Assessment of some cytokines levels in a pauci-immune crescentic glomerulonephritis patients

Abstract

Background: Glomerulonephritis is the common cause of end-stage of renal failure. Rapidly progressive glomerulonephritis (RPGN) is characterized by glomerular injuries and formation of crescents.  Moreover, anti-neutrophil cytoplasmic antibodies (ANCA), and pro-inflammatory cytokines play a damaging role in a crescent glomerulonephritis.

Objectives: The main goal of the current study was aimed to determine the ANCA autoantibodies, and the serum levels of pro-inflammatory cytokines (IL-6, IL-17, IL-18, INF-γ), as well as the relationship between these cytokines and ANCA test in a pauci-immune crescentic glomerulonephritis patients.

Methodology: The study was carried out in AL-Yarmouk teaching hospital and AL-Sader teaching hospital during the period from April 2022 to April 2023. This study was involved 90 patients with a crescentic glomerulonephritis disease, the diagnosis was made by the consultant medical staff. In addition to a 60 samples of healthy individuals as control group was involved to comparison the results. ANCA test was made by Indirect immunofluorescence method for the detection of ANCA autoantibodies in serum, in addition to measure the serum level of cytokines including IL6, IL-17, IL-18, and IFN-γ by using Enzyme Linked Immune Sorbent Assay methods.

Results: This study has shown that the majority of patients were male (66.7%). Moreover, the most effected age groups within the age ≥ 61 years in percentage (65.5%) followed by the age group 51-60 years old (28.8%). There were 59 (65.5%) positive cases for ANCA from total patients and all of these cases were MPO-ANCA. The total RPGN patients were showed a highly significant increased mean serum levels of IL-18, IL-17, IL-6, and INF-γ as compared to healthy controls, as well as, the same cytokines were showed significant increased levels in myeloperoxidase (MPO)-ANCA positive serum in crescent glomerulonephritis patients as compared to ANCA –negative serum of patients.  These results indicate a functional role of IL-6, IL-17, IL-18, and INF-γ in ANCA-mediated neutrophil activation by the interdependence of IL-6, IL-17, IL-18, and INF-γ priming for ANCA responses.

Conclusion: It can be drawn from the present study that, the pro-inflammatory cytokines play an integral role in determining the course of disease and it can be used as major drug targets for therapy, as well as these cytokines have the ability to priming neutrophils thus contribute in the progression of a pauci-immune crescentic glomerulonephritis disease.