Serum Concentration of Interleukin-6 Is Increased Both in Active and Remission Stages of Pemphigus Vulgaris

As most studies on pemphigus vulgaris (PV) pathogenesis concern its active stage, we aimed to evaluate the serum concentration of TNF-α, IL-1, and IL-6 in PV patients in clinical remission. The study group consisted of sera from 19 PV patients in active stage and from 24 patients in clinical remission. 19 sera taken from healthy subjects served as the controls. Serum IL-6 concentrations in PV active and PV remission group were significantly higher when compared to the controls (P < .05). In patients in active stage of PV, a significant correlation between serum IL-1 and IL-6 concentrations was found (rP = 0.46; P < .05). We also found a negative correlation between TNF-α level and pemphigus antibodies titer in the patients from the remission group (rS = −0.47303; P < .02). Our data suggest that IL-6 and TNF-α may be involved in maintaining immunological disturbances in remission stage of PV

Tumour necrosis factor-alpha polymorphism as one of the complex inherited factors in pemphigus.

The aim of our study was to analyse a significance of tumour necrosis factor (TNF)-alpha promoter gene polymorphisms in relation to the HLA-DR locus in genetic predisposition to pemphigus. TNF-alpha gene polymorphisms in position -238 and -308 were identified using a modified polymerase chain reaction-restriction fragment length polymorphism method in 53 patients with pemphigus (38 with pemphigus vulgaris, 15 with pemphigus foliaceus) and 87 healthy controls. The HLA-DRB1 locus was typed using the polymerase chain reaction SSO method in all the patients and 152 population controls. Carriers of the TNF-alpha polymorphic -308 A allele were found to be more frequent in the pemphigus foliaceus group in comparison with the control group (odds ratio (OR) = 8.12; p = 0.0005). A significant association between HLA-DRB1*04 (OR = 3.86; pcor = 0.0001) and DRB1*14 (OR = 8.4; pcor = 0.0001) and pemphigus vulgaris was found. In this group of patients a decreased frequency of HLA-DRB1*07 (OR = 0.08; pcor = 0.006) was also identified. We have shown for the first time a positive association of TNF-alpha polymorphism in position -308 with pemphigus foliaceus

Detection of pemphigus autoantibodies by IIF and ELISA tests in patients with pemphigus vulgaris and foliaceus and in healthy relatives

BACKGROUND: Pemphigus is a life-threatening, autoimmune blistering disease, mediated by IgG autoantibodies. The aim of our study was to assess the usefulness of a new enzyme-linked immunosorbent assay (ELISA) in detecting circulating pemphigus autoantibodies, and to compare its sensitivity and specificity with the indirect immunofluorescence (IIF) test. We also established the frequency of occurrence of pemphigus autoantibodies in relatives of our patients. MATERIAL/METHODS: IIF and ELISA tests were performed in 24 patients with pemphigus vulgaris, 13 with pemphigus foliaceus, 56 healthy relatives, and 50 controls, selected according to sex and age. RESULTS: The obtained results revealed high specificity and sensitivity of ELISA, comparable to the IIF test, especially in patients who were in the active stage of the disease. We also showed that the profile of anti-Dsg 1 and/or anti-Dsg 3 autoantibodies is associated with the clinical variant of pemphigus. The frequency of occurrence of pemphigus autoantibodies in the relatives (24/55) performed by IIF was significantly higher (p<0.001) than in the controls (0/50). The same antibodies detected by ELISA (11/56) were less frequent. CONCLUSIONS: In clinically doubtful cases, in which autoantibodies titres by IIF are equal on both substrates (monkey and guinea pig esophagus), the assessment of the exact antibody profile (anti-Dsg 1 and/or anti-Dsg 3) is important to establish the subtype of pemphigus. The frequency of pemphigus antibody occurrence in healthy relatives seems not to be incidental, but further studies should be performed to explain this phenomenon

Detection of pemphigus autoantibodies by IIF and ELISA tests in patients with pemphigus vulgaris and foliaceus and in healthy relatives

BACKGROUND: Pemphigus is a life-threatening, autoimmune blistering disease, mediated by IgG autoantibodies. The aim of our study was to assess the usefulness of a new enzyme-linked immunosorbent assay (ELISA) in detecting circulating pemphigus autoantibodies, and to compare its sensitivity and specificity with the indirect immunofluorescence (IIF) test. We also established the frequency of occurrence of pemphigus autoantibodies in relatives of our patients.MATERIAL/METHODS: IIF and ELISA tests were performed in 24 patients with pemphigus vulgaris, 13 with pemphigus foliaceus, 56 healthy relatives, and 50 controls, selected according to sex and age.RESULTS: The obtained results revealed high specificity and sensitivity of ELISA, comparable to the IIF test, especially in patients who were in the active stage of the disease. We also showed that the profile of anti-Dsg 1 and/or anti-Dsg 3 autoantibodies is associated with the clinical variant of pemphigus. The frequency of occurrence of pemphigus autoantibodies in the relatives (24/55) performed by IIF was significantly higher (p&lt;0.001) than in the controls (0/50). The same antibodies detected by ELISA (11/56) were less frequent.CONCLUSIONS: In clinically doubtful cases, in which autoantibodies titres by IIF are equal on both substrates (monkey and guinea pig esophagus), the assessment of the exact antibody profile (anti-Dsg 1 and/or anti-Dsg 3) is important to establish the subtype of pemphigus. The frequency of pemphigus antibody occurrence in healthy relatives seems not to be incidental, but further studies should be performed to explain this phenomenon.</p

Circulating pemphigus autoantibodies in healthy relatives of pemphigus patients:coincidental phenomenon with a risk of disease development?

Pemphigus is a severe autoimmune disease characterized by circulating and bound in vivo pemphigus autoantibodies. It was revealed that the autoantibodies occur in healthy first-degree relatives of pemphigus patients; however, their significance is not fully elucidated. Thus, the aim of the study was to assess the frequency of circulating IgG pemphigus autoantibodies in the healthy relatives of pemphigus patients and of their ability to bind in vivo in the epidermis. We also analyzed IgG subclasses distribution, both in the serum-positive relatives and in the patients. Our study included 67 healthy relatives, 50 healthy normal controls and 33 patients (25 at an active stage of the disease, 8 in clinical remission). To detect circulating pemphigus antibodies we applied indirect immunofluorescence and anti-desmoglein ELISA. Monoclonal anti-human IgG1, IgG2, IgG3, IgG4 antibodies were used to assess subclass distribution. The frequency of circulating pemphigus autoantibodies in the relatives, detected by IIF (30/67) was statistically higher (P <0.001) than in the control group (0/50). ELISA revealed anti-desmoglein 1 and/or 3 antibodies in 13 out of 67 relatives. Direct immunofluorescence performed in 25 out of 32 seropositive relatives did not show intercellular bound in vivo IgG and/or C3 in the epidermis in any cases. Circulating IgG2 subclass was observed in 60% of the examined relatives and IgG4 was detected in 23.3% of them. In the patients at an active stage of pemphigus IgG4 and IgG1 were the dominant subclasses (96 and 76% relatively) while in clinical remission antibodies predominantly belonged to the IgG2 (75%) and IgG4 (37.5%) subclass. The obtained results confirmed polyclonal production of pemphigus autoantibodies and their different distributions dependent on the disease activity. Statistical analysis showed that the frequency of IgG1 and IgG4 subclasses was significantly higher in the patients at an active stage of the disease when compared to the patients in clinical remission (P <0.001) or with seropositive healthy relatives (P <0.001). The relevance of the presence of IgG4 autoantibodies in the healthy relatives' sera requires further studies that focus on their potential pathogenicity