Apoptosis Inhibitor of Macrophage and Acute Inflammation in IgA Nephropathy

BACKGROUND: IgA nephropathy is characterized by mesangial deposits of IgA1-containing immune complex with complement 3 (C3). Our previous study demonstrated that apoptosis inhibitor of macrophage (AIM) plays a critical role in in situ IgA-containing immune complex formation and subsequent complement activation in murine IgA nephropathy. We further evaluated the clinicopathological role of AIM in human IgA nephropathy. METHODS: We enrolled 77 patients with IgA nephropathy, 5 patients with thin basement membrane disease as disease controls, and 40 age-matched healthy individuals as healthy controls. We analyzed the association between serum IgM-free AIM (sAIM)/glomerular AIM (gAIM) deposition area and clinicopathological features. RESULTS: sAIM level was higher in patients with IgA nephropathy at diagnosis than in disease and healthy controls (1.02 ± 0.49 µg/mL vs. 0.56 ± 0.19 µg/mL vs. 0.57 ± 0.20 µg/mL), significantly decreased to 0.67 ± 0.44 µg/mL after tonsillectomy and steroid pulse therapy, and was associated with serum IgA (r2 = 0.23) and IgA-IgG immune complex levels (r2 = 0.12). gAIM was colocalized with mesangial IgA and high intensity of gAIM was associated with the degree of hematuria (30-49/HPF vs. 10-19/HPF) and acute lesions, including those with Oxford classification scores of endocapillary hypercellularity (E1 3% vs. E0 2%) and crescent formation (C1 3% vs. C0 2%). Furthermore, gAIM deposition was positively correlated with glomerular C3 deposition (r2 = 0.54). Multivariate Cox regression analysis revealed sAIM as independent predictor of hematuria remission (HR = 1.86, 95% CI= 1.03-3.15). According to Kaplan-Meier analysis, patients with larger reduction of sAIM (≥ 0.45 µg/mL) following tonsillectomy and steroid pulse therapy showed a significantly improved hematuria (6 vs. 9 months). CONCLUSIONS: We suggest that IgA nephropathy patients with high sAIM levels have high disease activity and patients with high intensity of gAIM deposition have acute glomerular injuries leading to hematuria.