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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
. 1994 Aug 2;91(16):7747–7751. doi: 10.1073/pnas.91.16.7747

Common major histocompatibility complex class II markers in clinical variants of cicatricial pemphigoid.

J J Yunis 1, N Mobini 1, E J Yunis 1, C A Alper 1, R Deulofeut 1, A Rodriguez 1, C S Foster 1, D Marcus-Bagley 1, R A Good 1, A R Ahmed 1
PMCID: PMC44479  PMID: 8052655

Abstract

Cicatricial pemphigoid (CP) is a chronic autoimmune blistering disease affecting multiple mucous membranes derived from stratified squamous epithelium and occasionally the skin. CP has a wide spectrum of disease manifestations. Patients with oral pemphigoid (OP) have a benign self-limited disease in which pathological changes are restricted to the oral mucosa. On the other hand, patients with ocular cicatricial pemphigoid (OCP), a chronic condition marked with relapses and remissions, have ocular involvement and also perhaps involvement of other mucous membranes. All clinical subsets are characterized by the presence of a similar anti-basement zone autoantibody. The factors that determine the development of one form of CP or the other are not known. In a previous study, we described the association between OCP and the DQB1*0301 allele (P = 0.006). In this study, we have analyzed 22 Caucasian patients with OP and their family members for major histocompatibility complex DRB generic, DQA1, and DQB1 allele associations by PCR-sequence-specific oligonucleotide probe hybridization. The results were compared to those obtained from 17 Caucasian patients with OCP and to control Caucasian alleles and haplotypes. The DQB1*0301 allele frequency was 38.6% in OP, 52.9% in OCP, and 17.8% in controls. Statistically significant associations were detected between the DQB1*0301 allele and both OP (P = 0.0047) and OCP (P < 0.0001). In addition, DRB1*04 showed a statistically significant association (P = 0.005) with OCP when compared to controls. Analysis of major histocompatibility complex class II haplotypes showed significant statistical associations between both OCP and OP and the HLA-DRB1*04, DRB4*0101, DQA1*03, DQB1*0301 haplotype (P < 0.0001 and P = 0.0012, respectively). Our results indicate that DQB1*0301 is a marker of both oral and ocular forms of CP. The analysis of the amino acid sequence of the DQB1 alleles present in both OP and OCP suggested that amino acid residues at position 57 and positions 71-77 may also be markers of CP.

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Selected References

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

  1. Ahmed A. R., Foster S., Zaltas M., Notani G., Awdeh Z., Alper C. A., Yunis E. J. Association of DQw7 (DQB1*0301) with ocular cicatricial pemphigoid. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11579–11582. doi: 10.1073/pnas.88.24.11579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ahmed A. R., Hombal S. M. Cicatricial pemphigoid. Int J Dermatol. 1986 Mar;25(2):90–96. doi: 10.1111/j.1365-4362.1986.tb04544.x. [DOI] [PubMed] [Google Scholar]
  3. Ahmed A. R., Kurgis B. S., Rogers R. S., 3rd Cicatricial pemphigoid. J Am Acad Dermatol. 1991 Jun;24(6 Pt 1):987–1001. doi: 10.1016/0190-9622(91)70159-y. [DOI] [PubMed] [Google Scholar]
  4. Ahmed A. R., Yunis J. J., Marcus-Bagley D., Yunis E. J., Salazar M., Katz A. J., Awdeh Z., Alper C. A. Major histocompatibility complex susceptibility genes for dermatitis herpetiformis compared with those for gluten-sensitive enteropathy. J Exp Med. 1993 Dec 1;178(6):2067–2075. doi: 10.1084/jem.178.6.2067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Arnett F. C., Olsen M. L., Anderson K. L., Reveille J. D. Molecular analysis of major histocompatibility complex alleles associated with the lupus anticoagulant. J Clin Invest. 1991 May;87(5):1490–1495. doi: 10.1172/JCI115158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Khalil I., d'Auriol L., Gobet M., Morin L., Lepage V., Deschamps I., Park M. S., Degos L., Galibert F., Hors J. A combination of HLA-DQ beta Asp57-negative and HLA DQ alpha Arg52 confers susceptibility to insulin-dependent diabetes mellitus. J Clin Invest. 1990 Apr;85(4):1315–1319. doi: 10.1172/JCI114569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Marsh S. G., Bodmer J. G. HLA class II nucleotide sequences, 1992. Tissue Antigens. 1992 Nov;40(5):229–243. doi: 10.1111/j.1399-0039.1992.tb02050.x. [DOI] [PubMed] [Google Scholar]
  8. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Salazar M., Yunis J. J., Delgado M. B., Bing D., Yunis E. J. HLA-DQB1 allele typing by a new PCR-RFLP method: correlation with a PCR-SSO method. Tissue Antigens. 1992 Sep;40(3):116–123. doi: 10.1111/j.1399-0039.1992.tb02102.x. [DOI] [PubMed] [Google Scholar]
  10. Yunis J. J., Delgado M. B., Lee-Lewandroski E., Yunis E. J., Bing D. H. Rapid identification of HLA-DRw53-positive samples by a generic DRB-PCR amplification without further analysis. Tissue Antigens. 1992 Jul;40(1):41–44. doi: 10.1111/j.1399-0039.1992.tb01956.x. [DOI] [PubMed] [Google Scholar]
  11. Yunis J. J., Kineke E., Yunis E. J. Characterization of a new DRB1 allele, DRB1*1309, by PCR-SSOP and sequencing. Tissue Antigens. 1994 Jan;43(1):54–57. doi: 10.1111/j.1399-0039.1994.tb02298.x. [DOI] [PubMed] [Google Scholar]
  12. Yunis J. J., Salazar M., Delgado M. B., Alper C. A., Bing D. H., Yunis E. J. HLA-DQA1, DQB1 and DPB1 alleles on HLA-DQ2- and DQ9-carrying extended haplotypes. Tissue Antigens. 1993 Jan;41(1):37–41. doi: 10.1111/j.1399-0039.1993.tb01975.x. [DOI] [PubMed] [Google Scholar]

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