A Newly Characterized HLA DQ
            <sub>β</sub>
            Allele Associated with Pemphigus Vulgaris

Sinha, Animesh A.; Brautbar, Chaim; Szafer, Fanny; Friedmann, Adam; Tzfoni, Eli; Todd, John A.; Steinman, Lawrence; McDevitt, Hugh O.

doi:10.1126/science.2894075

Cited by 219 publications

(114 citation statements)

References 37 publications

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“…5). These findings are consistent with epidemiological studies showing a strong association of PV with HLA-DRB1*0402 (16) and HLA-DQB1*0503 (17,18) and a recent study from our group that identified Th cell responses to Dsg3 not only in PV patients but also in healthy carriers of the aforementioned PV-associated HLA class II alleles (22). These findings are in line with three independent studies demonstrating that Dsg3-specific TCC were restricted by HLA-DRB1*0402 (19,20,43).…”

Section: Discussionsupporting

confidence: 92%

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T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals

Veldman¹,

Gebhard²,

Uter

et al. 2004

The Journal of Immunology

107

104

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Pemphigus vulgaris is a severe autoimmune disease caused by autoantibodies against the cutaneous adhesion molecule, desmoglein 3 (Dsg3). The aim of this study was to characterize the specificity of autoreactive Th cells, which presumably regulate Dsg3-specific autoantibody production. Ninety-seven Th1 and Th2 clones isolated from 16 pemphigus patients and 12 HLA-matched healthy donors recognized the Dsg3 peptides, DG3(78-94), DG3(96-112), DG3(189-205), DG3(205-221), and DG3(250-266). Peptide DG3(96-112), and to a lesser extent DG3(250-266), was recognized by the majority of T cells from patients and healthy donors in association with HLA-DRB1*0402 and DQB1*0503 which were prevalent in the pemphigus patients and Dsg3-responsive healthy donors. Analyzing the Vβ-chain of the TCR of the DG3(96-112)-specific T cells showed no restricted TCR usage. Peptides DG3(342-358) and DG3(376-392) were exclusively recognized by T cell clones (n = 13) from patients while DG3(483-499) was only recognized by T cell clones (n = 3) from a healthy donor. All Dsg3 peptides contained conserved amino acids at relative positions 1, 4, and 6; amino acids with a positive charge at position 4 presumably represent anchor motifs for DRB1*0402. These findings demonstrate that T cell recognition of distinct Dsg3 peptides is restricted by distinct HLA class II molecules and is independent from the development of pemphigus vulgaris.

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Section: Discussionsupporting

confidence: 92%

“…PV is associated with the HLA class II allele, HLA-DRB1*0402, particularly in Jewish patients (16), whereas DRB1*14/DQB1*0503 is prevalent in non-Jewish patients (17,18). Recent evidence suggests that these HLA class II alleles are involved in the presentation of Dsg3 peptides to autoreactive T cells in PV patients (19 -22).…”

Section: P Emphigus Vulgaris (Pv)mentioning

confidence: 99%

T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals

Veldman¹,

Gebhard²,

Uter

et al. 2004

The Journal of Immunology

107

104

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“…All 3 alleles were increased in Caucasian lupus nephritis patients; however, only DQP1.1 and DQPl .AZH were independently associated with nephritis. DR2,DQPl.AZH and DRw6,DQP1.9 are both quite rare in the normal Caucasian population (normal haplotype frequency -1% and -4%, respectively [ 12, and have been found to be associated with other autoimmune disorders: I .AZH with insulindependent diabetes mellitus (20,26) and 1.9 with pemphigus vulgaris (27,28). Residues 28 and 30 are at the bottom of the antigen-binding cleft, pointing upwards into the site, according to the hypothesized 3-dimensional model of the class I1 molecule (55); this implicates involvement of the first HVR in antigen interaction.…”

Section: Discussionmentioning

confidence: 99%

“…Traditionally, factor B and the second and fourth complement components (BF, C2, and C4A and C4B) have been detected by protein electrophoresis (15)(16)(17). Such molecular techniques as restriction fragment length polymorphism (RFLP) using MHC locus-specific complementary DNA (cDNA) probes, sequence-specific oligonucleotide (SSO) analysis, and direct sequencing of the polymorphic first domain have refined the analysis of class I1 allelic polymorphism as well as the identification of C4A and C4B gene deletions (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”

mentioning

confidence: 99%

Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus

Fronek

Timmerman

Alper

et al. 1990

Arthritis & Rheumatism

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114

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Susceptibility to systemic lupus erythematosus is associated with major histocompatibility complex (MHC)-encoded genes. We have used nucleotide sequence analysis to better define the disease-associated MHC alleles. HLA-DR2, DQwl, and especially the rare allele DQPl.AZH confer high relative risk (RR = 14) for lupus nephritis in a Caucasian population of patients. Pilot studies using historical controls suggest that these genes also confer a high risk in non-Caucasian ethnic groups (RR = 24-78). We have found that DR4 is significantly decreased in patients with lupus nephritis. Fifty percent of the patients with lupus nephritis had either the DQP1.1, the DQPl.AZH, or the DQP1.9 alleles. These alleles share amino acid residues that have been predicted to be the contact points for antigen and the T cell receptor. These HLA alleles appear to have a direct role in the predisposition to lupus nephritis, whereas DR4 may have a "protective" effect.Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that involves the skin, joints, serosal surface, kidneys, central nervous system, and blood elements. It is characterized by abnormalities in B cell activation, with resultant autoantibody production, and by dysregulation of T cells, the complement cascade, and the clearing of immune complexes. Genetic factors in SLE have been implicated by results of studies of family aggregation of the disease ( l ) , increased concordance of SLE among monozygotic versus dizygotic twins (2), Gm markers (3), decreased red cell CRl receptors (4), abnormal T cell suppressor function in healthy relatives of SLE patients (3, and associations with several major histocompatibility complex (MHC) loci (summarized in refs. 6 and 7).Population studies have shown an increased association between SLE and class I1 MHC DR2 and/or DR3 antigen alleles, as well as an association with class 111 MHC C2 and C4A deficiencies (8,9). The strengths of these associations vary from study to study, and they can vary in ethnically different populations (7-10). The relative risk (RR) of SLE in a person positive for any 1 of these markers has been reported to be 3 or less. However, the RR is significantly increased if multiple alleles are present, such as homozygosity of C4A null (RR = 16) or C4A null and DR2 (RR = 25) (9), which supports the notion that susceptibility to this disease may be polygenic. The class 11 loci of the human major histocompatibility complex encode the HLA-D cell-surface

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“…Estudos imunogenéticos demonstram aumentada incidência de HLA-DR4 (em judeus ashkenazi) ou DRw6 (em outros grupos étni-cos). [34][35][36] Cerca de 90% dos pacientes com PV tem envolvimento oral, e percentual que varia de 50 a 70% dos doentes inicia o quadro com lesões exulceradas em mucosa oral. 32 O PV afeta igualmente ambos os sexos 33 e ocorre principalmente em pacientes entre a quarta e a sexta décadas de vida; 37 todavia, podem ser afetados indivíduos de qualquer idade, incluindo crianças e recém-nascidos de mães com PV.…”

Section: Pênfigo Vulgar Introduçãounclassified

Dermatoses bolhosas auto-imunes

Cunha

Barraviera²

2009

An. Bras. Dermatol.

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Resumo: Dermatoses bolhosas autoimunes são doenças cuja manifestação cutânea primária e fundamental consiste em vesículas e bolhas. Classificam-se conforme a localização da bolha, em intraepidérmica e subepidérmica. Os pacientes produzem autoanticorpos contra estruturas específicas da pele detectáveis por técnicas de imunofluorescência, immunobloting e Elisa. Os recentes avanços da biologia molecular e celular têm permitido conhecer esses autoantígenos, contra os quais os pacientes se sensibilizam e que estão localizados na epiderme ou na junção dermoepidérmica. São doenças de baixa incidência, porém de elevada morbidade e por vezes letais. O objetivo deste trabalho é revisar e descrever os progressos nos conhecimentos de quatro doenças vésico-bolhosas autoimunes: pênfigo foliáceo endêmico (fogo selvagem), pênfigo vulgar, penfigóide bolhoso e dermatite herpetiforme. Palavras-chave: Alergia e imunologia; Dermatite herpetiforme; Dermatopatias vesiculobolhosas; Penfigo; Penfigóide bolhoso Abstract: Abstract: Autoimmune bullous dermatoses are diseases in which blisters and vesicles are the primary and fundamental types of skin lesion. Their classification is based on the location of the blister: intraepidermal and subepidermal. Patients produce autoantibodies against self-specific structures of the skin detectable by immunofluorescence techniques, immunoblotting and ELISA. Recent advances in molecular and cellular biology have brought to knowledge these self-antigens, against which patients are sensitized, and which are found in epidermis or in the dermo-epidermal junction. These are low incidence, but high morbidity diseases that may be fatal. The aim of this article is to review and describe the progress of four autoimmune vesiculobullous disorders: endemic pemphigus foliaceous (wild fire), pemphigus vulgaris, bullous pemphigoid and dermatitis herpetiformis. Keyword: Allergy and immunology; Bullous pemphigoid; Dermatitis herpetiformis; Pemphigus; Skin diseases vesiculobullous histológicas comuns e ambos apresentam autoanticorpos da subclasse IgG4, cujo antígeno-alvo é a desmogleína 1, antígeno desmossomal de 160kd.O FS acomete mais frequentemente crianças, adolescentes e adultos jovens que vivem nas áreas rurais de regiões endêmicas, e é comum a ocorrência

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A Newly Characterized HLA DQ _β Allele Associated with Pemphigus Vulgaris

Cited by 219 publications

References 37 publications

T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals

T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals

Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus

Dermatoses bolhosas auto-imunes

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A Newly Characterized HLA DQ β Allele Associated with Pemphigus Vulgaris

Cited by 219 publications

References 37 publications

T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals

T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals

Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus

Dermatoses bolhosas auto-imunes

Contact Info

Product

Resources

About

A Newly Characterized HLA DQ _β Allele Associated with Pemphigus Vulgaris