Skip to main content

Selective IgA Deficiency

  • Chapter
  • First Online:
Humoral Primary Immunodeficiencies

Abstract

Selective IgA deficiency (IgAD) is the most common primary immunodeficiency with a wide range of clinical symptoms including respiratory and gastrointestinal infections, autoimmunity, allergic conditions, and, in some cases, progression to the more severe antibody deficiency, common variable immunodeficiency (CVID). Genetics, intrinsic defects in lymphocytes, and impairment of the cytokine profile are all thought to contribute to IgAD pathogenesis, but the underlying cause of the diseases still remains unknown. This, together with a wide range of clinical manifestations in the patients and the association between IgAD and other immune disorders, presents a challenge for clinicians and researchers in both diagnosing and treating IgAD.

In this chapter we have summarized the epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis, and treatment of IgAD.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Giedion A, Scheidegger JJ. Congenital immunological paresis in the absence of specific beta 2-globulin & normal quantities of gamma-globulin. Helv Paediatr Acta. 1957;12(3):241–59.

    CAS  PubMed  Google Scholar 

  2. Gutmann L, Lemli L. Ataxia-telangiectasia associated with hypogammaglobulinemia. Arch Neurol. 1963;8:318–27.

    Article  CAS  PubMed  Google Scholar 

  3. Primary Immunodeficiency Diseases. Report of an IUIS Scientific Committee. International Union of Immunological Societies. Clin Exp Immunol. 1999;118(Suppl 1):1–28.

    Google Scholar 

  4. Wang Z, Yunis D, Irigoyen M, Kitchens B, Bottaro A, Alt FW, et al. Discordance between IgA switching at the DNA level and IgA expression at the mRNA level in IgA-deficient patients. Clin Immunol. 1999;91(3):263–70. https://doi.org/10.1006/clim.1999.4702.

    Article  CAS  PubMed  Google Scholar 

  5. Suzuki H, Kaneko H, Fukao T, Jin R, Kawamoto N, Asano T, et al. Various expression patterns of alpha1 and alpha2 genes in IgA deficiency. Allergol Int. 2009;58(1):111–7.

    Article  CAS  PubMed  Google Scholar 

  6. Conley ME, Cooper MD. Immature IgA B cells in IgA-deficient patients. N Engl J Med. 1981;305(9):495–7.

    Article  CAS  PubMed  Google Scholar 

  7. Lawton AR, Royal SA, Self KS, Cooper MD. IgA determinants on B-lymphocytes in patients with deficiency of circulating IgA. J Lab Clin Med. 1972;80(1):26–33.

    CAS  PubMed  Google Scholar 

  8. Ramsay AJ, Husband AJ, Ramshaw IA, Bao S, Matthaei KI, Koehler G, et al. The role of interleukin-6 in mucosal IgA antibody responses in vivo. Science. 1994;264(5158):561–3.

    Article  CAS  PubMed  Google Scholar 

  9. Okahashi N, Yamamoto M, Vancott JL, Chatfield SN, Roberts M, Bluethmann H, et al. Oral immunization of interleukin-4 (IL-4) knockout mice with a recombinant Salmonella strain or cholera toxin reveals that CD4+ Th2 cells producing IL-6 and IL-10 are associated with mucosal immunoglobulin A responses. Infect Immun. 1996;64(5):1516–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Borte S, Pan-Hammarstrom Q, Liu C, Sack U, Borte M, Wagner U, et al. Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency. Blood. 2009;114(19):4089–98.

    Article  CAS  PubMed  Google Scholar 

  11. Farr M, Struthers GR, Scott DG, Bacon PA. Fenclofenac-induced selective IgA deficiency in rheumatoid arthritis. Br J Rheumatol. 1985;24(4):367–9.

    Article  CAS  PubMed  Google Scholar 

  12. Matsuoka H, Okada J, Takahashi T, Matsuoka M, Sato C, Torii S. Immunological study of IgA deficiency during anticonvulsant therapy in epileptic patients. Clin Exp Immunol. 1983;53(2):423–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Ilan Y, Shouval D, Ashur Y, Manns M, Naparstek Y. IgA deficiency associated with chronic hepatitis C virus infection. A cause or an effect? Arch Intern Med. 1993;153(13):1588–92.

    Article  CAS  PubMed  Google Scholar 

  14. Latiff AH, Kerr MA. The clinical significance of immunoglobulin A deficiency. Ann Clin Biochem. 2007;44(Pt 2):131–9. https://doi.org/10.1258/000456307780117993.

    Article  PubMed  Google Scholar 

  15. Lim CK, Dahle C, Elvin K, Andersson BA, Ronnelid J, Melen E, et al. Reversal of immunoglobulin A deficiency in children. J Clin Immunol. 2015;35(1):87–91.

    Article  CAS  PubMed  Google Scholar 

  16. Ammann AJ, Hong R. Selective IgA deficiency: presentation of 30 cases and a review of the literature. Medicine (Baltimore). 1971;50(3):223–36.

    Article  CAS  Google Scholar 

  17. Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clin Immunol. 2004;111(1):93–7.

    Article  CAS  PubMed  Google Scholar 

  18. Janzi M, Kull I, Sjoberg R, Wan J, Melen E, Bayat N, et al. Selective IgA deficiency in early life: association to infections and allergic diseases during childhood. Clin Immunol. 2009;133(1):78–85.

    Article  CAS  PubMed  Google Scholar 

  19. Jorgensen GH, Gardulf A, Sigurdsson MI, Sigurdardottir ST, Thorsteinsdottir I, Gudmundsson S, et al. Clinical symptoms in adults with selective IgA deficiency: a case-control study. J Clin Immunol. 2013;33(4):742–7.

    Article  CAS  PubMed  Google Scholar 

  20. Jesus AA, Liphaus BL, Silva CA, Bando SY, Andrade LE, Coutinho A, et al. Complement and antibody primary immunodeficiency in juvenile systemic lupus erythematosus patients. Lupus. 2011;20(12):1275–84.

    Article  CAS  PubMed  Google Scholar 

  21. Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al. Selective IgA deficiency in autoimmune diseases. Mol Med. 2011;17(11–12):1383–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 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;147(2):87–92.

    Article  CAS  PubMed  Google Scholar 

  23. Hammarstrom L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol. 2000;120(2):225–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Primary Immunodeficiency Diseases. Report of a WHO scientific group. Clin Exp Immunol. 1997;109(Suppl 1):1–28.

    Google Scholar 

  25. al-Attas RA, Rahi AH. Primary antibody deficiency in Arabs: first report from eastern Saudi Arabia. J Clin Immunol. 1998;18(5):368–71.

    Article  CAS  PubMed  Google Scholar 

  26. Kanoh T, Mizumoto T, Yasuda N, Koya M, Ohno Y, Uchino H, et al. Selective IgA deficiency in Japanese blood donors: frequency and statistical analysis. Vox Sang. 1986;50(2):81–6.

    Article  CAS  PubMed  Google Scholar 

  27. Schaffer FM, Monteiro RC, Volanakis JE, Cooper MD. IgA deficiency. Immunodefic Rev. 1991;3(1):15–44.

    CAS  PubMed  Google Scholar 

  28. Vorechovsky I, Zetterquist H, Paganelli R, Koskinen S, Webster AD, Bjorkander J, et al. Family and linkage study of selective IgA deficiency and common variable immunodeficiency. Clin Immunol Immunopathol. 1995;77(2):185–92.

    Article  CAS  PubMed  Google Scholar 

  29. Vorechovsky I, Webster AD, Plebani A, Hammarstrom L. Genetic linkage of IgA deficiency to the major histocompatibility complex: evidence for allele segregation distortion, parent-of-origin penetrance differences, and the role of anti-IgA antibodies in disease predisposition. Am J Hum Genet. 1999;64(4):1096–109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Basturk B, Sari S, Aral A, Dalgic B. Prevalence of selective immunoglobulin A deficiency in healthy Turkish school children. Turk J Pediatr. 2011;53(4):364–8.

    PubMed  Google Scholar 

  31. Conley ME, Delacroix DL. Intravascular and mucosal immunoglobulin A: two separate but related systems of immune defense? Ann Intern Med. 1987;106(6):892–9.

    Article  CAS  PubMed  Google Scholar 

  32. Fagarasan S, Honjo T. Intestinal IgA synthesis: regulation of front-line body defences. Nat Rev Immunol. 2003;3(1):63–72.

    Article  CAS  PubMed  Google Scholar 

  33. Brandtzaeg P, Johansen FE. Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties. Immunol Rev. 2005;206:32–63.

    Article  CAS  PubMed  Google Scholar 

  34. Gommerman JL, Rojas OL, Fritz JH. Re-thinking the functions of IgA(+) plasma cells. Gut Microbes. 2014;5(5):652–62.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Mantis NJ, Rol N, Corthesy B. Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol. 2011;4(6):603–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Helander A, Miller CL, Myers KS, Neutra MR, Nibert ML. Protective immunoglobulin A and G antibodies bind to overlapping intersubunit epitopes in the head domain of type 1 reovirus adhesin sigma1. J Virol. 2004;78(19):10695–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Apter FM, Lencer WI, Finkelstein RA, Mekalanos JJ, Neutra MR. Monoclonal immunoglobulin A antibodies directed against cholera toxin prevent the toxin-induced chloride secretory response and block toxin binding to intestinal epithelial cells in vitro. Infect Immun. 1993;61(12):5271–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Mathias A, Pais B, Favre L, Benyacoub J, Corthesy B. Role of secretory IgA in the mucosal sensing of commensal bacteria. Gut Microbes. 2014;5(6):688–95.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Roos A, Bouwman LH, van Gijlswijk-Janssen DJ, Faber-Krol MC, Stahl GL, Daha MR. Human IgA activates the complement system via the mannan-binding lectin pathway. J Immunol. 2001;167(5):2861–8.

    Article  CAS  PubMed  Google Scholar 

  40. Monteiro RC, Van De Winkel JG. IgA Fc receptors. Annu Rev Immunol. 2003;21:177–204.

    Article  CAS  PubMed  Google Scholar 

  41. Simister NE. Placental transport of immunoglobulin G. Vaccine. 2003;21(24):3365–9.

    Article  CAS  PubMed  Google Scholar 

  42. Hurley WL, Theil PK. Perspectives on immunoglobulins in colostrum and milk. Nutrients. 2011;3(4):442–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Munblit D, Sheth S, Abrol P, Treneva M, Peroni DG, Chow LY, et al. Exposures influencing total IgA level in colostrum. J Dev Orig Health Dis. 2016;7(1):61–7.

    Article  CAS  PubMed  Google Scholar 

  44. McKay E, Thom H. Observations on neonatal tears. J Pediatr. 1969;75(6):1245–56.

    Article  CAS  PubMed  Google Scholar 

  45. Cohen AB, Goldberg S, London RL. Immunoglobulins in nasal secretions of infants. Clin Exp Immunol. 1970;6(5):753–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Sutherland DB, Fagarasan S. IgA synthesis: a form of functional immune adaptation extending beyond gut. Curr Opin Immunol. 2012;24(3):261–8.

    Article  CAS  PubMed  Google Scholar 

  47. Husain Z, Holodick N, Day C, Szymanski I, Alper CA. Increased apoptosis of CD20+ IgA + B cells is the basis for IgA deficiency: the molecular mechanism for correction in vitro by IL-10 and CD40L. J Clin Immunol. 2006;26(2):113–25.

    Article  CAS  PubMed  Google Scholar 

  48. Yazdani R, Fatholahi M, Ganjalikhani-Hakemi M, Abolhassani H, Azizi G, Hamid KM, et al. Role of apoptosis in common variable immunodeficiency and selective immunoglobulin A deficiency. Mol Immunol. 2016;71:1–9.

    Article  CAS  PubMed  Google Scholar 

  49. Oen K, Petty RE, Schroeder ML. Immunoglobulin A deficiency: genetic studies. Tissue Antigens. 1982;19(3):174–82.

    Article  CAS  PubMed  Google Scholar 

  50. Frankowiack M, Kovanen RM, Repasky GA, Lim CK, Song C, Pedersen NL, et al. The higher frequency of IgA deficiency among Swedish twins is not explained by HLA haplotypes. Genes Immun. 2015;16(3):199–205.

    Article  CAS  PubMed  Google Scholar 

  51. Schroeder HW Jr. Genetics of IgA deficiency and common variable immunodeficiency. Clin Rev Allergy Immunol. 2000;19(2):127–40.

    Article  CAS  PubMed  Google Scholar 

  52. Schroeder HW Jr, Zhu ZB, March RE, Campbell RD, Berney SM, Nedospasov SA, et al. Susceptibility locus for IgA deficiency and common variable immunodeficiency in the HLA-DR3, -B8, −A1 haplotypes. Mol Med. 1998;4(2):72–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kralovicova J, Hammarstrom L, Plebani A, Webster AD, Vorechovsky I. Fine-scale mapping at IGAD1 and genome-wide genetic linkage analysis implicate HLA-DQ/DR as a major susceptibility locus in selective IgA deficiency and common variable immunodeficiency. J Immunol. 2003;170(5):2765–75.

    Article  CAS  PubMed  Google Scholar 

  54. Mohammadi J, Ramanujam R, Jarefors S, Rezaei N, Aghamohammadi A, Gregersen PK, et al. IgA deficiency and the MHC: assessment of relative risk and microheterogeneity within the HLA A1 B8, DR3 (8.1) haplotype. J Clin Immunol. 2010;30(1):138–43.

    Article  CAS  PubMed  Google Scholar 

  55. Olerup O, Smith CI, Hammarstrom L. Different amino acids at position 57 of the HLA-DQ beta chain associated with susceptibility and resistance to IgA deficiency. Nature. 1990;347(6290):289–90.

    Article  CAS  PubMed  Google Scholar 

  56. Ferreira RC, Pan-Hammarstrom Q, Graham RR, Gateva V, Fontan G, Lee AT, et al. Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency. Nat Genet. 2010;42(9):777–80.

    Article  CAS  PubMed  Google Scholar 

  57. Bronson PG, Chang D, Bhangale T, Seldin MF, Ortmann W, Ferreira RC, et al. Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency. Nat Genet. 2016;48(11):1425–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Haimila K, Einarsdottir E, de Kauwe A, Koskinen LL, Pan-Hammarstrom Q, Kaartinen T, et al. The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency. Genes Immun. 2009;10(2):151–61.

    Article  CAS  PubMed  Google Scholar 

  59. Reboldi A, Cyster JG. Peyer’s patches: organizing B-cell responses at the intestinal frontier. Immunol Rev. 2016;271(1):230–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Castigli E, Scott S, Dedeoglu F, Bryce P, Jabara H, Bhan AK, et al. Impaired IgA class switching in APRIL-deficient mice. Proc Natl Acad Sci U S A. 2004;101(11):3903–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Reboldi A, Arnon TI, Rodda LB, Atakilit A, Sheppard D, Cyster JG. IgA production requires B cell interaction with subepithelial dendritic cells in Peyer’s patches. Science. 2016;352(6287):aaf4822.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Cunningham-Rundles C. Physiology of IgA and IgA deficiency. J Clin Immunol. 2001;21(5):303–9.

    Article  CAS  PubMed  Google Scholar 

  63. Cao AT, Yao S, Gong B, Nurieva RI, Elson CO, Cong Y. Interleukin (IL)-21 promotes intestinal IgA response to microbiota. Mucosal Immunol. 2015;8(5):1072–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Mackay F, Schneider P. Cracking the BAFF code. Nat Rev Immunol. 2009;9(7):491–502.

    Article  CAS  PubMed  Google Scholar 

  65. Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, Casali P, et al. DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol. 2002;3(9):822–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Bergqvist P, Gardby E, Stensson A, Bemark M, Lycke NY. Gut IgA class switch recombination in the absence of CD40 does not occur in the Lamina Propria and is independent of germinal centers. J Immunol. 2006;177(11):7772–83.

    Article  CAS  PubMed  Google Scholar 

  67. Castigli E, Wilson SA, Scott S, Dedeoglu F, Xu S, Lam KP, et al. TACI and BAFF-R mediate isotype switching in B cells. J Exp Med. 2005;201(1):35–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Cerutti A, Rescigno M. The biology of intestinal immunoglobulin A responses. Immunity. 2008;28(6):740–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mackay F, Leung H. The role of the BAFF/APRIL system on T cell function. Semin Immunol. 2006;18(5):284–9.

    Article  CAS  PubMed  Google Scholar 

  70. Chu VT, Enghard P, Riemekasten G, Berek C. In vitro and in vivo activation induces BAFF and APRIL expression in B cells. J Immunol. 2007;179(9):5947–57.

    Article  CAS  PubMed  Google Scholar 

  71. Bossen C, Schneider P. BAFF, APRIL and their receptors: structure, function and signaling. Semin Immunol. 2006;18(5):263–75.

    Article  CAS  PubMed  Google Scholar 

  72. Ng LG, Sutherland AP, Newton R, Qian F, Cachero TG, Scott ML, et al. B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells. J Immunol. 2004;173(2):807–17.

    Article  CAS  PubMed  Google Scholar 

  73. Darce JR, Arendt BK, Wu X, Jelinek DF. Regulated expression of BAFF-binding receptors during human B cell differentiation. J Immunol. 2007;179(11):7276–86.

    Article  CAS  PubMed  Google Scholar 

  74. Hardenberg G, van Bostelen L, Hahne M, Medema JP. Thymus-independent class switch recombination is affected by APRIL. Immunol Cell Biol. 2008;86(6):530–4.

    Article  CAS  PubMed  Google Scholar 

  75. He B, Xu W, Santini PA, Polydorides AD, Chiu A, Estrella J, et al. Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity. 2007;26(6):812–26.

    Article  CAS  PubMed  Google Scholar 

  76. Xu W, He B, Chiu A, Chadburn A, Shan M, Buldys M, et al. Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI. Nat Immunol. 2007;8(3):294–303.

    Article  CAS  PubMed  Google Scholar 

  77. Aghamohammadi A, Cheraghi T, Gharagozlou M, Movahedi M, Rezaei N, Yeganeh M, et al. IgA deficiency: correlation between clinical and immunological phenotypes. J Clin Immunol. 2009;29(1):130–6.

    Article  CAS  PubMed  Google Scholar 

  78. Brandtzaeg P, Karlsson G, Hansson G, Petruson B, Bjorkander J, Hanson LA. The clinical condition of IgA-deficient patients is related to the proportion of IgD- and IgM-producing cells in their nasal mucosa. Clin Exp Immunol. 1987;67(3):626–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Richman LK, Brown WR. Immunochemical characterization of IgM in human intestinal fluids. J Immunol. 1977;119(4):1515–9.

    CAS  PubMed  Google Scholar 

  80. Sloper KS, Brook CG, Kingston D, Pearson JR, Shiner M. Eczema and atopy in early childhood: low IgA plasma cell counts in the jejunal mucosa. Arch Dis Child. 1981;56(12):939–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Bjorkander J, Bake B, Oxelius VA, Hanson LA. Impaired lung function in patients with IgA deficiency and low levels of IgG2 or IgG3. N Engl J Med. 1985;313(12):720–4.

    Article  CAS  PubMed  Google Scholar 

  82. Stead A, Douglas JG, Broadfoot CJ, Kaminski ER, Herriot R. Humoral immunity and bronchiectasis. Clin Exp Immunol. 2002;130(2):325–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Vendrell M, de Gracia J, Rodrigo MJ, Cruz MJ, Alvarez A, Garcia M, et al. Antibody production deficiency with normal IgG levels in bronchiectasis of unknown etiology. Chest. 2005;127(1):197–204.

    Article  CAS  PubMed  Google Scholar 

  84. McNabb PC, Tomasi TB. Host defense mechanisms at mucosal surfaces. Annu Rev Microbiol. 1981;35:477–96.

    Article  CAS  PubMed  Google Scholar 

  85. Allardyce RA, Bienenstock J. The mucosal immune system in health and disease, with an emphasis on parasitic infection. Bull World Health Organ. 1984;62(1):7–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Mantovani AP, Monclaro MP, Skare TL. Prevalence of IgA deficiency in adult systemic lupus erythematosus and the study of the association with its clinical and autoantibody profiles. Rev Bras Reumatol. 2010;50(3):273–82.

    Article  PubMed  Google Scholar 

  87. Cerutti F, Urbino A, Sacchetti C, Palomba E, Zoppo M, Tovo PA. Selective IgA deficiency in juvenile-onset insulin-dependent diabetes mellitus. Pediatr Med Chir. 1988;10(2):197–201.

    CAS  PubMed  Google Scholar 

  88. Chow MA, Lebwohl B, Reilly NR, Green PH. Immunoglobulin A deficiency in celiac disease. J Clin Gastroenterol. 2012;46(10):850–4.

    Article  CAS  PubMed  Google Scholar 

  89. Rachid R, Bonilla FA. The role of anti-IgA antibodies in causing adverse reactions to gamma globulin infusion in immunodeficient patients: a comprehensive review of the literature. J Allergy Clin Immunol. 2012;129(3):628–34.

    Article  CAS  PubMed  Google Scholar 

  90. Vyas GN, Perkins HA, Fudenberg HH. Anaphylactoid transfusion reactions associated with anti-IgA. Lancet. 1968;2(7563):312–5.

    Article  CAS  PubMed  Google Scholar 

  91. Laschinger C, Shepherd FA, Naylor DH. Anti-IgA-mediated transfusion reactions in Canada. Can Med Assoc J. 1984;130(2):141–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Sandler SG, Eder AF, Goldman M, Winters JL. The entity of immunoglobulin A-related anaphylactic transfusion reactions is not evidence based. Transfusion. 2015;55(1):199–204.

    Article  PubMed  Google Scholar 

  93. Sandler SG, Mallory D, Malamut D, Eckrich R. IgA anaphylactic transfusion reactions. Transfus Med Rev. 1995;9(1):1–8.

    Article  CAS  PubMed  Google Scholar 

  94. Hammarstrom L, Persson MA, Smith CI. Immunoglobulin subclass distribution of human anti-carbohydrate antibodies: aberrant pattern in IgA-deficient donors. Immunology. 1985;54(4):821–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Aittoniemi J, Koskinen S, Laippala P, Laine S, Miettinen A. The significance of IgG subclasses and mannan-binding lectin (MBL) for susceptibility to infection in apparently healthy adults with IgA deficiency. Clin Exp Immunol. 1999;116(3):505–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ferreira A, Garcia Rodriguez MC, Lopez-Trascasa M, Pascual Salcedo D, Fontan G. Anti-IgA antibodies in selective IgA deficiency and in primary immunodeficient patients treated with gamma-globulin. Clin Immunol Immunopathol. 1988;47(2):199–207.

    Article  CAS  PubMed  Google Scholar 

  97. Kowalczyk D, Mytar B, Zembala M. Cytokine production in transient hypogammaglobulinemia and isolated IgA deficiency. J Allergy Clin Immunol. 1997;100(4):556–62.

    Article  CAS  PubMed  Google Scholar 

  98. Soheili H, Abolhassani H, Arandi N, Khazaei HA, Shahinpour S, Hirbod-Mobarakeh A, et al. Evaluation of natural regulatory T cells in subjects with selective IgA deficiency: from senior idea to novel opportunities. Int Arch Allergy Immunol. 2013;160(2):208–14.

    Article  CAS  PubMed  Google Scholar 

  99. Aghamohammadi A, Abolhassani H, Biglari M, Abolmaali S, Moazzami K, Tabatabaeiyan M, et al. Analysis of switched memory B cells in patients with IgA deficiency. Int Arch Allergy Immunol. 2011;156(4):462–8.

    Article  CAS  PubMed  Google Scholar 

  100. Cataldo F, Marino V, Ventura A, Bottaro G, Corazza GR. Prevalence and clinical features of selective immunoglobulin A deficiency in coeliac disease: an Italian multicentre study. Italian Society of Paediatric Gastroenterology and Hepatology (SIGEP) and “Club del Tenue” Working Groups on Coeliac Disease. Gut. 1998;42(3):362–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Villalta D, Alessio MG, Tampoia M, Tonutti E, Brusca I, Bagnasco M, et al. Diagnostic accuracy of IgA anti-tissue transglutaminase antibody assays in celiac disease patients with selective IgA deficiency. Ann N Y Acad Sci. 2007;1109:212–20.

    Article  CAS  PubMed  Google Scholar 

  102. Albin S, Cunningham-Rundles C. An update on the use of immunoglobulin for the treatment of immunodeficiency disorders. Immunotherapy. 2014;6(10):1113–26.

    Article  CAS  PubMed  Google Scholar 

  103. Garcia JM, Espanol T, Gurbindo MD, Casas CC. Update on the treatment of primary immunodeficiencies. Allergol Immunopathol (Madr). 2007;35(5):184–92.

    Article  CAS  Google Scholar 

  104. Gustafson R, Gardulf A, Granert C, Hansen S, Hammarstrom L. Prophylactic therapy for selective IgA deficiency. Lancet. 1997;350(9081):865.

    Article  CAS  PubMed  Google Scholar 

  105. Marconi M, Plebani A, Avanzini MA, Maccario R, Pistorio A, Duse M, et al. IL-10 and IL-4 co-operate to normalize in vitro IgA production in IgA-deficient (IgAD) patients. Clin Exp Immunol. 1998;112(3):528–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Briere F, Bridon JM, Chevet D, Souillet G, Bienvenu F, Guret C, et al. Interleukin 10 induces B lymphocytes from IgA-deficient patients to secrete IgA. J Clin Invest. 1994;94(1):97–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Ludvigsson JF, Neovius M, Hammarstrom L. IgA deficiency and mortality: a population-based cohort study. J Clin Immunol. 2013;33(8):1317–24.

    Article  CAS  PubMed  Google Scholar 

  108. Jorgensen GH, Gardulf A, Sigurdsson MI, Arnlaugsson S, Hammarstrom L, Ludviksson BR. Health-related quality of life (HRQL) in immunodeficient adults with selective IgA deficiency compared with age- and gender-matched controls and identification of risk factors for poor HRQL. Qual Life Res. 2014;23(2):645–58.

    Article  CAS  PubMed  Google Scholar 

  109. Routes J, Costa-Carvalho BT, Grimbacher B, Paris K, Ochs HD, Filipovich A, et al. Health-related quality of life and health resource utilization in patients with primary immunodeficiency disease prior to and following 12 months of immunoglobulin G treatment. J Clin Immunol. 2016;36(5):450–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Cobain TJ, French MA, Christiansen FT, Dawkins RL. Association of IgA deficiency with HLA A28 and B14. Tissue Antigens. 1983;22(2):151–4.

    Article  CAS  PubMed  Google Scholar 

  111. Ferreira RC, Pan-Hammarstrom Q, Graham RR, Fontan G, Lee AT, Ortmann W, et al. High-density SNP mapping of the HLA region identifies multiple independent susceptibility loci associated with selective IgA deficiency. PLoS Genet. 2012;8(1):e1002476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Ambrus M, Hernadi E, Bajtai G. Prevalence of HLA-A1 and HLA-B8 antigens in selective IgA deficiency. Clin Immunol Immunopathol. 1977;7(3):311–4.

    Article  CAS  PubMed  Google Scholar 

  113. Cuccia-Belvedere M, Monafo V, Martinetti M, Plebani A, De Paoli F, Burgio GR. Recurrent extended HLA haplotypes in children with selective IgA deficiency. Tissue Antigens. 1989;34(2):127–32.

    Article  CAS  PubMed  Google Scholar 

  114. 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;7(4):209–14.

    PubMed  Google Scholar 

  115. Hammarstrom L, Smith CI. HLA-A, B, C and DR antigens in immunoglobulin A deficiency. Tissue Antigens. 1983;21(1):75–9.

    Article  CAS  PubMed  Google Scholar 

  116. Schaffer FM, Palermos J, Zhu ZB, Barger BO, Cooper MD, Volanakis JE. Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes. Proc Natl Acad Sci U S A. 1989;86(20):8015–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. French MA, Dawkins RL. Central MHC genes, IgA deficiency and autoimmune disease. Immunol Today. 1990;11(8):271–4.

    Article  CAS  PubMed  Google Scholar 

  118. Fiore M, Pera C, Delfino L, Scotese I, Ferrara GB, Pignata C. DNA typing of DQ and DR alleles in IgA-deficient subjects. Eur J Immunogenet. 1995;22(5):403–11.

    Article  CAS  PubMed  Google Scholar 

  119. Reil A, Bein G, Machulla HK, Sternberg B, Seyfarth M. High-resolution DNA typing in immunoglobulin A deficiency confirms a positive association with DRB1*0301, DQB1*02 haplotypes. Tissue Antigens. 1997;50(5):501–6.

    Article  CAS  PubMed  Google Scholar 

  120. 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;116(3):516–20.

    Article  Google Scholar 

  121. Wilton AN, Cobain TJ, Dawkins RL. Family studies of IgA deficiency. Immunogenetics. 1985;21(4):333–42.

    Article  CAS  PubMed  Google Scholar 

  122. 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;89(6):1914–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Cucca F, Zhu ZB, Khanna A, Cossu F, Congia M, Badiali M, et al. Evaluation of IgA deficiency in Sardinians indicates a susceptibility gene is encoded within the HLA class III region. Clin Exp Immunol. 1998;111(1):76–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37(8):829–34.

    Article  CAS  PubMed  Google Scholar 

  125. Pan-Hammarstrom Q, Salzer U, Du L, Bjorkander J, Cunningham-Rundles C, Nelson DL, et al. Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. Nat Genet. 2007;39(4):429–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Winter PM, Manndorff P. The frequency of IgA-deficiency in the Austrian population. A protocol for large-scale screening by ELISA and a study on 3056 blood donors. Infusionstherapie. 1988;15(5):221–4.

    CAS  PubMed  Google Scholar 

  127. Weber-Mzell D, Kotanko P, Hauer AC, Goriup U, Haas J, Lanner N, et al. Gender, age and seasonal effects on IgA deficiency: a study of 7293 Caucasians. Eur J Clin Investig. 2004;34(3):224–8.

    Article  CAS  Google Scholar 

  128. Clark JA, Callicoat PA, Brenner NA, Bradley CA, Smith DM Jr. Selective IgA deficiency in blood donors. Am J Clin Pathol. 1983;80(2):210–3.

    Article  CAS  PubMed  Google Scholar 

  129. Vyas GN, Perkins HA, Yang YM, Basantani GK. Healthy blood donors with selective absence of immunoglobulin A: prevention of anaphylactic transfusion reactions caused by antibodies to IgA. J Lab Clin Med. 1975;85(5):838–42.

    CAS  PubMed  Google Scholar 

  130. Cassidy JT, Burt A, Petty R, Sullivan D. Selective IgA deficiency in connective tissue diseases. N Engl J Med. 1969;280(5):275.

    CAS  PubMed  Google Scholar 

  131. Frommel D, Moullec J, Lambin P, Fine JM. Selective serum IgA deficiency. Frequency among 15,200 French blood donors. Vox Sang. 1973;25(6):513–8.

    Article  CAS  PubMed  Google Scholar 

  132. Ropars C, Muller A, Paint N, Beige D, Avenard G. Large scale detection of IgA deficient blood donors. J Immunol Methods. 1982;54(2):183–9.

    Article  CAS  PubMed  Google Scholar 

  133. Pereira LF, Sapina AM, Arroyo J, Vinuelas J, Bardaji RM, Prieto L. Prevalence of selective IgA deficiency in Spain: more than we thought. Blood. 1997;90(2):893.

    CAS  PubMed  Google Scholar 

  134. Feng L. Epidemiological study of selective IgA deficiency among 6 nationalities in China. Zhonghua Yi Xue Za Zhi. 1992;72(2):88–90, 128.

    CAS  PubMed  Google Scholar 

  135. Feng ML, Zhao YL, Shen T, Huang H, Yin B, Liu RZ, Qian KC, Liu DZ. Prevalence of immunoglobulin A deficiency in Chinese blood donors and evaluation of anaphylactic transfusion reaction risk. Transfus Med. 2011;21(5):338–43.

    Article  CAS  PubMed  Google Scholar 

  136. Bachmann R. Studies on the serum gamma-A-globulin level. 3. The frequency of A-gamma-A-globulinemia. Scand J Clin Lab Invest. 1965;17(4):316–20.

    Article  CAS  PubMed  Google Scholar 

  137. Palmer DS, O'Toole J, Montreuil T, Scalia V, Yi QL, Goldman M, et al. Screening of Canadian Blood Services donors for severe immunoglobulin A deficiency. Transfusion. 2010;50(7):1524–31.

    Article  CAS  PubMed  Google Scholar 

  138. Ezeoke A. Selective IgA deficiency (SIgAD) in Eastern Nigeria. Afr J Med Med Sci. 1988;17(1):17–21.

    CAS  PubMed  Google Scholar 

  139. Wells JV, McNally MP, King MA. Selective IgA deficiency in Australian blood donors. Aust NZ J Med. 1980;10(4):410–3.

    Article  CAS  Google Scholar 

  140. Shiva S, Zahra P, Asghar A, Akbar PA, Azam S, Maryam F, et al. Selective immunoglobulin A deficiency in Iranian blood donors: prevalence, laboratory and clinical findings. Iran J Allergy Asthma Immunol. 2008;7(3):157–62.

    Google Scholar 

  141. Kornstad L, Nordhagen R. Immunodeficiency and autoimmunity I Selective IgA deficiency in thyroid autoimmunity. Int Arch Allergy Appl Immunol. 1974;47(6):942–5.

    Article  CAS  PubMed  Google Scholar 

  142. Natvig JB, Harboe M, Fausa O, Tveit A. Family studies in individuals with selective absence of gamma-A-globulin. Clin Exp Immunol. 1971;8(2):229–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Koistinen J. Selective IgA deficiency in blood donors. Vox Sang. 1975;29(3):192–202.

    Article  CAS  PubMed  Google Scholar 

  144. Litzman J, Sevcikova I, Stikarovska D, Pikulova Z, Pazdirkova A, Lokaj J. IgA deficiency in Czech healthy individuals and selected patient groups. Int Arch Allergy Immunol. 2000;123(2):177–80.

    Article  CAS  PubMed  Google Scholar 

  145. Carneiro-Sampaio MM, Carbonare SB, Rozentraub RB, de Araujo MN, Riberiro MA, Porto MH. Frequency of selective IgA deficiency among Brazilian blood donors and healthy pregnant women. Allergol Immunopathol (Madr). 1989;17(4):213–6.

    CAS  Google Scholar 

  146. Gandolfi L, Pratesi R, Cordoba JC, Tauil PL, Gasparin M, Catassi C. Prevalence of celiac disease among blood donors in Brazil. Am J Gastroenterol. 2000;95(3):689–92.

    Article  CAS  PubMed  Google Scholar 

  147. Ulfarsson J, Gudmundsson S, Birgisdottir B, Kjeld JM, Jensson O. Selective serum IgA deficiency in Icelanders. Frequency, family studies and Ig levels. Acta Med Scand. 1982;211(6):481–7.

    Article  CAS  PubMed  Google Scholar 

  148. Velbri S, Pärlist M, Leito K. Primaarne immuunpuudulikkus. Eestis Eesti Arst. 2005;84:310–4.

    Google Scholar 

  149. Urbonas V, Sadauskaite J, Cerkauskiene R, Kaminskas A, Maki M, Kurppa K. Population-based screening for selective Immunoglobulin A (IgA) deficiency in lithuanian children using a rapid antibody-based fingertip test. Med Sci Monit. 2016;22:4773–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Giza S, Kotanidou E, Papadopoulou-Alataki E, Antoniou MC, Maggana I, Kyrgios I, et al. Prevalence of selective immunoglobulin A deficiency in Greek children and adolescents with type 1 diabetes. World J Pediatr. 2016;12(4):470–6.

    Article  CAS  PubMed  Google Scholar 

  151. Foudoulaki-Paparizos LVT, Stamoulis K, Kyriakis K, Fakitsa V, Stayropoulou-Gioka E. Prevalence of IgA deficiency in Greek blood donors. Haema. 2002;5:330–2.

    Google Scholar 

  152. Chandran S, Khetan D, Chaudhary R, Misra R, Aggarwal A. Low prevalence of IgA deficiency in north Indian population. Indian J Med Res. 2006;123(5):653–6.

    PubMed  Google Scholar 

  153. Sharon R, Amar A. IgA deficiency in Israeli blood donors. J Clin Pathol. 1982;35(5):582–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Duran J, Lopes C, Rangel G, Ruivo I. IgA deficiency in a Portuguese donor population. Vox Sang. 2008;95(S1):170–7.

    Google Scholar 

  155. Yadav M, Iyngkaran N. Low incidence of selective IgA deficiency in normal Malaysians. Med J Malaysia. 1979;24:145–8.

    Google Scholar 

  156. Holt PD, Tandy NP, Anstee DJ. Screening of blood donors for IgA deficiency: a study of the donor population of South-West England. J Clin Pathol. 1977;30(11):1007–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Hunt AF, Allen DL, Aries DL, Strange JJ. A protocol for sensitive large-scale screening of blood donors for IgA deficiency. Vox Sang. 1975;29:192–202.

    Article  Google Scholar 

  158. Yazdani R, Azizi G, Abolhassani H, Aghamohammadi A. Selective IgA deficiency: epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis and management. Scand J Immunol. 2017;85(1):3–12.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lennart Hammarström .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sofia Appelberg, K., Abolhassani, H., Hammarström, L. (2019). Selective IgA Deficiency. In: D'Elios, M., Rizzi, M. (eds) Humoral Primary Immunodeficiencies. Rare Diseases of the Immune System. Springer, Cham. https://doi.org/10.1007/978-3-319-91785-6_16

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-91785-6_16

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-91784-9

  • Online ISBN: 978-3-319-91785-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics