Altered erythrocyte C3b receptor expression, immune complexes, and complement activation in homosexual men in varying risk groups for acquired immune deficiency syndrome.

Abstract

We studied levels of erythrocyte C3b receptors (E-CR1) and correlated them to the level of circulating immune complexes (CIC) and complement activation in patients with or at risk for acquired immunodeficiency syndrome (AIDS). A significant reduction was found in patients with AIDS (185±93 CR1/cell), AIDS-related complex, and generalized lymphadenopathy, whereas healthy male homosexuals or normal controls had 434±193 and 509±140 CR1/cell, respectively (P < 0.001).Family studies indicate that this defect is acquired. Reduction in E-CR1 was associated with increased levels of CIC when assayed by binding to Raji cells, but not when tested by Clq binding. Complement activation was assessed by levels of C3bi/ C3d-g in plasma, measured with a monoclonal antibody specific for a neoantigen in C3d. AIDS patients had increased C3 activation (2.68±1.67%) when compared with normal controls (0.9±0.22%) (P < 0.01). The decreased E-CR1, the presence of CIC, and C3 activation suggest that complement activation by immune complexes may play a role in the clinical expression of the disease.

Macrophages and HIV-1: dangerous liaisons

“…Circulating immune complexes (CIC) may be abundant in chronic infections, which are common in developing countries where HIV/AIDS is highly prevalent. Moreover, since the very beginning of the AIDS pandemic it has been known that the levels of circulating immune complexes (including HIV-specific CIC) are elevated in HIV-positive patients, independent of other infections (Carini et al, 1987;Tausk et al, 1986). HIV-1 immune complexes may, however, facilitate HIV-1 entry through FcRs or complement receptors (Homsy, 1989;Takeda et al, 1990).…”

A Soluble Recombinant Multimeric Anti-Rh(D) Single-Chain Fv/CR1 Molecule Restores the Immune Complex Binding Ability of CR1-Deficient Erythrocytes

“…Physiologically CR1 density decreases during aging on normal E (8). E from patients suffering from systemic lupus erythematosus (SLE) (9,10), some hemolytic anemia (11), and HIV infection share an acquired reduction of the expression of CR1 (12)(13)(14). This low density of CR1 on E contributes to impairing IC transport mechanisms in patients with SLE, resulting in deposition of IC outside liver or spleen, which may induce tissue damage in susceptible organs, particularly kidney (15,16).…”

Processing of C3b-Opsonized Immune Complexes Bound to Non-Complement Receptor 1 (CR1) Sites on Red Cells: Phagocytosis, Transfer, and Associations with CR1

“…Studies in both in vitro and in vivo models delineate a mechanism for this transfer in which engagement of CR1-bound IC by macrophage Fc receptors leads to cleavage of CR1, resulting in loss of CR1 and the associated IC from the E (22,(25)(26)(27)(28). Thus, the transfer reaction is likely to explain, at least in part, the reduced CR1 levels in patients with a variety of diseases involving circulating IC (29), particularly autoimmune diseases (29,30) and AIDS (31). In the second case, E that have Abs and complement bound to other sites are removed and destroyed by fixed tissue macrophages (10 -15).…”