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Selective IgA Deficiency

  • K. Sofia Appelberg
  • Hassan Abolhassani
  • Lennart HammarströmEmail author
Chapter
Part of the Rare Diseases of the Immune System book series (RDIS)

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.

Keywords

IgA deficiency Primary immunodeficiency Infections Allergy Autoimmunity Antibody deficiency 

References

  1. 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.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Gutmann L, Lemli L. Ataxia-telangiectasia associated with hypogammaglobulinemia. Arch Neurol. 1963;8:318–27.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 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. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Conley ME, Cooper MD. Immature IgA B cells in IgA-deficient patients. N Engl J Med. 1981;305(9):495–7.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 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.PubMedPubMedCentralGoogle Scholar
  8. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 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.PubMedPubMedCentralGoogle Scholar
  10. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 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.PubMedPubMedCentralGoogle Scholar
  13. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 17.
    Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clin Immunol. 2004;111(1):93–7.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 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.PubMedPubMedCentralGoogle Scholar
  22. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Hammarstrom L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol. 2000;120(2):225–31.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Primary Immunodeficiency Diseases. Report of a WHO scientific group. Clin Exp Immunol. 1997;109(Suppl 1):1–28.Google Scholar
  25. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Schaffer FM, Monteiro RC, Volanakis JE, Cooper MD. IgA deficiency. Immunodefic Rev. 1991;3(1):15–44.PubMedPubMedCentralGoogle Scholar
  28. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 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.PubMedPubMedCentralGoogle Scholar
  31. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Fagarasan S, Honjo T. Intestinal IgA synthesis: regulation of front-line body defences. Nat Rev Immunol. 2003;3(1):63–72.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Brandtzaeg P, Johansen FE. Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties. Immunol Rev. 2005;206:32–63.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Gommerman JL, Rojas OL, Fritz JH. Re-thinking the functions of IgA(+) plasma cells. Gut Microbes. 2014;5(5):652–62.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 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.PubMedPubMedCentralGoogle Scholar
  38. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Monteiro RC, Van De Winkel JG. IgA Fc receptors. Annu Rev Immunol. 2003;21:177–204.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Simister NE. Placental transport of immunoglobulin G. Vaccine. 2003;21(24):3365–9.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Hurley WL, Theil PK. Perspectives on immunoglobulins in colostrum and milk. Nutrients. 2011;3(4):442–74.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    McKay E, Thom H. Observations on neonatal tears. J Pediatr. 1969;75(6):1245–56.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Cohen AB, Goldberg S, London RL. Immunoglobulins in nasal secretions of infants. Clin Exp Immunol. 1970;6(5):753–60.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Sutherland DB, Fagarasan S. IgA synthesis: a form of functional immune adaptation extending beyond gut. Curr Opin Immunol. 2012;24(3):261–8.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Oen K, Petty RE, Schroeder ML. Immunoglobulin A deficiency: genetic studies. Tissue Antigens. 1982;19(3):174–82.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Schroeder HW Jr. Genetics of IgA deficiency and common variable immunodeficiency. Clin Rev Allergy Immunol. 2000;19(2):127–40.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Reboldi A, Cyster JG. Peyer’s patches: organizing B-cell responses at the intestinal frontier. Immunol Rev. 2016;271(1):230–45.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Cunningham-Rundles C. Physiology of IgA and IgA deficiency. J Clin Immunol. 2001;21(5):303–9.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Mackay F, Schneider P. Cracking the BAFF code. Nat Rev Immunol. 2009;9(7):491–502.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Cerutti A, Rescigno M. The biology of intestinal immunoglobulin A responses. Immunity. 2008;28(6):740–50.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Mackay F, Leung H. The role of the BAFF/APRIL system on T cell function. Semin Immunol. 2006;18(5):284–9.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Bossen C, Schneider P. BAFF, APRIL and their receptors: structure, function and signaling. Semin Immunol. 2006;18(5):263–75.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 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.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Richman LK, Brown WR. Immunochemical characterization of IgM in human intestinal fluids. J Immunol. 1977;119(4):1515–9.PubMedPubMedCentralGoogle Scholar
  80. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Stead A, Douglas JG, Broadfoot CJ, Kaminski ER, Herriot R. Humoral immunity and bronchiectasis. Clin Exp Immunol. 2002;130(2):325–30.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    McNabb PC, Tomasi TB. Host defense mechanisms at mucosal surfaces. Annu Rev Microbiol. 1981;35:477–96.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 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.PubMedPubMedCentralGoogle Scholar
  86. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 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.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Chow MA, Lebwohl B, Reilly NR, Green PH. Immunoglobulin A deficiency in celiac disease. J Clin Gastroenterol. 2012;46(10):850–4.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Vyas GN, Perkins HA, Fudenberg HH. Anaphylactoid transfusion reactions associated with anti-IgA. Lancet. 1968;2(7563):312–5.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Laschinger C, Shepherd FA, Naylor DH. Anti-IgA-mediated transfusion reactions in Canada. Can Med Assoc J. 1984;130(2):141–4.PubMedPubMedCentralGoogle Scholar
  92. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Sandler SG, Mallory D, Malamut D, Eckrich R. IgA anaphylactic transfusion reactions. Transfus Med Rev. 1995;9(1):1–8.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 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.PubMedPubMedCentralGoogle Scholar
  95. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Garcia JM, Espanol T, Gurbindo MD, Casas CC. Update on the treatment of primary immunodeficiencies. Allergol Immunopathol (Madr). 2007;35(5):184–92.CrossRefGoogle Scholar
  104. 104.
    Gustafson R, Gardulf A, Granert C, Hansen S, Hammarstrom L. Prophylactic therapy for selective IgA deficiency. Lancet. 1997;350(9081):865.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Ludvigsson JF, Neovius M, Hammarstrom L. IgA deficiency and mortality: a population-based cohort study. J Clin Immunol. 2013;33(8):1317–24.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 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.PubMedPubMedCentralGoogle Scholar
  115. 115.
    Hammarstrom L, Smith CI. HLA-A, B, C and DR antigens in immunoglobulin A deficiency. Tissue Antigens. 1983;21(1):75–9.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    French MA, Dawkins RL. Central MHC genes, IgA deficiency and autoimmune disease. Immunol Today. 1990;11(8):271–4.PubMedCrossRefPubMedCentralGoogle Scholar
  118. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 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.CrossRefGoogle Scholar
  121. 121.
    Wilton AN, Cobain TJ, Dawkins RL. Family studies of IgA deficiency. Immunogenetics. 1985;21(4):333–42.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  125. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 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.PubMedPubMedCentralGoogle Scholar
  127. 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.CrossRefGoogle Scholar
  128. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 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.PubMedPubMedCentralGoogle Scholar
  130. 130.
    Cassidy JT, Burt A, Petty R, Sullivan D. Selective IgA deficiency in connective tissue diseases. N Engl J Med. 1969;280(5):275.PubMedPubMedCentralGoogle Scholar
  131. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  132. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 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.PubMedPubMedCentralGoogle Scholar
  134. 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.PubMedPubMedCentralGoogle Scholar
  135. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  136. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  137. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Ezeoke A. Selective IgA deficiency (SIgAD) in Eastern Nigeria. Afr J Med Med Sci. 1988;17(1):17–21.PubMedPubMedCentralGoogle Scholar
  139. 139.
    Wells JV, McNally MP, King MA. Selective IgA deficiency in Australian blood donors. Aust NZ J Med. 1980;10(4):410–3.CrossRefGoogle Scholar
  140. 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. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 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.PubMedPubMedCentralGoogle Scholar
  143. 143.
    Koistinen J. Selective IgA deficiency in blood donors. Vox Sang. 1975;29(3):192–202.PubMedCrossRefPubMedCentralGoogle Scholar
  144. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  145. 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.Google Scholar
  146. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  147. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Velbri S, Pärlist M, Leito K. Primaarne immuunpuudulikkus. Eestis Eesti Arst. 2005;84:310–4.Google Scholar
  149. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  151. 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. 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.PubMedPubMedCentralGoogle Scholar
  153. 153.
    Sharon R, Amar A. IgA deficiency in Israeli blood donors. J Clin Pathol. 1982;35(5):582–3.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 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. 155.
    Yadav M, Iyngkaran N. Low incidence of selective IgA deficiency in normal Malaysians. Med J Malaysia. 1979;24:145–8.Google Scholar
  156. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 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.CrossRefGoogle Scholar
  158. 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.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • K. Sofia Appelberg
    • 1
  • Hassan Abolhassani
    • 1
  • Lennart Hammarström
    • 1
    Email author
  1. 1.Division of Clinical Immunology, Department of Laboratory MedicineKarolinska Institute, Karolinska University HospitalStockholmSweden

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