• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Dec 1989; 86(23): 9489–9493.
PMCID: PMC298522

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


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (967K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Svejgaard A, Platz P, Ryder LP. HLA and disease 1982--a survey. Immunol Rev. 1983;70:193–218. [PubMed]
  • Kaufman JF, Auffray C, Korman AJ, Shackelford DA, Strominger J. The class II molecules of the human and murine major histocompatibility complex. Cell. 1984 Jan;36(1):1–13. [PubMed]
  • Kappler JW, Roehm N, Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. [PubMed]
  • Kappler JW, Staerz U, White J, Marrack PC. Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature. 1988 Mar 3;332(6159):35–40. [PubMed]
  • MacDonald HR, Schneider R, Lees RK, Howe RC, Acha-Orbea H, Festenstein H, Zinkernagel RM, Hengartner H. T-cell receptor V beta use predicts reactivity and tolerance to Mlsa-encoded antigens. Nature. 1988 Mar 3;332(6159):40–45. [PubMed]
  • Teh HS, 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. [PubMed]
  • Babbitt BP, Allen PM, Matsueda G, Haber E, Unanue ER. Binding of immunogenic peptides to Ia histocompatibility molecules. Nature. 317(6035):359–361. [PubMed]
  • Watts TH, McConnell HM. High-affinity fluorescent peptide binding to I-Ad in lipid membranes. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9660–9664. [PMC free article] [PubMed]
  • Guillet JG, Lai MZ, Briner TJ, Buus S, Sette A, Grey HM, Smith JA, Gefter ML. Immunological self, nonself discrimination. Science. 1987 Feb 20;235(4791):865–870. [PubMed]
  • Unanue ER, Allen PM. The basis for the immunoregulatory role of macrophages and other accessory cells. Science. 1987 May 1;236(4801):551–557. [PubMed]
  • Sette A, Buus S, Colon S, Smith JA, Miles C, Grey HM. Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells. Nature. 328(6129):395–399. [PubMed]
  • Todd JA, Bell JI, McDevitt HO. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987 Oct 15;329(6140):599–604. [PubMed]
  • Horn GT, Bugawan TL, Long CM, Erlich HA. 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. [PMC free article] [PubMed]
  • Morel PA, Dorman JS, Todd JA, McDevitt HO, 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. [PMC free article] [PubMed]
  • Sinha AA, Brautbar C, Szafer F, Friedmann A, Tzfoni E, Todd JA, Steinman L, McDevitt HO. A newly characterized HLA DQ beta allele associated with pemphigus vulgaris. Science. 1988 Feb 26;239(4843):1026–1029. [PubMed]
  • Scharf SJ, Friedmann A, Brautbar C, Szafer F, Steinman L, Horn G, Gyllensten U, Erlich HA. HLA class II allelic variation and susceptibility to pemphigus vulgaris. Proc Natl Acad Sci U S A. 1988 May;85(10):3504–3508. [PMC free article] [PubMed]
  • Scharf SJ, Freidmann A, Steinman L, Brautbar C, Erlich HA. 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. [PMC free article] [PubMed]
  • Hoffman RW, Shaw S, Francis LC, Larson MG, Petersen RA, Chylack LT, Glass DN. HLA-DP antigens in patients with pauciarticular juvenile rheumatoid arthritis. Arthritis Rheum. 1986 Sep;29(9):1057–1062. [PubMed]
  • Odum N, Morling N, Friis J, Heilmann C, Hyldig-Nielsen JJ, Jakobsen BK, Pedersen FK, Platz P, Ryder LP, Svejgaard A. Increased frequency of HLA-DPw2 in pauciarticular onset juvenile chronic arthritis. Tissue Antigens. 1986 Oct;28(4):245–250. [PubMed]
  • Pawelec G, Reekers P, Brackertz D, Sansom D, Schneider EM, Blaurock M, Müller C, Rehbein A, Balko I, Wernet P. HLA-DP in rheumatoid arthritis. Tissue Antigens. 1988 Feb;31(2):83–89. [PubMed]
  • Odum N, Hyldig-Nielsen JJ, 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. [PubMed]
  • Howell MD, Smith JR, Austin RK, Kelleher D, Nepom GT, Volk B, Kagnoff MF. An extended HLA-D region haplotype associated with celiac disease. Proc Natl Acad Sci U S A. 1988 Jan;85(1):222–226. [PMC free article] [PubMed]
  • Stastny P, Fink CW. Different HLA-D associations in adult and juvenile rheumatoid arthritis. J Clin Invest. 1979 Jan;63(1):124–130. [PMC free article] [PubMed]
  • Glass D, Litvin D, Wallace K, Chylack L, Garovoy M, Carpenter CB, Schur PH. 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. [PMC free article] [PubMed]
  • Morling N, Hellesen C, Jakobsen BK, Platz P, Ryder LP, 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. [PubMed]
  • 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]
  • Førre O, Dobloug JH, Høyeraal HM, Thorsby E. HLA antigens in juvenile arthritis. Genetic basis for the different subtypes. Arthritis Rheum. 1983 Jan;26(1):35–38. [PubMed]
  • Reekers P, Schretlen ED, van de Putte LB. Increase of HLA-"DRw6" in patients with juvenile chronic arthritis. Tissue Antigens. 1983 Oct;22(4):283–288. [PubMed]
  • Bugawan TL, Horn GT, Long CM, Mickelson E, Hansen JA, Ferrara GB, Angelini G, Erlich HA. 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]
  • Bugawan TL, Angelini G, Larrick J, Auricchio S, Ferrara GB, Erlich HA. 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. [PubMed]
  • Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, 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. [PubMed]
  • Mullis KB, Faloona FA. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Saiki RK, Bugawan TL, Horn GT, Mullis KB, Erlich HA. Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature. 1986 Nov 13;324(6093):163–166. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Lair B, Alber C, Yu WY, Watts R, Bahl M, Karr RW. 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]
  • Eckels DD, Lake P, Lamb JR, Johnson AH, Shaw S, Woody JN, Hartzman RJ. SB-restricted presentation of influenza and herpes simplex virus antigens to human T-lymphocyte clones. Nature. 1983 Feb 24;301(5902):716–718. [PubMed]
  • Amar A, Nepom GT, Mickelson E, Erlich H, Hansen JA. 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]
  • Odum N, Platz P, Jakobsen BK, Petersen CM, Jacobsen N, Møller J, Ryder LP, 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. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...