Mesangial IgA nephropathy: detection of defective reticulophagocytic function in vivo

The splenic component of the reticulophagocytic system (RPS) was studied in 20 patients with primary mesangial IgA nephropathy and 15 healthy controls. Eight patients were hypertensive, seven had renal failure and six had significant proteinuria. RPS function was assessed by the measurement of T1/2 clearance of altered, radio-labelled autologous erythrocytes. Three different methods were used to alter the red cells - thermal stress, sulfhydryl inhibition with N-ethylmaleimide (NEM) and antibody-coating - and in 12 patients two of these methods were used simultaneously in double-isotope-labelled studies. Impaired clearance was demonstrated in 16 of the 20 patients. T1/2 of NEM-altered cells was abnormal in 12 of 19 studies in 17 patients (i.e. T1/2 greater than 22.5 mins) while T1/2 of IgG-coated cells was abnormal in 8 of 10 patients (i.e. T1/2 greater than 62 mins). The clearance of thermally-damaged cells was not significantly different from that observed in controls (normal range: 10.5-17 mins). In the double-isotope studies, the clearance of NEM-altered cells correlated with the clearance of IgG-coated cells (P less than 0.05). There was no correlation between T1/2 clearance times and circulating immune complexes. These abnormalities of splenic function suggest there is a primary reticulophagocytic defect in patients with mesangial IgA nephropathy. This finding could bear relevance to the pathogenesis of the disease.