Milk-Related Antibodies Linked to Childhood Membranous Nephropathy

At least some cases of idiopathic membranous nephropathy in young children are associated with antibodies to bovine serum albumin, suggests a study in the New England Journal of Medicine.

In a sample of 50 patients with membranous nephropathy, the investigators found high levels of circulating anti—bovine serum albumin antibodies in 11 patients. This included four of nine children studied (age range 5–28 months). The antibodies were of both IgG1 and IgG4 subclasses. All patients with antibodies also had elevated levels of circulating bovine serum albumin, with no increase in circulating immune complex levels and no evidence of cow’s milk allergy.

Bovine serum albumin immunopurified from the serum of children with membranous nephropathy migrated in the basic range of pH, whereas bovine serum albumin from adult patients migrated in neutral regions as native bovine serum albumin. Bovine serum albumin was found in subepithelial immune deposits only in children with high levels of cationic circulating bovine serum albumin and bovine serum albumin—specific antibodies. These immune deposits colocalized with IgG, in the absence of M-type phospholipase A2 receptor. Eluted IgG from the subepithelial immune deposits showed specific anti—bovine serum albumin activity.

Membranous nephropathy is a rare cause of nephrotic syndrome in children. In recent studies, phospholipase A2 receptor was implicated as an antigen in 70 percent of cases of idiopathic membranous nephropathy. The antigens involved in other idiopathic and membranous nephropathies remain undefined.

This study demonstrated circulating cationic bovine serum albumin and anti—bovine serum albumin antibodies in some patients with idiopathic membranous nephropathy, including young children. These children might benefit from dietary elimination of bovine serum albumin. Future research may identify other food antigens as contributors to membranous nephropathy [Debiec H, et al. Early-childhood membranous nephropathy due to cationic bovine serum albumin. N Engl J Med 2011; 364:2101–2110].