A comparison of anti‐desmoglein antibodies and indirect immunofluorescence in the serodiagnosis of pemphigus vulgaris

Zagorodniuk, Irena; Weltfriend, Sara; Shtruminger, Lily; Sprecher, Eli; Коган, О С; Pollack, Shimon; Bergman, Reuven

doi:10.1111/j.1365-4632.2004.02541.x

Cited by 61 publications

(63 citation statements)

References 16 publications

(68 reference statements)

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“…While anti-Dsg1/3 ELISAs and IIF have an established complementary role in the diagnosis of pemphigus (10,19,44), their usefulness for disease monitoring, based on a possible correlation of autoantibody levels with disease activity, is still controversial. Especially with IIF titres, many studies have been performed with relatively small sample sizes, resulting in contradictory data (12-15, 21, 28, 31, 32, 45, 46).…”

Section: Discussionmentioning

confidence: 99%

Autoantibody Levels and Clinical Disease Severity in Patients with Pemphigus: Comparison of Aggregated Anti-desmoglein ELISA Values and Indirect Immunofluorescence Titres

Weiss¹,

Ristl²,

Griss³

et al. 2015

Acta Derm Venerol

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Detecting serum-autoantibodies by anti-Desmoglein-1 (anti-Dsg1) and anti-Dsg3 ELISAs as well as indirect immunofluorescence (IIF) are established complementary methods to diagnose pemphigus. Whether autoantibody levels also reflect clinical disease activity is still a matter of debate, as head-to-head comparisons of ELISA values and IIF titres with clinical activity over a longer treatment period are scarce. In our retrospective study, we compared aggregated repetitive intra-patient ELISA values and IIF titres with grades of clinical disease (1 = remission, 2 = moderate activity, 3 = exacerbation) in 47 patients suffering from pemphigus vulgaris (PV, n = 36) and pemphigus foliaceus (PF, n=11). We found that anti-Dsg1 ELISA values in PF and mucocutaneous PV as well as anti-Dsg3 ELISA values in PV best reflect disease activity. IIF titres, by contrast, did not show a significant association with disease severity. From these data we conclude that ELISA index values can be a valuable tool to monitor disease in patients with pemphigus, whereas IIF titres reflect clinical activity only insufficiently.

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Section: Discussionmentioning

confidence: 99%

Autoantibody Levels and Clinical Disease Severity in Patients with Pemphigus: Comparison of Aggregated Anti-desmoglein ELISA Values and Indirect Immunofluorescence Titres

Weiss¹,

Ristl²,

Griss³

et al. 2015

Acta Derm Venerol

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“…Although Dsg 1 antibody indeed appears to be a reliable serologic marker of PF and Dsg 3 antibody—that of PV, up to 58% of PF patients and 12% of patients with endemic PF (Fogo Selvagem) were reported to develop antibodies against both Dsg 1 and Dsg 3 [108,116,117]. Furthermore, it has been conclusively demonstrated that Dsg 1 and Dsg 3 testing cannot differentiate between various morphologic subtypes of PV [96,118,119]. In one study, for instance, 46% of PV patients did not have the PV phenotype (mucosal or mucocutaneous) predicted by their Dsg antibody profile [118].…”

Section: Pemphigus Autoantibodiesmentioning

confidence: 99%

Pemphigus autoimmunity: Hypotheses and realities

2011

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The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients.

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“…In (PV) patients showing both mucous membrane and skin involvement, Abs to both Dsg 3 and Dsg 1 may be detected (2,16,17). However, there are also cases where the Ab profile against Dsg 1 and 3 in PV does not strictly correlate with these clinical phenotypes (18,19). At present, direct evidence that the presence of Dsg 3-specific Abs in PV but not in PF may account for the more severe clinical phenotype of PV compared with PF patients is lacking.…”

mentioning

confidence: 99%

Pemphigus Vulgaris IgG Directly Inhibit Desmoglein 3-Mediated Transinteraction

Heupel

Zillikens

Drenckhahn

et al. 2008

The Journal of Immunology

124

135

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The autoimmune blistering skin disease pemphigus is caused by autoantibodies against keratinocyte surface Ags. In pemphigus vulgaris (PV), autoantibodies are primarily directed against desmosomal cadherins desmoglein (Dsg) 3 and Dsg 1, whereas pemphigus foliaceus (PF) patients only have Abs against Dsg 1. At present, it is unclear whether Dsg autoantibodies contribute to pemphigus pathogenesis by direct inhibition of Dsg transinteraction. Using atomic force microscopy, we provide evidence that PV-IgG directly interfere with homophilic Dsg 3 but, similar to PF-IgG, not with homophilic Dsg 1 transinteraction, indicating that the molecular mechanisms in PV and PF pathogenesis substantially differ. PV-IgG (containing Dsg 3 or Dsg 1 and Dsg 3 autoantibodies) as well as PV-IgG Fab reduced binding activity of Dsg 3 by ∼60%, comparable to Ca2+ depletion. Similarly, the mouse monoclonal PV Ab AK 23 targeting the N-terminal Dsg 3 domain and AK 23 Fab reduced Dsg 3 transinteraction. In contrast, neither PV-IgG nor PF-IgG blocked Dsg 1 transinteraction. In HaCaT monolayers, however, both PV- and PF-IgG caused keratinocyte dissociation as well as loss of Dsg 1 and Dsg 3 transinteraction as revealed by laser tweezer assay. These data demonstrate that PV-IgG and PF-IgG reduce Dsg transinteraction by cell-dependent mechanisms and suggest that in addition, Abs to Dsg 3 contribute to PV by direct inhibition of Dsg transinteraction.

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A comparison of anti‐desmoglein antibodies and indirect immunofluorescence in the serodiagnosis of pemphigus vulgaris

Abstract: The IIF and ELISA tests may be used as complementary tests for the serologic diagnosis of pemphigus.

Cited by 61 publications

References 16 publications

Autoantibody Levels and Clinical Disease Severity in Patients with Pemphigus: Comparison of Aggregated Anti-desmoglein ELISA Values and Indirect Immunofluorescence Titres

Autoantibody Levels and Clinical Disease Severity in Patients with Pemphigus: Comparison of Aggregated Anti-desmoglein ELISA Values and Indirect Immunofluorescence Titres

Pemphigus autoimmunity: Hypotheses and realities

Pemphigus Vulgaris IgG Directly Inhibit Desmoglein 3-Mediated Transinteraction

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