Defective Immune Complex Degradation by Monocytes in Patients with Systemic Lupus Erythematosus.

Abstract

The binding of 125I-labelled anti-bovine serum albumin (BSA)-BSA immune complexes (IC), giving a final molar antibody to antigen ratio of 1:1, to monocytes isolated from 18 patients with systemic lupus erythematosus (SLE) and from 10 normal healthy donors was quantitatively investigated. The degradation of the bound IC by the same monocytes was kinetically determined at the same time. The assays were performed on monocyte monolayers. Scatchard plots at 4 degrees C demonstrated that monocytes from patients with active SLE expressed a mean Fc gamma receptor (FcR) number that was 22% higher than that of the controls, although this did not reach statistical significance. The FcR number of normal monocytes and the degradation rate of anti-BSA-BSA complexes by the same cells showed a positive correlation. At the same time, the digestion of anti-BSA-BSA complexes by monocytes of SLE patients with active disease was prolonged, despite their enhanced FcR-ligand binding. The dissociation of FcR-ligand binding and FcR-mediated degradation suggests that the IC degradation is controlled by altered biochemical mechanisms in the monocytes of SLE patients.

Triggering of respiratory burst by phagocytosis in monocytes of patients with systemic lupus erythematosus

“…Our study is in good agreement with the data of Kimberly et at. [12] that the FcyR-dependent ligand inlernalization by SLE monocytes is defective, and with our earlier data [5] that immune complex degradation by SLE monocytes is defective. On the other hand, monocytes from patients with SLE have been shown to have normal phagocytosis of C3b-coated yeast particles [13].…”

“…They were selected with at least four of the revised ARA criteria for classiliealion of SLE [7], Nine patients had clinically active disease, which was defined by the presence of arthritis, nephritis, skin rash, high fever, hypocoinplcmcntaemia and high ds*ONA binding aetivity [5], Anti-DNA antibodies were present in the serum of all patients as assessed by Earr precipitation assay. Eleven of the patients received 10 tng/day of prednisone or more; none olthe patients received eytostatie agents at the time ofthe study.…”

“…When these cells interact with soluble or particulate matter, they respond with a respiratory burst tbat results in the production of superoxide anion {O: ), Monocytes from patients with systemic lupus erythematosus (SLE) have been shown to have impaired phagocytosis of st^luble and purticulatc immune complexes {1,2]. The defect in immune complex (IC) elimination may reflect diminished Fey receptor (Fc>'R) and C.^ complement receptor (CR3)-dependent ligand binding [3,4] and/or altered degradation of IC [5]. Some years ago we could not detect a significant dilTercnce between the montK'yte Fc-/R numbers to bovine serum albumin {BSA)-anti-BSA complex in patient and eontrol groups [5], It ean therefore be supposed ihat the in vitro IC degradation may he controlled by altered biochemical mechanisms in the monocytes of SLE palients rather than by their receptor blockade.…”

“…The defect in immune complex (IC) elimination may reflect diminished Fey receptor (Fc>'R) and C.^ complement receptor (CR3)-dependent ligand binding [3,4] and/or altered degradation of IC [5]. Some years ago we could not detect a significant dilTercnce between the montK'yte Fc-/R numbers to bovine serum albumin {BSA)-anti-BSA complex in patient and eontrol groups [5], It ean therefore be supposed ihat the in vitro IC degradation may he controlled by altered biochemical mechanisms in the monocytes of SLE palients rather than by their receptor blockade. The impaired signal transduetion mechanisms [6] may lead to decreased production of oxygen metabolites.…”

Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus

“…A number of observational studies showed that MFs have intrinsic defects in the phagocytosis of latex beads, apoptotic cells, IgG-ICs, bacteria, and yeast (10,34,35,53). Other studies found that phagocytosis is intact, but the ability to degrade the internalized cargo is impaired (35,54,55). We find that lupus-prone MRL/lpr MFs phagocytose and traffic IgG-ICs to lysosomal structures, but that the lysosomal structures were unable to mature and acidify.…”