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Excluded GM-specific IgG Subclass Genes in Health and Disease - Inborn Errors of Immunity

Oxelius, Vivi Anne LU (2026) In Journal of Clinical Immunology 46(1).
Abstract

Purpose: IgG subclass genes from chromosome 14q32.3 are assessed serologically by GM allotypes, genetic markers of the Fc part of the immunoglobulin constant heavy G chains, (IGHG(Fcγ)(GM) genes. Alternative GM allotypes of IgG3, IgG1 and IgG2, respectively, define 6 unique, precise GM-specific IgG subclass genes, inherited the Mendelian way with allelic exclusion, and linkage disequilibrium of IgG3-IgG1. Increased number of homozygous GM-specific IgG subclass genotypes with total loss of alternative IgG subclass molecules, inborn errors of immunity (IEI), are found in severe immunological diseases. Methods: A novel ELISA using GM-specific myeloma proteins and GM-specific monoclonals, identifies 6 alternative GM-specific IgG subclass... (More)

Purpose: IgG subclass genes from chromosome 14q32.3 are assessed serologically by GM allotypes, genetic markers of the Fc part of the immunoglobulin constant heavy G chains, (IGHG(Fcγ)(GM) genes. Alternative GM allotypes of IgG3, IgG1 and IgG2, respectively, define 6 unique, precise GM-specific IgG subclass genes, inherited the Mendelian way with allelic exclusion, and linkage disequilibrium of IgG3-IgG1. Increased number of homozygous GM-specific IgG subclass genotypes with total loss of alternative IgG subclass molecules, inborn errors of immunity (IEI), are found in severe immunological diseases. Methods: A novel ELISA using GM-specific myeloma proteins and GM-specific monoclonals, identifies 6 alternative GM-specific IgG subclass genes and molecules IgG3*b & IgG3*g, IgG1*f & IgG1*a and IgG2*n & IgG2*-n, with different structures and functions. 4 different IgG3-IgG1-IgG2 haplotypes encode 10 individual IGHG diplotypes from 10 innate lymphoid combined B cells in 587 healthy. Results: The alternative GM-specific IgG subclass genes have different structures and functions and respond differently in immunotherapy to antigen stimulation with virus, bacteria and allergens. In this report we focus on excluded GM-IgG subclass genes, inborn errors of immunity (IEI) dominating in severe immunological diseases, severe infections, primary immunodeficiencies (PIDs), JCA, asthma, diabetes type 1 and malignancy. By intravenous immunoglobulins (IVIG) the excluded IgG subclass molecules are supplied and may prevent primary virus attacks and exacerbations in autoimmune disorders. IgG subclass genes orchestrate additional immune factors of inflammation. Conclusion: Excluded GM-specific IgG subclass genes, IEI explore diagnosis, pathogenesis, prognosis and different phenotypes in immunological diseases, with IVIG as treatment.

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By mendelian inheritance the homozygous genotypes have excluded alternative IgG subclass genes with total loss of alternative IgG subclass molecules, IgG1 and IgG2 subclasses, IgG1*f & IgG1*a and IgG2*n & IgG2*-n on chromosome 14q32.3, Inborn errors of immunity, Precise alternative GM-specific Fc parts of heavy constant G chains of IgG3, Respectively: IgG3*b & IgG3*g, Significantly increased in immunological disease, With IVIG as possible treatment
in
Journal of Clinical Immunology
volume
46
issue
1
article number
37
publisher
Springer
external identifiers
  • scopus:105034877444
  • pmid:41863686
ISSN
0271-9142
DOI
10.1007/s10875-026-02001-5
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2026.
id
61a6c3ef-2d3b-4951-a4bb-f27882e1173a
date added to LUP
2026-05-21 14:44:39
date last changed
2026-06-04 15:42:37
@article{61a6c3ef-2d3b-4951-a4bb-f27882e1173a,
  abstract     = {{<p>Purpose: IgG subclass genes from chromosome 14q32.3 are assessed serologically by GM allotypes, genetic markers of the Fc part of the immunoglobulin constant heavy G chains, (IGHG(Fcγ)(GM) genes. Alternative GM allotypes of IgG3, IgG1 and IgG2, respectively, define 6 unique, precise GM-specific IgG subclass genes, inherited the Mendelian way with allelic exclusion, and linkage disequilibrium of IgG3-IgG1. Increased number of homozygous GM-specific IgG subclass genotypes with total loss of alternative IgG subclass molecules, inborn errors of immunity (IEI), are found in severe immunological diseases. Methods: A novel ELISA using GM-specific myeloma proteins and GM-specific monoclonals, identifies 6 alternative GM-specific IgG subclass genes and molecules IgG3*b &amp; IgG3*g, IgG1*f &amp; IgG1*a and IgG2*n &amp; IgG2*-n, with different structures and functions. 4 different IgG3-IgG1-IgG2 haplotypes encode 10 individual IGHG diplotypes from 10 innate lymphoid combined B cells in 587 healthy. Results: The alternative GM-specific IgG subclass genes have different structures and functions and respond differently in immunotherapy to antigen stimulation with virus, bacteria and allergens. In this report we focus on excluded GM-IgG subclass genes, inborn errors of immunity (IEI) dominating in severe immunological diseases, severe infections, primary immunodeficiencies (PIDs), JCA, asthma, diabetes type 1 and malignancy. By intravenous immunoglobulins (IVIG) the excluded IgG subclass molecules are supplied and may prevent primary virus attacks and exacerbations in autoimmune disorders. IgG subclass genes orchestrate additional immune factors of inflammation. Conclusion: Excluded GM-specific IgG subclass genes, IEI explore diagnosis, pathogenesis, prognosis and different phenotypes in immunological diseases, with IVIG as treatment.</p>}},
  author       = {{Oxelius, Vivi Anne}},
  issn         = {{0271-9142}},
  keywords     = {{By mendelian inheritance the homozygous genotypes have excluded alternative IgG subclass genes with total loss of alternative IgG subclass molecules; IgG1 and IgG2 subclasses; IgG1*f & IgG1*a and IgG2*n & IgG2*-n on chromosome 14q32.3; Inborn errors of immunity; Precise alternative GM-specific Fc parts of heavy constant G chains of IgG3; Respectively: IgG3*b & IgG3*g; Significantly increased in immunological disease; With IVIG as possible treatment}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer}},
  series       = {{Journal of Clinical Immunology}},
  title        = {{Excluded GM-specific IgG Subclass Genes in Health and Disease - Inborn Errors of Immunity}},
  url          = {{http://dx.doi.org/10.1007/s10875-026-02001-5}},
  doi          = {{10.1007/s10875-026-02001-5}},
  volume       = {{46}},
  year         = {{2026}},
}