High Expression of Collagen XVII Compensates for its Depletion Induced by Pemphigoid IgG in the Oral Mucosa

Abstract

The basement membrane zone consists of multiple components, including collagen XVII (COL17), which is the target of bullous pemphigoid. To our knowledge, no research has addressed the differences in basement membrane zone components between the skin and oral mucosa; therefore, we investigated the basement membrane zone proteins, with a focus on COL17. The mRNA and protein expression levels of COL17 were significantly higher in oral keratinocytes than in skin keratinocytes. Hemidesmosomal COL17 expression was markedly higher in oral keratinocytes than in skin keratinocytes, and its level was associated with adhesion strength. Oral keratinocytes adhered to the extracellular matrix more tightly than did skin keratinocytes in vitro. Based on these results, we attempt to explain the clinical diversity of bullous pemphigoid. COL17 depletion was more prominent in skin keratinocytes than in oral keratinocytes after treatment with COL17-NC16A mAbs, which have in vivo pathogenicity. COL17 C-terminus mAbs, which are not pathogenic, facilitated COL17 depletion in combination treatment with COL17-NC16A mAbs in both types of keratinocytes. In summary, the greater amount of COL17 in oral keratinocytes than in skin keratinocytes is associated with the higher strength of oral keratinocyte hemidesmosomal adhesion at the basement membrane zone. Our results may explain why bullous pemphigoid blistering tends to be more prevalent in the skin than in the oral mucosa.

Fc‐binding proteins enhance autoantibody‐induced BP180 depletion in pemphigoid

“…In a cell culture system, NC16A‐IgG, but not BP180 C‐term‐IgG, depletes BP180. However, we recently reported the possible pathogenicity of BP180 C‐term‐IgG . Stimulation with BP180 C‐term‐IgG enhanced the depletion of BP180 in combination with NC16A‐IgG.…”

Normal human skin is superior to monkey oesophagus substrate for detection of circulating BP 180‐ NC 16A‐specific IgG antibodies in bullous pemphigoid

“…Despite these limitations, which should be addressed more rigorously in future studies, we think that in patients with BP the use of NHS as a sensitive substrate for serum Ab screening, detection and titration is advantageous over the use of ME, also with regard to a desirable replacement and reduction of the use of animals in research and routine diagnostics . As expression of the BP180 protein differs in the different anatomical locations of human skin and mucous membranes, use of NHS from specific sites for diagnostic purposes may be advisable.…”

Risk Factors for Mucosal Involvement in Bullous Pemphigoid and the Possible Mechanism: A Review

“…Because BP mainly affects the skin and mucous manifestations are relatively rare, it will be important to determine whether the autoantibody-targeted BMZ of the mucosa differs from the BMZ in skin. BP180 mRNA and protein expression levels are higher in oral keratinocytes than in skin keratinocytes, which may be a mechanism to compensate for antibody-induced depletion ( 60 ). The adhesion strength of the BMZ in oral mucosa is tighter and more difficult to disrupt than that in the skin, which may be one reason why BP patients rarely show oral lesions ( 60 ).…”

“…BP180 mRNA and protein expression levels are higher in oral keratinocytes than in skin keratinocytes, which may be a mechanism to compensate for antibody-induced depletion ( 60 ). The adhesion strength of the BMZ in oral mucosa is tighter and more difficult to disrupt than that in the skin, which may be one reason why BP patients rarely show oral lesions ( 60 ). Differences between other components of the BMZ in skin and mucosa, such as BP230 and laminin 332, will also be important topics for future research.…”