056 Anti-thyroid peroxidase antibodies may contribute to blister formation in pemphigus vulgaris

Sajda, Thomas; Seiffert-Sinha, Kristina; Sinha, Animesh A.

doi:10.1016/j.jid.2017.02.069

Cited by 4 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The following reports testify to the fact that non-Dsg AuAbs developed by PV patients contribute to PV pathophysiology: (i) gross blisters were induced in mouse skin by the PVIgG depleted of anti-Dsg3 AuAb (21); (ii) passive transfer of PVIgG lacking anti-Dsg1 AuAb to neonatal Dsg3 Ϫ/Ϫ mice induced PV-like phenotype featuring widespread blistering, which means that blisters were induced by targeting antigens other than Dsg1 and Dsg3 (22); (iii) preabsorption of PV sera with recombinant pemphaxin, a low affinity receptor for acetylcholine, eliminated acantholytic activity and eluted antibody immunoprecipitated native pemphaxin. The addition of anti-pemphaxin antibody back to the preabsorbed PVIgG fraction restored its acantholytic activity in neonatal mice (23); the anti-pemphaxin AuAb induced acantholysis in a keratinocyte monolayer (23); (iv) adsorption of anti-mitochondrial AuAbs abolished the ability of PVIgG to cause acantholysis both in vitro and in vivo (24); and (v) IgG antibodies directed against thyroid peroxidase induced keratinocyte fragmentation in vitro and caused a significant increase in p38 MAPK phosphorylation and increased [Ca 2ϩ ] i concentrations, both of which are associated with the pathogenicity of PVIgG (25,26).…”

Section: Autoimmunity Of Non-desmoglein Pemphigusmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Autoimmunity Of Non-desmoglein Pemphigusmentioning

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

View full text Add to dashboard Cite

show abstract

“…In a separate study, a commercially available antithyroid peroxidase antibody and the mouse monoclonal anti‐Dsg 3 antibody AK23 produced increased fragmentation in keratinocyte dissociation assays in vitro when used in combination, as compared to each individual antibody …”

Section: Evidence Of Synergy Of Anti‐dsg and Non‐dsg Antibodies In Pementioning

confidence: 97%

Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology

Ahmed

Carrozzo

Caux

et al. 2016

Experimental Dermatology

View full text Add to dashboard Cite

This viewpoint highlights major, partly controversial concepts about the pathogenesis of pemphigus. The monopathogenic theory explains intra-epidermal blistering through the "desmoglein (Dsg) compensation" hypothesis, according to which an antibodydependent disabling of Dsg 1-and/or Dsg 3-mediated cell-cell attachments of keratinocytes (KCs) is sufficient to disrupt epidermal integrity and cause blistering. The multipathogenic theory explains intra-epidermal blistering through the "multiple hit" hypothesis stating that a simultaneous and synchronized inactivation of the physiological mechanisms regulating and/or mediating intercellular adhesion of KCs is necessary to disrupt epidermal integrity. The major premise for a multipathogenic theory is that a single type of autoantibody induces only reversible changes, so that affected KCs can recover due to a self-repair. The damage, however, becomes irreversible when the salvage pathway and/or other cell functions are altered by a partnering autoantibody and/or other pathogenic factors. Future studies are needed to (i) corroborate these findings, (ii) characterize in detail patient populations with non-Dsgspecific autoantibodies, and (iii) determine the extent of the contribution of non-Dsg antibodies in disease pathophysiology.

show abstract

“…Cellular enzymes are also targeted by pemphigus autoimmunity. The association between PV and anti-thyroid peroxidase AuAb has been documented in several studies [21][22][23], but its connection to pemphigus pathophysiology remains to be elucidated. The secretory pathway Ca 2+ /Mn 2+ -ATPase isoform 1 (SPCA1) is targeted in 43% of patients with PV compared to 8% in matched controls [5].…”

Section: Auabs To Keratinocyte Adhesion Moleculesmentioning

confidence: 99%

Atypical pemphigus: autoimmunity against desmocollins and other non-desmoglein autoantigens

Gualtieri¹,

Marzano²,

Grando³

2021

Ital J Dermatol Venereol

View full text Add to dashboard Cite

show abstract

056 Anti-thyroid peroxidase antibodies may contribute to blister formation in pemphigus vulgaris

Cited by 4 publications

References 0 publications

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

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

Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology

Atypical pemphigus: autoimmunity against desmocollins and other non-desmoglein autoantigens

Contact Info

Product

Resources

About