Abstract
Although secretory immunoglobulin A (IgA) is important in mucosal immunity, selective IgA deficiency is the most common primary immunodeficiency of humans. In most cases this defect is not associated with any illness. The reasons for this are unknown, but other immunological compensations might provide sufficient or complete restitution. Alternatively, it is possible that IgA deficiency alone may not predispose to disease, but additional immunological abnormalities might be present in symptomatic individuals. Some IgA-deficient individuals have a reduced antibody response to immunizations (even with normal IgG and IgM levels) and others have deficient responses to bacterial polysaccharides when IgG subclass levels are normal. The physiological role of IgA, the frequency and causes of IgA deficiency, the diseases associated with its absence, and current limited understanding of the pathogenesis of selective IgA deficiency will be reviewed.
Similar content being viewed by others
REFERENCES
Tomasi TB: The discovery of secretory IgA and the mucosal immune system. Immunol Today 13:416–418, 1992
Mestecky J, McGhee JR: Immunoglobulin A (IgA): Molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv Immunol 40:153–245, 1987
Lamm ME: Current concepts in mucosal immunity IV. How epithelial transport of IgA antibodies relates to host defense. Am J Pathol 614–617, 1998
Mostov KE, Friedlander M, Blobel G: The receptor for transepithelial transport of IgA and IgM contains multiple immunoglobulin–like domains. Nature 308:37–43, 1984
Singer KL, Mostov KE: Dimerization of thepolymeric immunoglobulin receptor controls its trancytotic trafficking. Mol Biol Cell 9:901–915, 1998
Fallgreen–Gebauer E, Gebauer W, Bastian A, Kratzin HD, Eiffert H, Zimmermann B, Karas M, Hilschmann N: The covalent linkage of secretory component to IgA. Structure of slgA. Biol Chem Hoppe Seyler 374:1023–1028, 1993
Mazanec MB, Kaetzel CS, Lamm ME, Fletcher D, Nedrud JG: Intracellular neutralization of virus by immunoglobulin A antibodies. Proc Natl Acad Sci USA 89:6901–6905, 1992
Kaetzel CS, Robinson JK, Chintalacharuvu KR, Vaerman JP, Lamm ME: The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: A local defense function for IgA. Proc Natl Acad Sci USA 88:8796–8800, 1991
Kerr MA: The structure and function of human IgA. J Biochem 271:285–296, 1990
Monteiro RC, Kubagawa H, Cooper MD: Cellular distribution, regulation, and biochemical nature of an Fc alpha receptor in humans. J Exp Med 171:597–613, 1990
Conley ME, Delacroix DL: Intravascular and mucosal immunoglobulin A: Two separate but related systems of immune defence? Ann Intern Med 106:892–899, 1987
Thieffry S, Arthuis M, Aicardi J, Lyon G: L'ataxie–telangiectasie (7 observations personnelles). Rev Neurol (Paris) 105:390–405, 1961
Hanson LA: Selective IgA–deficiency. In Primary and Secondary Immunodeficiency Disorders, RK Chandra (ed). New York, Churchill Livingstone, 1983, pp 62–84
Natvig IB, Johansen FE, Nordeng TW, Haraldsen G, Brandtzaeg P: Mechanism for enhanced external transfer of dimeric IgA over pentameric IgM: studies of diffusion, binding to the human polymeric Ig receptor, and epithelial transcytosis. J Immunol 159:4330–4340, 1997
Barros MD, Porto MHO, Leser PG, Greemach AS, Carniero–Sampaio MMS: Study of colostrum of a patient with selective IgA deficiency. Allergol Immunopathol 13:331–334, 1985
Klemola T: Immunohistochemical findings in the intestine of IgA–deficient persons. J Pediatr Gastroenterol Nutr 7:537–543, 1988
Savilahti E, Klemola T, Carlsson B, Mellander L, Stenvile M, Hovi T: Inadequacy of mucosal IgM antibodies in selective IgA deficiency: Excretion of attenuated polio viruses is prolonged. J Clin Immunol 8:89–94, 1988
Richman LK, Brown WR: Immunochemical characterization of IgM in intestinal fluids. J Immunol 199:1515–1521, 1977
Norhagen GE, Enaptrom PE, Hammerstrom L, Sder P, Smith CIE: Immunoglobulin levels in saliva in individuals with selective IgA deficiency. Compensatory IgM secretion and its correlation with HLA and susceptibility to infections. J Clin Immunol 9:279–286, 1989
Nilssen DE, Friman V, Theman K, Bjørkander J, Kilarder A, Holmgren J, Hanson LÅ, Brandtzaeg P: B cell activation in duodenal mucosa after oral cholera vaccination in IgA–deficient subjects with or without IgG subclass deficiency. Scand J Immunol 38:201–208, 1993
Ammann AJ, Hong R: Selective IgA deficiency: Presentation of 30 cases and a review of the literature. Medicine 60:223–236, 1971
Burks AW Jr, Steele RW. Selective IgA deficiency. Ann Allergy 57:3–13, 1986
Strober W, Sneller MC: IgA deficiency. Ann Allergy 66:363–375, 1991
Schaffer FM, Monteiro RC, Volanakis JE, Cooper MD: IgA deficiency. Immunodefic Rev 3:15–44, 1991
Cunningham–Rundles C: Disorders of the IgA system. In Immunologic Disorders of Infants and Children, 4th edi., ER Stiehm (ed). 1996, pp 423–442
Hammarstrom L, Vorechovsky I, Webster D: Selective IgA defi–ciency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol 120:225–231, 2000
Oxelius VA, Laurell AB, Linquist B, Golebiowska H, Axelsson U, Bjørkander J, Hanson LÅ: IgG subclasses in selective IgA deficiency. N Engl J Med 304:1476–1477, 1981
Bjørkander J, Bake B, Oxelius VA, Hanson LÅ: Impaired lung function in patients with IgA deficiency and low levels of IgG2 or IgG3. N Engl J Med 313:720–724, 1985
Crabbe PA, Carbonara AO, Heremans JF: The normal human intestinal mucosa as a major source of plasma cells containing gamma–A immunoglobulin. Lab Invest 14:235–248, 1965
Heneghan MA, Stevens FM, Cryan EM, Warner RH, McCarthy CF: Celiac sprue and immunodeficiency states: A 25–year review. J Clin Gastroenterol. 25:421–425, 1997
Buckley RH, Dees SC. Correlation of milk precipitins with IgA deficiency. N Engl J Med 281:465–469, 1969
Cunningham–Rundles C, Brandies W, Good RA, Day NK: Milk precipitins, circulating immune complexes and IgA deficiency. Proc Natl Acad Sci USA 75:3387–3389, 1978
Cunningham–Rundles C, Brandeis WE, Good RA, Day NK: Bovine antigens and the formation of circulating immune complexes in selective IgA deficiency. J Clin Invest 64:270–272, 1979
Vyas GN, Perkins HA, Fudenberg HH: Anaphylactoid transfusion reactions associated with anti–IgA. Lancet 2:312–315, 1968
Sandler SG, Mallory D, Malamut D, Eckrich R: IgA anaphylactic transfusion reactions. IgA anaphylactic transfusion reactions. Transfus Med Rev. 9:1–8, 1995
Laschinger C, Shepherd FA, Naylor DH Anti–IgA–mediated transfusion reactions in Canada. Can Med Assoc J 130:141–144, 1984
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 gammaglobulin. Clin Immunol Immunopathol 47:199–207, 1988
Sloper KS, Brook CGD, Kingston D, Pearson JR, Shiner M: Eczema and atopy in early childhood: Low IgA plasma cell counts in the jejunal mucosa. Arch Dis Child 56:939–943, 1981
Kanoh T, Mizumoto T, Yasuda N, Koya M, Ohno Y, Uchino H, Yoshimura K, Ohkubo Y, Yamaguchi H: Selective IgA deficiency in Japanese blood donors: Frequency and statistical analysis. Vox Sang 50:81–86, 1986
Yadav M, Iyngkaran N: Low incidence of selective IgA deficiency in normal Malaysians. Med J Malaysia 34:145–148, 1979
Oen K, Petty RE, Schroeder ML. Immunoglobulin A deficiency in genetic studies. Tissue Antigens 19:174–182, 1982
Koistinen J: Selective IgA deficiency in blood donors. Vox Sang 29:192–202, 1975
Vorechovsky I, Cullen M, Carrington M, Hammarstrom L, Webster AD: Fine mapping of IGADI in IgA deficiency and common variable immunodeficiency: Identification and characterization of haplotypes shared by affected members of 101 multiple–case families. J Immunol. 164:4408–4416, 2000
Petty RE, Sherry DD, Johannson J: Anti–IgA antibodies in pregnancy. N Engl J Med 313:1620–1625, 1985
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. 64:1096–1099, 1999
Wilton AN, Cobain TJ, Dawkins RL: Family studies of IgA deficiency. Immunogenetics 21:333–342, 1985
Cobain TJ, Stuckey MS, McCluskey J, Wilton A, Gedeon A, Garlepp MJ, Christiansen FT, Dawkins RL: The coexistence of IgA deficiency, and 21–hydroxylase deficiency marked by specific supra types. Ann NY Acad Sci 458:76–84, 1985
Schroeder HW Jr, Zhu ZB, March RE, Campbell RD, Berney SM, Nedospasov SA, Turetskaya RL, Atkinson TP, Go RC, Cooper MD, Volanakis JE: Susceptibility locus for IgA deficiency and common variable immunodeficiency in the HLA–DR3,–B8,–A1 haplotypes. Mol Med 14:72–86, 1998
Alper CA, Marcus–Bagley D, Awdeh Z, Kruskall MS, Eisenbarth GS, Brink SJ, Katz AJ, Stein R, Bing DH, Yunis EJ, Schur PH: Prospective analysis suggests susceptibility genes for deficiencies of IgA and several other immunoglobulins on the [HLA–B8, SC01, DR3] conserved extended haplotype. Tissue Antigens 56:207–216, 2000
Wilson MG, Towner JW, Forsman L, Siris E: Syndromes associated with the deletion of the long arm of chromosome 18. Am J Med Genet 8:155–174, 1979
Lewkonia RM, Lin CC, Haslam RHA. Selective IgA deficiency with 18q+ and 18q– karyotypic anomalies. J Med Genet 17:453–456, 1980
Vorechovsky I, Blennow E, Nordenskjold M, Webster AD, Hammarstrom L: A putative susceptibility locus on chromosome 18 is not a major contributor to human selective IgA deficiency: Evidence from meiotic mapping of 83 multiple–case families. J Immunol. 15;163:2236–2242, 1999
Hammarstrom L, Ringden O, Lonngvist B, Smith CIE, Wiebe T: Transfer of IgA deficiency to a bone marrow grafted patient with aplastic anemia Lancet 1:778–781, 1985
Lawton AR, Royal SA, Self KS, Cooper MD: IgA determinants on B lymphocytes in patients with deficiency of circulating IgA. J Lab Clin Med 80:26–33, 1972
Conley ME, Cooper MD: Immature IgA B cells in IgA–deficient patients. N Engl J Med 305:495–497, 1981
Wang Z, Yunis D, Irigoyen M, Kitchens B, Bottaro A, Alt FW, Alper CA: Discordance between IgA switching at the DNA level and IgA expression at the mRNA level in IgA–deficient patients. Clin Immunol 91:263–270, 1999
Wu LYF, Lawton AR; Copper MD: Analysis of IgG subclass production in cell cultures for IgA deficient patients and in normal controls as a function of age. J Clin Invest 52:3180–3189, 1973
King MA, Wells JV, Nelson DS: IgA synthesis by peripheral blood mononuclear cells from normal and selectively IgA deficient subjects. Clin Exp Immunol 38:306–315, 1979
Stavnezer J: Immunology. A touch of antibody class. Science. 288:984–985, 2000
Muller F, Aukrust P, Nilssen DE, Froland SS: Reduced serum level of transforming growth factor–beta in patients with IgA deficiency. Clin Immunol Immunopathol 76:203–208, 1995
Friman V, Hanson LA, Bridon JM, Tarkowski A, Banchereau J, Briere F: IL–10–driven immunoglobulin production by B lymphocytes from IgA–deficient individuals correlates to infection proneness. Clin Exp Immunol 104:432–438, 1996
Harriman GR, Bogue M, Rogers P, Finegold M, Pacheco S, Bradley A, Zhang Y, Mbawuike IN: Targeted deletion of the IgA constant region in mice leads to IgA deficiency with alterations in expression of other Ig isotypes. J Immunol 162:2521–2529, 1999
Mbawuike IN, Pacheco S, Acuna CL, Switzer KC, Zhang Y, Harriman GR: Mucosal immunity to influenza without IgA: An IgA knockout mouse model. J Immunol 162:2530–2537, 1999
van Ginkel FW, Wahl SM, Kearney JF, Kweon MN, Fujihashi K, Burrows PD, Kiyono H, McGhee JR: Partial IgA–deficiency with increased Th2–type cytokines in TGF–beta 1 knockout mice J Immunol 163:1951–1957, 1999
Cazac BB, Roes J: TGF–beta receptor controls B cell responsiveness and induction of IgA in vivo. Immunity 13:443–451, 2000
Hiroi T, Yanagita M, Iijima H, Iwatani K, Yoshida T, Takatsu K, Kiyono H: Deficiency of IL–5 receptor alpha–chain selectively influences the development of the common mucosal immune system independent IgA–producing B–1 cell in mucosa–associated tissues. J Immunol 15(162):821–828, 1999
Felsburg, PJ, Glickman LT, Shofer F, Kirkpatrick CE, HogenEsch H: Clinical immunologic and epidemiologic characteristics of canine selective IgA deficiency. Adv Exp Med Biol 216B:1461–1470, 1987
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cunningham-Rundles, C. Physiology of IgA and IgA Deficiency. J Clin Immunol 21, 303–309 (2001). https://doi.org/10.1023/A:1012241117984
Issue Date:
DOI: https://doi.org/10.1023/A:1012241117984