Self-reactive IgE and anti-IgE therapy in autoimmune diseases

Growing evidence indicates the pathogenic role of autoreactive IgE in autoimmune diseases. Incidence of autoimmune and allergic diseases in the industrialized countries is consistently icreasing, thus leading to concerted efforts to comprehend the regulation of IgE-mediated mechanisms. The first reports of a presence of IgE autoantibodies in patients with autoimmune diseases have been published a long time ago, and it is now recognized that self-reactive IgE can mediate inflammatory response in bullous pemhigoid, systemic lupus erythematosus, chronic urticaria, and atopic dermatitis. The advances in understanding the pathomechanisms of these disorders brought to a successful use of anti-IgE strategies in their management. The present review discusses the current state of knowledge on the IgE-mediated autoimmunity and anti-IgE treatment, and pave the way for further exploration of the subject

Expression of pattern recognition receptors in liver biopsy specimens of children chronically infected with HBV and HCV

Pattern recognition receptors (PRRs) constitute a pivotal arm of innate immunity. Their distribution is widespread and not limited to cells of the immune system. Following our previous findings concerning the expression of Toll-like receptors (TLRs) 2, 3 and 4 in chronic viral hepatitis C of children, we wished to search for other PRRs, including other TLRs, NOD-like receptors (NLRs) and RIG-1-like helicase receptors (RLR) in infected hepatocytes. Liver biopsy fragments from ten children with chronic hepatitis B and C were used and two others in which hepatotropic virus infection was excluded. Frozen sections of liver samples were subjected to ABC immunohistochemistry (IHC) following incubation with a set of antibodies. Results of IHC findings were screened for correlation with clinical/laboratory data of patients. It was found that several PRRs could be shown in affected hepatocytes, but the incidence was higher in hepatitis C than in B. In hepatitis C, TLR1, 2, 4, NALP and RIG-1 helicase showed the most marked expression. In hepatitis B, TLR1, 3, 9, NOD1 and NALP expression were the most conspicuous. Expression PRRs in liver from hepatitis of unknown origin was much lower. It was also the case in cytospins from human hepatoma cell line. Several correlations between PRRs expression and clinical findings in patients could be shown by statistical exploration. In conclusion, this data suggests some role for PRRs in the pathogenesis of chronic viral hepatitis. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 3, pp. 410–416

Detection and Significance of Cytotoxic Cell Subsets in Biopsies of HCV-Infected Human Livers

Chronic viral hepatitis C still remains the clinical challenge. Attempts of the immune system to cope with this infection are unsatisfactory. There is a conviction that the main site of interaction between virus (Hepatitis C virus, HCV) and immune system is in situ, i.e., in liver. Natural killer (NK) cells appeared relevant in the acute hepatitis. Less is known about the immune response in the chronic HCV infection. The aim of this study was to evaluate the prevalence of various cytotoxic cell subsets in chronic HCV(+) liver tissue and to seek links between them and laboratory data of patients. Sections from paraffin blocks of liver biopsy tissues of HCV(+) untreated patients were subjected to the reaction with antibodies vs. cytotoxic cell subsets and immunohistochemistry. Positive cells were searched in cellular infiltrates in portal areas and in liver parenchyma. They were classified on the “Yes” or “No” basis. Majority of liver biopsies exhibited cellular infiltrates in portal spaces and as single cells in liver parenchyma. Infiltrates consisted of CD8(+) T cells, CD56(+) NK ones, including CD158i(+) and CD158b(+). The latter were rarely seen. There were also granzyme B(+) cells. The most abundant were NKG2D(+) cells, much more common than NK CD56(+) ones. It implied that NKG2D was also expressed on T cells. Prevalence of NKG2D(+) cells correlated with high activity of liver enzymes such as alanine aminotransferase, aspartate aminotransferase and a greater histological severity of liver injury. NKG2D(+) cells form the bulk of cells infiltrating HCV-infected human liver. Correlation of NKG2D(+) cells with some laboratory parameters of patients suggests their role in hepatitis C pathogenesis

Changes in Inflammatory Markers after Administration of Tocilizumab in COVID-19: A Single-Center Retrospective Study

The COVID-19 pandemic requires the development of effective methods for the treatment of severe cases. We aimed to describe clinical outcomes and changes in inflammatory markers in Polish patients treated with tocilizumab. The medical charts of SARS-CoV-2-positive patients treated in the Department of Infectious Diseases between 4 March and 2 September 2020 were retrospectively analyzed. The patients who received tocilizumab according to the Polish Association of Epidemiologists and Infectiologists guidelines were selected for the study. We identified 29 individuals who received tocilizumab, out of whom 11 (37.9%) died. The individuals who died had significantly higher maximal interleukin-6 (IL-6) and lactate dehydrogenase (LDH) serum levels than survivors. After administration of tocilizumab, further increase in LDH and IL-6 was a prognostic factor for unfavorable outcomes. Among inflammatory markers, 7-day mean of IL-6 serum concentration was the best predictor of death (cut-off: ≥417 pg/mL; area under ROC curve = 0.81 [95% Confidence Interval: 0.63–0.98]). The serum concentrations of inflammatory markers before administration of tocilizumab did not predict the outcome, whereas IL-6 and LDH measurements after administration of tocilizumab seemed to be of predictive value

The prevalence of mixed genotype infections in Polish patients with hepatitis C

Objectives: Hepatitis C virus (HCV) genotype has been described as an independent predictor of the response to therapy. A mixed infection with two types of HCV is probably an uncommon event. The aim of this study was to determine the occurrence of mixed infection with two different HCV genotypes in adult patients with chronic hepatitis C eligible for treatment. Methods: Plasma samples and clinical and demographic data were collected from 1159 patients with hepatitis C. The INNO-LiPA HCV assay was used to identify the HCV genotypes. Results: The dominant genotype was genotype 1, which was found to be responsible for 83.9% of infections, with subtype 1b being the most common. A mixed genotype infection was detected in 26 patients (2.2%). The most common mixed genotype was 1a+1b detected in 17/26 patients (65%). Antiviral therapy led to complete elimination of both genotypes in 50% of patients with 1b+3a infection and in 33% of patients with 1b+4a infection. Conclusions: The results obtained showed that infection with mixed HCV genotypes in Polish patients with hepatitis C is uncommon. The selective elimination of genotypes 3a and 4a after therapy confirms the greater resistance to treatment of genotype 1b. In the context of new anti-HCV drug development, further investigations are needed to determine the clinical importance of mixed HCV infection