Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1995 Feb;99(2):211–215. doi: 10.1111/j.1365-2249.1995.tb05534.x

Linkage of IgA deficiency to Gm allotypes; the influence of Gm allotypes on IgA-IgG subclass deficiency.

V A Oxelius 1, A M Carlsson 1, L Hammarström 1, J Björkander 1, L A Hanson 1
PMCID: PMC1534286  PMID: 7851013

Abstract

IgA deficiency (IgAD) is the most common immunodeficiency, characterized by an arrest in B cell differentiation. It has a sporadic occurrence or variable inheritance pattern, and is also linked to the HLA genes. IgA deficiency is sometimes associated with IgG subclass deficiency. In this study the Gm allotypes, as genetic characteristics of the IgG1, IgG2 and IgG3, were analysed in 83 Caucasian IgAD individuals. Half of the patients presented with IgG4 < 0.01 g/l compared with 5% (P < 0.001) in a healthy population. Three of the 83 had significantly low IgG2 and four had significantly low IgG3 levels. Gm allotype frequencies in IgAD deviated compared with a normal population. Of the 83 patients, 44 (53%) showed homozygous G2 m(",") expression on the IgG2 locus (33% in controls, P < 0.01). In IgAD the Gm(a,",g) haplotype was more frequent (43%) compared with controls (31%, P < 0.01). The Gm homozygous phenotype Gm(a,",g/a,",g) was most common, found in 20 of 83 patients (24%, P < 0.05) compared with controls (14%). On the other hand the Gm(f,n,b) haplotype of IgAD was rare (28%) compared with controls (45%, P < 0.001). The low IgG4, < 0.01 g/l, found in 50% of the patients, was even more frequent (56-69%) among the G2 m(",") phenotypes. IgG subclass levels were given for different Gm phenotypes of the IgAD group and compared with controls. Significantly low IgG4 was revealed in the Gm(a,",g/a,",g) phenotype (P < 0.01) and significantly low IgG2 in the Gm(a,",g/f,",b) phenotype (P < 0.01). The Gm(a,",g/f,",b) phenotype contained the three patients found with IgG2 levels < -2 s.d., and the four patients with IgG3 levels < -2 s.d. were present among those with the homozygous Gm(a,",g/a,",g) phenotype; both phenotypes with G2 m(",") on the IgG2 locus. The 'compensatory' increase of IgG was significant for both IgG1 and IgG3 in all Gm phenotypes, but in the Gm(a,",g/f,",b). Thus, the susceptibility of IgAD with the additional IgG antibody deficiencies, down-regulated IgG4 and IgG2/IgG3, is associated with Gm allotypes, especially the homozygous G2 m(",") expression on the IgG2 locus.

Full text

PDF
213

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ambrus M., Hernádi E., Bajtai G. Prevalence of HLA-A1 and HLA-B8 antigens in selective IgA deficiency. Clin Immunol Immunopathol. 1977 May;7(3):311–314. doi: 10.1016/0090-1229(77)90062-9. [DOI] [PubMed] [Google Scholar]
  2. Cunningham-Rundles C., Oxelius V. A., Good R. A. IgG2 and IgG3 subclass deficiencies in selective IgA deficiency in the United States. Birth Defects Orig Artic Ser. 1983;19(3):173–175. [PubMed] [Google Scholar]
  3. Granoff D. M., Suarez B. K., Pandey J. P., Shackelford P. G. Genes associated with the G2m(23) immunoglobulin allotype regulate the IgG subclass responses to Haemophilus influenzae type b polysaccharide vaccine. J Infect Dis. 1988 Jun;157(6):1142–1149. doi: 10.1093/infdis/157.6.1142. [DOI] [PubMed] [Google Scholar]
  4. Hammarström L., Axelsson U., Björkander J., Hanson L. A., Möller E., Smith C. I. HLA antigens in selective IgA deficiency: distribution in healthy donors and patients with recurrent respiratory tract infections. Tissue Antigens. 1984 Jul;24(1):35–39. doi: 10.1111/j.1399-0039.1984.tb00395.x. [DOI] [PubMed] [Google Scholar]
  5. Hammarström L., Carlsson B., Smith C. I., Wallin J., Wieslander L. Detection of IgA heavy chain constant region genes in IgA deficient donors: evidence against gene deletions. Clin Exp Immunol. 1985 Jun;60(3):661–664. [PMC free article] [PubMed] [Google Scholar]
  6. Hammarström L., Grubb R., Smith C. I. Gm allotypes in IgA deficiency. J Immunogenet. 1985 Jun;12(3):125–130. doi: 10.1111/j.1744-313x.1985.tb00839.x. [DOI] [PubMed] [Google Scholar]
  7. Legrand L., Rivat-Perran L., Huttin C., Dausset J. HLA-and Gm-linked genes affecting the degradation rate of antigens (sheep red blood cells) endocytized by macrophages. Hum Immunol. 1982 Feb;4(1):1–13. doi: 10.1016/0198-8859(82)90045-3. [DOI] [PubMed] [Google Scholar]
  8. Morell A., Skvaril F., Steinberg A. G., Van Loghem E., Terry W. D. Correlations between the concentrations of the four sub-classes of IgG and Gm Allotypes in normal human sera. J Immunol. 1972 Jan;108(1):195–206. [PubMed] [Google Scholar]
  9. Natvig J. B., Harboe M., Fausa O., Tveit A. Family studies in individuals with selective absence of gamma-A-globulin. Clin Exp Immunol. 1971 Feb;8(2):229–236. [PMC free article] [PubMed] [Google Scholar]
  10. Oxelius V. A., Carlsson A. M. Quantitation of Gm allotypes. Scand J Immunol. 1993 Feb;37(2):143–148. doi: 10.1111/j.1365-3083.1993.tb01749.x. [DOI] [PubMed] [Google Scholar]
  11. Oxelius V. A. Correlation between atopy and Gm allotypes. Int Arch Allergy Appl Immunol. 1990;91(1):54–57. doi: 10.1159/000235089. [DOI] [PubMed] [Google Scholar]
  12. Oxelius V. A. Gm allotype genes and gene dosage affecting both IgG subclass and IgE levels in atopic patients. Int Arch Allergy Appl Immunol. 1990;91(1):58–61. doi: 10.1159/000235090. [DOI] [PubMed] [Google Scholar]
  13. Oxelius V. A. Lack of the G2m(n) allotype in IgG subclass deficiency, in IgG2 deficiency together with lack of G1m(a) and G3m(g), and in IgG3 deficiency together with lack of G1m(f) and G3m(b). Scand J Immunol. 1990 Feb;31(2):243–247. doi: 10.1111/j.1365-3083.1990.tb02765.x. [DOI] [PubMed] [Google Scholar]
  14. Oxelius V. A., Laurell A. B., Lindquist B., Golebiowska H., Axelsson U., Björkander J., Hanson L. A. IgG subclasses in selective IgA deficiency: importance of IgG2-IgA deficiency. N Engl J Med. 1981 Jun 11;304(24):1476–1477. doi: 10.1056/NEJM198106113042408. [DOI] [PubMed] [Google Scholar]
  15. Oxelius V. A. Serum IgG and IgG subclass contents in different Gm phenotypes. Scand J Immunol. 1993 Feb;37(2):149–153. doi: 10.1111/j.1365-3083.1993.tb01750.x. [DOI] [PubMed] [Google Scholar]
  16. Pandey J. P., Fudenberg H. H., Virella G., Kyong C. U., Loadholt C. B., Galbraith R. M., Gotschlich E. C., Parke J. C., Jr Association between immunoglobulin allotypes and immune responses to Haemophilus influenzae and Meningococcus polysaccharides. Lancet. 1979 Jan 27;1(8109):190–192. doi: 10.1016/s0140-6736(79)90584-1. [DOI] [PubMed] [Google Scholar]
  17. ROCKEY J. H., HANSON L. A., HEREMANS J. F., KUNKEL H. G. BETA-2A AGLOBULINEMIA IN TWO HEALTHY MEN. J Lab Clin Med. 1964 Feb;63:205–212. [PubMed] [Google Scholar]
  18. Rautonen N., Seppälä I., Hallberg T., Grubb R., Mäkelä O. Determination of homozygosity or heterozygosity for the G2m(n) allotype by a monoclonal, precipitating antibody. Exp Clin Immunogenet. 1989;6(1):31–38. [PubMed] [Google Scholar]
  19. Sarvas H., Rautonen N., Sipinen S., Mäkelä O. IgG subclasses of pneumococcal antibodies--effect of allotype G2m(n). Scand J Immunol. 1989 Feb;29(2):229–237. doi: 10.1111/j.1365-3083.1989.tb01120.x. [DOI] [PubMed] [Google Scholar]
  20. Schaffer F. M., Palermos J., Zhu Z. B., Barger B. O., Cooper M. D., Volanakis J. E. 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 Oct;86(20):8015–8019. doi: 10.1073/pnas.86.20.8015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Steinberg A. G., Morell A., Skvaril F., van Loghem E. The effect of Gm(23) on the concentration of IgG2 and IgG4 in normal human serum. J Immunol. 1973 Jun;110(6):1642–1645. [PubMed] [Google Scholar]
  22. Yount W. J., Kunkel H. G., Litwin S. D. Studies of the Vi (gamma-2c) subgroup of gamma-globulin. A relationship between concentration and genetic type among normal individuals. J Exp Med. 1967 Jan 1;125(1):177–190. doi: 10.1084/jem.125.1.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. van Loghem E. Familial occurrence of isolated IgA deficiency associated with antibodies to IgA. Evidence against a structural gene defect. Eur J Immunol. 1974 Jan;4(1):57–60. doi: 10.1002/eji.1830040115. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES