Apoptosis Inhibitor of Macrophage and Acute Inflammation in IgA Nephropathy

Serum IgM-free apoptosis inhibitor of macrophage reflects disease activity in human IgA nephropathy. Glomerular apoptosis inhibitor of macrophage deposition was colocalized with mesangial IgA and reflected the acute glomerular injuries by complement activation. Multivariate Cox regression analysis revealed serum IgM-free apoptosis inhibitor of macrophage as an independent predictor of hematuria remission in patients.

IgA nephropathy is characterized by mesangial deposits of IgA1-containing immune complex with complement 3. 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 clinicopathologic role of AIM in human IgA nephropathy.

We enrolled 77 patients with IgA nephropathy, five 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 clinicopathologic features.

sAIM level was higher in patients with IgA nephropathy at diagnosis than in disease and healthy controls (1.02±0.49 versus 0.56±0.19 versus 0.57±0.20 µ g/ml), significantly decreased to 0.67±0.44 µ g/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 versus 10-19 per high-power field) and acute lesions, including those with Oxford classification scores of endocapillary hypercellularity (E1 3% versus E0 2%) and crescent formation (C1 3% versus C0 2%). Furthermore, gAIM deposition was positively correlated with glomerular complement 3 deposition ( r2 =0.54). Multivariate Cox regression analysis revealed sAIM as an independent predictor of hematuria remission (hazard ratio, 1.86; 95% confidence interval, 1.03 to 3.15). According to Kaplan-Meier analysis, patients with larger reduction of sAIM (≥0.45 µ g/ml) after tonsillectomy and steroid pulse therapy showed a significantly improved hematuria (6 versus 9 months).

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.