IgA autoantibodies to gliadin nonapeptides, tissue transglutaminase and epidermal transglutaminase are associated, but unrelated to neutrophil elastase expression in lesional skin in human dermatitis herpetiformis

Abstract

A Ad dd dr re es ss s f fo or r c co or rr re es sp po on nd de en nc ce e: : Assist. Prof Original paper A b s t r a c t I In nt tr ro od du uc ct ti io on n: : In dermatitis herpetiformis (DH), activation of neutrophils via IgA Fc receptors (e.g. CD89) and immunocomplexes containing IgA1 may lead to the release of proteolytic enzymes, mainly neutrophil elastase (NE), destruction of the dermal-epidermal junction and blister formation. A Ai im m: : To analyze whether there are associations between levels of circulating IgA autoantibodies to epidermal (eTG) and tissue (tTG) transglutaminases, nonapeptides of gliadin (npG) and the intensity of cutaneous NE expression in patients with DH. M Ma at te er ri ia al l a an nd d m me et th ho od ds s: : Altogether, 31 patients with DH were studied. The levels of serum IgA autoantibodies to eTG, tTG and npG were evaluated with ELISAs. The intensity of NE expression was estimated with immunohistochemistry using NE monoclonal antibody and quantitative digital morphometry. Statistical analysis was done using Spearman's rank correlation coefficient. R Re es su ul lt ts s: : There were no statistically significant correlations between the intensity of cutaneous NE expression and the levels of serum IgA autoantibodies to eTG, tTG, npG in patients with DH. There were statistically significant correlations between the levels of IgA autoantibodies to eTG, tTG, npG. C Co on nc cl lu us si io on ns s: : It seems that in human DH the activation of neutrophils, judged by the NE expression, is unrelated to the levels of serum IgA autoantibodies to eTG/tTG/npG, but all those autoantibodies in DH are produced in a coordinated way.K Ke ey y w wo or rd ds s: : dermatitis herpetiformis, neutrophil elastase, transglutaminases, gliadin.

A comparative study of expression of Fc receptors in relation to the autoantibody-mediated immune response and neutrophil elastase expression in autoimmune blistering dermatoses

“…Altogether,87ADBpatients(28pemphigus,28 DH,31BP)beforeinitiationoftreatmentswereexamined.TheNEwasanalysedinthesesamepatients asCD32andCD89.However,thegroupofpatients withNEanalysiswasgreaterbecauseitwasthesubjectofourpreviousanalysis [1,4,5,7]andherewe trytoextendtheinvestigationwithFcRs.…”

“…We previously postulated that the plausible immunopathogenesis of DH involves activation of neutrophilsbyengagingtheirCD89receptorswith IgA(particularlyIgA1)immunocomplexes(IC) [5]. However, it seems that this series of events are independent of the release of NE proteases, which degrades the dermal-epidermal junction and finally induces the blister formation [5].…”

“…Inlightoftheabove,CD32Amaybeinvolvedinthe activationofproductionofvariouscytokinesduring acantholysis in pemphigus and dermal-epidermal junction destruction in BP. Our previous studies on NE expression revealed that the mean intensity of NE expression in pemphigus and BP patients was statisticallysignificantlylowerthaninDHpatients, but it was not significantly different in pemphigus and BP [1,5,7]. Thus, probably CD32A is more involved in blister formation in pemphigus and BP, andNEseemstobethekeypathogenicfactorinDH.…”

“…Epidermal transglutaminase (eTG,TG3), tissue transglutaminase (tTG,TG2), and nonapeptides of gliadin (npG) may be considered in the pathomechanism/diagnostics of DH [3,4,5].DetectedautoantibodiesinpemphigusandBP usually belong to the IgG class and IgG4 subclass, whereasthemainautoantigensinDHareplausibly recognised by principally IgA/IgA1 autoantibodies [5,6].ItisestablishedthatDHisaccompaniedby gluten-sensitiveenteropathy(GSE) [3,7].…”

“…neutrophil elastase (NE) [5,7].NEwaspostulatedtobethecentralenzyme responsible for degradation of many components of dermal-epidermal junction/desmosomal junctions andfinallyforblisterdevelopmentinABDs [7].…”