We and others have shown an association between autoimmune disorders and the major histocompatibility complex extended haplotype HLA-A1,-B8,-SCO1,-DR3. The primary gene or genes within this haplotype conferring such susceptibility, however, have not been defined. In this study, we tested the hypothesis that linkage disequilibrium in this haplotype extends through the DP locus, and that DP type may be linked to membranoproliferative glomerulonephritis (MPGN) and systemic lupus erythematosus (SLE). DP and DQ typing was performed by restriction fragment length polymorphism analysis for 43 chromosomes (19 healthy controls, 9 SLE, 15 MPGN) bearing the-A1,-B8,-SCO1,-DR3 extended haplotype. Although all were DQw2, a variety of DP types were identified (DPw1, 0.26; DPw2, 0.09; DPw3, 0.14; DPw4, 0.44). Although DPw1 was represented on extended haplotypes with greater frequency than on 113 non-A1,-B8,-SCO1,-DR3 haplotypes (0.26 vs. 0.03;P<0.001), there were no significant differences between healthy individuals with this haplotype and those with autoimmune disease. We conclude that the strong linkage disequilibrium of this haplotype breaks down between the DQ and DP loci. Loci important to disease susceptibility, therefore, are more likely to occur telomeric to DP.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Welch TR, Beischel L, Balakrishnan K, Quinlan M, West CD (1986) Major-histocompatibility-complex extended haplotypes in membranoproliferative glomerulonephritis. N Engl J Med 314: 1476
Raum D, Awdeh Z, Yunis EJ, Alper CA, Gabbay KH (1984) Extended major histocompatibility complex haplotypes in type I diabetes mellitus. J Clin Invest 74: 449
Alper CA, Fleischnick E, Awdeh Z, Katz AJ, Yunis EJ (1987) Extended major histocompatibility complex haplotypes in patients with gluten-sensitive enteropathy. J Clin Invest 79: 251
Welch TR, Beischel LS, Balakrishnan K, Quinlan M, West CD (1988) Major histocompatibility complex extended haplotypes in systemic lupus erythematosus. Dis Markers 6: 247
Matsui Y, Alosco SM, Awdeh Z, Duquesnoy RJ, Page PL, Hartzman RJ, Alper CA, Yunis EJ (1984) Linkage disequilibrium of HLA-SB1 with the HLA-A1,B8,DR3,SCO1 and of HLA-SB4 with the HLA-A26,Bw38,Dw10,DR4,SC21 extended haplotypes. Immunogenetics 20: 623
Bolsover WJ, Hall MA, Vaughan RW, Welsh KI, Ciclitira PJ (1991) A family study confirms that the HLA-DP associations with celiac disease are the result of an extended HLA-DR3 haplotype. Hum Immunol 31: 100
West CD, McAdams AJ (1983) Membranoproliferative glomerulonephritis. In: Massry SG, Glassock RJ (eds) Textbook of Nephrology, vol 1. Williams and Wilkins, Baltimore, pp 6.46–6.52
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25: 1271
Bell GI, Karam JH, Rutter WJ (1981) Polymorphic DNA region adjacent to the 5′ end of the human insulin gene. Proc Natl Acad Sci USA 78: 5759
Paulsen G, Markussen G, Demopulos J, Tiercy JM, Tonder S van, Quillivic F (1989) RFLP standardization report for DQ Beta/HindIII In: DuPont, B (ed) Immunobiology of HLA. Springer, New York, Berlin Heidelberg 1: 629
Mitsuishi Y, Urlacher A, Mayer S, Tongio MM (1989) DP RFLP studies of the 72 core cell lines selected for the Southern blot protocol. In: DuPont, B (ed) Immunobiology of HLA. Springer, New York Berlin Heidelberg 1: 916
Angelini G, Bugawan TL, Delfino L, Erlich HA, Ferrara GB (1989) HLA-DP typing by DNA amplification and hybridization with specific oligonucleotides. Hum Immunol 26: 169
Fernandez-Vina M, Moraes ME, Stastny P (1991) DNA typing for class II HLA antigens with allele-specific or group-specific amplification. Hum Immunol 30: 60
Hall MA, Lanchbury JSS, Bolsover WJ, Welsh KI, Ciclitira PJ (1990) Celiac disease is associated with an extended HLA-DR3 haplotype which includes HLA-DPwl. Hum Immunol 27: 220
McDevitt HO, Bodmer WF (1972) Histocompatibility antigens, immune responsiveness and susceptibility to disease. Am J Med 52: 1
Fielder AHL, Walport MJ, Batchelor JR, Rynes RI, Black CM, Dodi IA, Hughes GRV (1983) Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility. BMJ 286: 425
Rich S, O'Neill G, Dalmasso AP, Nerl C, Barbosa J (1985) Complement and HLA: further definition of high-risk haplotypes in insulin-dependent diabetes. Diabetes 34: 504
Awdeh ZL, Raum D, Yunis EJ, Alper CA (1983) Extended HLA/complement allele haplotypes: evidence for T/t-like complex in man. Proc Natl Acad Sci USA 80: 259
Whitehead AS, Truedsson L, Schneider PM, Awdeh ZL, Fleischnick E, Blumenthal M, Costello W, Gerald PS, Yunis EJ, Alper CA (1988) The distribution of human C4 DNA variants in relation to major histocompatibility complex alleles and extended haplotypes. Hum Immunol 21: 23
Dawkins RL, Leaver A, Cameron PU, Martin E, Kay PH, Christiansen FT (1989) Some disease-associated ancestral haplotypes carry a polymorphism of TNF. Hum Immunol 26: 91
Khalil I, Auriol L d', Gobet M, Morin L, Lepage V, Deschamps I. Park MS, Degos L, Galibert F, Hors J (1990) A combination of HLA-DQß Asp57-negative and HLA DQα Arg52 confers susceptibility to insulin-dependent diabetes mellitus. J Clin Invest 85: 1315
Hoffman RW, Shaw S, Francis LC, Larson MG, Petersen RA, Chylack LT, Glass DN (1986) HLA-DP antigens in patients with pauciarticular juvenile rheumatoid arthritis. Arthritis Rheum 29: 1057
Amar A, Nepom GT, Mickelson E, Erlich H, Hansen JA (1987) HLP-DP and HLA-DO genes in presumptive HLA-identical siblings: structural and functional identification of allelic variation. J Immunol 138: 1947
Shaw S, Pollack MS, Payne SM, Johnson AH (1980) HLA-linked B cell antigens of a new segregant series: population and family studies of the SB antigens. Hum Immunol 1: 177
About this article
Cite this article
Bishof, N.A., Welch, T.R., Beischel, L.S. et al. DP polymorphism in HLA-A1,-B8,-DR3 extended haplotypes associated with membranoproliferative glomerulonephritis and systemic lupus erythematosus. Pediatr Nephrol 7, 243–246 (1993). https://doi.org/10.1007/BF00853205
- Membranoproliferative glomerulonephritis
- Systemic lupus erythematosus
- Major histocompatibility complex