Laboratory diagnosis of pemphigus: direct immunofluorescence remains the gold standard

Giurdanella, Federica; Diercks, Gilles F.H.; Jonkman, Marcel F.; Pas, Hendrikus

doi:10.1111/bjd.14408

Cited by 40 publications

(27 citation statements)

References 7 publications

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“…They potentially offer advantages over IIF, such as increased sensitivity, but are not helpful in cases in which there are other antigens . Therefore, IIF and ELISA should be considered complementary and DIF remains the gold‐standard diagnostic investigation . Five millilitres of blood is sufficient for both IIF and ELISA.…”

Section: Laboratory Diagnosismentioning

confidence: 99%

British Association of Dermatologists’ guidelines for the management of pemphigus vulgaris 2017

et al. 2017

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Section: Laboratory Diagnosismentioning

confidence: 99%

British Association of Dermatologists’ guidelines for the management of pemphigus vulgaris 2017

et al. 2017

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“…This opens the possibility that in patients autoantibodies targeting other antigens may be additionally required to cause disease. A number of cases of acute PV with positive anti-keratinocyte antibodies by direct and/or indirect immunofluorescence but negative Dsg1 and Dsg3 ELISA have been reported, indicating that the level of circulating anti-Dsg antibody is not sufficiently detectable in these cases or that non-Dsg antibodies alone can be responsible for disease development (Belloni-Fortina et al, 2009;Cozzani et al, 2013;Giurdanella et al, 2016;Jamora et al, 2003;Sardana et al, 2013;Sharma et al, 2006;Zagorodniuk et al, 2005). A good although rare example is Dsc3 pemphigus, in which autoantibodies targeting Dsc3, even in the absence of antibodies directed to Dsg1 or Dsg3, have been shown to be pathogenic in vitro and in vivo (Mao et al, 2010;Rafei et al, 2011;Spindler et al, 2009).…”

Section: Relevance Of Autoantibodies Targeting Antigens Others Than Dmentioning

confidence: 99%

Mechanisms Causing Loss of Keratinocyte Cohesion in Pemphigus

Spindler

Eming

Schmidt

et al. 2018

Journal of Investigative Dermatology

114

102

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The autoimmune blistering skin disease pemphigus is caused by IgG autoantibodies against desmosomal cadherins, but the precise mechanisms are in part a matter of controversial discussions. This review focuses on the currently existing models of the disease and highlights the relevance of desmoglein-specific versus nondesmoglein autoantibodies, the contribution of nonautoantibody factors, and the mechanisms leading to cell dissociation and blister formation in response to autoantibody binding. As the review brings together the majority of laboratories currently working on pemphigus pathogenesis, it aims to serve as a solid basis for further investigations for the entire field.

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“…1 and 2). However, on average 10 -15% of acute PV patients with anti-keratinocyte AuAbs detectable by direct and/or indirect immunofluorescence are negative for Dsg1/3 ELISA (3)(4)(5)(6)(7)(8)(9). Although there are no known clinical and pathological differences between PV patients with versus without anti-Dsg AuAbs, the immunopathological mechanisms of acantholysis may be different.…”

mentioning

confidence: 99%

Synergy among non-desmoglein antibodies contributes to the immunopathology of desmoglein antibody–negative pemphigus vulgaris

Chernyavsky¹,

Amber

Agnoletti³

et al. 2019

Journal of Biological Chemistry

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Edited by Peter Cresswell Pemphigus vulgaris (PV) is a potentially lethal mucocutaneous blistering disease characterized by IgG autoantibodies (AuAbs) binding to epidermal keratinocytes and inducing this devastating disease. Here, we observed that non-desmoglein (Dsg) AuAbs in the sera of patients with Dsg1/3 AuAb-negative acute PV are pathogenic, because IgGs from these individuals induced skin blistering in neonatal mice caused by suprabasal acantholysis. Serum levels of AuAbs to desmocollin 3 (Dsc3), M3 muscarinic acetylcholine receptor (M3AR), and secretory pathway Ca 2؉/ Mn 2؉ -ATPase isoform 1 (SPCA1) correlated with the disease stage of PV. Moreover, AuAb absorption on recombinant Dsc3, M3AR, or SPCA1 both prevented skin blistering in the passive transfer of AuAbs model of PV in BALB/c mice and significantly decreased the extent of acantholysis in a neonatal mouse skin explant model. Although acantholytic activities of each of these immunoaffinity-purified AuAbs could not induce a PV-like phenotype, their mixture produced a synergistic effect manifested by a positive Nikolskiy sign in the skin of neonatal mice. The downstream signaling of all pathogenic non-Dsg AuAbs involved p38 mitogen-activated protein kinase (MAPK)-mediated phosphorylation and elevation of cytochrome c release and caspase 9 activity. Anti-Dsc3 and anti-SPCA1 AuAbs also activated SRC proto-oncogene, nonreceptor tyrosine kinase (SRC). Of note, although a constellation of non-Dsg AuAbs apparently disrupted epidermal integrity, elimination of a single pathogenic AuAb could prevent keratinocyte detachment and blistering. Therefore, anti-Dsg1/3 AuAb-free PV can be a model for elucidating the roles of non-Dsg antigenspecific AuAbs in the physiological regulation of keratinocyte cell-cell adhesion and blister development.

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Laboratory diagnosis of pemphigus: direct immunofluorescence remains the gold standard

Cited by 40 publications

References 7 publications

British Association of Dermatologists’ guidelines for the management of pemphigus vulgaris 2017

British Association of Dermatologists’ guidelines for the management of pemphigus vulgaris 2017

Mechanisms Causing Loss of Keratinocyte Cohesion in Pemphigus

Synergy among non-desmoglein antibodies contributes to the immunopathology of desmoglein antibody–negative pemphigus vulgaris

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