Prediction of desmoglein-3 peptides reveals multiple shared T-cell epitopes in HLA DR4- and DR6- associated Pemphigus vulgaris

Tong, Joo Chuan; Tan, Tin Wee; Sinha, Animesh A.; Ranganathan, Shoba

doi:10.1186/1471-2105-7-s5-s7

Cited by 26 publications

(25 citation statements)

References 52 publications

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“…Since 2000, a few studies have shown a strong association between chronic urticaria and HLA-DRB1, *12, *0901 and DRB4 [13,19]. The authors found the same correlation as Oztas et al [6] between the presence of HLA-DRB4 (endogenous peptide L-plastin 581–595) and CSU.…”

Section: Discussionsupporting

confidence: 74%

HLA Status in Patients with Chronic Spontaneous Urticaria

Bożek

Krajewska

Filipowska

et al. 2010

Int Arch Allergy Immunol

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Chronic spontaneous urticaria (CSU) is the most common form of chronic urticaria. A considerable amount of data supports an immunological basis for CSU. Some research has focused on the association between chronic urticaria and specific human leukocyte antigen (HLA) alleles. The aim of this study was to investigate the HLA status of Polish patients diagnosed with CSU. Methods: The standard complement-dependent microlymphocytotoxicity assay and PCR amplification with sequence-specific primers were used to analyze HLA alleles in 115 patients diagnosed with CSU, and the results were compared to those from 162 healthy, genetically unrelated individuals. Results: Among the HLA-A alleles, A-33 occurred significantly more often in the control group (p < 0.01). Analysis of the HLA-B allele frequencies revealed the prevalence of the B44 antigen in the study group (p < 0.0001). Frequencies of HLA-C alleles and HLA-DQ did not differ significantly between the groups. Among the HLA class II alleles, DRB1*04 was observed significantly more often in the study population (p < 0.001), mainly in the autoimmunological subtype of urticaria. Conclusion: HLA alleles may be involved in CSU development or play a protective role in CSU.

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Section: Discussionsupporting

confidence: 74%

HLA Status in Patients with Chronic Spontaneous Urticaria

Bożek

Krajewska

Filipowska

et al. 2010

Int Arch Allergy Immunol

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“…These amino acids of HLA-DRB1*04:02 -coded molecules have been proposed to contribute to the shape and the charge of the HLA-DR molecule, and thereby play a role in effective binding of Dsg3-derived peptides and their presentation to auto-reactive T cells in PV (43, 44). Using a structure based model, another group proposed that HLA-DRB1*04:02 -coded molecules bind in particular to peptides derived from the transmembrane and extracellular Dsg3 domains (45). …”

Section: Pv Desmoglein 3 and Hla-drb1*0402mentioning

confidence: 99%

A reciprocal HLA-Disease Association in Rheumatoid Arthritis and Pemphigus Vulgaris

Drongelen

Holoshitz

2017

Front Biosci

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Human leukocyte antigens (HLA) have been extensively studied as being antigen presenting receptors, but many aspects of their function remain elusive, especially their association with various autoimmune diseases. Here we discuss an illustrative case of the reciprocal relationship between certain HLA-DRB1 alleles and two diseases, rheumatoid arthritis (RA) and pemphigus vulgaris (PV). RA is strongly associated with HLA-DRB1 alleles that encode a five amino acid sequence motif in the 70-74 region of the DRβ chain, called the shared epitope (SE), while PV is associated with the HLA-DRB1*04:02 allele that encodes a different sequence motif in the same region. Interestingly, while HLA-DRB1*04:02 confers susceptibility to PV, this and other alleles that encode the same sequence motif in the 70-74 region of the DRβ chain are protective against RA. Currently, no convincing explanation for this antagonistic effect is present. Here we briefly review the immunology and immunogenetics of both diseases, identify remaining gaps in our understanding of their association with HLA, and propose the possibility that the 70-74 DRβ epitope may contribute to disease risk by mechanisms other than antigen presentation.

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“…The majority of genetic studies in patients with pemphigus show associations between PV and the major histocompatibility complex class II antigens, in particular, HLA-DR4 or HLA-DQ1. 9,10,38,39 Currently and with the advent of molecular sequencing, 2 HLA class II subtypes (DRB1*0402 and DQB1*0503) have been recognized as present in more than 95% of patients with PV. 11 Although the genetic predisposition is essential, it is not independently sufficient to initiate the autoimmune pathogenic mechanism leading to the diseases, as proven by the reports of pemphigus in one of two monozygotic twins and in only two of three siblings with identical predisposing haplotype.…”

Section: Etiology Genetic Backgroundmentioning

confidence: 99%