THSD7A-Associated Membranous Nephropathy in a Patient with IgA Lambda Myeloma

Introduction: Membranous nephropathy (MN) is a pattern of glomerular injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. At least 14 target antigens have been identified, accounting for 80%–90% of cases of MN. Thrombospondin type-I domain-containing 7A (THSD7A) was discovered in 2014, but is seen in only 2% cases of MN (both primary and associated with neoplasms). We describe a rare case of THSD7A mediated MN in a patient with concomitant IgA lambda multiple myeloma Case Description: A 77-year-old male with history of hypertension was admitted with nephrotic syndrome. Cr 1 mg/dL, Sr albumin 1.9 g/dL, and 24 hour urinary protein 6604 mg. SPEP and SIFE revealed 1 IgA lambda monoclonal protein 0.19 mg/dL. Serum PLA2R was negative and serum THSD7A was positive [Mayo Clinic based, titer not available]. Kidney biopsy revealed a membranous pattern of GN with IFTA < 10%. IF: IgG (4+), IgA (4+), IgM (1+), C3 (2+), C1q (trace), kappa LC (3+) and lambda LC (4+) along the capillary loops. Pronase IF was negative. Electron microscopy revealed subepithelial and intramembranous electron dense deposits which were finely granular. Diffuse foot process effacement was noted. PLA2R was negative in the glomeruli while THSD7A IF was positive in the glomeruli. Congo red staining was in kidney biopsy. BM biopsy showed 15% IgA lambda restricted plasma cells. Extensive workup for AL amyloid was negative. A diagnosis of IgA lambda smoldering multiple myeloma was made. Clone based therapy was not initiated and a wait-and-watch approach was implemented. Conservative management including ARBs were started. Patient has now attained complete remission of proteinuria with negative serum THSD7A levels. Discussion: THSD7A associated MN, in the majority of cases, is a prototypical example of a primary MN, with anti-THSD7A antibodies, predominantly of the IgG4 subclass, directed against THSD7A that is endogenously expressed on podocytes. Disease activity correlates with the titer and trajectory of antibodies and responds to immunosuppression. 16% have a concurrent malignancy; circulating anti-THSD7A antibodies have been reported as a consequence of THSD7A expression by a malignant tumor. Co-occurance with underlying IgA Lambda Smoldering Myeloma has not been reported thus far.