Membranous Nephropathy with Lambda Light Chain Restriction: A Rare Form with Serum Negative and Tissue Positive PLA2R Ab

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Subepithelial polyclonal immunoglobulin deposits and >70% M-type phospholipase A2 receptor antibody positivity are typical findings in idiopathic MN. A 58-year-old female patient was admitted with clinical presentation of nephrotic syndrome. Autoimmune diseases, infections, and malignancies were ruled out after clinical and laboratory evaluations. Diagnostic work-up revealed serum PLA2R antibody negativity and diffuse thickening of glomerular capillary wall on biopsy, while glomerular capillary wall IgG, C3, and Lambda monotypic light chain deposition and PLA2R1 positivity were detected by immunofluorescence and immunohistochemical examination, respectively. Following prednisolone treatment, creatinine and proteinuria were markedly regressed. The MN cases with a light chain deposits are rare and experience regarding their treatment are insufficient.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits associated with parvovirus B19

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is included in the group of dysproteinaemias causing renal disease. Only a minority of cases are associated with a haematological malignancy. Two cases have been linked to acute parvovirus B19 infections. We report a 36-year-old African-American woman who presented with renal dysfunction, proteinuria, haematuria and a kidney biopsy reported as PGNMID with IgG3-kappa deposits. Her evaluation for a haematological malignancy was unrevealing. Her parvovirus IgM and IgG levels were positive. The patient was initially treated with an ACE inhibitor and spontaneously remitted with minimal proteinuria after 1 month. Repeat parvovirus B19 serologies 6 months later showed persistent IgG and DNA by PCR positivity but IgM negativity. Given the clinical scenario, we believe that her PGNMID was induced by acute parvovirus B19 infection, which appeared to resolve once her acute infection abated. In this report, we describe our latest understanding of PGNMID.

Therapeutic B-cell depletion reverses progression of Alzheimer’s disease

The function of B cells in Alzheimer’s disease (AD) is not fully understood. While immunoglobulins that target amyloid beta (Aβ) may interfere with plaque formation and hence progression of the disease, B cells may contribute beyond merely producing immunoglobulins. Here we show that AD is associated with accumulation of activated B cells in circulation, and with infiltration of B cells into the brain parenchyma, resulting in immunoglobulin deposits around Aβ plaques. Using three different murine transgenic models, we provide counterintuitive evidence that the AD progression requires B cells. Despite expression of the AD-fostering transgenes, the loss of B cells alone is sufficient to reduce Aβ plaque burden and disease-associated microglia. It reverses behavioral and memory deficits and restores TGFβ+ microglia, respectively. Moreover, therapeutic depletion of B cells at the onset of the disease retards AD progression in mice, suggesting that targeting B cells may also benefit AD patients.