Mechanisms of synergy of autoantibodies to M3 muscarinic acetylcholine receptor and secretory pathway Ca2+/Mn2+-ATPase isoform 1 in patients with non-desmoglein pemphigus vulgaris

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

“…Furthermore, the acantholytic activity of pre-absorbed PV IgGs can be restored by adding the eluted AuAbs [47]. Similar results were observed in the in vitro models of PVthe neonatal mouse skin explant and the 3D organ culture of human epidermis [46,47]. However, when given alone, neither of these AuAbs induce acantholysis on their own, suggesting that a simultaneous hit by a pool of non-Dsg AuAbs to different self-antigens is required to disrupt the integrity of epidermis.…”

“…On average, 10-15% of acute PV patients are negative for anti-Dsg1/3 AuAbs [39][40][41][42][43][44][45]. Since the immunopathologic mechanisms of acantholysis in these PV patients may be different, such "non-Dsg PV" (the term coined by Chernyavsky et al [46]) is considered to be atypical. Thus far, the best studied self-antigens in non-Dsg PV are Dsc3, M3AR and SPCA1 [47].…”

“…The role for autoimmunity against keratinocyte M3AR in non-Dsg PV was evaluated using 1-day old M3AR -/mice [46]. Compared to wild-type (WT) mice, the intact M3AR knockout mice demonstrated an increase of intercellular spaces due to mild shrinkage of epidermal cells.…”

“…The anti-SPCA1 PV AuAb causes shrinkage of keratinocytes in 3D organ culture of human epidermis [46], which may represent activation of the cellular apoptotic program. Indeed, anti-SPCA1 AuAb can activate caspase-2 (Cs-2) in keratinocytes and induce the cytochrome c (CytC) release abolishable by Cs-2 inhibitors [46], suggesting the pivotal role of Cs-2 in the proapoptotic effects of anti-SPCA1 AuAb in non-Dsg PV.…”

A Scoping Review of the Role of Metalloproteinases in the Pathogenesis of Autoimmune Pemphigus and Pemphigoid

“…The pemphigoid group is now known to include at least eight disorders for which the molecular target antigens have been identified [4], although controversy exists regarding the pathogenic mechanisms of blistering [5]. In pemphigus, distinct autoantibody profiles and, in particular, the presence/absence and type of antibodies to cadherins determines the acantholytic signaling pathways [6,7] and possibly the clinical phenotype [8,9]. Despite advances in understanding the pathophysiology of these disorders, however, the mainstay of treatment is the use of corticosteroids and immune suppressants and, significantly, no mechanism-based treatments have been successfully translated to patient care.…”