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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Dec;86(23):9489–9493. doi: 10.1073/pnas.86.23.9489

A specific HLA-DP beta allele is associated with pauciarticular juvenile rheumatoid arthritis but not adult rheumatoid arthritis.

A B Begovich 1, T L Bugawan 1, B S Nepom 1, W Klitz 1, G T Nepom 1, H A Erlich 1
PMCID: PMC298522  PMID: 2512583

Abstract

Nonradioactive sequence-specific oligonucleotide probes specific for the HLA-DP beta locus have been used in a simple dot-blot format to type samples amplified by the polymerase chain reaction from 44 patients with pauciarticular juvenile rheumatoid arthritis, 32 patients with adult rheumatoid arthritis, and 50 random controls. The sequences of four new DP beta alleles derived from these patients and controls are reported, bringing the total number of alleles identified thus far to 19. The DPB2.1 allele is significantly increased in juvenile rheumatoid arthritis patients over controls; this allele is not increased in patients with adult rheumatoid arthritis. The association of juvenile rheumatoid arthritis with the DPB2.1 allele is independent of linkage with previously defined HLA-D region markers of disease. Analysis of the DPB2.1 sequence shows that it differs from the nonsusceptible DPB4.2 allele by only 1 amino acid at position 69 in the beta 1 domain.

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Selected References

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

  1. Amar A., Nepom G. T., Mickelson E., Erlich H., Hansen J. A. HLA-DP and HLA-DO genes in presumptive HLA-identical siblings: structural and functional identification of allelic variation. J Immunol. 1987 Mar 15;138(6):1947–1953. [PubMed] [Google Scholar]
  2. Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
  3. Balogh Z., Gyodi E., Petranyi G., Meretey K., Bozsoky S. HLA-DR antigens in juvenile chronic arthritis. J Rheumatol. 1982 May-Jun;9(3):448–450. [PubMed] [Google Scholar]
  4. Bugawan T. L., Angelini G., Larrick J., Auricchio S., Ferrara G. B., Erlich H. A. A combination of a particular HLA-DP beta allele and an HLA-DQ heterodimer confers susceptibility to coeliac disease. Nature. 1989 Jun 8;339(6224):470–473. doi: 10.1038/339470a0. [DOI] [PubMed] [Google Scholar]
  5. Bugawan T. L., Horn G. T., Long C. M., Mickelson E., Hansen J. A., Ferrara G. B., Angelini G., Erlich H. A. Analysis of HLA-DP allelic sequence polymorphism using the in vitro enzymatic DNA amplification of DP-alpha and DP-beta loci. J Immunol. 1988 Dec 1;141(11):4024–4030. [PubMed] [Google Scholar]
  6. Eckels D. D., Lake P., Lamb J. R., Johnson A. H., Shaw S., Woody J. N., Hartzman R. J. SB-restricted presentation of influenza and herpes simplex virus antigens to human T-lymphocyte clones. Nature. 1983 Feb 24;301(5902):716–718. doi: 10.1038/301716a0. [DOI] [PubMed] [Google Scholar]
  7. Førre O., Dobloug J. H., Høyeraal H. M., Thorsby E. HLA antigens in juvenile arthritis. Genetic basis for the different subtypes. Arthritis Rheum. 1983 Jan;26(1):35–38. doi: 10.1002/art.1780260106. [DOI] [PubMed] [Google Scholar]
  8. Glass D., Litvin D., Wallace K., Chylack L., Garovoy M., Carpenter C. B., Schur P. H. Early-onset pauciarticular juvenile rheumatoid arthritis associated with human leukocyte antigen-DRw5, iritis, and antinuclear antibody. J Clin Invest. 1980 Sep;66(3):426–429. doi: 10.1172/JCI109872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Guillet J. G., Lai M. Z., Briner T. J., Buus S., Sette A., Grey H. M., Smith J. A., Gefter M. L. Immunological self, nonself discrimination. Science. 1987 Feb 20;235(4791):865–870. doi: 10.1126/science.2433769. [DOI] [PubMed] [Google Scholar]
  10. Hoffman R. W., Shaw S., Francis L. C., Larson M. G., Petersen R. A., Chylack L. T., Glass D. N. HLA-DP antigens in patients with pauciarticular juvenile rheumatoid arthritis. Arthritis Rheum. 1986 Sep;29(9):1057–1062. doi: 10.1002/art.1780290901. [DOI] [PubMed] [Google Scholar]
  11. Horn G. T., Bugawan T. L., Long C. M., Erlich H. A. Allelic sequence variation of the HLA-DQ loci: relationship to serology and to insulin-dependent diabetes susceptibility. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6012–6016. doi: 10.1073/pnas.85.16.6012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Howell M. D., Smith J. R., Austin R. K., Kelleher D., Nepom G. T., Volk B., Kagnoff M. F. An extended HLA-D region haplotype associated with celiac disease. Proc Natl Acad Sci U S A. 1988 Jan;85(1):222–226. doi: 10.1073/pnas.85.1.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
  14. Kappler J. W., Staerz U., White J., Marrack P. C. Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature. 1988 Mar 3;332(6159):35–40. doi: 10.1038/332035a0. [DOI] [PubMed] [Google Scholar]
  15. Kaufman J. F., Auffray C., Korman A. J., Shackelford D. A., Strominger J. The class II molecules of the human and murine major histocompatibility complex. Cell. 1984 Jan;36(1):1–13. doi: 10.1016/0092-8674(84)90068-0. [DOI] [PubMed] [Google Scholar]
  16. Lair B., Alber C., Yu W. Y., Watts R., Bahl M., Karr R. W. A newly characterized HLA-DP beta-chain allele. Evidence for DP beta heterogeneity within the DPw4 specificity. J Immunol. 1988 Aug 15;141(4):1353–1357. [PubMed] [Google Scholar]
  17. MacDonald H. R., Schneider R., Lees R. K., Howe R. C., Acha-Orbea H., Festenstein H., Zinkernagel R. M., Hengartner H. T-cell receptor V beta use predicts reactivity and tolerance to Mlsa-encoded antigens. Nature. 1988 Mar 3;332(6159):40–45. doi: 10.1038/332040a0. [DOI] [PubMed] [Google Scholar]
  18. Morel P. A., Dorman J. S., Todd J. A., McDevitt H. O., Trucco M. Aspartic acid at position 57 of the HLA-DQ beta chain protects against type I diabetes: a family study. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8111–8115. doi: 10.1073/pnas.85.21.8111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morling N., Hellesen C., Jakobsen B. K., Platz P., Ryder L. P., Svejgaard A., Thomsen M. HLA-A, B, C, D, DR antigens and primed lymphocyte typing (PLT) defined DP-antigens in juvenile chronic arthritis. Tissue Antigens. 1981;17(4):433–441. doi: 10.1111/j.1399-0039.1981.tb00725.x. [DOI] [PubMed] [Google Scholar]
  20. Mullis K. B., Faloona F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. doi: 10.1016/0076-6879(87)55023-6. [DOI] [PubMed] [Google Scholar]
  21. Odum N., Hyldig-Nielsen J. J., Morling N., Sandberg-Wollheim M., Platz P., Svejgaard A. HLA-DP antigens are involved in the susceptibility to multiple sclerosis. Tissue Antigens. 1988 May;31(5):235–237. doi: 10.1111/j.1399-0039.1988.tb02088.x. [DOI] [PubMed] [Google Scholar]
  22. Odum N., Morling N., Friis J., Heilmann C., Hyldig-Nielsen J. J., Jakobsen B. K., Pedersen F. K., Platz P., Ryder L. P., Svejgaard A. Increased frequency of HLA-DPw2 in pauciarticular onset juvenile chronic arthritis. Tissue Antigens. 1986 Oct;28(4):245–250. doi: 10.1111/j.1399-0039.1986.tb00490.x. [DOI] [PubMed] [Google Scholar]
  23. Odum N., Platz P., Jakobsen B. K., Petersen C. M., Jacobsen N., Møller J., Ryder L. P., Lamm L., Svejgaard A. HLA-DP and bone marrow transplantation: DP-incompatibility and severe acute graft versus host disease. Tissue Antigens. 1987 Nov;30(5):213–216. doi: 10.1111/j.1399-0039.1987.tb01624.x. [DOI] [PubMed] [Google Scholar]
  24. Pawelec G., Reekers P., Brackertz D., Sansom D., Schneider E. M., Blaurock M., Müller C., Rehbein A., Balko I., Wernet P. HLA-DP in rheumatoid arthritis. Tissue Antigens. 1988 Feb;31(2):83–89. doi: 10.1111/j.1399-0039.1988.tb02068.x. [DOI] [PubMed] [Google Scholar]
  25. Reekers P., Schretlen E. D., van de Putte L. B. Increase of HLA-"DRw6" in patients with juvenile chronic arthritis. Tissue Antigens. 1983 Oct;22(4):283–288. doi: 10.1111/j.1399-0039.1983.tb01204.x. [DOI] [PubMed] [Google Scholar]
  26. Saiki R. K., Bugawan T. L., Horn G. T., Mullis K. B., Erlich H. A. Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature. 1986 Nov 13;324(6093):163–166. doi: 10.1038/324163a0. [DOI] [PubMed] [Google Scholar]
  27. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  28. Saiki R. K., Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. doi: 10.1126/science.2999980. [DOI] [PubMed] [Google Scholar]
  29. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Scharf S. J., Freidmann A., Steinman L., Brautbar C., Erlich H. A. Specific HLA-DQB and HLA-DRB1 alleles confer susceptibility to pemphigus vulgaris. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6215–6219. doi: 10.1073/pnas.86.16.6215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Scharf S. J., Friedmann A., Brautbar C., Szafer F., Steinman L., Horn G., Gyllensten U., Erlich H. A. HLA class II allelic variation and susceptibility to pemphigus vulgaris. Proc Natl Acad Sci U S A. 1988 May;85(10):3504–3508. doi: 10.1073/pnas.85.10.3504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sette A., Buus S., Colon S., Smith J. A., Miles C., Grey H. M. Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells. 1987 Jul 30-Aug 5Nature. 328(6129):395–399. doi: 10.1038/328395a0. [DOI] [PubMed] [Google Scholar]
  33. Sinha A. A., Brautbar C., Szafer F., Friedmann A., Tzfoni E., Todd J. A., Steinman L., McDevitt H. O. A newly characterized HLA DQ beta allele associated with pemphigus vulgaris. Science. 1988 Feb 26;239(4843):1026–1029. doi: 10.1126/science.2894075. [DOI] [PubMed] [Google Scholar]
  34. Stastny P., Fink C. W. Different HLA-D associations in adult and juvenile rheumatoid arthritis. J Clin Invest. 1979 Jan;63(1):124–130. doi: 10.1172/JCI109265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Svejgaard A., Platz P., Ryder L. P. HLA and disease 1982--a survey. Immunol Rev. 1983;70:193–218. doi: 10.1111/j.1600-065x.1983.tb00715.x. [DOI] [PubMed] [Google Scholar]
  36. Teh H. S., Kisielow P., Scott B., Kishi H., Uematsu Y., Blüthmann H., von Boehmer H. Thymic major histocompatibility complex antigens and the alpha beta T-cell receptor determine the CD4/CD8 phenotype of T cells. Nature. 1988 Sep 15;335(6187):229–233. doi: 10.1038/335229a0. [DOI] [PubMed] [Google Scholar]
  37. Todd J. A., Bell J. I., McDevitt H. O. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987 Oct 15;329(6140):599–604. doi: 10.1038/329599a0. [DOI] [PubMed] [Google Scholar]
  38. Unanue E. R., Allen P. M. The basis for the immunoregulatory role of macrophages and other accessory cells. Science. 1987 May 1;236(4801):551–557. doi: 10.1126/science.2437650. [DOI] [PubMed] [Google Scholar]
  39. Watts T. H., McConnell H. M. High-affinity fluorescent peptide binding to I-Ad in lipid membranes. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9660–9664. doi: 10.1073/pnas.83.24.9660. [DOI] [PMC free article] [PubMed] [Google Scholar]

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