Serum level of interleukin-13 receptor alpha 2 in infants with biliary atresia - is it of value?

AIM OF THE STUDY: We aimed to assess the utility of serum level IL-13Rα2 receptors as a non-invasive marker for early diagnosis of biliary atresia (BA) and selection of BA patients indicated for Kasai portoenterostomy. MATERIAL AND METHODS: The study included 60 infants with neonatal cholestasis in three groups; early BA group (n = 20), delayed BA group (n = 20) and non-BA cholestasis group (n = 20). A fourth group of 20 healthy neonates (n = 20) served as controls. IL-13Rα2 was measured by enzyme-linked immunosorbent assay in all patients and controls. RESULTS: The mean value of IL-13Rα2 was significantly higher in delayed BA group (11.05 ± 10.9 ng/ml) compared to early BA (0.34 ± 0.37 ng/ml), non-BA (0.54 ± 0.85 ng/ml) and control (0.24-0.2 ng/ml) groups. The levels of serum IL-13Rα2 increase with the severity of the degree of fibrosis. IL-13Rα2 at a cutoff level > 0.782 ng/ml could predict late fibrosis with accuracy of 77.55% (p < 0.0001). IL-13Rα2 could differentiate between preserved and disturbed liver architecture at a cut off value of more than 0.42 ng/ml with an accuracy of 81.6%. CONCLUSIONS: Serum IL-13Rα2 not a diagnostic marker for BA however it could be used as a noninvasive marker for detection of advanced liver fibrosis and presence of disturbed liver architecture that helps in patient selection for undergoing Kasai operation. Serum IL-13Rα2 could be a future therapeutic target for management of BA patients and any fibrotic liver disease.

Expression of intrahepatic CD3, CD4, and CD8 T cells in biliary atresia.

AIM OF THE STUDY: Assessment of the expression of cluster of differentiation (CD)3, CD4, and CD8 T cells in biliary atresia (BA) cases in comparison to neonatal cholestasis other than BA. MATERIAL AND METHODS: This study included 79 patients: 34 patients with BA (BA group) and 35 patients with neonatal cholestasis due to causes other than BA (cholestasis group), and 10 normal liver donor as a control group. Immunohistochemical staining or CD3, CD4, and CD8 T cells in liver tissues for the 3 groups were evaluated. RESULTS: Presence of clay stool, high gamma-glutamyl transferase levels, thrombocytosis, and non-contractibility of the gallbladder was the main clinical, laboratory, and radiological findings, distinguishing BA from other disorders causing neonatal cholestasis. Portal ductular proliferation, bile plugs in portal ductules, and advanced grades of fibrosis were more predominant in liver biopsy specimens of BA patients. The CD3+, CD4+, and CD8+ expression in patients with BA were significantly higher than in both cholestasis and control groups, while it was comparable in the cholestasis and control groups, with cutoff values of 25, 12, and 2.5 cells/portal tract, respectively, differentiating between BA and cholestatic patients. CONCLUSIONS: Immune-mediated destruction of bile ducts is incriminated in the pathogenesis of BA. Lymphocytic infiltrate in portal tract is primarily composed of CD3, CD4, and CD8 T cells. Immunostaining of liver tissue for CD3, CD4, and CD8 T cells can help in ensuring diagnosis of BA.

Assessment of intrahepatic regulatory T cells in children with autoimmune hepatitis.

UNLABELLED:  Background. T-cell populations regulate the balance of immune responses. The CD (Cluster of differentiation) 4+CD25+ regulatory T cells (Tregs) are crucial for maintaining negative control of various immune responses. There are different T-cell subpopulations with regulatory functions, as natural killer T cells, CD8+ and CD28. The forkhead box P3 (FOXP3) regulates Treg development and is required for its suppressive function. AIM: To evaluate the hepatic expression of the intrahepatic Tregs, Ig (immunoglobulin) G and IgM plasma cells in autoimmune hepatitis (AIH) and other chronic liver diseases (CLDs). MATERIAL AND METHODS: This study included 100 pediatric patients; 50 AIH and 50 CLDs other than AIH. All patients were subjected to routine investigations of CLDs plus immune-staining of liver tissue for FOXp3, IgG and IgM plasma cells, CD4 and CD8 T-cells. RESULTS: The FOXP3+ T cells in patients with AIH (6.3 ± 5) were significantly higher than that in the non-AIH (2.1 ± 2.6). FOXP3+ T cells were abundant in liver tissue with marked inflammatory cellular infiltrate. CD4+ and CD8+ infiltrating the liver tissue and IgG positive cells were significantly higher in AIH group, while the expression of IgM positive cells showed no significant difference. The IgG/IgM was significantly higher in the AIH treatment responders (3 ± 3) than non-responders (1.6 ± 0.5), while there was no significant difference regarding the intrahepatic expression of FOXP3+, CD4+, CD8+ cells, T-cells, IgG and IgM plasma cells. CONCLUSION: Intrahepatic Tregs were increased in number in patients with AIH in the initial presentation, and their presence is associated with increased activity and inflammation in liver biopsy.

Monocyte-derived dendritic cells in children with chronic hepatitis C: correlation with interferon and ribavirin therapy.

BACKGROUND: Hepatitis C virus (HCV) infection is a major health problem worldwide. Defective dendritic cell (DC) activation of T cells may underlie poor T-cell responsiveness in HCV infection. OBJECTIVE: To evaluate the DCs' functions in chronically infected HCV patients and its correlation with the response to therapy. PATIENTS AND METHODS: This prospective study included 30 chronic hepatitis C (CHC) patients and 30 healthy age-matched and sex-matched controls. The first group received combined pegylated interferon-α-2b (Peg-IFN-α2b)/ribavirin therapy for 48 weeks. A quantitative HCV-RNA PCR was performed for all patients before treatment and at 12, 24, 48, and 24 weeks after treatment. To clarify the functions of DCs, we induced maturation of peripheral DCs from blood samples of CHC patients and healthy controls using Resiquimod (R848). The functions of DCs were assessed by measurement of the levels of IFN-γ and interleukin-10 (IL-10). RESULTS: Sixteen (53.3%) of the patients were treatment responders and the other 14 (46.4%) were nonresponders. The current study showed a statistically significant difference between CHC patients and the control group in IFN-γ production, which was higher in the control group (1.53±0.38 IU/ml) than in the CHC patients (1.19±0.21 IU/ml); in contrast, IL-10 was higher in CHC (249.4±27.6 pg/ml) than the control group (217.0±29.9 pg/ml). However, there was no significant difference between treatment responders and nonresponders in both IFN-γ and IL-10 levels. CONCLUSION: HCV infection is associated with impaired production of IFN-γ, which may be an indication of a defect in DC function.