Congenital IL-12R1β Receptor Deficiency and Thrombophilia in a Girl Homozygous for an IL12RB1 Mutation and Compound Heterozygous for MTFHR Mutations: A Case Report and Literature Review

Overview

Journal Eur J Microbiol Immunol (Bp)

Publisher Akademiai Kiado

Specialty Allergy & Immunology

Date 2014 Mar 29

PMID 24678409

Citations 6

Authors

H H Akar

M Kose

O Ceylan

T Patiroglu

J Bustamante

J L Casanova

B N Akyildiz

S Doganay

Affiliations

Soon will be listed here.

Abstract

Interleukin-12 (IL-12) plays an important role in the production of interferon gamma from T cells and natural killer cells and is essential for protection against intra-macrophagic pathogens such as Mycobacterium and Salmonella. Here, we describe a 16-year-old girl with homozygous mutation in exon 12 of the IL12RB1 gene, which causes complete IL-12Rβ1 deficiency in association with heterozygous mutation (C677T and A1298C) in the methylenetetrahydrofolate reductase gene. She presented with disseminated Mycobacterium tuberculosis complex infection, retroperitoneal fungal abscess and also thrombosis in the superior mesenteric-portal vein junction. This is the first case report of a primary immunodeficiency associated with a genetically determined venous thrombosis.

Citing Articles

Discovering the link between IL12RB1 gene polymorphisms and tuberculosis susceptibility: a comprehensive meta-analysis.

Huang J, He Q, Huang L, Liu L, Yang P, Chen M Front Public Health. 2024; 12:1249880.

PMID: 38317798 PMC: 10839023. DOI: 10.3389/fpubh.2024.1249880.

Disseminated multidrug-resistant tuberculosis and SARS-CoV-2 co-infection in a child with IL-12Rβ1 deficiency.

San-Juan D, Perez Melgoza M, Zavaleta Martinez O, Lopez R, Salazar A, Bastida J Indian J Tuberc. 2023; 70(1):129-133.

PMID: 36740310 PMC: 9055382. DOI: 10.1016/j.ijtb.2022.04.008.

Role of Genetic Polymorphisms in in Chronic Obstructive Pulmonary Disease.

Fu Y, Liu L, Wu H Int J Chron Obstruct Pulmon Dis. 2022; 17:1671-1683.

PMID: 35923356 PMC: 9342432. DOI: 10.2147/COPD.S366844.

Inherited IL-12Rβ1 Deficiency in a Child With BCG Adenitis and Oral Candidiasis: A Case Report.

Hatipoglu N, Guvenc B, Deswarte C, Koksalan K, Boisson-Dupuis S, Casanova J Pediatrics. 2017; 140(5).

PMID: 29025965 PMC: 5654388. DOI: 10.1542/peds.2016-1668.

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood.

Boisson-Dupuis S, Bustamante J, El-Baghdadi J, Camcioglu Y, Parvaneh N, El Azbaoui S Immunol Rev. 2015; 264(1):103-20.

PMID: 25703555 PMC: 4405179. DOI: 10.1111/imr.12272.

References

Gursoy G, Cimbek A, Acar Y, Erol B, Dal H, Evrin N . Combined portal, splenic and mesenteric venous thrombosis in inactive ulcerative colitis with heterozygous mutation in MTHFR gene: A rare case of thrombophilia. J Res Med Sci. 2012; 16(11):1500-6. PMC: 3430070. View

Al-Muhsen S, Casanova J . The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. J Allergy Clin Immunol. 2008; 122(6):1043-51. DOI: 10.1016/j.jaci.2008.10.037. View

Leebeek F, Smalberg J, Janssen H . Prothrombotic disorders in abdominal vein thrombosis. Neth J Med. 2012; 70(9):400-5. View

Rohrer J, Ribeiro R, Auerbach A, Mirro B, Conley M . Wiskott-Aldrich syndrome in a family with Fanconi anemia. J Pediatr. 1996; 129(1):50-5. DOI: 10.1016/s0022-3476(96)70189-0. View

de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M . Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. J Exp Med. 2008; 205(7):1543-50. PMC: 2442631. DOI: 10.1084/jem.20080321. View

Filipe-Santos O, Bustamante J, Chapgier A, Vogt G, de Beaucoudrey L, Feinberg J . Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features. Semin Immunol. 2006; 18(6):347-61. DOI: 10.1016/j.smim.2006.07.010. View

Puel A, Cypowyj S, Marodi L, Abel L, Picard C, Casanova J . Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis. Curr Opin Allergy Clin Immunol. 2012; 12(6):616-22. PMC: 3538358. DOI: 10.1097/ACI.0b013e328358cc0b. View

Szczeklik A, Sanak M, Jankowski M, Dropinski J, Czachor R, Musial J . Mutation A1298C of methylenetetrahydrofolate reductase: risk for early coronary disease not associated with hyperhomocysteinemia. Am J Med Genet. 2001; 101(1):36-9. DOI: 10.1002/ajmg.1315. View

Tanir G, Dogu F, Tuygun N, Ikinciogullari A, Aytekin C, Aydemir C . Complete deficiency of the IL-12 receptor beta1 chain: three unrelated Turkish children with unusual clinical features. Eur J Pediatr. 2006; 165(6):415-7. DOI: 10.1007/s00431-005-0078-8. View

10.

Prando C, Samarina A, Bustamante J, Boisson-Dupuis S, Cobat A, Picard C . Inherited IL-12p40 deficiency: genetic, immunologic, and clinical features of 49 patients from 30 kindreds. Medicine (Baltimore). 2013; 92(2):109-122. PMC: 3822760. DOI: 10.1097/MD.0b013e31828a01f9. View

11.

de Beaucoudrey L, Samarina A, Bustamante J, Cobat A, Boisson-Dupuis S, Feinberg J . Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries. Medicine (Baltimore). 2010; 89(6):381-402. PMC: 3129625. DOI: 10.1097/MD.0b013e3181fdd832. View

12.

Jurcut R, Pop I, Coriu D, Grasu M, Zilisteanu D, Giusca S . Compound heterozygosity for the C677T and A1298C mutations of the MTHFR gene in a case of hyperhomocysteinemia with recurrent deep thrombosis at young age. Rom J Intern Med. 2009; 46(3):255-9. View

13.

Bustamante J, Picard C, Boisson-Dupuis S, Abel L, Casanova J . Genetic lessons learned from X-linked Mendelian susceptibility to mycobacterial diseases. Ann N Y Acad Sci. 2012; 1246:92-101. PMC: 3315101. DOI: 10.1111/j.1749-6632.2011.06273.x. View

14.

Boisson-Dupuis S, El Baghdadi J, Parvaneh N, Bousfiha A, Bustamante J, Feinberg J . IL-12Rβ1 deficiency in two of fifty children with severe tuberculosis from Iran, Morocco, and Turkey. PLoS One. 2011; 6(4):e18524. PMC: 3076373. DOI: 10.1371/journal.pone.0018524. View

15.

Ehlayel M, de Beaucoudrey L, Fike F, Nahas S, Feinberg J, Casanova J . Simultaneous presentation of 2 rare hereditary immunodeficiencies: IL-12 receptor beta1 deficiency and ataxia-telangiectasia. J Allergy Clin Immunol. 2008; 122(6):1217-9. DOI: 10.1016/j.jaci.2008.07.005. View

16.

Casanova J, Abel L . Genetic dissection of immunity to mycobacteria: the human model. Annu Rev Immunol. 2002; 20:581-620. DOI: 10.1146/annurev.immunol.20.081501.125851. View

17.

Feinberg J, Fieschi C, Doffinger R, Feinberg M, Leclerc T, Boisson-Dupuis S . Bacillus Calmette Guerin triggers the IL-12/IFN-gamma axis by an IRAK-4- and NEMO-dependent, non-cognate interaction between monocytes, NK, and T lymphocytes. Eur J Immunol. 2004; 34(11):3276-84. DOI: 10.1002/eji.200425221. View

18.

Puel A, Cypowyj S, Bustamante J, Wright J, Liu L, Lim H . Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science. 2011; 332(6025):65-8. PMC: 3070042. DOI: 10.1126/science.1200439. View

19.

Verspyck E, Le Cam-Duchez V, Borg J, Marpeau L . [Inherited thrombophilia and pregnancy]. J Gynecol Obstet Biol Reprod (Paris). 2000; 29(3):227-9. View