Cryoglobulins, circulating immune complexes, and complement activation in cerebral malaria

Abstract

A total of 32 patients with Plasmodium falciparum malaria were studied. Of these, 23 had benign infections, and 9 had typical cerebral malaria. Cryoglobulins, circulating immune complexes detected by a C1q-binding assay, and hypocomplementemia were found in eight of nine patients with cerebral malaria. Raised levels of complement component 3 breakdown products (C3d) were found in the seven patients tested. Peak levels of circulating immune complexes and C3d were associated with thrombocytopenia. In contrast, in patients with benign Plasmodium falciparum malaria, cryoglobulins and circulating immune complexes were found only in 3 of 23 patients. Similarly, hypocomplementemia was detected only in 5 of 23 patients. These observations suggest that the intensity of the immune response and of the associated complement activation may be important factors in the pathogenesis of cerebral malaria.

ThePlasmodium falciparumblood stages acquire factor H family proteins to evade destruction by human complement

“…For example, it was shown that the parasite digestive vacuole, which during schizont rupture is released together with the MZs into the blood stream, activates the ACP (Dasari et al, 2012(Dasari et al, , 2014. Malaria infection-induced complement activation of the classical pathway via the formation of antigen-antibody immune complexes as well as activation of the mannose-binding lectin pathway have also been reported (Jhaveri et al, 1997;Adam et al, 1981;Klabunde et al, 2002;Garred et al, 2003;Stoute et al, 2003).…”

Distinct pattern of class and subclass antibodies in immune complexes of children with cerebral malaria and severe malarial anaemia

“…Also, by cross‐linking Fc receptors on effector cells such as macrophages and monocytes, ICs can stimulate the production of pro‐inflammatory cytokines (16) that have been proposed to have a role in the pathogenesis of severe malaria (17). Despite the accumulating evidence linking ICs to the pathogenesis of malaria (2,5,6,18–20), no clear pattern of association between antibody class or subclass and the clinical form of severe malaria has emerged. Therefore, the main objective of this study was to determine the composition of ICs in terms of antibody class/subclass and to relate this to the severity of P. falciparum malaria.…”

“…ICs can activate complement and deposit in tissues stimulating an inflammatory response (4). Therefore, some investigators have suggested a possible role for ICs in the pathogenesis of SMA and CM (5,6).…”

Platelet interactions with viruses and parasites

“…A possible explanation for platelet activation in malaria is complement formation. The formation of C3d, indicating complement activation, was associated with thrombocytopenia in malaria-infected patients [101]. Nevertheless activation of platelets in malaria could also be related to direct interaction with the parasites [102,103].…”