Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Reactivation of latent tuberculosis with TNF inhibitors: critical role of the beta 2 chain of the IL-12 receptor

Cellular & Molecular Immunology volume 18, pages 1644–1651 (2021)Cite this article

Subjects

Abstract

Tumor necrosis factor (TNF) inhibitors have improved a lot the treatment of numerous diseases, with the well-known example of rheumatoid arthritis (RA). In the early 2000s, postmarketing data quickly revealed an alarming number of severe tuberculosis (TB) under such treatment. These findings were consistent with previous results in mice where TNF is essential for lymph node formation and granuloma organization. The effects of TNF inhibition on RA synovium structure are very similar to those on granuloma, with changes in cellular interactions, cytokine, and chemokine production. In addition to the role of TNF in granuloma, the interleukin (IL)-12/interferon (IFN)-γ pathway is required for an efficient host defense against TB. Primary and secondary immunodeficiencies affecting this pathway lead to severe bacillus Calmette-Guérin (BCG) reaction or full TB. Any chronic inflammation as in RA induces a systemic Th1 defect that predisposes to TB through specific downregulation of the IL-12Rß2 chain. When TNF inhibitors are initiated, this transiently increases this risk of TB, through effects on cellular interactions in a latent TB granuloma. At a later stage, when a better control disease activity is obtained, the risk of TB is reduced but not abrogated. Given the clear benefit from TNF inhibition, latent TB infection screening at baseline is essential for an optimal safety.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Furin, J., Cox, H. & Pai, M. Tuberculosis. Lancet 393, 1642–1656 (2019).

    Article  PubMed  Google Scholar 

  2. Pai, M. et al. Tuberculosis. Nat. Rev. Dis. Prim. 2, 16076 (2016).

    Article  PubMed  Google Scholar 

  3. Drain, P. K. et al. Incipient and subclinical tuberculosis: a clinical review of early stages and progression of infection. Clin. Microbiol. Rev. 31, e00021–18 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Getahun, H., Matteelli, A., Chaisson, R. E. & Raviglione, M. Latent Mycobacterium tuberculosis infection. N. Engl. J. Med. 372, 2127–2135 (2015).

    Article  CAS  PubMed  Google Scholar 

  5. Manca, C. et al. Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-alpha /beta. Proc. Natl Acad. Sci. USA 98, 5752–5757 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kaufmann, S. H. Protection against tuberculosis: cytokines, T cells, and macrophages. Ann. Rheum. Dis. 61, ii54–ii58 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Goletti, D. et al. Preventive therapy for tuberculosis in rheumatological patients undergoing therapy with biological drugs. Expert. Rev. Anti. Infect. Ther. 16, 501–512 (2018).

    Article  CAS  PubMed  Google Scholar 

  8. Keane, J. et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N. Engl. J. Med. 345, 1098–1104 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Kindler, V., Sappino, A. P., Grau, G. E., Piguet, P. F. & Vassalli, P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell 56, 731–740 (1989).

    Article  CAS  PubMed  Google Scholar 

  10. Miller, E. A. & Ernst, J. D. Illuminating the black box of TNF action in tuberculous granulomas. Immunity 29, 175–177 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Flynn, J. L. et al. Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2, 561–572 (1995).

    Article  CAS  PubMed  Google Scholar 

  12. Akdis, M. et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor beta, and TNF-alpha: Receptors, functions, and roles in diseases. J. Allergy Clin. Immunol. 138, 984–1010 (2016).

    Article  CAS  PubMed  Google Scholar 

  13. Noack, M. & Miossec, P. Selected cytokine pathways in rheumatoid arthritis. Semin. Immunopathol. 39, 365–383 (2017).

    Article  CAS  PubMed  Google Scholar 

  14. Alexopoulou, L., Pasparakis, M. & Kollias, G. A murine transmembrane tumor necrosis factor (TNF) transgene induces arthritis by cooperative p55/p75 TNF receptor signaling. Eur. J. Immunol. 27, 2588–2592 (1997).

    Article  CAS  PubMed  Google Scholar 

  15. Brennan, F. M., Chantry, D., Jackson, A., Maini, R. & Feldmann, M. Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 2, 244–247 (1989).

    Article  CAS  PubMed  Google Scholar 

  16. Kalliolias, G. D. & Ivashkiv, L. B. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat. Rev. Rheumatol. 12, 49–62 (2016).

    Article  CAS  PubMed  Google Scholar 

  17. Kawashima, M. & Miossec, P. Decreased response to IL-12 and IL-18 of peripheral blood cells in rheumatoid arthritis. Arthritis Res. Ther. 6, R39–R45 (2004).

    Article  CAS  PubMed  Google Scholar 

  18. Minozzi, S. et al. Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis. Expert Opin. Drug Saf. 15, 11–34 (2016).

    Article  CAS  PubMed  Google Scholar 

  19. Bustamante, J., Boisson-Dupuis, S., Abel, L. & Casanova, J. L. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-gamma immunity. Semin. Immunol. 26, 454–470 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Salmon, D. GTI and AFSSAPS. Groupe Tuberculose et infliximab. Agence Française de Sécurité Sanitaire de Produits de Santé. Recommendations about the prevention and management of tuberculosis in patients taking infliximab. Jt. Bone Spine 69, 170–172 (2002).

    Article  CAS  Google Scholar 

  21. Furst, D. E., Wallis, R., Broder, M. & Beenhouwer, D. O. Tumor necrosis factor antagonists: different kinetics and/or mechanisms of action may explain differences in the risk for developing granulomatous infection. Semin. Arthritis Rheum. 36, 159–167 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Botsios, C. Safety of tumour necrosis factor and interleukin-1 blocking agents in rheumatic diseases. Autoimmun. Rev. 4, 162–170 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. Maini, R. et al. et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 354, 1932–1939 (1999).

    Article  CAS  PubMed  Google Scholar 

  24. Furst, D. E., Cush, J., Kaufmann, S., Siegel, J. & Kurth, R. Preliminary guidelines for diagnosing and treating tuberculosis in patients with rheumatoid arthritis in immunosuppressive trials or being treated with biological agents. Ann. Rheum. Dis. 61, ii62–ii63 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gomez-Reino, J. J. et al. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum. 48, 2122–2127 (2003).

    Article  CAS  PubMed  Google Scholar 

  26. Murdaca, G. et al. Infection risk associated with anti-TNF-alpha agents: a review. Expert Opin. Drug Saf. 14, 571–582 (2015).

    Article  CAS  PubMed  Google Scholar 

  27. Redelman-Sidi, G. & Sepkowitz, K. A. IFN-gamma release assays in the diagnosis of latent tuberculosis infection among immunocompromised adults. Am. J. Respir. Crit. Care Med. 188, 422–431 (2013).

    Article  CAS  PubMed  Google Scholar 

  28. Cantini, F. et al. Guidance for the management of patients with latent tuberculosis infection requiring biologic therapy in rheumatology and dermatology clinical practice. Autoimmun. Rev. 14, 503–509 (2015).

    Article  PubMed  Google Scholar 

  29. Jauregui-Amezaga, A. et al. Risk of developing tuberculosis under anti-TNF treatment despite latent infection screening. J. Crohns Colitis 7, 208–212 (2013).

    Article  PubMed  Google Scholar 

  30. Lee, E. H. et al. Active tuberculosis incidence and characteristics in patients treated with tumor necrosis factor antagonists according to latent tuberculosis Infection. Sci. Rep. 7, 6473 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sartori, N. S., Picon, P., Papke, A., Neyeloff, J. L. & da Silva Chakr, R. M. A population-based study of tuberculosis incidence among rheumatic disease patients under anti-TNF treatment. PLoS One 14, e0224963 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chen, D. Y. et al. Biphasic emergence of active tuberculosis in rheumatoid arthritis patients receiving TNFalpha inhibitors: the utility of IFNgamma assay. Ann. Rheum. Dis. 71, 231–237 (2012).

    Article  CAS  PubMed  Google Scholar 

  33. Soare, A. et al. Risk of active tuberculosis in patients with inflammatory arthritis receiving TNF inhibitors: a look beyond the baseline tuberculosis screening protocol. Clin. Rheumatol. 37, 2391–2397 (2018).

    Article  PubMed  Google Scholar 

  34. Dixon, W. G. et al. Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann. Rheum. Dis. 69, 522–528 (2010).

    Article  CAS  PubMed  Google Scholar 

  35. Sartori, N. S., de Andrade, N. P. B. & da Silva Chakr, R. M. Incidence of tuberculosis in patients receiving anti-TNF therapy for rheumatic diseases: a systematic review. Clin. Rheumatol. 39, 1439–1447 (2020).

    Article  PubMed  Google Scholar 

  36. Kaufmann, S. H. How can immunology contribute to the control of tuberculosis? Nat. Rev. Immunol. 1, 20–30 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. Pasparakis, M., Alexopoulou, L., Episkopou, V. & Kollias, G. Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J. Exp. Med 184, 1397–1411 (1996).

    Article  CAS  PubMed  Google Scholar 

  38. Tracey, D., Klareskog, L., Sasso, E. H., Salfeld, J. G. & Tak, P. P. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol. Ther. 117, 244–279 (2008).

    Article  CAS  PubMed  Google Scholar 

  39. Gommerman, J. L. & Browning, J. L. Lymphotoxin/light, lymphoid microenvironments and autoimmune disease. Nat. Rev. Immunol. 3, 642–655 (2003).

    Article  CAS  PubMed  Google Scholar 

  40. Aloisi, F. & Pujol-Borrell, R. Lymphoid neogenesis in chronic inflammatory diseases. Nat. Rev. Immunol. 6, 205–217 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Miossec, P. & Kolls, J. K. Targeting IL-17 and TH17 cells in chronic inflammation. Nat. Rev. Drug. Discov. 11, 763–776 (2012).

    Article  CAS  PubMed  Google Scholar 

  42. Matsumoto, M., Fu, Y. X., Molina, H. & Chaplin, D. D. Lymphotoxin-alpha-deficient and TNF receptor-I-deficient mice define developmental and functional characteristics of germinal centers. Immunol. Rev. 156, 137–144 (1997).

    Article  CAS  PubMed  Google Scholar 

  43. van de Pavert, S. A. & Mebius, R. E. New insights into the development of lymphoid tissues. Nat. Rev. Immunol. 10, 664–674 (2010).

    Article  PubMed  Google Scholar 

  44. Matsumoto, M. et al. Role of lymphotoxin and the type I TNF receptor in the formation of germinal centers. Science 271, 1289–1291 (1996).

    Article  CAS  PubMed  Google Scholar 

  45. Ramakrishnan, L. Revisiting the role of the granuloma in tuberculosis. Nat. Rev. Immunol. 12, 352–366 (2012).

    Article  CAS  PubMed  Google Scholar 

  46. Senaldi, G. et al. Corynebacterium parvum- and Mycobacterium bovis bacillus Calmette-Guerin-induced granuloma formation is inhibited in TNF receptor I (TNF-RI) knockout mice and by treatment with soluble TNF-RI. J. Immunol. 157, 5022–5026 (1996).

    Article  CAS  PubMed  Google Scholar 

  47. Bean, A. G. et al. Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin. J. Immunol. 162, 3504–3511 (1999).

    Article  CAS  PubMed  Google Scholar 

  48. Roach, D. R. et al. TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection. J. Immunol. 168, 4620–4627 (2002).

    Article  CAS  PubMed  Google Scholar 

  49. Arbués, A. et al. TNF-α antagonists differentially induce TGF-β1-dependent resuscitation of dormant-like Mycobacterium tuberculosis. PLoS Pathog. 16, e1008312 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Corsiero, E. et al. Role of lymphoid chemokines in the development of functional ectopic lymphoid structures in rheumatic autoimmune diseases. Immunol. Lett. 145, 62–67 (2012).

    Article  CAS  PubMed  Google Scholar 

  51. Weyand, C. M. & Goronzy, J. J. Ectopic germinal center formation in rheumatoid synovitis. Ann. N. Y Acad. Sci. 987, 140–149 (2003).

    Article  CAS  PubMed  Google Scholar 

  52. Braun, A., Takemura, S., Vallejo, A. N., Goronzy, J. J. & Weyand, C. M. Lymphotoxin beta-mediated stimulation of synoviocytes in rheumatoid arthritis. Arthritis Rheum. 50, 2140–2150 (2004).

    Article  CAS  PubMed  Google Scholar 

  53. Tak, P. P. et al. Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity. Arthritis Rheum. 40, 217–225 (1997).

    Article  CAS  PubMed  Google Scholar 

  54. Tak, P. P. et al. Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis. Arthritis Rheum. 39, 1077–1081 (1996).

    Article  CAS  PubMed  Google Scholar 

  55. Catrina, A. I. et al. Evidence that anti-tumor necrosis factor therapy with both etanercept and infliximab induces apoptosis in macrophages, but not lymphocytes, in rheumatoid arthritis joints: extended report. Arthritis Rheum. 52, 61–72 (2005).

  56. Smeets, T. J., Kraan, M. C., van Loon, M. E. & Tak, P. P. Tumor necrosis factor alpha blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue. Arthritis Rheum. 48, 2155–2162 (2003).

    Article  CAS  PubMed  Google Scholar 

  57. Klaasen, R. et al. The relationship between synovial lymphocyte aggregates and the clinical response to infliximab in rheumatoid arthritis: a prospective study. Arthritis Rheum. 60, 3217–3224 (2009).

    Article  CAS  PubMed  Google Scholar 

  58. Cantaert, T. et al. B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis. J. Immunol. 181, 785–794 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. Salinas, G. F. et al. Anti-TNF treatment blocks the induction of T cell-dependent humoral responses. Ann. Rheum. Dis. 72, 1037–1043 (2013).

    Article  CAS  PubMed  Google Scholar 

  60. Page, G. & Miossec, P. Paired synovium and lymph nodes from rheumatoid arthritis patients differ in dendritic cell and chemokine expression. J. Pathol. 204, 28–38 (2004).

    Article  CAS  PubMed  Google Scholar 

  61. Watford, W. T. et al. Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Immunol. Rev. 202, 139–156 (2004).

    Article  CAS  PubMed  Google Scholar 

  62. Trinchieri, G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat. Rev. Immunol. 3, 133–146 (2003).

    Article  CAS  PubMed  Google Scholar 

  63. Parham, C. et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J. Immunol. 168, 5699–5708 (2002).

    Article  CAS  PubMed  Google Scholar 

  64. Oppmann, B. et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13, 715–725 (2000).

    Article  CAS  PubMed  Google Scholar 

  65. Teng, M. W. et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat. Med. 21, 719–729 (2015).

    Article  CAS  PubMed  Google Scholar 

  66. Rogge, L. et al. Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J. Exp. Med. 185, 825–831 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Szabo, S. J., Dighe, A. S., Gubler, U. & Murphy, K. M. Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J. Exp. Med. 185, 817–824 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Boraschi, D. & Dinarello, C. A. IL-18 in autoimmunity: review. Eur. Cytokine Netw. 17, 224–252 (2006).

    CAS  PubMed  Google Scholar 

  69. Okamura, H., Tsutsui, H., Kashiwamura, S., Yoshimoto, T. & Nakanishi, K. Interleukin-18: a novel cytokine that augments both innate and acquired immunity. Adv. Immunol. 70, 281–312 (1998).

    Article  CAS  PubMed  Google Scholar 

  70. Nakahira, M. et al. Synergy of IL-12 and IL-18 for IFN-gamma gene expression: IL-12-induced STAT4 contributes to IFN-gamma promoter activation by up-regulating the binding activity of IL-18-induced activator protein 1. J. Immunol. 168, 1146–1153 (2002).

    Article  CAS  PubMed  Google Scholar 

  71. Dinarello, C. A., Novick, D., Kim, S. & Kaplanski, G. Interleukin-18 and IL-18 binding protein. Front. Immunol. 4, 289 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Toh, M. L. et al. IL-17 inhibits human Th1 differentiation through IL-12R beta 2 downregulation. Cytokine 48, 226–230 (2009).

    Article  CAS  PubMed  Google Scholar 

  73. Cruz, A. et al. Cutting edge: IFN-gamma regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection. J. Immunol. 177, 1416–1420 (2006).

    Article  CAS  PubMed  Google Scholar 

  74. Toh, M. L., Kawashima, M., Hot, A., Miossec, P. & Miossec, P. Role of IL-17 in the Th1 systemic defects in rheumatoid arthritis through selective IL-12Rbeta2 inhibition. Ann. Rheum. Dis. 69, 1562–1567 (2010).

    Article  CAS  PubMed  Google Scholar 

  75. Schulz, O. et al. CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal. Immunity 13, 453–462 (2000).

    Article  CAS  PubMed  Google Scholar 

  76. Altare, F. et al. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280, 1432–1435 (1998).

    Article  CAS  PubMed  Google Scholar 

  77. Altare, F. et al. Inherited interleukin 12 deficiency in a child with bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J. Clin. Investig. 102, 2035–2040 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. de Jong, R. et al. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science 280, 1435–1438 (1998).

    Article  PubMed  Google Scholar 

  79. Pai, M. et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin. Microbiol. Rev. 27, 3–20 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Chang, B. et al. Interferon-gamma release assay in the diagnosis of latent tuberculosis infection in arthritis patients treated with tumor necrosis factor antagonists in Korea. Clin. Rheumatol. 30, 1535–1541 (2011).

    Article  PubMed  Google Scholar 

  81. Meier, N. R. et al. Risk factors for indeterminate interferon-gamma release assay for the diagnosis of tuberculosis in children-a systematic review and meta-analysis. Front. Pediatr. 7, 208 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Boisson-Dupuis, S. et al. IL-12Rbeta1 deficiency in two of fifty children with severe tuberculosis from Iran, Morocco, and Turkey. PLoS One 6, e18524 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Boisson-Dupuis, S. et al. Inherited and acquired immunodeficiencies underlying tuberculosis in childhood. Immunol. Rev. 264, 103–120 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Lotte, A. et al. BCG complications. Estimates of the risks among vaccinated subjects and statistical analysis of their main characteristics. Adv. Tuberc. Res. 21, 107–193 (1984).

    CAS  PubMed  Google Scholar 

  85. Emile, J. F. et al. Correlation of granuloma structure with clinical outcome defines two types of idiopathic disseminated BCG infection. J. Pathol. 181, 25–30 (1997).

    Article  CAS  PubMed  Google Scholar 

  86. Jouanguy, E. et al. Interferon-gamma-receptor deficiency in an infant with fatal bacille Calmette-Guerin infection. N. Engl. J. Med. 335, 1956–1961 (1996).

    Article  CAS  PubMed  Google Scholar 

  87. Mackay, A. et al. Fatal disseminated BCG infection in an 18-year-old boy. Lancet 2, 1332–1334 (1980).

    Article  CAS  PubMed  Google Scholar 

  88. Rosain, J. et al. Mendelian susceptibility to mycobacterial disease: 2014-2018 update. Immunol. Cell. Biol. 97, 360–367 (2019).

    Article  PubMed  Google Scholar 

  89. Newport, M. J. et al. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N. Engl. J. Med. 335, 1941–1949 (1996).

    Article  CAS  PubMed  Google Scholar 

  90. Altare, F. et al. A causative relationship between mutant IFNgR1 alleles and impaired cellular response to IFNgamma in a compound heterozygous child. Am. J. Hum. Genet. 62, 723–726 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kilic, S. S. et al. Severe disseminated mycobacterial infection in a boy with a novel mutation leading to IFN-gammaR2 deficiency. J. Infect. 65, 568–572 (2012).

    Article  PubMed  Google Scholar 

  92. Sarrafzadeh, S. A. et al. Molecular, immunological, and clinical features of 16 Iranian patients with mendelian susceptibility to mycobacterial disease. J. Clin. Immunol. 39, 287–297 (2019).

    Article  CAS  PubMed  Google Scholar 

  93. de Beaucoudrey, L. et al. Revisiting human IL-12Rbeta1 deficiency: a survey of 141 patients from 30 countries. Medicine 89, 381–402 (2010).

    Article  PubMed  Google Scholar 

  94. Prando, C. et al. Inherited IL-12p40 deficiency: genetic, immunologic, and clinical features of 49 patients from 30 kindreds. Medicine 92, 109–122 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Kawashima, M. & Miossec, P. mRNA quantification of T-bet, GATA-3, IFN-gamma, and IL-4 shows a defective Th1 immune response in the peripheral blood from rheumatoid arthritis patients: link with disease activity. J. Clin. Immunol. 25, 209–214 (2005).

    Article  CAS  PubMed  Google Scholar 

  96. Geremia, A., Biancheri, P., Allan, P., Corazza, G. R. & Di Sabatino, A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun. Rev. 13, 3–10 (2014).

    Article  CAS  PubMed  Google Scholar 

  97. Raphael, I., Nalawade, S., Eagar, T. N. & Forsthuber, T. G. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 74, 5–17 (2015).

    Article  CAS  PubMed  Google Scholar 

  98. Yun, J. E. et al. The incidence and clinical characteristics of Mycobacterium tuberculosis infection among systemic lupus erythematosus and rheumatoid arthritis patients in Korea. Clin. Exp. Rheumatol. 20, 127–132 (2002).

    CAS  PubMed  Google Scholar 

  99. Allali, F., Rkain, H., Faik, A., El Hassani, S. & Hajjaj-Hassouni, N. Prevalence and clinical characteristics of tuberculosis in rheumatoid arthritis patients. Clin. Rheumatol. 24, 656–657 (2005).

    Article  PubMed  Google Scholar 

  100. Kawashima, M. & Miossec, P. Effect of treatment of rheumatoid arthritis with infliximab on IFN gamma, IL4, T-bet, and GATA-3 expression: link with improvement of systemic inflammation and disease activity. Ann. Rheum. Dis. 64, 415–418 (2005).

    Article  CAS  PubMed  Google Scholar 

  101. Ayelign, B., Negash, M., Genetu, M., Wondmagegn, T. & Shibabaw, T. Immunological impacts of diabetes on the susceptibility of mycobacterium tuberculosis. J. Immunol. Res. 2019, 6196532 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Kosmaczewska, A. et al. Patients with the most advanced rheumatoid arthritis remain with Th1 systemic defects after TNF inhibitors treatment despite clinical improvement. Rheumatol. Int. 34, 243–253 (2014).

    Article  CAS  PubMed  Google Scholar 

  103. Miossec, P. Local and systemic effects of IL-17 in joint inflammation: a historical perspective from discovery to targeting. Cell. Mol. Immunol. 18, 1–6 (2021).

    Article  Google Scholar 

  104. Gopal, R. et al. Unexpected role for IL-17 in protective immunity against hypervirulent Mycobacterium tuberculosis HN878 infection. PLoS Pathog. 10, e1004099 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Torrado, E. & Cooper, A. M. IL-17 and Th17 cells in tuberculosis. Cytokine Growth Factor Rev. 21, 455–462 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Nogueira, M., Warren, R. B. & Torres, T. Risk of tuberculosis reactivation with interleukin (IL)-17 and IL-23 inhibitors in psoriasis - time for a paradigm change. J. Eur. Acad. Dermatol. Venereol. 35, 824–834 (2021).

    Article  CAS  PubMed  Google Scholar 

  107. Fowler, E., Ghamrawi, R. I., Ghiam, N., Liao, W. & Wu, J. J. Risk of tuberculosis reactivation during interleukin-17 inhibitor therapy for psoriasis: a systematic review. J. Eur. Acad. Dermatol. Venereol. 34, 1449–1456 (2020).

    Article  CAS  PubMed  Google Scholar 

  108. Martin, D. A. et al. A phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and early clinical response of brodalumab, a human anti-IL-17R antibody, in methotrexate-resistant rheumatoid arthritis. Arthritis Res. Ther. 15, R164 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Blanco, F. J. et al. Secukinumab in active rheumatoid arthritis: a phase III randomized, double-blind, active comparator- and placebo-controlled study. Arthritis Rheumatol. 69, 1144–1153 (2017).

    Article  CAS  PubMed  Google Scholar 

  110. Genovese, M. C. et al. Safety and efficacy of open-label subcutaneous ixekizumab treatment for 48 weeks in a phase II study in biologic-naive and TNF-IR patients with rheumatoid arthritis. J. Rheumatol. 43, 289–297 (2016).

    Article  CAS  PubMed  Google Scholar 

  111. Elewski, B. E. et al. Association of secukinumab treatment with tuberculosis reactivation in patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis. JAMA Dermatol. 157, 43–51 (2021).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

M.R. is supported by the Ecole de l’Inserm Liliane Bettencourt. P.M. is a senior member of the Institut Universitaire de France. His laboratory is supported in part by the IHU OPERA. This review is based on a talk given during the 17th International Congress of Immunology that took place on 19–23 October 2019 in Beijing, China.

Author information

Authors and Affiliations

  1. Department of Clinical Immunology and Rheumatology, and immunogenomics and inflammation research unit, University of Lyon, Hôpital Edouard Herriot, Lyon, France

    Marie Robert & Pierre Miossec

Authors
  1. Marie Robert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pierre Miossec
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.R.: writing and figures. P.M.: concept and proof reading.

Corresponding author

Correspondence to Pierre Miossec.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Robert, M., Miossec, P. Reactivation of latent tuberculosis with TNF inhibitors: critical role of the beta 2 chain of the IL-12 receptor. Cell Mol Immunol 18, 1644–1651 (2021). https://doi.org/10.1038/s41423-021-00694-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41423-021-00694-9

Keywords

This article is cited by

Search

Advanced search

Quick links