Mitra Mehrazma, Fatemeh Gharehdaghli, Shahrzad Ossareh, Fereshteh Saddadi, Morteza Ziaheidari, Alireza Amanollahi
CD68+ macrophage infiltration is closely associated with active and chronic lesions in IgAN, particularly endocapillary hypercellularity and tubular atrophy. Quantification of CD68+ macrophage may serve as a valuable histological marker for assessing disease activity and guiding prognosis in IgAN.
INTRODUCTION: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. The Oxford classification (MEST-C) a standardized histopathological scoring system evaluating mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), interstitial fibrosis/tubular atrophy (T), and cellular or fibrocellular crescents (C), provides a histopathological framework to predict disease progression. However, the role of immune cell infiltration-particularly CD68+ macrophages-in these pathological features remains underexplored.
OBJECTIVE: To investigate the association between renal CD68+ macrophage infiltration and the Oxford classification parameters in patients with IgA nephropathy.
METHODS: This study included 146 patients with biopsy-proven IgAN at Hasheminejad Kidney Center between 2013 and 2020. Immunohistochemical staining for CD68 was performed on paraffin-embedded kidney biopsy sections. CD68+ macrophages were quantified separately in the glomerular and interstitial compartments. Finally, the associations between macrophage counts and Oxford classification components (M, E, S, T, C) were analyzed.
RESULTS: Glomerular CD68+ cell counts were significantly higher in samples with M1, E1, T1, and C1 lesions (P < .05). Interstitial CD68+ cells were significantly elevated in T1 lesions (mean: 10.6 vs. 4.7 in T0; P < .001). Receiver operating characteristic (ROC) analysis demonstrated high diagnostic accuracy for interstitial CD68+ cells in predicting T1 (AUC = 0.98) and for glomerular CD68⁺ macrophage in predicting E1 (AUC = 0.88).
CONCLUSION: CD68+ macrophage infiltration is closely associated with active and chronic lesions in IgAN, particularly endocapillary hypercellularity and tubular atrophy. Quantification of CD68+ macrophage may serve as a valuable histological marker for assessing disease activity and guiding prognosis in IgAN.