Skip to main content
Log in

HLA class II genes and antibodies against recombinant U1-nRNP proteins in patients with systemic lupus erythematosus

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

To investigate a possible involvement of HLA-class II alleles in the genetic predisposition for the formation of anti-U1-nRNP antibody in systemic lupus erythematosus (SLE), genomic DNA of 178 patients was typed for the DRB1, DQA1 and DQB1 alleles using a polymerase chain reaction (PCR) and non-radioactive-oligonucleotide typing. Antibodies against recombinant U1-nRNP proteins (U1-A- U1-C-and 70K-protein) were determined by ELISA. Anti-U1-C antibody was found in 26 (14.7%), anti-U1-A in 34 (19.2%) and anti-70K in 17 (9.6%) patients. A joint occurrence was observed for these antibodies against the recombinant U1-nRNP proteins: anti-U1-C and anti-U1-A antibodies occurred together more frequently than alone and than together with anti-U1-70K antibodies. The frequency of DRB1 * 04 was slightly increased in the patients with anti-U1-C as compared to the patients without anti-U1-C (P<0.05, Pcorr=n.s., RR=2.4). The DQA1 * 0301 allele, which is in linkage disequilibrium with DRB1 * 04, is found more frequently in anti-U1-C-positive than in antibody-negative patients. The DQB1 * 0303 allele, detected in 12 of 176 SLE patients, was absent in the patients with any of the antibodies against the U1-nRNP proteins. All these deviations may be due to chance alone. We concluded that the presence of antibodies against recombinant U1-nRNP proteins was not significantly associated with any HLA DRB1, DQA1 and DQB1 allele in our group of SLE patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hardin JA (1986) The lupus autoantigens and the pathogenesis of systemic lupus erythematosus. Arthritis Rheum 29:457–460

    Google Scholar 

  2. Lerner MR, Steitz JA (1979) Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc Natl Acad Sci USA 76:5495–5499

    Google Scholar 

  3. Rokeach LA, Hoch SO (1992) B-cell epitopes of Sm autoantigens. Mol Biol Rep 16:165–174

    Google Scholar 

  4. Arnett FC, Reveille JD, Wilson RW, Provost TT, Bias WB (1984) Systemic lupus erythematosus: current state of the genetic hypothesis. Semin Arthritis Rheum 14:24–35

    Google Scholar 

  5. Seelig HP, Ehrfeld H, Schroeter H, Heim C, Renz M (1991) A recombinant 70K protein ELISA. Screening for antibodies against U1-snRNP proteins in human sera. J Immunol Methods 143:11–24

    Google Scholar 

  6. Parker MD (1973) Ribonucleoprotein antibodies: frequency and clinical significance in systemic lupus erythematosus, scleroderma, and mixed connective tissue disease. J Lab Clin Med 82:769

    Google Scholar 

  7. Maddison PJ, Mogavero H, Reichlin M (1978) Pattens of clinical disease associated with antibodies to nuclear ribonucleoprotein. J Rheumatol 5:407

    Google Scholar 

  8. Ehrfeld H, Hartung K, Renz M, Coldewey R Deicher H, Fricke M, Kalden JR, Lakomekk J, Peter HH, Schendel D, Seelig HP, members of SLE study group (1992) MHC associations of autoantibodies against recombinant Ro and La proteins in systemic lupus erythematosus. Rheumatol Int 12:169–173

    Google Scholar 

  9. Hartung K, Ehrfeld H, Lakomek HJ, Coldewey R, Lang B, Krapf F Müller R, Schendel D, Deicher H Seelig HP, members of SLE study group (1992) The genetic basis of Ro and La antibody formation in systemic lupus erythematosus. Rheumatol Int 11:243–249

    Google Scholar 

  10. Yao Z, Hartung K, Ehrfeld H, Seelig HP, Deicher HRG, Brünnler G, Keller E, Albert E, members of SLE study group (1993) No direct correlation between HLA-DPB1 and antibodies against recombinant Ro (SS-A)/La (SS-B) proteins in systemic lupus erythematosus. Rheumatol Int 13:155–158

    Google Scholar 

  11. Hartung K, Coldewey R, Corvetta A, Deicher H, Kalden JR, Krapf F, Lang B, Lakomek HJ, Liedvogel B, Peter HH, Schendel D, Specker CH, Stangel W, members of SLE study group (1992) MHC gene products and anticardiolipin antibodies in systemic lupus erythematosus. Results of a multicenter study. Autoimmunity 13:95–99

    Google Scholar 

  12. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ (1982) 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    Google Scholar 

  13. Ehrfeld H, Hartung K, Renz M, Deicher H, Seelig HP (1994) Autoantikörper gegen rekombinante ENA-Antigene und klinische Assoziationen beim SLE. Z Arztl Fortbild (in press)

  14. Hartung K, Baur MP, Coldewey R, Fricke M, Kalden JR, Lakomek HJ, Peter HH, Schendel D, Schneider PM, Seucheter SA, Stangel W, Deicher HRG (1992) Major histocompatibility complex haplotypes and complement C4 alleles in systemic lupus erythematosus. Results of a multicenter study. J Clin Invest 90:1346–1351

    Google Scholar 

  15. Yao Z, Kimura A, Hartung K, Haas PJ, Volgger A, Brünnler G, Bönisch J, Albert ED, members of SLE study group (1993) Polymorphism of the DQA1 promoter region (QAP) and DRB1, QAP, DQA1, DQB1 haplotypes in systemic lupus erythematosus. Immunogenetics 38:421–429

    Google Scholar 

  16. Yao Z, Hartung K, Deicher HRG, Brünnler G, Bettinotti MP, Keller E, Paul C, Gawron C, Mikschl S, Albert E, members of SLE study group (1993) DNA typing for HLA-DPB1-alleles in German patients with systemic lupus erythematosus using the polymerase chain reaction and dig-ddUTP-labeled oligonucleotide probes. Eur J Immunogenet 20:259–266

    Google Scholar 

  17. Nevinny-Stickel C, Bettinotti MdlP, Andreas A, Hinzpeter M, Mühlegger K, Schmitz G, Albert ED (1991) Non-radioactive HLA class II typing using polymerase chain reaction and digoxigenin-11-2′-3′-dedeoxyuridine-triphosphate labeled oligonucleotide probes. Hum Immunol 31:7–13

    Google Scholar 

  18. Nevinny-Stickel C, Hinzpeter M, Andreas A, Albert ED (1991) Non-radioactive oligotyping for HLA-DR1-DRw10 using polymerase chain reaction, digoxigenin-labelled oligonucleotides and chemiluminescent detection. Eur J Immunogenet 18:323–332

    Google Scholar 

  19. Kimura A, Sasazuki T (1992) Eleventh International Histocompatibility Workshop reference protocol for the HLA DNA-typing technique. In: Tsuji K, Aizawa M, Sasazuki T (eds) HLA 1991, vol I Oxford Scientific Publications, Oxford

    Google Scholar 

  20. Genth E, Zarnowski H, Mierau R, Wohltmann D, Hartl PW (1987) HLA-DR4 and Gm (1, 3; 5, 21) are associated with U1-nRNP antibody positive connective tissue disease. Ann Rheum Dis 46:189–196

    Google Scholar 

  21. Black CM, Maddison PJ, Welsh KI, Bernstein R, Woodrow JC, Pereira RS, (1988) HLA and immunoglobulin allotypes in mixed connective tissue disease. Arthritis Rheum 31:131–134

    Google Scholar 

  22. Hoffman RW, Rettenmaier LJ, Takeda Y, Hewett JE, Pettersson I, Nyman U, Luger AM, Sharp GC (1990) Human autoantibodies against the 70-kd polypeptide of U1 small nuclear RNP are associated with HLA-DR4 among connective tissue disease patients. Arthritis Rheum 33:667–673

    Google Scholar 

  23. Kaneoka H, Hsu KC, Takeda Y, Sharp GC, Hoffman RW (1992) Molecular genetic analysis of HLA-DR and HLA-DQ genes among anti-U1-70-kd autoantibody positive connective tissue disease patients. Arthritis Rheum 35:83–94

    Google Scholar 

  24. Hsu KC, Hill DL, Hoffman RW (1992) HLA-DPB1*0401 is associated with the presence of autoantibodies reactive with the U1-70kD polypeptide antigen of U1-small nuclear ribonucleoprotein among connective tissue disease patients. Tissue Antigens 39:272–275

    Google Scholar 

  25. Bell DA, Maddison PJ (1980) Serologic subsets in systemic lupus erythematosus: an examination of autoantibodies in relationship to clinical features of disease and HLA antigens. Arthritis Rheum 23:1268–1273

    Google Scholar 

  26. Ahearn JM, Provost TT, Dorsch CA, Stevens MB, Bias WB, Arnett FC (1982) Interrelationship of HLA-DR, MB, and MT phenotypes, autoantibody expression, and clinical features in systemic lupus erythematosus. Arthritis Rheum 25:1031–1040

    Google Scholar 

  27. Smolen JS, Klippel JH, Penner E, Reichlin M, Steinberg AD, Chused TM, Scherak O, Graninger W, Hartter E, Zielinski CC, Wolf A, Davey RJ, Mann DL, Mayr WR (1987) HLA-DR antigens in systemic lupus erythematosus: association with specificity of autoantibody responses to nuclear antigens. Ann Rheum Dis 46:457–462

    Google Scholar 

  28. Harley JB, Sestak AL, Willis LG, Fu SM, Hansen JA, Reichlin M (1989) A model for disease heterogeneity in systemic lupus erythematosus: relationship between histocompatibility antigens, autoantibodies, and lymphopenia or renal disease. Arthritis Rheum 32:826–836

    Google Scholar 

  29. Hamilton RG, Harley JB, Bias WB, Roebber M, Reichlin M, Hochberg MC, Arnett FC (1988) Two Ro (SS-A) autoantibody responses in systemic lupus erythematosus: correlation of HLA-DR/DQ specificities with quantitative expression of Ro (SS-A) autoantibody. Arthritis Rheum 31:496–505

    Google Scholar 

  30. Results of 6th European Consensus Finding Study, presented at meeting of European Consensus Finding Study Group on autoantibodies, March 1994, Gent, Belgium

  31. James K, Meek G (1992) Evaluation of commercial immunoassays compared to immuno fluorescence and double diffusion for autoantibodies associated with autoimmune diseases. Am J Clin Pathol 97:559–565

    Google Scholar 

  32. Delpech A, Gilbert D, Daliphard S, Le Loet X, Godin M, Tron F (1993) Antibodies to Sm, RNP and SSB detected by solidphase ELISAs using recombinant antigens: a comparison study with counter immunoelectrophoresis and immunoblotting. J Clin Lab Anal 7:197–202

    Google Scholar 

  33. van Venrooij WJ, Sillekens PTG (1989) Small nuclear RNA associated proteins: auto-antigens in connective tissue diseases. Clin Exp Rheumatol 7:635–645

    Google Scholar 

  34. Wagatsuma M, Asami N, Miyachi J, Uchida S, Watanabe H, Amann (1993) Antibody recognition of the recombinant human nuclear antigens RNP 70kD, SS-A, SS-B, SmB and SmD by autoimmune sera. Mol Immunol 30:1491–1498

    Google Scholar 

  35. Rokeach LA, Jannatipour M, Haselby JA, Hoch SO (1992) Mapping of the immuno-reactive domains of a small nuclear ribonucleoprotein associated Sm-D autoantigen. Clin Immunol Immunopathol 65:315–324

    Google Scholar 

  36. Bettinotti MP, Hartung K, Deicher H, Keller E, Mikschl S, Albert E (1993) DR2 haplotypes (DRB1, DQA1, DQB1) associated with systeme lupus erythematosus. Immunogenetics 38:74–77

    Google Scholar 

  37. Olsen MJ, Arnett FC, Reveille JD (1993) Contrasting molecular patterns of MHC class II associated with the anti-Sm and anti-RNP precipitin autoantibodies in systemic lupus erythematosus. Arthritis Rheum 36:94–104

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Consortia

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yao, Z., Seelig, H.P., Ehrfeld, H. et al. HLA class II genes and antibodies against recombinant U1-nRNP proteins in patients with systemic lupus erythematosus. Rheumatol Int 14, 63–69 (1994). https://doi.org/10.1007/BF00300249

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00300249

Key words

Navigation