Membranoproliferative glomerulonephritis associated with IgA-λ monoclonal gammopathy

Abstract

Dear Editor, From September 2008 to April 2013, 4 patients were found to have amonoclonal IgA-λ component by serum immunofixation electrophoresis among 29 membranoproliferative glomerulonephritis (MPGN) patients, pathologically confirmed via renal biopsy during the same period in our facility (Table 1). All patients were male, and the median age was 53.0(45–65) years. The severity of proteinuria and renal insufficiency varied among patients. The extent of plasma cell dyscrasia was categorized as monoclonal gammopathy of undetermined significance (MGUS) in three patients and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) in the other. The diagnosis of MPGN was made via light microscopic observations, and interestingly, no IgA or λ light chain deposit was detected by immunofluorescence surveys. Electron microscopy revealed thickening of basement membrane (inner layer in particular), cellular interposition, diffuse effacement of the foot processes of podocytes, and scattered deposits in subendothelial and mesangial regions (Fig. 1). Patient 1 was treated with prednisone and cyclophosphamide, and proteinuria decreased from 1.86 to 0.34 g/24 h at 3year follow-up. Patient 2 was treated with dexamethasone and thalidomide, but proteinuria increased from 0.24 to 0.81 g/24 h after 1 year. Patients 3 and 4 did not get any specific treatment. The serum creatinine level was stable in all patients during follow-up (0.72– 1.22 mg/dl). The spectrum of renal involvement secondary to plasma cell diseases have been drastically expanded recently. Aside from previously acknowledged entities, including myeloma cast nephropathy, AL amyloidosis, monoclonal immunoglobulin deposition disease, and light chain proximal tubulopathy, the territory of primary glomerulonephritis has also been shattered [1, 2]. Proliferative glomerulonephritis secondary to monoclonal IgG, IgA, or immunoglobulin light chain deposits has been well-described since 2004 [3–5]. The most recent candidate for this heterogeneous group was proposed by Sethi et al. in 2010. In a single-center study, they identified 28 monoclonal/biclonal Igs among total 126 MPGN patients, in which 68 cases were hepatitis negative and evaluated for gammopathy [6]. IgM-κ and IgG-κ were most commonly encountered, and more than half of the patients were categorized as MGUS. Under these circumstances, a recent perspective article in Blood proposed the terminology “monoclonal gammopathy of renal significance (MGRS)” [2]. Here, we presented the first report of MPGN associated with IgA-λ monoclonal gammopathy. Along with the other two patients with IgM-κ and IgG-κ paraproteins, the overall occurrence of monoclonal gammopathy among MPGN B. Wu :W. Wang : F. Li (*) : S. Zou :Y. Cheng Department of Hematology, Zhongshan Hospital Fudan University, 180 Fenglin Road, Shanghai 200032, China e-mail: li.feng@zs-hospital.sh.cn