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

Setterfield, Jane; Theron, J.; Vaughan, R. W.; Welsh, Ken I.; Mallon, E.; Wojnarowska, Fenella; Challacombe, Stephen; Black, Martin M.

doi:10.1046/j.1365-2133.2001.04380.x

Cited by 93 publications

(52 citation statements)

References 37 publications

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“…The articles identified from our search included 63 case reports7–58 and 10 case series,24, 59–66 representing 141 patients with laryngeal involvement of MMP. No clinical trials or comparative trials of laryngeal MMP were found.…”

Section: Resultsmentioning

confidence: 99%

Laryngeal mucous membrane pemphigoid: A systematic review and pooled‐data analysis

2010

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Section: Resultsmentioning

confidence: 99%

Laryngeal mucous membrane pemphigoid: A systematic review and pooled‐data analysis

2010

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“…4–10 The association of MMP with human leukocyte antigen (HLA) major histocompatibility class II HLA-DQB1*0301 has been demonstrated. 11–13 The cause is usually unknown, but there are a few reports of MMP triggered by medications such as methyldopa, clonidine and D-penicillamine. 14, 15 …”

Section: Introductionmentioning

confidence: 99%

Mucous Membrane Pemphigoid

Werth²,

Parisi³

et al. 2013

Dental Clinics of North America

155

150

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“…Genetic and epidemiological findings have strongly implicated polymorphic sites within MHC class II molecules in the pathogenesis of autoimmune diseases. [26][27][28] Recently HLA-DRB1*11 has been identified as a risk factor for the development of acquired TTP. It has been observed that the HLA-DRB1*11 is more frequent in patients with acquired TTP when compared with a control population.…”

Section: Introductionmentioning

confidence: 99%

Preferential HLA-DRB1*11–dependent presentation of CUB2-derived peptides by ADAMTS13-pulsed dendritic cells

Sorvillo

Haren

Kaijen

et al. 2013

Blood

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Key Points• ADAMTS13 derived peptides presented on HLA-DR; implications for acquired TTP.• CUB2 domain peptide binds to risk-allele HLA-DRB1*11.Autoantibodies directed against ADAMTS13 prohibit the processing of von Willebrand factor multimers, initiating a rare and life-threatening disorder called acquired thrombotic thrombocytopenic purpura (TTP). Recently, HLA-DRB1*11 has been identified as a risk factor for the development of acquired TTP. Here, we identified ADAMTS13-derived peptides presented on MHC class II alleles from 17 healthy donors. Dendritic cells from a panel of both HLA-DRB1*11-positive and -negative donors were pulsed with ADAMTS13, and the HLA-DR-presented peptide repertoire was analyzed by mass spectrometry. Interestingly, at low antigen concentrations, HLA-DRB1*11-or DRB1*03-positive donors presented a limited number of CUB2-derived peptides. Pulsing of dendritic cells using higher concentrations of ADAMTS13 resulted in the presentation of larger numbers of ADAMTS13-derived peptides by both HLA-DRB1*11-positive and -negative donors. Although the presented peptides were derived from several ADAMTS13 domains, inspection of the peptide profiles revealed that CUB2 domainderived peptides were presented with a higher efficiency when compared with other peptides. Remarkably, dendritic cells from DRB1*11 donors pulsed with higher concentrations of ADAMTS13-present derivatives of a single CUB2-derived peptide. We hypothesize that functional presentation of CUB2-derived peptides on HLA-DRB1*11 contributes to the onset of acquired TTP by stimulating low-affinity, self-reactive CD41 T cells. (Blood. 2013;121(17):3502-3510) Introduction Acquired thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening disorder characterized by the production of autoantibodies directed toward ADAMTS13, a plasma metalloprotease responsible for the cleavage of ultra-large von Willebrand factor (UL-VWF) multimers.1-3 Deficiency of ADAMTS13 causes the accumulation of UL-VWF strings on the surface of endothelial cells of the vessel wall and in the circulation. 4 Prolonged exposure of UL-VWF strings on the surface of endothelial cells promotes platelet adhesion, leading to low platelet counts and microvascular thrombosis. 5,6 The majority of the inhibitory anti-ADAMTS13 antibodies that develop in patients affected by acquired TTP targets a single epitope composed of Arg568, Phe592, Arg660, Tyr661, and Tyr665 on the outer surface of the spacer domain. This exposed region is crucial for binding of ADAMTS13 to unfolded VWF A2 domain.7-9 Antibodies targeting the CUB 1-2 and TSP2-8 regions of ADAMTS13 have also been detected in the plasma of several patients with acquired TTP. 10,11 The pathogenic role of anti-TSP2-8 and anti-CUB1-2 is still unclear. The carboxy-terminal ADAMTS13 TSP2-8 and CUB 1-2 regions not only modulate processing of VWF under flow 12-14 but are also necessary for the binding of ADAMTS13 to endothelial cells. 15A number of studies have shown that anti-ADAMTS13 antibodies detected in the plasma ...

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

Cited by 93 publications

References 37 publications

Laryngeal mucous membrane pemphigoid: A systematic review and pooled‐data analysis

Laryngeal mucous membrane pemphigoid: A systematic review and pooled‐data analysis

Mucous Membrane Pemphigoid

Preferential HLA-DRB1*11–dependent presentation of CUB2-derived peptides by ADAMTS13-pulsed dendritic cells

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