SPATIAL ARRANGEMENT OF IGA AND C3 AS A PROGNOSTIC INDICATOR OF IGA NEPHROPATHY

The histological picture of primary glomerulonephritis with glomerular IgA deposition (IgA nephropathy and Henoch-Schonlein disease) can var y from minimal mesangial involvement to severe endocapillary and/or ex tracapillary proliferation. Local activation of the complement cascade by glomerular IgA deposits and release of anaphylactoid factors are c onsidered to be major triggers of inflammation, but clear-cut correlat ions between the severity of the histological findings and the intensi ty of glomerular deposition of immunoglobulin and complement fractions are still lacking. The purpose of this study was to investigate the s patial distribution of IgA and complement in mesangial deposits with c onfocal laser scanning microscopy (CLSM) and to correlate specific pat terns of IgA-complement interaction with glomerular damage. Two groups of patients have been studied, one with mild to moderate diffuse mesa ngial proliferation and the other with diffuse proliferative endocapil lary and/or extracapillary patterns. In milder forms of the disease, t he majority of the immune deposits are composed of both IgA and C3, co ated by an outer layer of IgA alone. Large C3 deposits, or deposits co mposed ofIgA and C3 without an outer coat ofIgA, were associated with more severe histological lesions. The results suggest that free access of active complement components to cell and/or mesangial matrix recep tors could trigger a cytolytic reaction and that immunoglobulins seem to act as a protective layer on C3 components.