PTU-002 Dendritic cell subsets and serum interleukin-12 are linked to renal injury in schistosomal hepatic fibrosis

• Published in: Gut Vol. 68; no. Suppl 2; p. A112
• Main Authors: Aggan, Hayam El, Salem, Mona, Gendy, Wessam El, Gebaly, Wageh El, Gohary, Eman El
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2019
• Subjects: Angiogenesis; CD11c antigen; CD123 antigen; Cell activation; Cell surface; Chronic infection; Coagulation factors; Cytokines; Dendritic cells; Enzyme-linked immunosorbent assay; Epidermal growth factor receptors; Fibrosis; Flow cytometry; Glomerular filtration rate; Histocompatibility antigen HLA; Immune response (cell-mediated); Immunotherapy; Interleukin 1; Interleukin 12; Liver diseases; Lymphocytes T; Peripheral blood; Schistosomiasis; Serum levels
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2019-BSGAbstracts.211

IntroductionChronic infection with schistosomiasis is associated with down-regulation of T-cell immune responses that require activation by innate immune cells like dendritic cells (DCs). The present work was designed to study the DC subsets (myeloid and plasmacytoid) in peripheral blood and serum levels of interleukin (IL)-12 in patients with schistosomal hepatic fibrosis (SHF) in relation to severity of liver disease and renal injury.MethodsForty five patients with SHF and 15 healthy subjects were included in the study. The severity of liver disease was assessed using Child-Pugh classification and the Model of End Stage Liver Disease (MELD) score. Renal injury was assessed by measuring urinary albumin excretory rate (UAER) and estimated glomerular filtration rate (eGFR). The percentages of DC subsets in peripheral blood were detected using 3-color flow cytometric assay. Dendritic cells were identified as lineage marker negative (lin-)/HLA-DR positive cells and the differentiation of myeloid DC subset from lymphoid DC subset was based on the expression of CD11c or CD123 on the cell surface respectively. Quantitative determination of IL-12p70 heterodimer in serum was performed using enzyme-linked immunosorbent assay. Renal biopsies from patients with macroalbuminuria were examined by immunohistochemical technique for DCs and angiogenesis using antibodies against OX62 and factor VIII-related antigen respectively.ResultsThe percentages of circulating CD11c+ and CD123+ DC cells, CD11c+DC/CD123+DC ratio and serum IL-12 levels showed significant decreases in patients with micro- and macro-albuminuria compared with patients with normo-albuminuria and healthy subjects (P < 0.01). Renal tissues from patients with macroalbuminuria showed significant increases in the number of DCs and angiogenesis compared with normal renal tissues (P < 0.01). The percentages of circulating DC subsets and serum IL-12 levels were inversely correlated with Child-Pugh score, MELD score, number of renal DCs, renal angiogenesis and UAER and were positively correlated with eGFR. The number of renal DCs showed positive correlations with UAER and renal angiogenesis and negative correlation with eGFR (P < 0.05).ConclusionsDCs and IL12 seems to play a role in the progression of liver disease and renal injury in SHF. DC-based vaccines may provide a potential new goal for immunotherapy in SHF.