The Significance of Immunohistochemical Detection of IgG4 in Membranous Nephropathy
Misti Coronel, John L Farber, Peter McCue. Thomas Jefferson University Hospital, Philadelphia, PA
Background: Membranous nephropathy (MN) is a common cause of the nephrotic syndrome in adults. MN is primary (autoantibodies to phospholipase A2 receptor, aldose reductase, superoxide dismutase, or α-enolase) or secondary (cancers, infections, autoimmune diseases, medications). The characteristic finding on pathology is immune complex formation/deposition on the sub-epithelial side of the glomerular basement membrane (GBM), leading to complement activation, podocyte dysfunction, proteinuria, and even progressive loss of renal function. In idiopathic MN, the immunoglobulin G in the immune complexes is predominantly restricted to subclass 4 (IgG4), whereas in secondary causes other subclasses are typically found. While previous studies have identified IgG4 antibodies in patient serum, immunohistochemical characterization of this protein in renal biopsies has not previously been described.
Design: Seventy-seven cases of MN were evaluated retrospectively. Formalin-fixed, paraffin-embedded tissue was stained for mouse monoclonal IgG4 (Cell Marque) and evaluated for presence or absence of IgG4 in the GBM. The slides were scored semi-quantitatively (0-3).
In addition, the cases were evaluated for the presence of IgG4 positive plasma cells (PCs) in the interstitium. These results were compared with the clinical determination, based on review of the patient's medical record, of a primary versus secondary etiology of the MN.
Results: Thirty-three cases had positive IgG4 staining in the GBM, and 44 were negative. Of the positive cases, 29 had no evidence of a secondary etiology. The remaining 4 had a history of a malignancy. Of the negative cases, 34 had a secondary diagnosis, including 21 with class V (membranous) lupus nephritis. The overall positive predictive value of glomerular IgG4 staining was 88% (74% sensitivity). Negative staining had a negative predictive value of 77% (89% specificity). IgG4 positive PCs were detected only in cases of lupus nephritis (11 of 21).
Conclusions: The presence of glomerular IgG4 staining in a case of MN supports a diagnosis of primary disease and may help to limit the workup these patients undergo to rule out a secondary cause. In addition, the presence of interstitial IgG4 positive PCs is highly suggestive of underlying systemic lupus.
Category: Kidney (does not include tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 229, Monday Afternoon