Genetic Association in Familial Common Variable Immunodeficiency (CVID) and IgA Deficiency (IgAD)

Document Type : Original Article

Authors

1 Department of Life Science, Faculty of New Science and Technology, University of Tehran, Tehran, Iran.

2 Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden

Abstract

Background/objectives: Common variable immunodeficiency (CVID) is a heterogeneous syndrome described by defective antibody production and occurrence of multiple clinical manifestations including autoimmune, lymphoproliferative, and granulomatous diseases. Genes within the major histocompatibility complex (MHC) region have previously been reported to be involved in the pathogenesis of the disease.
Methods: To elucidate the human leukocyte antigen (HLA) association, PCR was performed to clarify type HLA B, DR, and DQ alleles in a large sample of Iranian and Swedish CVID patients.
Results: No HLA association was observed between Iranian patients with “sporadic” CVID (n=50) and controls. A slight HLA association (B8, DR3, DQ2) was found in Swedish CVID patients (n=95). However, the latter was entirely due to an association in the familial form of the disease. Using 13 informative multiplex families with patients affected by CVID and IgA deficiency (IgAD), shared haplotypes such as HLA-B8-DR3-DQ2; HLA-DR1-DQ5; HLA- DR4- DQ3, and HLA-DR7-DQ2 were observed.
Conclusions: Based on our results, we hypothesize that only the familial form of CVID/IgAD may have a common HLA-associated genetic background, whereas “sporadic” cases show no HLA association.

Keywords

References

1. Hammarstrom L, Smith CI. Genetic approach to common variable immunodeficiency and IgA deficiency (Ochs, H., Puck, J. Primary immunodeficiency diseases a molecular and genetic approach) Oxford pp. 313-325: Oxford university press; 2007. 2. Burrows PD, Cooper MD. IgA deficiency. Adv Immunol. 1997;65:245-76. 3. Schroeder HW, Jr., Schroeder HW, 3rd, Sheikh SM. The complex genetics of common variable immunodeficiency. J Investig Med. 2004 Mar;52(2):90-103. 4. Aghamohammadi A, Mohammadi J, Parvaneh N, Rezaei N, Moin M, Espanol T, et al. Progression of selective IgA deficiency to common variable immunodeficiency. Int Arch Allergy Immunol. 2008 Jun 3;147(2):87-92. 5. Oen K, Petty RE, Schroeder ML. Immunoglobulin A deficiency: genetic studies. Tissue Antigens. 1982 Mar;19(3):174-82. 6. Hammarstrom L, Smith CI. HLA-A, B, C and DR antigens in immunoglobulin A deficiency. Tissue Antigens. 1983 Jan;21(1):75-9. 7. Mohammadi J, Pourpak Z, Jarefors S, Saghafi S, Zendehdel K, Pourfathollah AA, et al. Human Leukocyte Antigens (HLA) Associated with Selective IgA Deficiency in Iran and Sweden. Iran J Allergy Asthma Immunol. 2008 Dec;7(4):209-14. 8. Olerup O, Aldener A, Fogdell A. HLA-DQB1 and -DQA1 typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours. Tissue Antigens. 1993 Mar;41(3):119-34. 9. Payami H, Joe S, Farid NR, Stenszky V, Chan SH, Yeo PP, et al. Relative predispositional effects (RPEs) of marker alleles with disease: HLA-DR alleles and Graves disease. Am J Hum Genet. 1989 Oct;45(4):541-6. 10. Olerup O, Smith CI, Bjorkander J, Hammarstrom L. Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA-DQB1 gene, in IgA deficiency and common variable immunodeficiency. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10653-7. 11. Volanakis JE, Zhu ZB, Schaffer FM, Macon KJ, Palermos J, Barger BO, et al. Major histocompatibility complex class III genes and susceptibility to immunoglobulin A deficiency and common variable immunodeficiency. J Clin Invest. 1992 Jun;89(6):1914-22. 12. de la Concha EG, Fernandez-Arquero M, Martinez A, Vidal F, Vigil P, Conejero L, et al. HLA class II homozygosity confers susceptibility to common variable immunodeficiency (CVID). Clin Exp Immunol. 1999 Jun;116(3):516-20. 13. Howe HS, So AK, Farrant J, Webster AD. Common variable immunodeficiency is associated with polymorphic markers in the human major histocompatibility complex. Clin Exp Immunol. 1991 Mar;83(3):387-90. 14. Aghamohammadi A, Farhoudi A, Moin M, Rezaei N, Kouhi A, Pourpak Z, et al. Clinical and immunological features of 65 Iranian patients with common variable immunodeficiency. Clin Diagn Lab Immunol. 2005 Jul;12(7):825-32.
Immunology and Genetics Journal
Volume 1, Issue 1
September 2018
Pages 24-33

Files

Share

How to cite

Statistics