IGG Subclass Staining in Allograft Membranous Nephropathy.
Nicole Kearney, Jennifer Podolak, Donald Houghton, Megan Troxell. OHSU, Portland, OR
Background: Membranous glomerulopathy (MGN) recurs in the renal allograft 10-50% of the time, but may also occur de novo in about 2% of all grafts. The mechanisms of glomerular injury in recurrent and de novo MGN are likely to be different, possibly analogous to the difference between “idiopathic” and secondary MGN in native kidneys, including different profiles of IgG subclasses in the immune deposits. IgG4 in subepithelial deposits is generally associated with “idiopathic” MGN, and was recently shown to have specificity for PLA2R on podocytes in most patients. Differential deposition, with a predominance of IgG1, IgG2 or IgG3, has been found in native kidneys with secondary MGN, associated with malignancy, lupus, and probably infection. Our study examines the IgG subclass distributions in MGN in allograft kidneys.
Design: Department of Pathology files were searched for allograft kidneys with MGN from 2003-2010 with available frozen tissue containing glomeruli. Specimens from 10 patients were identified, ranging in age from 8-75. No patient had a known malignancy, Hepatitis B or C. Of these, 6 were apparently recurrent MGN, and 4 were de novo MGN. Frozen sections were immunofluorescently stained with antibodies to IgG1, IgG2, IgG3, IgG4 (The Binding Site), and examined under UV light. Granular capillary loop immunofluorescence was scored independently on a scale of 0-3+ by 3 observers blinded to clinical history.
Results: IgG4 was dominant or co-dominant IgG subclass in the capillary loop deposits in all 6 cases of recurrent MGN. In contrast, IgG4 was not dominant in any of the 4 cases of de novo MGN (0/4), with generally weak staining. Instead, IgG1 staining was strongest in 3 of 4 de novo MGN cases; IgG1 and IgG3 were co-dominant in the fourth case, in a young boy transplanted for obstructive uropathy. The average intensity of IgG1 staining was comparable across the recurrent and de novo MGN groups (1.75), while the average IgG4 staining score was higher in recurrent (2.1) as compared to de novo MGN (1.0).
Conclusions: Our cases demonstrate dominance or co-dominance of IgG4 in capillary loop immune deposits in recurrent MGN, as reported in “idiopathic” MGN in native kidneys. In contrast, cases of de novo MGN in allografts demonstrate a different IgG subclass profile, with dominance of IgG1 or IgG3, and generally less IgG4. IgG subclass staining these cases provides further evidence of different pathophysiologies of recurrent and de novo MGN in renal allografts. Further studies are indicated to confirm these findings, to better establish their diagnostic importance, and to correlate them with PLA2R antibody assays, as they become available.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 276, Wednesday Afternoon