Immunologic studies in IgA nephropathy

Abstract

Circulating immune complexes (CIC) were detected in 43.6% of 78 patients with primary IgA nephropathy by the solid-phase Clq radioimmunoassay. The IC were intermediate (9 to 17S) in size and contained IgA, IgG, and less commonly IgM. CIC were often present intermittently, correlating with episodes of macroscopic hematuria. Elevated serum IgA concentrations (38.7%) did not correlate with the detection of CIC. Similar findings were observed in sera samples from patients with Henoch Schonlein purpura and in IgA glomerulonephritis associated with alcoholic cirrhosis and/or portal systemic shunts. The factors responsible for the mesangial localization of the IC are not clear, but elevations in serum antibody titers to respiratory pathogens (mycoplasma pneumoniae, herpes virus, influenza), gut flora (E. coli 07), and bovine serum albumin suggest that common exogenous antigens may be involved in the pathogenesis. Primary defects in either mucosal antigen exclusion or reticuloendothelial IC sequestration are proposed to account for these findings.

Association of liver cirrhosis related IgA nephropathy with portal hypertension

“…PH also decreases small intestinal motility promoting bacterial overgrowth [31,32] , while in the same time increases intestinal permeability [33] . In this regard, increased circulating IgA and IgAIC may represent an exaggerated response of immune system to excess gut antigen exposure [34,35] , resulting from diminished mucosal integrity and spillage of IgA into the circulation. Another mechanism could involve the endotoxemia that frequently accompanies LC with PH [36] , suggested to be generated by gut flora through bacterial translocation [37,38] favored by dysfunction of intestinal barrier [33,37] .…”

Dysregulated LIGHT expression on T cells mediates intestinal inflammation and contributes to IgA nephropathy

“…Previous studies have suggested a basic dysregulation of IgA production by showing increased serum levels of IgA, IgA-containing immune complexes, and pIgA, and enhanced IgA-specific T helper activity in human patients (10)(11)(12). T cells are implicated in the pathogenesis of this disorder; however, the direct role of T cells in the pathogenesis of IgAN is unclear, as few T cells can be identified in glomerular mesangium.…”

Increased Frequency of Surface IgA-Positive Plasma Cells in the Intestinal Lamina Propria and Decreased IgA Excretion in Hyper IgA (HIGA) Mice, a Murine Model of IgA Nephropathy with Hyperserum IgA

“…Five, 10,20,25,30, and 50 days after the initiation of BrdU administration, the mice were sacrificed and intestinal LP lymphocytes were isolated. The LP lymphocytes were stained for membrane IgA (mIgA) and cytoplasmic BrdU by the method described previously with minor modifications (21).…”

“…IgA nephropathy is the most common form of human glomerulonephritis worldwide, characterized by the deposition of IgA in the glomeruli (9). Although the mechanism of human IgA nephropathy has not been fully elucidated, high serum IgA levels, enhanced IgA-specific Th cells, and diminished numbers of IgAspecific regulatory T cells suggest that there is a basic dysregulation of IgA production in patients with this disease (10,11). Moreover, clinical association of relapses with mucosal infections, elevated serum Ab titers to respiratory pathogens, and dietary components in these patients indicate that mucosal immunity may also be involved in the pathogenesis of IgA nephropathy (12,13).…”