Isotypes and Antigenic Profiles of Pemphigus Foliaceus and Pemphigus Vulgaris Autoantibodies

Hacker, Mary K.; Janson, Marleen M.; Fairley, Janet A.; Lin, Mong-Shang

doi:10.1006/clim.2002.5259

Cited by 46 publications

(50 citation statements)

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“…Numerous studies demonstrated that abs in pemphigus mainly belong to the IgG1 and IgG4 subclass [7,27,37,[67][68][69][70]. However, the relevance of IgG subclasses for acantholysis in pemphigus still remains a matter of debate [16].…”

Section: Discussionmentioning

confidence: 99%

Clinical immunology Immunoglobulin G4 is prevailing over immunoglobulin G1 in autoimmunity of pemphigus and bullous pemphigoid: analysis of tissue-bound antibodies in active diseases

Gornowicz‐Porowska¹,

Pietkiewicz²,

Bowszyc‐Dmochowska³

et al. 2013

cejoi

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Section: Discussionmentioning

confidence: 99%

Clinical immunology Immunoglobulin G4 is prevailing over immunoglobulin G1 in autoimmunity of pemphigus and bullous pemphigoid: analysis of tissue-bound antibodies in active diseases

Gornowicz‐Porowska¹,

Pietkiewicz²,

Bowszyc‐Dmochowska³

et al. 2013

cejoi

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“…Overall, PV can be considered as a Th2-driven autoimmune disorder because most of the autoantibodies belong to the IgG 4 and IgE subclasses (7,(33)(34)(35)(36)(37). Moreover, patients with PV have significantly lower frequencies of peripheral IL-10-secreting Dsg3-reactive type 1 regulatory T (Tr1) cells than healthy carriers of HLA-DRB1*04:02 that suppress proliferative responses of T effector cells in vitro (38).…”

Section: Discussionmentioning

confidence: 99%

Pathogenic IgG Antibodies against Desmoglein 3 in Pemphigus Vulgaris Are Regulated by HLA-DRB1*04:02–Restricted T Cells

Eming

Hennerici

Bäcklund

et al. 2014

The Journal of Immunology

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Pemphigus vulgaris (PV) is considered as a model for an autoantibody-mediated organ-specific autoimmune disorder. IgG autoantibodies directed against the desmosomal cadherin desmoglein 3 (Dsg3), the major autoantigen in PV, cause loss of epidermal keratinocyte adhesion, resulting in blisters and erosions of the skin and mucous membranes. The association of human autoimmune diseases with distinct HLA alleles is a well-known phenomenon, such as the association with HLA-DRB1*04:02 in PV. However, direct evidence that HLA-DRB1*04:02–restricted autoreactive CD4+ T cells recognizing immunodominant epitopes of Dsg3 initiate the production of Dsg3-reactive IgG autoantibodies is still missing. In this study, we show in a humanized HLA-DRB1*04:02–transgenic mouse model that HLA-DRB1*04:02–restricted T cell recognition of human Dsg3 epitopes leads to the induction of pathogenic IgG Abs that induce loss of epidermal adhesion, a hallmark in the immune pathogenesis of PV. Activation of Dsg3-reactive CD4+ T cells by distinct human Dsg3 peptides that bind to HLA-DRβ1*04:02 is tightly regulated by the HLA-DRB1*04:02 allele and leads, via CD40-CD40L–dependent T cell–B cell interaction, to the production of IgG Abs that recognize both N- and COOH-terminal epitopes of the human Dsg3 ectodomain. These findings demonstrate key cellular and humoral immune events in the autoimmune cascade of PV in a humanized HLA-transgenic mouse model. We show that CD4+ T cells recognizing immunodominant Dsg3 epitopes in the context of the PV-associated HLA-DRB1*04:02 induce the secretion of Dsg3-specific IgG in vivo. Finally, these results identify Dsg3-reactive CD4+ T cells as potential therapeutic targets in the future.

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“…11 Intercellular adhesion of the epidermis is a vital function. When the self-tolerance mechanism is broken down, cell-cell detachment occurs due to the binding of autoantibodies to epidermal autoantigens, resulting in blister formation.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 In PV, it has been demonstrated that this response is predominantly of the IgG4 subclass in active cases, and IgG1 is the subclass involved in disease remission. [9][10][11] The profile of IgG subclass autoimmune response in FS is similar to PV, showing an IgG4 response in active disease and IgG1 in preclinical stages or in disease remission. [11][12][13][14][15] Recent studies 13 have shown that due to an intramolecular epitope spreading of desmoglein 1, the autoantigen involved in FS, there is a heterogeneous IgG subclass response in this disease.…”

mentioning

confidence: 87%

“…[9][10][11] The profile of IgG subclass autoimmune response in FS is similar to PV, showing an IgG4 response in active disease and IgG1 in preclinical stages or in disease remission. [11][12][13][14][15] Recent studies 13 have shown that due to an intramolecular epitope spreading of desmoglein 1, the autoantigen involved in FS, there is a heterogeneous IgG subclass response in this disease. In preclinical stages and in clinical remission of FS, IgG1 autoantibodies are directed to the carboxy terminal EC-5 of desmoglein 1.…”

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confidence: 87%

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Endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris: immunoglobulin G heterogeneity detected by indirect immunofluorescence

et al. 2004

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Pemphigus are autoimmune intraepidermal blistering diseases in which immunoglobulin G (IgG) autoantibodies are directed against desmosomal glycoproteins. The aim of this study was to determine the IgG subclass profile of endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris utilizing indirect immunofluorescence. PATIENTS AND METHODS:Twenty-five patients with pemphigus vulgaris, 25 with endemic pemphigus foliaceus (fogo selvagem), and 25 healthy controls were analyzed by indirect immunofluorescence for circulating autoantibodies (total IgG and its subclasses).RESULTS: Our data revealed a significant correlation (P <.05) of disease activity and autoantibody levels in both forms of pemphigus, i.e., negative titers related to clinical remission, whereas positive results related to active disease. Immunoglobulin G subclass analysis in fogo selvagem demonstrated that in patients in remission, 56% showed positive immunoglobulin G4; in active disease, immunoglobulin G4 was the predominant subclass (100% positive in all cases). The IgG subclass profile in pemphigus vulgaris showed that in patients in remission, only 10% were positive for immunoglobulin G4; in active disease, positivity for immunoglobulin G4 was present in 78% to 88% of the cases.CONCLUSION: Subclass characterization of immunoglobulin G autoantibodies is a useful tool for pemphigus followup, since immunoglobulin G4 (IgG4) is the subclass that is closely related to recognition of pathogenic epitopes, and consequently with disease activity. Careful monitoring should be performed for fogo selvagem in clinical remission with a homogeneous IgG4 response, since this may indicate more frequent relapses.

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Isotypes and Antigenic Profiles of Pemphigus Foliaceus and Pemphigus Vulgaris Autoantibodies

Cited by 46 publications

References 47 publications

Clinical immunology Immunoglobulin G4 is prevailing over immunoglobulin G1 in autoimmunity of pemphigus and bullous pemphigoid: analysis of tissue-bound antibodies in active diseases

Clinical immunology Immunoglobulin G4 is prevailing over immunoglobulin G1 in autoimmunity of pemphigus and bullous pemphigoid: analysis of tissue-bound antibodies in active diseases

Pathogenic IgG Antibodies against Desmoglein 3 in Pemphigus Vulgaris Are Regulated by HLA-DRB1*04:02–Restricted T Cells

Endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris: immunoglobulin G heterogeneity detected by indirect immunofluorescence

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