Tubulointerstitial Infiltration of M2 Macrophages in Henoch-Schönlein Purpura Nephritis Indicates the Presence of Glomerular Crescents and Bad Clinical Parameters

Abstract

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children, and renal involvement (HSP nephritis, HSPN) is a severe manifestation. HSPN is histologically classified by the International Study of Kidney Disease in Children (ISKDC) based on mesangial hypercellularity and the extent of glomerular crescents. Macrophages, categorized as M1 or M2, frequently infiltrate in various glomerular and tubulointerstitial diseases and infiltration of specific subtypes is associated with disease progression. Therefore, to identify whether infiltration of M1 or M2 macrophages has clinical significance, we quantified the subtypes of macrophages in 49 HSPN specimens and correlated the counts with histologic features and clinical parameters. Higher tubulointerstitial M2 counts were associated with chronic renal failure (CRF), ISKDC classes III-IV, and crescents (P<0.001, 0.002, 0.001). Glomerular M2 counts were significantly related to ISKDC classes III-IV and crescents (area under curve, AUC 0.804, 0.833). Tubulointerstitial M2 counts were associated with CRF, ISKDC classes III-IV, and crescents (AUC 0.872, 0.778, 0.830). Tubulointerstitial M2 counts also revealed higher AUC than tubulointerstitial M1 counts for CRF (P=0.036) and ISKDC classes III-IV (P=0.047). Glomerular M2 counts revealed higher AUC than glomerular M1 counts for ISKDC classes III–IV (P=0.024). Tubulointerstitial M2 counts were the most powerful parameter for CRF (AUC 0.872) and revealed even higher AUC than ISKDC classification (AUC 0.716) with borderline significance (P=0.086) for CRF. In summary, tubulointerstitial M2 counts were a superior parameter to tubulointerstitial M1 counts and even to ISKDC classification indicating the presence of CRF.

Associations between clinical features and therapy with macrophage subpopulations and T cells in inflammatory lesions in the aorta from patients with Takayasu arteritis

“…Endogenous peroxidase was blocked with a 10-vol concentration H 2 O 2 solution for 10 min. The following primary antibodies were incubated for 30…”

M2 macrophage polarization in cutaneous polyarteritis nodosa: an immunohistochemical study

“…A similar trend was observed in patients with ANCA-associated pauci-immune glomerulonephritis, suggesting that M2 cells may be indicative of a poor prognosis in vasculitis with renal impairment. 9,34 The hypothesis that M2 macrophages could influence the interval and frequency of relapses in chronic vasculitis has also been suggested. Ohlsson et al compared the number of M2 cells in patients diagnosed with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) during the active and remission phases.…”

“…7 Recent studies revealed that these cells are an important pathogenic factor in the development of various types of vasculitis, including giant cell arteritis, Kawasaki disease, Henoch-Schönlein purpura, and ANCA-associated vasculitis. [8][9][10][11] However, the role of macrophages in patients with CPAN has never been reported. Therefore, the objectives of this study were to investigate the distribution of M1 and M2 macrophage phenotypes in CPAN and to describe the clinical characteristics of affected patients.…”

Predicting renal outcomes in immunoglobulin A vasculitis nephritis; from ISKDC classification to Oxford MEST-C classification

“…For example, it was shown that infiltration of inflammatory cells, including macrophages and neutrophils in the interstitium, mostly macrophage infiltration, commonly detected in tubuleinterstitial diseases, may have a prognostic significance. Accordingly, the intensity of macrophage infiltration has been shown to be related to the intensity of glomerular injury too (26)(27)(28)(29)(30). The original Oxford classification of IgAN, covered four morphologic aspects of mesangial hypercellularity (mesangial proliferation) score (M); segmental glomerulosclerosis (S), endocapillary hypercellularity (E) and tubular atrophy/interstitial fibrosis (T), and was named as MEST score.…”