Prospective Assessment of C4d Deposits on Circulating Cells, Glomeruli, and Peritubular Capillaries in Lupus Nephritis (LN)
I Batal, S Bastacky, KV Liang, LP Kiss, T McHale, NL Wilson, B Paul, A Lertratanakul, JM Ahearn, SM Manzi, AH Kao. University of Pittsburgh, Pittsburgh, PA
Background: Classical complement activation plays a key role in the pathogenesis of LN. Studies have suggested an association between C4d deposition in native renal tissue and LN severity. Cell-bound complement activation products have not been systematically studied in LN. We aimed to compare the C4d deposition on circulating cells and renal tissues between LN and non-systematic lupus erythematosus (SLE) renal disease controls and to determine the association of C4d deposition with LN class and disease activity.
Design: We prospectively evaluated 13 LN and 7 non-SLE renal control subjects who underwent renal biopsy. Concurrent C4d levels on circulating erythrocytes and platelets (EC4d, PC4d) were measured by flow cytometry. The distribution of immunoperoxidase C4d on formalin-fixed, paraffin-embedded renal biopsy tissues was semiquantitatively assessed (0-3; negative to diffuse) in peritubular capillaries (PTC) and glomeruli [GBM and/or mesangium]. LN histologic class, and activity (AI) and chronicity (CI) indices were assessed using the 2004 ISN/RPS classification and the NIH scoring systems, respectively.
Results: Six LN subjects (46%) had class IV [IV(S) (3) and IV(G) (3)]; the remainder had classes II (15%), III (23%) and/or V (38%). Median AI and CI were 6 and 2, respectively. Median EC4d levels of LN subjects were higher compared to controls (19.2 vs. 7.0, p=0.03). PC4d was detected in 6/13 (46%) LN subjects vs. 0/7 (0%) controls (p=0.05). EC4d level significantly correlated with LN AI (r=0.67, p=0.01). Furthermore, subjects with class IV LN had higher median EC4d levels compared to other classes (33.2 vs. 16.2, p=0.046). In renal tissues, mean glomerular C4d score was higher in LN (2.3+/-1.2) compared to controls (1.3+/-1.1, p=0.03), while PTC C4d score showed no significant difference. This C4d staining was associated with glomerular immune complex deposits. Neither glomerular nor PTC C4d score correlated with LN class or AI. Neither glomerular nor extraglomerular immune complex deposits correlated with EC4d levels.
Conclusions: This pilot study revealed that circulating cell and glomerular C4d levels were significantly higher in LN subjects compared to the non-SLE renal controls. In contrast to glomerular and PTC C4d, EC4d levels significantly correlated with LN disease activity. These findings suggest a potential role of C4d on circulating cells as a biomarker for LN.
Category: Kidney (does not include tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 205, Monday Morning