Abstract
After artificial immunization (immunotherapy) with ragweed antigens, specific immunoglobulin G (IgG) antibody (Ab) response to Ra5 was significantly associated with HLA-Dw2 (P less than 0.0001). From a total of 61 treated patients, all 22 Dw2+ subjects made good IgG Ab responses to Ra5 by year 2 of therapy (21 by year 1), even though 8 of them had no detectable IgG Ab and 9 had no detectable IgE Ab before therapy. The prevalence of IgG Ab response among 39 Dw2- subjects was markedly lower; only 11 (28%) responded well after 1-9 yr of therapy. Both by univariate and multivariate statistical analysis, Dw2 was also found to be strongly associated with the quantity of IgG Ab produced. In particular, both the strength and significance of the association between Dw2 and log[IgG Ab] response to Ra5 increased over a 3-yr period of ragweed therapy (P = 10(-9) by year 3). Multiple regression analysis also revealed a weak association with HLA-B13, which became apparent only after year 2 of therapy. Genetic hypotheses for these findings are discussed. In particular, the possibility of a second Ir gene, Ir-Ra5', separate from HLA-Dw2 and possibly located elsewhere in the genome, is considered.
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Selected References
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- Benacerraf B. Role of MHC gene products in immune regulation. Science. 1981 Jun 12;212(4500):1229–1238. doi: 10.1126/science.6165083. [DOI] [PubMed] [Google Scholar]
- Binz H., Wigzell H. Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. I. Demonstration of similar or identical idiotypes on IgG molecules and T-cell receptors with specificity for the same alloantigens. J Exp Med. 1975 Jul 1;142(1):197–211. doi: 10.1084/jem.142.1.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freidhoff L. R., Meyers D. A., Bias W. B., Chase G. A., Hussain R., Marsh D. G. A genetic-epidemiologic study of human immune responsiveness to allergens in an industrial population: I. Epidemiology of reported allergy and skin-test positivity. Am J Med Genet. 1981;9(4):323–340. doi: 10.1002/ajmg.1320090409. [DOI] [PubMed] [Google Scholar]
- HALDANE J. B. The estimation and significance of the logarithm of a ratio of frequencies. Ann Hum Genet. 1956 May;20(4):309–311. doi: 10.1111/j.1469-1809.1955.tb01285.x. [DOI] [PubMed] [Google Scholar]
- Jones P. P., Murphy D. B., McDevitt H. O. Two-gene control of the expression of a murine Ia antigen. J Exp Med. 1978 Oct 1;148(4):925–939. doi: 10.1084/jem.148.4.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lichtenstein L. M., Norman P. S., Winkenwerder W. L. Clinical and in vitro studies on the role of immunotherapy in ragweed hay fever. Am J Med. 1968 Apr;44(4):514–524. doi: 10.1016/0002-9343(68)90052-1. [DOI] [PubMed] [Google Scholar]
- Marsh D. G., Hsu S. H., Hussain R., Meyers D. A., Freidhoff L. R., Bias W. B. Genetics of human immune response to allergens. J Allergy Clin Immunol. 1980 May;65(5):322–332. doi: 10.1016/0091-6749(80)90208-0. [DOI] [PubMed] [Google Scholar]
- Marsh D. G., Hsu S. H., Roebber M., Ehrlich-Kautzky E., Freidhoff L. R., Meyers D. A., Pollard M. K., Bias W. B. HLA-Dw2: a genetic marker for human immune response to short ragweed pollen allergen Ra5. I. Response resulting primarily from natural antigenic exposure. J Exp Med. 1982 May 1;155(5):1439–1451. doi: 10.1084/jem.155.5.1439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norman P. S. An overview of immunotherapy: implications for the future. J Allergy Clin Immunol. 1980 Feb;65(2):87–96. doi: 10.1016/0091-6749(80)90191-8. [DOI] [PubMed] [Google Scholar]
- Norman P. S., Lichtenstein L. M., Marsh D. G. Studies on allergoids from naturally occurring allergens. IV. Efficacy and safety of long-term allergoid treatment of ragweed hay fever. J Allergy Clin Immunol. 1981 Dec;68(6):460–470. doi: 10.1016/0091-6749(81)90200-1. [DOI] [PubMed] [Google Scholar]
- Norman P. S., Lichtenstein L. M. The clinical and immunologic specificity of immunotherapy. J Allergy Clin Immunol. 1978 Jun;61(6):370–377. doi: 10.1016/0091-6749(78)90116-1. [DOI] [PubMed] [Google Scholar]
- Prouvost-Danon A., Mouton D., Abadie A., Mevel J. C., Biozzi G. Genetic regulation of IgE and agglutinating antibody synthesis in lines of mice selected for high and low immune responsiveness. Eur J Immunol. 1977 Jun;7(6):342–348. doi: 10.1002/eji.1830070604. [DOI] [PubMed] [Google Scholar]
- Schwartz R. H., David C. S., Dorf M. E., Benacerraf B., Paul W. E. Inhibition of dual Ir gene-controlled T-lymphocyte proliferative response to poly (Glu56Lys35Phe9)n with anti-Ia antisera directed against products of either I-A or I-C subregion. Proc Natl Acad Sci U S A. 1978 May;75(5):2387–2391. doi: 10.1073/pnas.75.5.2387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Uhr J. W., Capra J. D., Vitetta E. S., Cook R. G. Organization of the immune response genes. Science. 1979 Oct 19;206(4416):292–297. doi: 10.1126/science.113876. [DOI] [PubMed] [Google Scholar]
- Vaz N. M., Levine B. B. Immune responses of inbred mice to repeated low doses of antigen: relationship to histocompatibility (H-2) type. Science. 1970 May 15;168(3933):852–854. doi: 10.1126/science.168.3933.852. [DOI] [PubMed] [Google Scholar]
- Vaz N. M., Phillips-Quagliata J. M., Levine B. B., Vaz E. M. H-2-linked genetic control of immune responsiveness to ovalbumin and ovomucoid. J Exp Med. 1971 Nov 1;134(5):1335–1348. doi: 10.1084/jem.134.5.1335. [DOI] [PMC free article] [PubMed] [Google Scholar]