Selective elevation of monomeric IgA1 in IgA nephropathy patients with normal renal function

The molecular form of the pathognomonic IgA in IgA nephropathy (IgAN) remains controversial. Because characterization of the molecular form of IgA molecules can lend insight into their origin (systemic v mucosal), we developed immunoassays to measure both total and J chain-containing (polymeric) IgA1 and IgA2. These assays were used to measure IgA in sera from two groups of IgAN patients (with normal or decreased renal function), as well as from a group of normal individuals. IgA1 levels were higher in both groups of patients with IgAN when compared with the controls. The elevation appeared to be restricted to non-J chain-containing (monomeric) IgA1 in patients with normal renal function, whereas polymeric IgA1 was also slightly elevated in patients whose renal function was diminished. While there were no significant differences between the groups in terms of the levels of total IgA2, the patient group with normal kidney function appeared to have lower levels of polymeric IgA2. The observation that the elevation in serum IgA appears to be restricted to the monomeric form of IgA1, at least when renal function is normal, implies a systemic origin of the pathognomonic IgA in IgAN and further suggests an abnormality in the regulation of IgA secretion by immunoglobulin-producing cells in bone marrow, the site of systemic IgA synthesis.