Rheumatology International

, Volume 13, Issue 2, pp 65–69 | Cite as

Analysis of the HLA-DR gene frequencies in Japanese cases of juveniles rheumatoid arthritis and rheumatoid arthritis by oligonucleotide DNA typing

  • H. Okubo
  • K. Itou
  • S. Tanaka
  • N. Watanabe
  • N. Kashiwagi
  • F. Obata


HLA-DR gene frequencies in 59 Japanese children with juvenile rheumatoid arthritis (JRA) and 62 Japanese adults with rheumatoid arthritis (RA) were analyzed by oligonucleotide DNA typing. As in other studies, the frequency of DRB1*0405 in RA patients was significantly higher than in the Japanese controls. In a comparison of non-calssified JRA patients with Japanese controls, no significant differences were observed in the frequency of DR types. However, when the JRA patients were classified into four clinical types, i.e., a rheumatoid factor-positive [RF(+)] polyarticular type, a rheumatoid factor-negative [RF(-)] polyarticular type, a pauciarticular type, and a systemic onset type, DRB1*0405 was found to be significantly higher in the RF(+) polyarticular JRA patients than in the controls (P>0.05). Thus, the RF(+) polyarticular type of JRA had the same HLA association as RA. This result is consistent with the fact that both RF(+) polyarticular JRA and RA cases have a similar clinical course.

Key words

Juvenile rheumatoid arthritis Rheumatoid arthritis HLA-DR gene frequencies Oligonucleotide DNA typing 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Vehe RK, Begovich AB, Nepom BS (1990) HLA susceptibility genes in rheumatoid factor positive juvenile rheumatoid arthritis. J Rheumatol 17 [Suppl 26]:11–15Google Scholar
  2. 2.
    Clemens LE, Albert E, Ansell BM (1983) HLA studies in IgM rheumatoid-factor-positive arthritis of childhood. Ann Rheum Dis 42:431–434Google Scholar
  3. 3.
    Stastny P (1978) Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med 298:869–871Google Scholar
  4. 4.
    Nepom GT, Seyfried CE, Holbeck SL, Wilske KR, Nepom BS (1986) Identification of HLA-Dw14 genes in DR4 positive rheumatoid arthritis. Lancet II:1002–1005Google Scholar
  5. 5.
    Zoschke D, Segall M (1986) Dw Subtypes of DR4 in rheumatiod arthritis: evidence for a preferential association with Dw4. Hum Immunol 15:118–124Google Scholar
  6. 6.
    Nepom GT, Byers P, Seyfried C, Healey LA, Wilske KR, Stage D, Nepom BS (1989) HLA genes associated with rheumatoid arthritis. Arthritis Rheum 32:15–21Google Scholar
  7. 7.
    Gregersen PK, Silver J, Winchester RJ (1987) The shared epitope hypothesis: an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30:1205–1213Google Scholar
  8. 8.
    Stastny P, Gao X, Fernandez-Vina M (1991) Immunogenetics of rheumatoid arthritis and juvenile arthritis. Recenti Prog Med 82:409–416Google Scholar
  9. 9.
    Marcelo A, Fernandez-Vina A, Fink CW, Stastny P (1990) HLA antigens in juvenile arthritis: pauciarticular and polyarticular juvenile arthritis are immunogenetically distinct. Arthritis Rheum 33:1787–1794Google Scholar
  10. 10.
    Begovich AB, Bugawan TL, Nepom BS, Klitz W, Nepom GT, Erlich HA (1989) A specific HLA-DP β allele is associated with pauciarticular juvenile rheumatoid arthritis but not adult rheumatoid arthritis. Proc Natl Acad Sci USA 86:9489–9493Google Scholar
  11. 11.
    Ohta N, Nishimura YK, Tanimoto K, Yoshihiko H Abe C, Shiokawa W, Abe T, Katagiri M, Yoshiki T, Sasazuki T (1982) Association between HLA and Japanese patients with rheumatoid arthritis. Hum Immunol 5:123–132Google Scholar
  12. 12.
    Cohen N, Mickelson E, Amar A, Battat S, Hansen JA, Brautbar C (1987) HLA-Dw clusters associated with DR4 in Israeli Jews and the definition of a new DR4 associated subtype: Dw-“SHA”. Hum Immunol 19:179–188Google Scholar
  13. 13.
    Gao M, Brautbar C, Gazit E, Segal R, Naparstek Y, Livneh A, Stastny P (1991) A variant of HLA-DR4 determines susceptibility to rheumatoid arthritis in a subset of Israeli Jews. Arthritis Rheum 34:547–551Google Scholar
  14. 14.
    Jaraquemada D, Ollier W, Awad J, Young A, Silman A, Roitt IM, Corbett M, Hay F, Cosh JA, Maini RN, Venables RJ, Ansell B, Holborow J, Reeback J, Currey HLF, Festenstein H (1986) HLA and rheumatoid arthritis: a combined analysis of 440 British patients. Ann Rheum Dis 45:627–636Google Scholar
  15. 15.
    Ollier W, Carthy D, Cutbush S, Okoye R, Awad J, Fielder A, Silman A, Festenstein H (1988) HLA-DR4 associated Dw types in rheumatoid arthritis. Tissue Antigens 33:30–37Google Scholar
  16. 16.
    Watanabe Y, Tokunaga K, Matsuki K, Matsuki F, Takeuchi K, Matsuta H, Maeda, K, Omoto T. Juji (1989) Putative amino acid sequence of HLA-DRβ chain contributing to rheumatoid arthritis susceptibility. J Exp Med 169:2263–2268Google Scholar
  17. 17.
    Cassidy JT, Levinson JE, Bass JC, Baum J, Brewer EJ, Fink CW, Hanson V, Jacobs JC, Masi AT, Schaller JG, Fries JF, Mcshane D, Young D (1986) A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. Arthritis Rheum 29:274–281Google Scholar
  18. 18.
    Arnett FC, Edworthy S, Bloch DA, McShane DJ, Fries JF, the ARA Rheumatoid Arthritis Criteria Subcommittee (1987) The 1987 revised ARA criteria for rheumatoid arthritis (RA). Arthritis Rheum 30:S17Google Scholar
  19. 19.
    Obata F, Ito K, Kaneko T, Yang Y-g, Onda K, Ito I, Yabe N, Watanabe K, Kashiwagi N (1991) HLA-DR gene frequencies in the Japanese population obtained by oligonucleotide genotyping. Tissue antigens 38:124–132Google Scholar
  20. 20.
    Nepom BS, Nepom GT, Mickelson E, Schaller JG, Antonelli P, Hansen JA (1984) Specific HLA-DR4-associated histocompatibility molecules characterize patients with seropositive juvenile rheumatoid arthritis. J Clin Invest 74:287–291Google Scholar
  21. 21.
    Hall PJ, Burman SJ, Laurent MR, Briggs DC, Venning HE, Leak AM, Bedford PA, Ansell BM (1986) Genetic susceptibility to early onset pauciarticular juvenile chronic arthritis: a study of HLA and complement markers in 158 British patients. Ann Rheum Dis 45:464–474Google Scholar
  22. 22.
    Barron KS, Joseph AK, Macleod M, Gonzales JC, Owerbach D, Reveille J (1991) DNA analysis of HLA-DR, DQ and DP genes in pauciarticular juvenile rheumatoid arthritis. J Rheumatol 18:1723–1729Google Scholar
  23. 23.
    Forre O, Boblong JH, Hoyeraal HM, Thorsby E (1983) HLA antigens in juvenile arthritis: genetic basis for the different subtypes. Arthritis Rheum 26:35–38Google Scholar
  24. 24.
    Brautbar C, Mukamel M, Yaron M, Naparstek Y, Korman SH, Amar A, Cohen I, Ludomirsky A, Lotan C, Scharf J, Brick R, Sharon R, Cohen T, Albert ED (1986) Immunogenetics of juvenile chronic arthritis in Israel. J Rheumatol 13:1072–1075Google Scholar
  25. 25.
    Maksymowych WP, Glass DN (1988) Population genetics and molecular biology of the childhood chronic arthropathies. Balliere's Clin Rheumatol 2:649–671Google Scholar
  26. 26.
    Reekers P, Schretlen EDAM, Putte LBA van de (1983) Increase of HLA-“DRw6” in patients with juvenile chronic arthritis. Tissue Antigens 22:283–288Google Scholar
  27. 27.
    Ansell BM, Clemens LE (1982) Chronic arthritis of childhood. In: Dawkins RL, Christiansen FT, Zilko PJ (eds) Immunogenetics in rheumatology. Excerpta Medica, Amsterdam, pp 164–166Google Scholar
  28. 28.
    Manners PJ, McCluskey J, Dawkins RL (1982) HLA and complement C4 in chronic arthritis of childhood. In: Dawkins RL, Christiansen FT, Zilko PJ (eds) Immunogenetics in rheumatology. Excerpta Medica Amsterdam, pp 167–171Google Scholar
  29. 29.
    Miller ML, Aaron S, Jackson J, Fraser P, Cairns L, Hoch S, Borel Y, Larson M, Glass DN (1985) HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis. Arthritis Rheum 28:146–150Google Scholar
  30. 30.
    Stastny P, Fink CW (1979) Different HLA-D associations in adult and juvenile rheumatoid arthritis. J Clin Invest 63:124–130Google Scholar
  31. 31.
    Morling N, Friis J, Heilmann C, Hellesen C, Jakobsen BK, Jorgensen B, Pedersen FK, Svejgaard A, Thomsen K (1985) HLA antigen frequencies in juvenile chronic arthritis. Scand J Rheumatol 14:209–216Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • H. Okubo
    • 1
  • K. Itou
    • 2
  • S. Tanaka
    • 1
  • N. Watanabe
    • 1
  • N. Kashiwagi
    • 2
  • F. Obata
    • 2
  1. 1.Department of PediatricsKyorin University School of MedicineMitaka-city, TokyoJapan
  2. 2.Department of ImmunologyKitasato University School of MedicineKanagawaJapan

Personalised recommendations