Toward a Working Definition of C3 Glomerulopathy by Immunofluorescence
Jean Hou, Glen S Markowitz, Leal C Herlitz, Michael B Stokes, Vivette D D'Agati. Columbia University, College of Physicians and Surgeons, New York, NY
Background: In the past, membranoproliferative glomerulonephritis (MPGN) was subdivided into types 1-3 according to light microscopic and ultrastructural findings. Based on new understanding of the role of alternative pathway (AP) complement dysregulation, the term C3 glomerulopathy (C3G) now encompasses DDD (type 2) and those forms of type 1 and 3 with isolated deposits of C3. Precise immunofluorescence (IF) criteria for C3G remain to be defined. Our aims were to: 1) test hierarchical IF criteria with varying stringency for C3G; 2) determine if "C3 only" is a practicable criterion; 3) apply these criteria to analyze the incidence of C3G in types 1 and 3 MPGN.
Design: A total of 818 biopsies coded as MPGN pattern in the Columbia Renal Pathology Laboratory from 1998-2002 were retrospectively reviewed. After exclusion of those cases with clear etiology (such as hepatitis C, cryoglobulinemia, and dysproteinemia), we identified 444 cases of primary MPGN types 1-3. We retrospectively analyzed detailed IF reports and coded cases using the following criteria: Glomerular deposits of: C3 only (Group 1); C3 dominant and ≤1+ IgM only (Group 2); C3 dominant and at least 2 orders of intensity stronger than any combination of IgG, IgM, IgA, C1q (Group 3).
Results: The findings are summarized in tabular form.
The most restrictive criterion of "C3 only” captured only 41% of DDD (compared to 5% of type 1 and 8% of type 3), whereas adding the most liberal definition identified 80% of DDD (compared to 22% of type 1 and 35% of type 3). The 20% unaccounted DDD had stronger intensity of Ig staining, but never exceeding the intensity of C3.
Conclusions: 1) “C3 only” is an impractical definition of C3G. 2) A less restrictive approach that allows for low-level Ig trapping or deposition is needed. 3) C3G is more common in MPGN type 3 than type 1. These criteria provide a framework for future correlations with functional and genetic measures of AP dysregulation in MPGN.
Category: Kidney (does not include tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 253, Monday Morning