POS-459 Immunofluorescence Staining for Immunoglobulin Heavy Chain/Light Chain on Kidney Biopsies is a Valuable Ancillary Technique For the Diagnosis of Monoclonal Gammopathy-Associated Nephropathies

Abstract

Heavy chain/light chain (HLC) antibodies target conformational epitopes at the junctions of the heavy chain and light chain constant regions (CH1 and CL) of serum IgGκ, IgGλ, IgAκ, IgAλ, IgMκ, and IgMλ to provide quantitation of intact HLC pairs. This assay is currently approved for the measurement of clonal expansion and monitoring of patients with multiple myeloma, and has been shown to have a prognostic utility. To our knowledge, the use of HLC antibodies in renal pathology has not tested. We developed an HLC tissue immunofluorescence (IF) protocol to test if it can complement conventional IF in the diagnosis of monoclonal gammopathy-associated nephropathies. HLC IF was performed on archival frozen tissue of 93 kidney biopsies. The sensitivity and specificity of HLC IF was confirmed by testing cases of lupus nephritis, other polyclonal immunoglobulin nephropathies, and light chain nephropathies (AL and LCDD). Testing of 6 HCDD cases revealed negative staining for all HLC antibodies in 4 (67%), consistent with CH1 deletion, whereas 3 cases of LHCDD were positive for IgGκ or IgGλ. Testing of 13 cases of PGNMID excluded monoclonal deposits in 4 (31%) by revealing positivity for IgGκ and IgGλ in 2 of 10 PGNMID-IgG3 cases and positivity for IgMκ and IgMλ in 2 of 2 PGNMID-IgM cases. Testing of 11 cases of monotypic IgA nephropathy excluded monoclonal deposits in 5 (45%) by revealing staining for IgAκ and IgAλ. Testing of 6 cases of monotypic fibrillary GN excluded monoclonal deposits in 3 (50%) by revealing positivity for IgGκ and IgGλ. Testing of 18 cases of cryoglobulinemic GN showed better correlation with serum cryoprecipitate immunofixation than conventional IF with regards to the type of cryoglobulin in 47% of cases. HLC IF is a valuable ancillary technique in renal pathology for the diagnosis of monoclonal gammopathy-associated nephropathies, and could be utilized to confirm or exclude the monoclonal nature of deposits.