Mendelian susceptibility to mycobacterial disease: Clinical and immunological findings of patients suspected for IL12Rβ1 deficiency
Main Article Content
Keywords
Primary immunodeficiency, Mendelian susceptibility to mycobacterial diseases, Vaccination side effects, IL12R1
Abstract
Background: Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by increased susceptibility to weakly virulent mycobacteria (Bacillus Calmette-Guérin [BCG] vaccines and environmental mycobacteria), Mycobacterium tuberculosis, Candida spp. and Salmonella spp. The aim of this study is to evaluate clinical features and immunological findings of MSMD patients with interleukin 12 receptor beta 1 (IL12Rβ1) deficiency.
Methods: Among 117 screened patients with BCG infection following vaccination, 23 suspected MSMD subjects were recruited to this study by the exclusion of severe combined immunodeficiencies and chronic granulomatous diseases. Flow cytometric assessment for surface expression of IL12Rβ1 was performed. Moreover, the clinical and immunological data from the patients was evaluated.
Results: A significant decrease (less than 1%) in the surface expression of IL12Rβ1 was reported in six cases which showed a significant increase in the count of lymphocytes (p = 0.009) and CD8+ T cells (p = 0.008) as compared to MSMD subjects with normal expression of surface IL12Rβ1. The frequency of disseminated BCGosis (50% vs. 20%, p = 0.29), recurrent infection (83.3% vs. 40%, p = 0.14) and salmonellosis (33.3% vs. 0.0%, p = 0.07) was higher in IL12Rβ1 deficient subjects than IL12Rβ1 sufficient individuals.
Conclusion: MSMD patients with childhood-onset of mycobacteriosis (mostly after BCG vaccination) and recurrent salmonellosis could be evaluated for IL12Rβ1 expression with flow cytometry for punctual diagnosis.
References
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29. de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M, et al. Mutations in STAT3 and IL12R1 impair the development of human IL-17-producing T cells. J Exp Med. 2008;205:1543-50.
30. Filipe-Santos O, Bustamante J, Chapgier A, Vogt G, de Beaucoudrey L, Feinberg J, et al. Inborn errors of IL-12/23- and IFN-gamma mediated immunity: molecular, cellular, and clinical features. Semin Immunol. 2006;18:347-61.
31. Wei P, Kou W, Sun R, Hu GH, Hu D, Feng J, et al. Association study between interleukin-12 receptor beta1/beta2 genes and allergic rhinitis in the Chinese Han population. Eur Arch Otorhinolaryngol. 2015;272:889-93.
32. Takahashi N, Akahoshi M, Matsuda A, Ebe K, Inomata N, Obara K, et al. Association of the IL12R1 promoter polymorphisms with increased risk of atopic dermatitis and other allergic phenotypes. Hum Mol Genet. 2005;14:3149-59.
33. Robinson RT, Khader SA, Martino CA, Fountain JJ, TeixeiraCoelho M, Pearl JE, et al. Mycobacterium tuberculosis infection induces IL12R1 splicing to generate a novel IL12Rbeta1 isoform that enhances DC migration. J Exp Med. 2010;207:591-605.
34. de Jong R, Altare F, Haagen IA, Elferink DG, Boer T, van Breda Vriesman PJ, et al. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science. 1998;280:1435-8.
35. Ottenhoff TH, de Boer T, Verhagen CE, Verreck FA, van Dissel JT. Human deficiencies in type 1 cytokine receptors reveal the essential role of type 1 cytokines in immunity to intracellular bacteria. Microbes Infect. 2000;2:1559-66.
36. Orange JS. Natural killer cell deficiency. J Allergy Clin Immunol. 2013;132:515-25 [quiz 26].
37. Van Acker HH, Capsomidis A, Smits EL, Van Tendeloo VF. CD56 in the immune system: more than a marker for cytotoxicity? Front Immunol. 2017;8:892.
38. Voss M, Bryceson YT. Natural killer cell biology illuminated by primary immunodeficiency syndromes in humans. Clin Immunol. 2017;177:29-42.
39. Altare F, Jouanguy E, Lamhamedi S, Doffinger R, Fischer A, Casanova JL. Mendelian susceptibility to mycobacterial infection in man. Curr Opin Immunol. 1998;10:413-7.
40. Wang L-H, Yen C-L, Chang T-C, Liu C-C, Shieh C-C. Impact of molecular diagnosis on treating Mendelian susceptibility to mycobacterial diseases. J Microbiol Immunol Infect. 2012;45:411-7.
2. Bustamante J, Boisson-Dupuis S, Abel L, Casanova JL. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-gamma immunity. Semin Immunol. 2014;26:454-70.
3. Al-Muhsen S, Casanova JL. The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. J Allergy Clin Immunol. 2008;122:1043-51 [quiz 52-3].
4. Guia S, Cognet C, de Beaucoudrey L, Tessmer MS, Jouanguy E, Berger C, et al. A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo. Blood. 2008;111:5008-16.
5. Norouzi S, Aghamohammadi A, Mamishi S, Rosenzweig SD, Rezaei N. Bacillus Calmette-Guerin (BCG) complications associated with primary immunodeficiency diseases. J Infect. 2012;64:543-54.
6. Sharifi Asadi P, Aghamohammadi A, Mahmoudi S, Pourakbari B, Saboui F, Mamishi S. Clinical, laboratory and imaging findings of the patients with disseminated bacilli Calmette-Guerin disease. Allergol Immunopathol. 2015;43:254-8.
7. Boisson-Dupuis S, Bustamante J, El-Baghdadi J, Camcioglu Y, Parvaneh N, El Azbaoui S, et al. Inherited and acquired immunodeficiencies underlying tuberculosis in childhood. Immunol Rev. 2015;264:103-20.
8. Aghamohammadi A, Mohammadinejad P, Abolhassani H, Mirminachi B, Movahedi M, Gharagozlou M, et al. Primary immunodeficiency disorders in Iran: update and new insights from the third report of the national registry. J Clin Immunol. 2014;34:478-90.
9. Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35:696-726.
10. Dorman SE, Holland SM. Interferon-gamma and interleukin-12 pathway defects and human disease. Cytokine Growth Factor Rev. 2000;11:321-33.
11. Mendez-Samperio P. Role of interleukin-12 family cytokines in the cellular response to mycobacterial disease. Int J Infect Dis. 2010;14:e366-71.
12. Gaffen SL, Jain R, Garg AV, Cua DJ. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014;14:585-600.
13. Blauvelt A, Lebwohl MG, Bissonnette R. IL-23/IL-17A dysfunction phenotypes inform possible clinical effects from anti-IL-17A therapies. J Invest Dermatol. 2015;135:1946-53.
14. Lichtenauer-Kaligis EG, de Boer T, Verreck FA, van Voorden S, Hoeve MA, van de Vosse E, et al. Severe Mycobacterium bovis BCG infections in a large series of novel IL-12 receptor beta1 deficient patients and evidence for the existence of partial IL-12 receptor beta1 deficiency. Eur J Immunol. 2003;33:59-69.
15. Tan C, Cagdas-Ayvaz D, Metin A, Keskin O, Tezcan I, Sanal O. Clinical and genetic features of IL12R1 deficiency: single center experience of 18 patients. Turk J Pediatr. 2016;58: 356-61.
16. Ramirez-Alejo N, Blancas-Galicia L, Yamazaki-Nakashimada M, Garcia-Rodriguez SE, Rivas-Larrauri F, Paolo-Cienfuegos DP, et al. Molecular analysis for patients with IL-12 receptor beta1 deficiency. Clin Genet. 2014;86:161-6.
17. van de Vosse E, de Paus RA, van Dissel JT, Ottenhoff TH. Molecular complementation of IL-12Rbeta1 deficiency reveals functional differences between IL-12Rbeta1 alleles including partial IL-12Rbeta1 deficiency. Hum Mol Genet. 2005;14:3847-55.
18. de Beaucoudrey L, Samarina A, Bustamante J, Cobat A, BoissonDupuis S, Feinberg J, et al. Revisiting human IL-12Rbeta1 deficiency: a survey of 141 patients from 30 countries. Medicine. 2010;89:381-402.
19. Staretz-Haham O, Melamed R, Lifshitz M, Porat N, Fieschi C, Casanova JL, et al. Interleukin-12 receptor beta1 deficiency presenting as recurrent Salmonella infection: an official publication of the Infectious Diseases Society of America. Clin Infect Dis. 2003;37:137-40.
20. Fieschi C, Bosticardo M, de Beaucoudrey L, Boisson-Dupuis S, Feinberg J, Santos OF, et al. A novel form of complete IL12/IL-23 receptor beta1 deficiency with cell surface-expressed nonfunctional receptors. Blood. 2004;104:2095-101.
21. Potjewijd J, de Paus RA, van Wengen A, Damoiseaux J, Verbon A, van de Vosse E. Disseminated Mycobacterium genavense infection in a patient with a novel partial interleukin-12/23 receptor beta1 deficiency. Clin Immunol. 2012;144:83-6.
22. Kano S, Sato K, Morishita Y, Vollstedt S, Kim S, Bishop K, et al. The contribution of transcription factor IRF1 to the interferongamma interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells. Nat Immunol. 2008;9:34-41.
23. Toyoda H, Ido M, Hayashi T, Gabazza EC, Suzuki K, Bu J, et al. Impairment of IL-12-dependent STAT4 nuclear translocation in a patient with recurrent Mycobacterium avium infection. J Immunol. 2004;172:3905-12.
24. Robinson RT. IL12Rbeta1: the cytokine receptor that we used to know. Cytokine. 2015;71:348-59.
25. Fieschi C, Dupuis S, Catherinot E, Feinberg J, Bustamante J, Breiman A, et al. Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications. J Exp Med. 2003;197:527-35.
26. Doffinger R, Dupuis S, Picard C, Fieschi C, Feinberg J, BarcenasMorales G, et al. Inherited disorders of IL-12- and IFNgammamediated immunity: a molecular genetics update. Mol Immunol. 2002;38:903-9.
27. Lee SB, Kim BC, Jin SH, Park YG, Kim SK, Kang TJ, et al. Missense mutations of the interleukin-12 receptor beta 1(IL12R1) and interferon-gamma receptor 1 (IFNGR1) genes are not associated with susceptibility to lepromatous leprosy in Korea. Immunogenetics. 2003;55:177-81.
28. Hoeve MA, de Boer T, Langenberg DM, Sanal O, Verreck FA, Ottenhoff TH. IL-12 receptor deficiency revisited: IL-23- mediated signaling is also impaired in human genetic IL-12 receptor beta1 deficiency. Eur J Immunol. 2003;33:3393-7.
29. de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M, et al. Mutations in STAT3 and IL12R1 impair the development of human IL-17-producing T cells. J Exp Med. 2008;205:1543-50.
30. Filipe-Santos O, Bustamante J, Chapgier A, Vogt G, de Beaucoudrey L, Feinberg J, et al. Inborn errors of IL-12/23- and IFN-gamma mediated immunity: molecular, cellular, and clinical features. Semin Immunol. 2006;18:347-61.
31. Wei P, Kou W, Sun R, Hu GH, Hu D, Feng J, et al. Association study between interleukin-12 receptor beta1/beta2 genes and allergic rhinitis in the Chinese Han population. Eur Arch Otorhinolaryngol. 2015;272:889-93.
32. Takahashi N, Akahoshi M, Matsuda A, Ebe K, Inomata N, Obara K, et al. Association of the IL12R1 promoter polymorphisms with increased risk of atopic dermatitis and other allergic phenotypes. Hum Mol Genet. 2005;14:3149-59.
33. Robinson RT, Khader SA, Martino CA, Fountain JJ, TeixeiraCoelho M, Pearl JE, et al. Mycobacterium tuberculosis infection induces IL12R1 splicing to generate a novel IL12Rbeta1 isoform that enhances DC migration. J Exp Med. 2010;207:591-605.
34. de Jong R, Altare F, Haagen IA, Elferink DG, Boer T, van Breda Vriesman PJ, et al. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science. 1998;280:1435-8.
35. Ottenhoff TH, de Boer T, Verhagen CE, Verreck FA, van Dissel JT. Human deficiencies in type 1 cytokine receptors reveal the essential role of type 1 cytokines in immunity to intracellular bacteria. Microbes Infect. 2000;2:1559-66.
36. Orange JS. Natural killer cell deficiency. J Allergy Clin Immunol. 2013;132:515-25 [quiz 26].
37. Van Acker HH, Capsomidis A, Smits EL, Van Tendeloo VF. CD56 in the immune system: more than a marker for cytotoxicity? Front Immunol. 2017;8:892.
38. Voss M, Bryceson YT. Natural killer cell biology illuminated by primary immunodeficiency syndromes in humans. Clin Immunol. 2017;177:29-42.
39. Altare F, Jouanguy E, Lamhamedi S, Doffinger R, Fischer A, Casanova JL. Mendelian susceptibility to mycobacterial infection in man. Curr Opin Immunol. 1998;10:413-7.
40. Wang L-H, Yen C-L, Chang T-C, Liu C-C, Shieh C-C. Impact of molecular diagnosis on treating Mendelian susceptibility to mycobacterial diseases. J Microbiol Immunol Infect. 2012;45:411-7.
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Oct 15, 2019
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Moradi, L., Cheraghi , T., Yazdani, R., Azizi, G., Rasouli, S., Zavareh, F., Parvaneh, L., Parvaneh, N., Sohani, M., Delavari, S., Abolhassani, H., Rezaei, N., & Aghamohammadi, A. (2019). Mendelian susceptibility to mycobacterial disease: Clinical and immunological findings of patients suspected for IL12Rβ1 deficiency. Allergologia Et Immunopathologia, 47(5), 491-498. https://www.all-imm.com/index.php/aei/article/view/291
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Moradi, L., Cheraghi , T., Yazdani, R., Azizi, G., Rasouli, S., Zavareh, F., Parvaneh, L., Parvaneh, N., Sohani, M., Delavari, S., Abolhassani, H., Rezaei, N., & Aghamohammadi, A. (2019). Mendelian susceptibility to mycobacterial disease: Clinical and immunological findings of patients suspected for IL12Rβ1 deficiency. Allergologia Et Immunopathologia, 47(5), 491-498. https://www.all-imm.com/index.php/aei/article/view/291