engleski

Macrophage polarization in Henoch-Schönlein’s purpura nephritis

Introduction: Macrophages frequently infiltrate injured glomerular and tubulointerstitial tissue, and it is possible that the degree and subtype of macrophage infiltration (M1 macrophages, which show proinflammatory features, and M2 macrophages, with their immunosuppressive features) varies depending on the type and severity of renal injury. Although renal involvement in patients with Henoch-Schönlein's purpura (HSP) is the main cause of morbidity and mortality and a significant prognostic determinant for the disease outcome, a reliable prognostic factor for severe forms of HSP nephritis (HSPN) is yet to be determined. Objectives: The aim of this research was to determine macrophage subclasses in renal biopsy specimens of HSPN patients and to analyze their quantity in regard with patients' clinical parameters and histologic features. Methods: We performed an immunohistochemical study on renal tissue samples of patients with HSPN, diagnosed by EULAR/PRINTO/PRES criteria and followed for at least 6 months. Patient clinical and laboratory data was retrieved from hospitals' medical records. Renal biopsy samples were marked with antibodies for CD68, iNOS and arginase. The number of immunoreactive cells was counted in each glomerulus by two independent experts. Results: Laboratory and histologic data for 25 patients with HSPN was evaluated in regard with macrophage infiltration of the renal tissue. The median glomerular M1 and M2 counts (q1, q3) were 2.3 (0.9, 12.2) and 7.6 (4.4, 13.9), respectively. M1 macrophages were found statistically significantly less frequent in the glomeruli in comparison with M2 macrophages (p < 0.001, b = -0, 289 ± 0.053). Collected laboratory data included inflammatory markers and markers of kidney function. There was no significant correlation between M1 and M2 macrophage count and laboratory parameters. Four pathohistological classifications were used: ISKDC, Haas classification, Oxford classification, and SQC classification. Classification stages/total classification scores and all histological variables were evaluated for possible correlation with macrophage count. Statistically significant negative correlation was found between segmental glomerulosclerosis (Oxford classification) and M2 macrophages (p = 0, 001, b = -1, 050 ± 0, 275). An indication of negative correlations was also noted between M2 macrophages and segmental sclerosis, and M2 macrophages and adhesions (SQC classification). Conclusion: Glomeruli in HSPN showed predominant M2 polarization of macrophages. M2 macrophage infiltration of glomeruli was highlighted as a possible negative predictor for segmental glomerulosclerosis. Grant/research support: Croatian Science Foundation project PURPURAPREDICTORS IP-2019-04- 8822 and University of Rijeka, Croatia grant No. Uni-ri-biomed-18-110.

arginasa-1 ; iNOS ; macrophages ; nephritis ; purpura ; Henoch-Schönlein

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