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. 1983 Feb 5;286(6363):425–428. doi: 10.1136/bmj.286.6363.425

Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility.

A H Fielder, M J Walport, J R Batchelor, R I Rynes, C M Black, I A Dodi, G R Hughes
PMCID: PMC1546768  PMID: 6401549

Abstract

The families of 29 patients with systemic lupus erythematosus and 42 normal subjects were studied to determine the inheritance of the HLA-A, B, C, and DR antigens and also the complement polymorphisms for C2, C4A, C4B, and Bf, which are encoded in the same region of the sixth chromosome. Null (silent) alleles for C4A, C4B, or C2 were found in 24 of the 29 (83%) patients compared with 18 of the 42 (43%) normal controls. HLA-DR3 was present in 20 (69%) of the patients and seven out of 39 (18%) of the normal controls. There was strong linkage disequilibrium between DR3 and the null alleles for C4A and C4B. The data did not permit the relative contributions of DR3 and null factors of C4A and C4B as genetic risk factors to be distinguished. The known association of systemic lupus erythematosus with uncommon inherited and acquired deficiencies of complement components suggests, however, that the presence of null alleles for C4A and C4B, as well as C2, found in most of the patients, is relevant to their genetic susceptibility to 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. Alper C. A., Boenisch T., Watson L. Genetic polymorphism in human glycine-rich beta-glycoprotein. J Exp Med. 1972 Jan;135(1):68–80. doi: 10.1084/jem.135.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Awdeh Z. L., Alper C. A. Inherited structural polymorphism of the fourth component of human complement. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3576–3580. doi: 10.1073/pnas.77.6.3576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Awdeh Z. L., Raum D., Alper C. A. Genetic polymorphism of human complement C4 and detection of heterozygotes. Nature. 1979 Nov 8;282(5735):205–207. doi: 10.1038/282205a0. [DOI] [PubMed] [Google Scholar]
  4. Bruun-Petersen G., Lamm L. U., Sørensen I. J., Buskjaer L., Mortensen J. P. Family studies of complement C4 and HLA in man. Hum Genet. 1981;58(3):260–267. doi: 10.1007/BF00294919. [DOI] [PubMed] [Google Scholar]
  5. Fu S. M., Kunkel H. G., Brusman H. P., Allen F. H., Jr, Fotino M. Evidence for linkage between HL-A histocompatibility genes and those involved in the synthesis of the second component of complement. J Exp Med. 1974 Oct 1;140(4):1108–1111. doi: 10.1084/jem.140.4.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Glass D., Raum D., Gibson D., Stillman J. S., Schur P. H. Inherited deficiency of the second component of complement. Rheumatic disease associations. J Clin Invest. 1976 Oct;58(4):853–861. doi: 10.1172/JCI108538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kohler P. F., Percy J., Campion W. M., Smyth C. J. Hereditary angioedema and "familial" lupus erythematosus in identical twin boys. Am J Med. 1974 Mar;56(3):406–411. doi: 10.1016/0002-9343(74)90623-8. [DOI] [PubMed] [Google Scholar]
  8. Lachmann P. J., Hobart M. J. Complement genetics in relation to HLA. Br Med Bull. 1978 Sep;34(3):247–252. doi: 10.1093/oxfordjournals.bmb.a071505. [DOI] [PubMed] [Google Scholar]
  9. Meo T., Atkinson J. P., Bernoco M., Bernoco D., Ceppellini R. Structural heterogeneity of C2 Complement protein and its genetic variants in man: a new polymorphism of the HLA region. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1672–1675. doi: 10.1073/pnas.74.4.1672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. O'Neill G. J., Miniter P., Pollack M. S., Dupont B. Different HLA antigen associations for the functionally active and inactive products of the complement C4F1 allele. Hum Immunol. 1980 Jul;1(1):23–30. doi: 10.1016/0198-8859(80)90006-3. [DOI] [PubMed] [Google Scholar]
  11. O'Neill G. J., Yang S. Y., Dupont B. Two HLA-linked loci controlling the fourth component of human complement. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5165–5169. doi: 10.1073/pnas.75.10.5165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. O'Neill G. J., Yang S. Y., Tegoli J., Berger R., Dupont B. Chido and Rodgers blood groups are distinct antigenic components of human complement C4. Nature. 1978 Jun 22;273(5664):668–670. doi: 10.1038/273668a0. [DOI] [PubMed] [Google Scholar]
  13. Phillips J. M., Dresser D. W. Isoelectric spectra of different classes of anti-erythrocyte antibodies. Eur J Immunol. 1973 Aug;3(8):524–527. doi: 10.1002/eji.1830030816. [DOI] [PubMed] [Google Scholar]
  14. Pincus T., Schur P. H., Rose J. A., Decker J. L., Talal N. Measurement of serum DNA-binding activity in systemic lupus erythematosus. N Engl J Med. 1969 Sep 25;281(13):701–705. doi: 10.1056/NEJM196909252811304. [DOI] [PubMed] [Google Scholar]
  15. Rittner C., Bertrams J. On the significance of C2, C4, and factor B polymorphisms in disease. Hum Genet. 1981;56(3):235–247. doi: 10.1007/BF00274674. [DOI] [PubMed] [Google Scholar]
  16. Rynes R. I. Inherited complement deficiency states and SLE. Clin Rheum Dis. 1982 Apr;8(1):29–47. [PubMed] [Google Scholar]
  17. Schifferli J. A., Bartolotti S. R., Peters D. K. Inhibition of immune precipitation by complement. Clin Exp Immunol. 1980 Nov;42(2):387–394. [PMC free article] [PubMed] [Google Scholar]
  18. Takahashi M., Takahashi S., Brade V., Nussenzweig V. Requirements for the solubilization of immune aggregates by complement. The role of the classical pathway. J Clin Invest. 1978 Aug;62(2):349–358. doi: 10.1172/JCI109135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Walport M. J., Black C. M., Batchelor J. R. The immunogenetics of SLE. Clin Rheum Dis. 1982 Apr;8(1):3–21. [PubMed] [Google Scholar]
  20. Wooley P. H., Griffin J., Panayi G. S., Batchelor J. R., Welsh K. I., Gibson T. J. HLA-DR antigens and toxic reaction to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis. N Engl J Med. 1980 Aug 7;303(6):300–302. doi: 10.1056/NEJM198008073030602. [DOI] [PubMed] [Google Scholar]

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