Possible apoptotic mechanism in epidermal cell acantholysis induced by pemphigus vulgaris autoimmunoglobulins

Wang, X; Brégégère, François; Frušić-Zlotkin, Marina; Feinmesser, Meora; Michel, Beno; Milner, Yoram

doi:10.1023/b:appt.0000018795.05766.1f

Cited by 111 publications

(170 citation statements)

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“…One possibility is that Igthyroid antibodies could trigger CD95 (Fas/Apo-1)-mediated apoptosis in keratinocytes as Ig autoantibodies do in pemphigus vulgaris [16]. Then, the apoptotic bodies could be internalised and processed by surrounding keratinocytes or APC cells leading to subsequent T cell activation.…”

Section: Discussionmentioning

confidence: 99%

Possible link between Hashimoto's thyroiditis and oral lichen planus: a novel association found

et al. 2012

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Objectives Hashimoto's thyroiditis as well as lichen planus has been associated to a number of disorders, generally of auto-immune origin. A novel possible association between oral lichen planus (OLP) and Hashimoto's thyroiditis (HT) is here proposed on the basis of a cross-sectional survey. Materials and methods One hundred and five unrelated OLP patients were considered. Diagnosis of HT was based on positive serum anti-TPO, anti-Tg, TSH levels and the typical ultrasound pattern of the thyroid gland. Results In the present survey, the prevalence of HT in the OLP group was 14.3 % whereas the prevalence of HTrelated hypothyroidism in the general population was reported to be equal to 1 %. By Fisher's exact test, it was revealed that the difference between our data and historical prevalence of HT was found statistically significant. Conclusion Actually, there is no definitive hypothesis that could explain the coexistence of OLP and HT. However, considering the onset timing of HT followed by OLP in 93.3 % of our series, we suspected a causal or predisposing role for HT. Specifically, we believe that in HT patients, circulating thyroid antibodies could contribute to trigger an organ-specific auto-immune response also in the oral mucosa or skin, leading to the development of LP lesions. Clinical relevance Because of the large number of cases of asymptomatic chronic auto-immune thyroiditis, it would be useful that women over 40 years of age affected by OLP were screened for thyroid dysfunction, particularly HT.

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Section: Discussionmentioning

confidence: 99%

Possible link between Hashimoto's thyroiditis and oral lichen planus: a novel association found

et al. 2012

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“…For example, muscarinic receptor 3 is found only in basal keratinocytes, whereas muscarinic receptor 4 is expressed exclusively in suprabasal cells. 5 It is obvious that in PV, additional mechanisms such as altered plakoglobin signaling leading to c-Myc overexpression, 22,24 activation of protein kinase C and of p38 mitogen-activated kinase, 27,28 activation of epidermal growth factor receptor and Src, 29,30 endocytosis and degradation of Dsg 3, [31][32][33] and apoptosis 34 are involved in the mechanisms finally leading to skin blistering. In contrast, for PF pathogenesis, such data are lacking at present.…”

Section: Skin Blistering As a Multistep Process Involving Different Mmentioning

confidence: 99%

Pemphigus IgG Causes Skin Splitting in the Presence of Both Desmoglein 1 and Desmoglein 3

Spindler

Drenckhahn

Zillikens

et al. 2007

The American Journal of Pathology

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According to the desmoglein (Dsg) compensation concept, different epidermal cleavage planes observed in pemphigus vulgaris and pemphigus foliaceus have been proposed to be caused by different autoantibody profiles against the desmosomal proteins Dsg 1 and Dsg 3. According to this model, Dsg 1 autoantibodies would only lead to epidermal splitting in those epidermal layers in which no Dsg 3 is present to compensate for the functional loss of Dsg 1. We provide evidence that both pemphigus foliaceus-IgG containing Dsg 1-but not Dsg 3-specific antibodies and pemphigus vulgaris-IgG with antibodies to Dsg 1 and Dsg 3 were equally effective in causing epidermal splitting in human skin and keratinocyte dissociation in vitro. These effects were present where keratinocytes expressed both Dsg 1 and Dsg 3, demonstrating that Dsg 3 does not compensate for Dsg 1 inactivation. Rather, the cleavage plane in intact human skin caused by pemphigus autoantibodies was similar to the plane of keratinocyte dissociation in response to toxin B-mediated inactivation of Rho GTPases. Because we recently demonstrated that pemphigus-IgG causes epidermal splitting by inhibition of Rho A, we propose that Rho GTPase inactivation contributes to the mechanisms accounting for the cleavage plane in pemphigus skin splitting. Pemphigus is an autoimmune blistering skin disease caused by autoantibodies directed to the cadherin-type adhesion molecules desmoglein (Dsg) 1 and 3.1-4 Antibodies against other antigens, including cholinergic receptors, have also been implicated in the pathogenesis.5-9 Several theories have been proposed to explain the mechanisms underlying blister formation by Dsg autoantibodies. However, the different clinical phenotypes of pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are still not fully understood. 10 -12 It is well established that PV is characterized by deep (suprabasal) epidermal blistering, whereas PF exhibits superficial blistering (involving granular or spinous cell layers). In PF, mucous membranes are not involved; whereas in PV, mucosal disease is a regular finding, and skin involvement may occur in addition. 4 Interestingly, these phenotypes usually correlate with different autoantibody profiles. PV patients with only mucosal lesions show autoantibodies to Dsg 3 but not to Dsg 1. PF patients (skin involvement only) reveal autoantibodies to Dsg 1 but not to Dsg 3. In PV patients with both mucous membrane and skin involvement, autoantibodies to Dsg 3 and Dsg 1 may be detected. 4,13,14 These observations, together with studies reporting that Dsg 1 is predominantly expressed in superficial epidermal layers but absent in the suprabasal layer, whereas Dsg 3 is restricted to deep epidermal layers, and that Dsg 1 is less abundantly expressed in mucosal epithelia, have led to the desmoglein compensation hypothesis as an explanation for the different epidermal cleavage planes in PV and PF. 3,4,[15][16][17] According to this model, in the deep epidermis, Dsg 3 compensates for the functional loss of Dsg 1 induced by Ds...

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“…We were aware of the reports that caspase inhibitors prevented PVIgG-induced acantholysis in keratinocyte monolayers and skin organ cultures. 13,14 Surprisingly, the caspase inhibitors DEVD-CHO (10 mol/L), Z-DEVD-FMK (10 mol/L), and Z-DCB-MK (100 mol/L), given alone or as a mixture, inhibited acantholysis completely only in the monolayers treated with PVIgG-2b (P Ͻ 0.05) but caused only a moderate decrease of the acantholytic activity of PVIgG-1b (P Ͼ 0.05) ( Figure 3A). At the same time, these inhibitors blocked caspase 3 activity induced by both PVIgGs equally efficiently ( Figure 3B).…”

Section: Differential Effects Of Caspase 3 and Calpain Inhibitors On mentioning

confidence: 99%

“…9 PVIgG and sera have been shown to induce biomolecular markers of apoptosis in keratinocyte monolayers and skin organ cultures, 10 -12 with caspase inhibitors abolishing the PVIgG-induced acantholysis. 13,14 We have reported that ability to induce keratinocyte apoptosis determines pathogenicity of PVIgGs. 15 More recently, determination of caspase 3 activity in the HaCaT culture treated with PVIgG has been proposed as a test for pathogenic activity of the autoantibodies.…”

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confidence: 99%

Novel Mechanisms of Target Cell Death and Survival and of Therapeutic Action of IVIg in Pemphigus

Arredondo

Chernyavsky

Karaouni

et al. 2005

The American Journal of Pathology

112

139

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Possible apoptotic mechanism in epidermal cell acantholysis induced by pemphigus vulgaris autoimmunoglobulins

Cited by 111 publications

References 50 publications

Possible link between Hashimoto's thyroiditis and oral lichen planus: a novel association found

Possible link between Hashimoto's thyroiditis and oral lichen planus: a novel association found

Pemphigus IgG Causes Skin Splitting in the Presence of Both Desmoglein 1 and Desmoglein 3

Novel Mechanisms of Target Cell Death and Survival and of Therapeutic Action of IVIg in Pemphigus

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