of the interferon-gamma release assay and the tuberculin skin test for contact investigation of tuberculosis in BCG-vaccinated health care workers. Scand J Infect Dis 2008;40:373-80.
  66. Inui N, Suda T, Chida K. Use of the QuantiFERON-TB Gold test in Japanese patients with sarcoidosis. Respir Med 2008;102:313-5.
  67. Ferrara G, Losi M, D'Amico R. Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study. Lancet 2006;367:1328-34.
  68. Gupta D, Kumar S, Verma I, Agarwal R. Interferon gamma release assay (IGRA) in sarcoidosis patients from a high tuberculosis (TB) prevalence country. Am J Respir Crit Care Med 2010;181:A2366.
  69. Levy H, Feldman C, Wadee AA, Rabson AR. Differentiation of sarcoidosis from tuberculosis using an enzyme-linked immunosorbent assay for the detection of antibodies against Mycobacterium tuberculosis. Chest 1988;94:1254-5.
  70. Moller DR. Potential etiologic agents in sarcoidosis. Proc Am Thorac Soc 2007;4:465-8.
  71. Dubaniewicz A, Kampfer S, Singh M. Serum antimycobacterial heat shock proteins antibodies in sarcoidosis and tuberculosis. Tuberculosis (Edin) 2006;86:60-7.
  72. Agarwal R, Gupta D, Srinivas R, Verma I. Role of proteins encoded by RD1 of Mycobacterium tuberculosis in differentiating tuberculosis (TB) from sarcoidosis in a high TB prevalence country. Chest 2009;136:44S-f-
  73. Saltini C, Pallante M, Puxeddu E, Contini S, Voorter CE, Drent M, et al. M. avium binding to HLA-DR expressed alleles in silico: a model of phenotypic susceptibility to sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2008;25:100-16.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.