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. 1986 Aug;78(2):533–538. doi: 10.1172/JCI112605

Combined influences of Gm and HLA phenotypes upon multiple sclerosis susceptibility and severity.

J P Salier, R Sesboüé, C Martin-Mondière, M Daveau, P Cesaro, B Cavelier, A Coquerel, L Legrand, J M Goust, J D Degos
PMCID: PMC423590  PMID: 3461005

Abstract

In some Caucasian populations, multiple sclerosis (MS) susceptibility has been independently related to given alleles of HLA or Gm systems that respectively code for major histocompatibility complex class I and II antigens or immunoglobulin G heavy chains. Whether given combinations of alleles at both series of loci simultaneously influence MS susceptibility and/or severity was investigated by comparing 147 French MS patients and 226 geographically-matched healthy controls. The G2m(-23)/HLA-B35 phenotype and G1m(-1)/HLA-B7(-)/HLA-DR2 phenotype were respectively associated with significant protection against (relative risk = 0.05) and susceptibility to (relative risk = 4.3) MS. When considering MS severity, the presence of HLA-B7 antigen correlated with a more severe disease in Gm1/Gm3 heterozygous patients, but not in Gm3/Gm3 homozygous patients. Conversely, an HLA-B12-associated milder disease was restricted to Gm3/Gm3 homozygotes. These results demonstrate the combined influence on MS of genetic loci that are unlinked but immune response-associated. Combined Gm and HLA typing is very likely able to serve as a prognostic indicator in this disease.

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Selected References

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

  1. Bertrams J., Kuwert E., Liedtke U. HL-A antigens and multiple sclerosis. Tissue Antigens. 1972;2(5):405–408. doi: 10.1111/j.1399-0039.1972.tb00060.x. [DOI] [PubMed] [Google Scholar]
  2. Cohen D., Cohen O., Marcadet A., Massart C., Lathrop M., Deschamps I., Hors J., Schuller E., Dausset J. Class II HLA-DC beta-chain DNA restriction fragments differentiate among HLA-DR2 individuals in insulin-dependent diabetes and multiple sclerosis. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1774–1778. doi: 10.1073/pnas.81.6.1774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Degos L., Dausset J. Letter: Histocompatibility determinants in multiple sclerosis. Lancet. 1974 Feb 23;1(7852):307–308. doi: 10.1016/s0140-6736(74)92609-9. [DOI] [PubMed] [Google Scholar]
  4. Goust J. M., Hoffman P. M., Pryjma J., Hogan E. L., Fudenberg H. H. Defective immunoregulation in multiple sclerosis. Ann Neurol. 1980 Nov;8(5):526–533. doi: 10.1002/ana.410080510. [DOI] [PubMed] [Google Scholar]
  5. Goust J. M., Hogan E. L., Arnaud P. Abnormal regulation of IgG production in multiple sclerosis. Neurology. 1982 Mar;32(3):228–234. doi: 10.1212/wnl.32.3.228. [DOI] [PubMed] [Google Scholar]
  6. Haile R. W., Goldstein A., Field L., Marazita M. L. A linkage analysis of the Gm locus and multiple sclerosis. Genet Epidemiol. 1985;2(1):29–34. doi: 10.1002/gepi.1370020104. [DOI] [PubMed] [Google Scholar]
  7. Haile R. W., Hodge S. E., Iselius L. Genetic susceptibility to multiple sclerosis: a review. Int J Epidemiol. 1983 Mar;12(1):8–16. doi: 10.1093/ije/12.1.8. [DOI] [PubMed] [Google Scholar]
  8. Herndon R. M., Rudick R. A. Multiple sclerosis. The spectrum of severity. Arch Neurol. 1983 Sep;40(9):531–532. doi: 10.1001/archneur.1983.04050080031002. [DOI] [PubMed] [Google Scholar]
  9. Ho H. Z., Tiwari J. L., Haile R. W., Terasaki P. I., Morton N. E. HLA-linked and unlinked determinants of multiple sclerosis. Immunogenetics. 1982;15(5):509–517. doi: 10.1007/BF00345910. [DOI] [PubMed] [Google Scholar]
  10. Jersild C., Fog T., Hansen G. S., Thomsen M., Svejgaard A., Dupont B. Histocompatibility determinants in multiple sclerosis, with special reference to clinical course. Lancet. 1973 Dec 1;2(7840):1221–1225. doi: 10.1016/s0140-6736(73)90970-7. [DOI] [PubMed] [Google Scholar]
  11. Kurtzke J. F. Neurologic impairment in multiple sclerosis and the disability status scale. Acta Neurol Scand. 1970;46(4):493–512. doi: 10.1111/j.1600-0404.1970.tb05808.x. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. McFarlin D. E., McFarland H. F. Multiple sclerosis (first of two parts). N Engl J Med. 1982 Nov 4;307(19):1183–1188. doi: 10.1056/NEJM198211043071905. [DOI] [PubMed] [Google Scholar]
  14. Mittal K. K., Mickey M. R., Singal D. P., Terasaki P. I. Serotyping for homotransplantation. 18. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation. 1968 Nov;6(8):913–927. doi: 10.1097/00007890-196811000-00006. [DOI] [PubMed] [Google Scholar]
  15. Pandey J. P., Goust J. M., Salier J. P., Fudenberg H. H. Immunoglobulin G heavy chain (Gm) allotypes in multiple sclerosis. J Clin Invest. 1981 Jun;67(6):1797–1800. doi: 10.1172/JCI110220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pandey J. P., Shannon B. T., Tsang K. Y., Fudenberg H. H., Camblin J. G. Heterozygosity at Gm loci associated with humoral immunity to osteosarcoma. J Exp Med. 1982 Apr 1;155(4):1228–1232. doi: 10.1084/jem.155.4.1228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pollard P. A., Shafar J., Knowlson P. A., Tallett E. R. Clonidine in migraine. Lancet. 1972 Jun 3;1(7762):1242–1243. doi: 10.1016/s0140-6736(72)90965-8. [DOI] [PubMed] [Google Scholar]
  18. Propert D. N., Bernard C. C., Simons M. J. Gm allotypes and multiple sclerosis. J Immunogenet. 1982 Oct;9(5):359–361. doi: 10.1111/j.1744-313x.1982.tb00994.x. [DOI] [PubMed] [Google Scholar]
  19. Roos R. P. B-cell abnormalities in multiple sclerosis. A hypothesis. Arch Neurol. 1985 Jan;42(1):73–75. doi: 10.1001/archneur.1985.04060010079020. [DOI] [PubMed] [Google Scholar]
  20. SCHUMACHER G. A., BEEBE G., KIBLER R. F., KURLAND L. T., KURTZKE J. F., MCDOWELL F., NAGLER B., SIBLEY W. A., TOURTELLOTTE W. W., WILLMON T. L. PROBLEMS OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS: REPORT BY THE PANEL ON THE EVALUATION OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS. Ann N Y Acad Sci. 1965 Mar 31;122:552–568. doi: 10.1111/j.1749-6632.1965.tb20235.x. [DOI] [PubMed] [Google Scholar]
  21. Salier J. P., Martin-Mondiere C., Sesboü R., Daveau M., Goust J. M., Govaerts A., Schuller E., Degos J. D. HLA-DR-dependent variation of intrathecal IgG1 (Gm) allotype synthesis in multiple sclerosis. J Immunol. 1985 Mar;134(3):1551–1554. [PubMed] [Google Scholar]
  22. Sandberg-Wollheim M., Baird L. G., Schanfield M. S., Knoppers M. H., Youker K., Tachovsky T. G. Association of CSF IgG concentration and immunoglobulin allotype in multiple sclerosis and optic neuritis. Clin Immunol Immunopathol. 1984 May;31(2):212–221. doi: 10.1016/0090-1229(84)90241-1. [DOI] [PubMed] [Google Scholar]
  23. Sesboü R., Daveau M., Degos J. D., Martin-Mondiere C., Goust J. M., Schuller E., Rivat-Peran L., Coquerel A., Dujardin M., Salier J. P. IgG (Gm) allotypes and multiple sclerosis in a French population: phenotype distribution and quantitative abnormalities in CSF with respect to sex, disease severity, and presence of intrathecal antibodies. Clin Immunol Immunopathol. 1985 Nov;37(2):143–153. doi: 10.1016/0090-1229(85)90145-x. [DOI] [PubMed] [Google Scholar]
  24. Stendahl-Brodin L., Link H., Möller E., Norrby E. Genetic basis of multiple sclerosis: HLA antigens, disease progression, and oligoclonal IgG in CSF. Acta Neurol Scand. 1979 Jun;59(6):297–308. doi: 10.1111/j.1600-0404.1979.tb02940.x. [DOI] [PubMed] [Google Scholar]
  25. Svejgaard A., Jersild C., Nielsen L. S., Bodmer W. F. HL-A antigens and disease. Statistical and genetical considerations. Tissue Antigens. 1974;4(2):95–105. doi: 10.1111/j.1399-0039.1974.tb00230.x. [DOI] [PubMed] [Google Scholar]
  26. Uno H., Sasazuki T., Tamai H., Matsumoto H. Two major genes, linked to HLA and Gm, control susceptibility to Graves' disease. Nature. 1981 Aug 20;292(5825):768–770. doi: 10.1038/292768a0. [DOI] [PubMed] [Google Scholar]
  27. Waksman B. H., Reynolds W. E. Multiple sclerosis as a disease of immune regulation. Proc Soc Exp Biol Med. 1984 Mar;175(3):282–294. doi: 10.3181/00379727-175-41798. [DOI] [PubMed] [Google Scholar]
  28. Xu X. H., McFarlin D. E. Oligoclonal bands in CSF: twins with MS. Neurology. 1984 Jun;34(6):769–774. doi: 10.1212/wnl.34.6.769. [DOI] [PubMed] [Google Scholar]

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