The splenic component of reticulophagocytic function (RPF) was examined in 29 insulin-treated diabetic subjects (13 type I and 16 type II) by measurement of clearance of altered, radiolabeled, autologous erythrocytes. Double-isotope studies were performed with cells altered by: (1) preincubation with N-ethylmaleimide (NEM) and (2) coating with IgG antibody to the Rhesus (Rh) D antigen, labeled with 99mTc and 51Cr, respectively. HLA typing for the A, B, and DR loci was performed in those patients showing a defect in the clearance of IgG-coated cells. Values for half-life (t½ were correlated with the incidence of diabetic complications, levels of HbA15 and circulating immune complexes (CIC). Two patterns of abnormal clearance were observed: first, an isolated defect of IgG-coated cell clearance in 7 patients (3 had the HLA B8/DR3 haplotype) and second, abnormal removal of both types of cell in a further 7 patients (3 had B8/DR3). There was no correlation between half-lives as measured by the two methods, although exclusion of the patients with a defect of IgG-coated cell clearance alone yielded a highly significant correlation for the remaining 15 Rh-positive patients (P < 0.01). Abnormalities of IgG-coated cell clearance were more frequent in patients with HbA1 > 9% (P < 0.02), while t½ of NEM-altered cells was significantly greater in patients with CIC (P < 0.05). There was no correlation between t½ and the incidence of peripheral complications.
The influence of splenic blood flow (as measured by organ weight and retention of injected radiolabeled microspheres) on the t½ of NEM-altered cells was examined in rabbits. The t½ correlated with both splenic weight (P < 0.001) and retention of microspheres (P < 0,001).
Our data emphasize the value of double-isotope studies in assessing RPF in vivo. The isolated abnormality of IgG-coated cell clearance probably resulted from a specific defect of the splenic macrophage receptor and the B8/DR3 haplotype, and blood sugar control appeared to influence this abnormality. In addition to these factors, our animal studies suggested that splenic blood flow could contribute to the dual defect seen in a further 7 patients. These factors could hinder the removal of potentially tissue damaging macromolecules from the circulation of patients with diabetes.
