The 45 kD ocular cicatricial pemphigoid antigen is a keratin

Smith, E. B. F; Zone, JJ; Egan, CA; Taylor, TB; Meyer, LJ; Petersen, MJ

doi:10.1016/s0923-1811(98)83220-9

Cited by 3 publications

(5 citation statements)

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“…1,8 We believe that those IgA antibodies are easily overlooked by routine indirect immunofluorescence using higher screening dilutions in BP compared with the low dilutions used to detect circulating autoantibodies in linear IgA disease (LAD) and cicatricial pemphigoid (CP). [9][10][11] Our findings are in concordance with those of Sarret et al; they used CP sera undiluted and obtained a higher yield of positive results with a high proportion of IgA anti-BMZ antibodies compared with previous studies using dilute sera. 9 The high prevalence of IgA in children remains unexplained.…”

Section: Discussionsupporting

confidence: 91%

“…The antigenic specificity of IgA anti-BMZ antibodies in subepidermal bullous diseases is not well understood ( Table 2). [9][10][11][13][14][15][16][17][18][19][20][21][22][23][24][25][26] CP is divided immunopathologically into two major groups with regard to the target antigens bound by IgG antibodies. 27,28 IgA anti-BMZ autoantibodies in CP are shown to detect several different antigens in epidermal extracts.…”

Section: Discussionmentioning

confidence: 99%

“…13 Smith et al described a distinct 45 kDa polypeptide in ocular cicatricial pemphigoid recognized by IgA autoantibodies only; recently, the authors showed some evidence that this polypeptide may be a keratin. 10 In epidermolysis bullosa acquisita it has been shown that the target antigen (collagen type VII) may be detected by sole IgA antibodies in certain patients, although a IgG response is more common in this disease. 21,22,24,25 In LAD a variety of epidermal and dermal proteins have been detected by circulating autoantibodies (Table 2).…”

Section: Discussionmentioning

confidence: 99%

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IgA basement membrane zone autoantibodies in bullous pemphigoid detect epidermal antigens of 270-280 kDa, 230 kDa, and 180 kDa molecular weight by immunoblotting

Kirtschig

Wojnarowska

1999

Clinical and Experimental Dermatology

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Bullous pemphigoid (BP) is an acquired subepidermal blistering disease characterized by circulating IgG autoantibodies binding to the 230 and 180 kDa hemidesmosomal proteins. Associated basement membrane zone (BMZ) autoantibodies of the IgA class have been reported in few BP patients. The incidence and clinical relevance of these IgA antibodies, as well as their target antigens are unknown. Sera of 26 patients with BP were analysed for circulating IgG- and IgA-anti-BMZ autoantibodies by indirect immunofluorescence on salt-split human skin. All of the patients had circulating IgG autoantibodies and, in addition, nine (35%) also had circulating anti-BMZ IgA antibodies, that bound to the epidermal side of salt-split skin. By immunoblotting, IgA antibodies in seven of nine sera recognized either the 180 kDa, the 230 kDa, or both BP antigens. Moreover, IgA anti-BMZ antibodies in seven sera also detected an epidermal protein of 270-280 kDa. IgA antibodies did not identify specific bands on immunoblots of dermal extracts. There was no clinical difference between BP patients with or without circulating anti-BMZ-IgA.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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IgA basement membrane zone autoantibodies in bullous pemphigoid detect epidermal antigens of 270-280 kDa, 230 kDa, and 180 kDa molecular weight by immunoblotting

Kirtschig

Wojnarowska

1999

Clinical and Experimental Dermatology

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“…Others have looked for site‐specific target antigens in an attempt to explain the diverse clinical spectrum. In ocular cicatricial pemphigoid (OCP) two target antigens have been proposed: a 45‐kDa antigen targeted by IgA antibodies, with amino acid sequence homology to keratin 5 and 14 5,6 and the intracellular domain of the β4 integrin, targeted by IgG antibodies 7,8 . In a further subgroup of CP patients, an uncharacterized 168 kDa antigen has been identified in buccal mucosa 9 .…”

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confidence: 99%

Mucous membrane pemphigoid: HLA-DQB1*0301 is associated with all clinical sites of involvement and may be linked to antibasement membrane IgG production

Setterfield

Theron

Vaughan

et al. 2008

British Journal of Dermatology

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Background Class I human leucocyte antigens (HLA) ‐A, ‐B, ‐Cw and class II HLA‐DRB1, ‐DQB1 alleles were determined in 131 British Caucasian patients with mucous membrane pemphigoid (MMP) using serological and DNA‐based methods. Objectives To analyse the class I and II alleles expressed in well‐defined clinical and immunopathological subgroups of MMP, in order to establish whether specific alleles or haplotypes might in part explain disease susceptibility, clinical sites of involvement or disease severity. Methods Subgroups of patients were analysed according to the following clinical criteria: age of onset, sex, sites of clinical involvement (oral, ocular, skin, nasal, genital, pharyngeal, oesophageal, laryngeal, perianal), disease severity and history of autoimmune disease. Subgroups were also analysed according to the following immunopathological criteria: autoantibody profile, the presence of circulating antibasement membrane IgG or IgA antibodies and the detection of target basement membrane zone (BMZ) antigens (BP230 and BP180) by IgG autoantibodies. Results Class I HLA typing showed no significant disease or subgroup associations. Class II DRB1 typing showed a significantly increased allelic frequency in MMP vs. controls for DRB1*11 (RR = 2·08, Pc < 0·0000056). For DQB1, MMP vs. controls, there was a significantly increased allelic frequency for DQB1*0301 (Pc < 0·00000028) in both males and females; all clinical sites of involvement, with the exception of laryngeal, oesophageal and perianal sites and in patients with detectable circulating anti‐BMZ IgG compared with those negative for IgG (P < 0·0096, Pc < 0·019). A positive trend was noted in patients with ocular involvement compared with no ocular involvement and in patients with a clinical score 10 compared with < 10. We found no difference in DQB1*0301 allele frequency between subgroups with or without BP180 or BP230 target antigens. Haplotype frequencies showed an increase in DRB1*04, DQB1*0301 (Pc < 0·000066) and DRB1*11, DQB1*0301 (Pc < 0·000002) among patients compared with controls. Conclusions The DQB1*0301 allele confers a predisposition to all subgroups of MMP and may have a role in T‐cell recognition of basement membrane antigens, resulting in the production of anti‐BMZ IgG autoantibodies. The positive trend between increased allelic expression of DQB1*0301 in patients with ocular disease and in those with a higher clinical score, further suggests a role for this allele in disease severity.

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“…Others have looked for site-specific target antigens in an attempt to explain the diverse clinical spectrum. In ocular cicatricial pemphigoid (OCP) two target antigens have been proposed: a 45-kDa antigen targeted by IgA antibodies, with amino acid sequence homology to keratin 5 and 14 5,6 and the intracellular domain of the b4 integrin, targeted by IgG antibodies. 7,8 In a further subgroup of CP patients, an uncharacterized 168 kDa antigen has been identified in buccal mucosa.…”

mentioning

confidence: 99%

Mucous membrane pemphigoid: HLA-DQB1*0301 is associated with all clinical sites of involvement and may be linked to antibasement membrane IgG production

Setterfield¹,

Theron²,

Vaughan³

et al. 2001

Br J Dermatol

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The DQB1*0301 allele confers a predisposition to all subgroups of MMP and may have a role in T-cell recognition of basement membrane antigens, resulting in the production of anti-BMZ IgG autoantibodies. The positive trend between increased allelic expression of DQB1*0301 in patients with ocular disease and in those with a higher clinical score, further suggests a role for this allele in disease severity.

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The 45 kD ocular cicatricial pemphigoid antigen is a keratin

Cited by 3 publications

References 0 publications

IgA basement membrane zone autoantibodies in bullous pemphigoid detect epidermal antigens of 270-280 kDa, 230 kDa, and 180 kDa molecular weight by immunoblotting

IgA basement membrane zone autoantibodies in bullous pemphigoid detect epidermal antigens of 270-280 kDa, 230 kDa, and 180 kDa molecular weight by immunoblotting

Mucous membrane pemphigoid: HLA-DQB1*0301 is associated with all clinical sites of involvement and may be linked to antibasement membrane IgG production

Mucous membrane pemphigoid: HLA-DQB1*0301 is associated with all clinical sites of involvement and may be linked to antibasement membrane IgG production

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