Abstract:Whereas it has been shown that neutrophil elastase (NE) is a crucial enzyme degrading the dermal-epidermal junction (DEJ) in bullous pemphigoid (BP), experimental studies on the role of NE in dermatitis herpetiformis (DH), a disease in which, as in BP, an intra-lamina lucida blister is formed, are scanty. The aim of this study was to analyse whether there is a correlation between levels of serum IgA antibodies to the epidermal transglutaminase (TG3), an enzyme believed to be the autoantigen of DH, and expression of NE in lesional skin in DH. A series of 21 consecutive patients with DH was studied. The levels of IgA antibodies to TG3 in sera were calculated with ELISA. The expressions of NE were examined with immunohistochemical technique in sections of lesional skin using a mouse monoclonal antibody to human NE. The digital microscopic image analysis with the appropriate software was then used to measure intensities of NE expression. The correlation between the intensity of NE expression in lesional skin and the level of serum IgA antibodies to TG3 in DH was of low strength. Thus, it is speculated that in DH the engagement of IgA autoantibodies to the enzyme, TG3, on cutaneous neutrophils might not be a principal stimulus to releasing NE, the enzyme known to degrade DEJ in subepidermal blistering diseases with autoimmunity to DEJ structural proteins. REPORTThe plausible pathophysiology of dermatitis herpetifomis (DH) is that the Fc region of IgA autoantibody to epidermal transglutaminase (TG3), an enzyme believed to be the most disease-specific autoantigen of DH, [1] activates neutrophils by engaging their CD89 receptor which leads to the release of neutrophil elastase (NE), NE-mediated destruction of the dermal-epidermal junction (DEJ) and the formation of an intra-lamina lucida blister. Whereas it was shown that NE is crucial DEJ-degrading enzyme in bullous pemphigoid (BP), [2][3] experimental studies on the role of NE in DH are scanty. Early data suggested that in blister fluids in patients with DH an activity of elastase, probably NE, can be detected [4][5]. The aim of this study was to analyse whether there is a correlation between levels of serum IgA antibodies to TG3 and expression of NE in lesional skin in DH.NE deposits and IgA antibodies to TG3 were evaluated in a series of 21 consecutive dapsone-untreated patients with DH, regardless whether they had concomitant intestinal problems or not. The diagnosis of DH in each case was made when whichever pattern of possible 7 diagnostic patterns of granular IgA deposition was detected with direct immunofluorescence of nonlesional skin [6][7][8]. The levels of IgA antibodies to TG3 in sera were calculated with ELISA in AU/ml (manufacturer's cut-off value 18AU/ml) (Immundiagnostic, Germany). The expressions of NE were examined with immunohistochemical technique in sections of lesional *Address correspondence to this author at the Department of Dermatology, University School of Medicine, Pozna , Poland; E-mail: dmoch@sylaba.poznan.pl skin showing histolo...

Abstract:The study aimed at examination of tissue expression of polysaccharides and secretory mucin 5AC (MUC5AC) in young patients (up to 25 years of age) with a symptomatic gallstones. For comparison, patients most frequently subjected to cholecystectomy were studied, i.e. patients of approximately 50 years of age with the same diagnosis. In quantitative studies on tissue expression of both mucus components, the modern technique of spatial visualization was applied for the first time. Application of the technique permitted to demonstrate significant positive relationships between expression of glycoproteins (immunocytochemical ABC technique for detection of MUC5AC) and expression of sugar components in mucus (PAS technique) and to confirm suitability of the technique for quantitative appraisal of both histochemical and immunocytochemical reactions. An even higher expression of polysaccharides in the entire mucosa and of MUC5AC was detected in gallbladder epithelium of 50-year-old patients, as compared to young patients with symptomatic gallstones. In the young patients, expression of polysaccharides correlated with inflammatory activity (grading), width of gallbladder wall and PLT level in peripheral blood. A significantly higher expression of polysaccharides in gallbladder epithelium was demonstrated in young patients admitted in the emergency mode to the hospital. These correlations in young patients may suggest a role of both mucus components in pathogenesis of cholelithiasis in this age group. A quantitative appraisal of mucus component expression in the two parts of gallbladder mucosa (epithelium vs. entire mucosa) using spatial visualization technique permitted to more accurately compare production of glycoproteins and of polysaccharides in patients with cholelithiasis and to demonstrate additional correlations of a potential clinical significance.

Aim of the studyDeregulation of insulin-like growth factor I (IGF-I) production and decreased hepatic estrogen levels were associated with development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) infected cirrhotic patients. The aim of our study was to determine serum levels of IGF-I, insulin and 17-β estradiol (17-βE) in relation to other markers of liver injury in chronic hepatitis C (CHC) patients.Material and methodsThirty anti-viral treatment-naïve CHC patients and 10 healthy subjects were examined. HCV infection was confirmed by presence of anti-HCV and HCV-RNA in serum. Serum levels of IGF-I, insulin and of 17-βE were evaluated using ELISA methods.ResultsSerum levels of IGF-I and 17-βE were significantly lower in CHC patients than in controls while insulin levels were similar in both groups. A lower IGF-I level (but not the level of 17-βE) was observed in cirrhotic CHC patients in comparison to non-cirrhotic ones. Decreased serum level of IGF-I was associated with more advanced staging and liver steatosis, higher levels of alpha-fetoprotein (AFP) and gamma globulin levels, and higher aspartate transaminase (AST) activity in CHC patients. Insulin and 17-βE levels positively correlated with patient's age. A positive correlation was observed between insulin level on one hand and staging, liver steatosis and levels of gamma globulins in CHC patients on the other. A negative correlation between IGF-I and insulin levels was noted only in HCV infected patients.ConclusionsDecreased IGF-I levels and increased levels of insulin better than estradiol serum levels characterize staging and liver steatosis in CHC patients. The lower serum level of 17-βE in the CHC group than in control patients suggests that CHC patients carry higher risk of liver injury and of HCC development.