Association of HLA-DR4 with ocular cicatricial pemphigoid

Zaltas, Mandi M.; Ahmed, Razzaque A.; Foster, C. Stephen

doi:10.3109/02713688908995191

Cited by 38 publications

(10 citation statements)

References 22 publications

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“…The antibody in pemphigus vulgaris is directed against a protein of the epidermal intercellular cement substance (31), whereas the antigen(s) of OCP have not been definitively characterized (32). Although both diseases are associated with HLA-DR4 (11,33) in some patients, in other respects the MHC associations are, quite different. In this report, we have shown that the HLA-DR4 increase in OCP appears to be secondary to the increase in DQw7 and not to a DR4-carrying extended haplotype.…”

Section: Methodsmentioning

confidence: 99%

Association of DQw7 (DQB1*0301) with ocular cicatricial pemphigoid.

Ahmed

Maleki

Zaltas

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Ocular cicatricial pemphigoid (OCP) is an autoimmune blistering disease that affects the conjunctiva and multiple mucous membranes. Class I and H and complement genetic markers of the major histocompatibility complex were studied in 20 Caucasian OCP patients and members of their families. Frequencies of individual alleles and common fixed or extended haplotypes in the patients were compared with those in normal family control haplotypes and with overall normal Caucasian haplotypes. The most striking increase compared with overall controls was noted in HLA-DQw3 (P = 0.006), unassociated with any extended haplotype. All but 1 of the 20 patients carried DQw3 in linkage with HLA-DR4 (increased significantly with P = 0.042 compared with overall normal genotype controls) or DR5. The DQw3, on analysis by restriction fragment length polymorphism in genomic DNA, was, in every instance, DQw7 (3.1, DQB1*0301). The frequency of DQB1*0301 in patient haplotypes compared with overall normal DR4 and DR5 DQw3-bearing haplotypes was statistically significantly increased (P < 0.003, relative risk = 9.6). The distribution of homozygotes and heterozygotes for DQB1*0301 among the patients was consistent with dominant but not recessive inheritance of DQB1*0301 or a gene, probably a class H allele, in linkage disequilibrium with it as the major histocompatibility complex susceptibility gene for OCP.Ocular cicatricial pemphigoid (OCP) is an autoimmune blistering disease that affects multiple mucous membranes (1-3). If not treated or treated inappropriately when it affects the eyes, it can cause blindness. The pathologic processes of chronic cicatrizing conjunctivitis and progressive conjunctival subepithelial fibrosis that characterize this disease result in severe xerosis of the eye and ocular keratinization.The deposition of immunoglobulins and complement components at the basement membrane zone (BMZ) (4-6) of the involved mucosa appears to be pathogenetic. Inflammatory mediators in the preocular tear film contribute to the final pathologic changes (3). Circulating antibodies to BMZ have been demonstrated in the serum of OCP patients, using skin and buccal mucosa as substrate (7,8).There have only been a few studies of HLA antigen frequencies in patients with OCP. The initial reports (6, 9) of an increased frequency of HLA-B12 (HLA-B44 or B45) were not confirmed in later studies (3, 10). Recently (11), we reported an increase in the frequency of the HLA-DR4 allele in OCP patients. In patients with pemphigus vulgaris, the increased frequency of DR4 is ascribable to the increased frequency oftwo haplotypes, SC21, DR4, DQw8] and SC31, DR4, DQw8], particularly in Ashkenazi Jewish patients (12). The first of these is a known extended haplotype (13) (a haplotype with fixed DNA over at least the HLA-B/DR interval) in this ethnic group. In a number of major histocompatibility complex (MHC) alleleassociated diseases, the increase in specific alleles is secondary to the increase in one or more extended haplotypes that carry suscepti...

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Section: Methodsmentioning

confidence: 99%

Association of DQw7 (DQB1*0301) with ocular cicatricial pemphigoid.

Ahmed

Maleki

Zaltas

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…Initially, HLA-B12 was reported to be associated with OCP [13]. This association was not confirmed by a later study [15], and HLA-DR4. -DR5.…”

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confidence: 86%

“…-DR5. -DQw3, -B8, -B35 and -B49 were reported to be associated with OCP [15]. Subsequently, restriction fragment length polymorphism analyses sub typed DQw3 to be the DQw7 (DQB 1*0301) allele [ 16], Ail the previous studies, however, appeared to include a clini cally and immunopathologically heterogeneous group of patients.…”

mentioning

confidence: 99%

“…Many of these patients had skin disease [ 13] and could represent anti-bullous-pemphigoid antigen mucosal pemphigoid [9] or antiepiligrin mucosal pemphigoid [10]. In other studies, sufficient clinical information was not pro vided to classify the patients [14][15][16], In addition to a lack of definite clinical classification, the previous HLA studies employed indirect methods [13][14][15][16]. We therefore used a direct HLA typing method [17,18] to define the HLA-DQB 1*0301 association with immune-mediated subepithe lial mucous membrane blistering diseases subtyped accord ing to clinical, immunopathological and molecular charac teristics [91.…”

mentioning

confidence: 99%

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High Frequency of HLA-DQB1*0301 Allele in Patients with Pure Ocular Cicatricial Pemphigoid

Chan

Wang²,

Wang³

et al. 1994

Dermatology

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Two factors, its classification and its immunogenetics, may have contributed to an incomplete understanding of the pathogenic mechanism in the disease group commonly termed ‘cicatricial pemphigoid’. We have previously demonstrated that pure ocular cicatricial pemphigoid (OCP) is a unique clinical and immunopathological entity. In an effort to better define the immunogenetic characteristics for patients with pure OCP, we performed HLA typing for the class II MHC gene HLA-DQB 1*0301 allele, by amplifying genomic DNA extracted from patients with polymerase chain reaction, followed by hybridization with a sequence-specific oligonucleotide probe on dot-blotted and Southern-blotted amplified DNA samples. Ninety percent (9/10) of patients with pure OCP had the DQB1*0301 allele, in contrast to 52% (17/33) of normal individuals who had the DQB 1*0301 allele. The high frequency of the HLA-DQB 1*0301 allele in patients with pure OCP may point to a distinct immunogenetic pattern and possibly a distinct pathomechanism for the disease.

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“…O HLA de classe I não parece estar associado à doença (1) , embora Mondino et al (40)(41)(42) tenham sugerido associação com o antígeno HLA-B12. Em 1989, foi sugerida a associação com os antígenos HLA-A2, -B8, -B35 e -B49 (43) .…”

Section: Penfigóide Cicatricial Ocularunclassified