IgG3κ Monoclonal Membranous Nephropathy Associated With Acquired Lecithin Cholesterol Acyltransferase Deficiency.

Lecithin cholesterol acyltransferase (LCAT) deficiency, inherited or acquired, is characterized by markedly low plasma high-density lipoprotein (HDL) cholesterol levels and increased unesterified cholesterol. We report a case of an elderly patient with persistently very low HDL and proteinuria. Serum cholesteryl esters were markedly low, and kidney biopsy revealed diffuse global glomerular lipid deposition, classic for LCAT deficiency, whereas genetic testing for variants associated with LCAT deficiency was negative. Kidney biopsy also showed concomitant monoclonal (IgG3κ) membranous nephropathy (MN). Proteomic analysis of glomeruli detected spectra for LCAT and serum amyloid P (SAP), suggesting that LCAT could be a target antigen in monoclonal MN with SAP enrichment and associated LCAT deficiency. Furthermore, lipidomic analysis revealed an accumulation of phosphatidylcholines and sphingomyelin and a decrease in ceramides. The patient was treated with daratumumab, and at 22 months follow-up his proteinuria was decreased while HDL level remained low.