Cyclo-oxygenase 2 is present in the majority of lesional skin from patients with autoinmune blistering diseases

Abstract

Introduction: The in situ immune response within skin biopsies from patients affected by autoimmune skin blistering diseases (ABDs) is not well characterized. Aim: Based on the fact that the ABD immune response is considered an adaptive immune response, both an innate immune response and inflammation would be expected in these diseases. Our investigation investigates the presence of cyclo-oxygenase-2 (COX-2), since this enzyme is commonly involved in innate immune responses. Methods: We utilized immunohistochemistry (IHC) to evaluate the presence of COX-2 in lesional skin biopsies of patients affected by ABDs. We tested 30 patients with endemic pemphigus foliaceus (EPF), 15 controls from the endemic area, and 15 biopsies from healthy controls from the USA. We also tested archival biopsies from patients with selected ABDs, including 20 patients with bullous pemphigoid, 20 with pemphigus vulgaris, 8 with pemphigus foliaceus and 12 with dermatitis herpetiformis. Results: Most ABD biopsies stained positive for COX-2 in the lesional blister and/or the dermal inflammatory infiltrate, accentuated in the upper neurovascular plexus. In BP and EPF, the COX-2 staining was also seen in the sweat glands. All controls were negative. Conclusions: We document that COX-2 is expressed in lesional skin of patients with ABDs.

Autoantibodies to full body vascular cell junctions colocalize with MYZAP, ARVCF, desmoplakins I and II and p0071 in endemic pemphigus in Colombia, South America

“…Our data correlates with a recent study demonstrating cardiovascular alterations in patients with inflammatory skin diseases (including pemphigus and pemphigoid) versus controls; 2002–2012 US national inpatient hospitalizations ( n = 72 108, 077 adults) were reviewed and correlated with cardiovascular and cerebrovascular associated diseases . In our current and previous studies, we present evidence for vascular alterations in most autoimmune skin diseases …”

“…In El Bagre‐EPF and in other autoimmune blistering diseases including PF, bullous pemphigoid (BP), pemphigus vulgaris (PV), epidermolysis bullosa acquisita, linear IgA disease, and dermatitis herpetiformis, we have noted patient vessels overexpressing HLA‐DPDQDR antigen, ribosomal protein s6‐ps240, cyclo‐oxygenase 2, and C5‐b9/MAC. These patient biopsies also revealed vascular rouleaux phenomenon and other vascular inflammatory markers, including CD3, CD20, CD1a, HAM56, CD68, and S100, and autoantibodies to the vessels . We confirmed our data by IHC, which prevents the “autofluorescence” possible when using DIF/IIF.…”

“…These patient biopsies also revealed vascular rouleaux phenomenon and other vascular inflammatory markers, including CD3, CD20, CD1a, HAM56, CD68, and S100, and autoantibodies to the vessels. 16,[18][19][20][21][22][23][24][25] We confirmed our data by IHC, which prevents the "autofluorescence" possible when using DIF/IIF. In most skin biopsies on all autoimmune skin blistering diseases, dilated vessels and papillary dermal edema are noted under the blisters, with additional mild dermal perivascular inflammation.…”

“…We confirmed our data by IHC, which prevents the “autofluorescence” possible when using DIF/IIF. In most skin biopsies on all autoimmune skin blistering diseases, dilated vessels and papillary dermal edema are noted under the blisters, with additional mild dermal perivascular inflammation …”

“…It is possible that the autoantibodies stimulate endothelial cells to express adhesion molecules and various chemokines; this may lead to a recruitment of monocytes, leukocyte recruitment with the secretion of cytokines and other inflammatory markers. Deposition of fibrin, fibrinogen and activated platelets on damaged endothelium may expresses tissue and von Willebrand factor, creating a prothrombotic milieu and leading to clinical vascular disorders . The polyclonality of the immune response may partially result from pollution by metals and metalloids in the endemic area, as well as patient exposure to tropical and parasitic diseases …”