Autoimmunity, phospholipid-reacting antibodies and malaria immunity

Abstract

Several questions regarding the production and functioning of autoantibodies (AAb) during malaria infection remain open. Here we provide an overview of studies conducted in our laboratory that shed some light on the questions of whether antiphospholipid antibodies (aPL) and other AAb associated with autoimmune diseases (AID) can recognize Plasmodia antigens and exert anti-parasite activity; and whether anti-parasite phospholipid antibodies, produced in response to malaria, can inhibit phospholipid-induced inflammatory responses and protect against the pathogenesis of severe malaria. Our work showed that sera from patients with AID containing AAb against dsDNA, ssDNA, nuclear antigens (ANA), actin, cardiolipin (aCL) and erythrocyte membrane antigens recognize plasmodial antigens and can, similarly to monoclonal AAb of several specificities including phospholipid, inhibit the growth of P. falciparum in vitro. However, we did not detect a relationship between the presence of anti-glycosylphosphatidylinositol (GPI) antibodies in the serum and asymptomatic malaria infection, although we did register a relationship between these antibodies and parasitemia levels in infected individuals. Taken together, these results indicate that autoimmune responses mediated by AAb of different specificities, including phospholipid, may have anti-plasmodial activity and protect against malaria, although it is not clear whether anti-parasite phospholipid antibodies can mediate the same effect. The potential effect of anti-parasite phospholipid antibodies in malarious patients that are prone to the development of systemic lupus erythematosus or antiphospholipid syndrome, as well as the (possibly protective?) role of the (pathogenic) aPL on the malaria symptomatology and severity in these individuals, remain open questions.

CD28 deficiency leads to accumulation of germinal-center independent IgM+ experienced B cells and to production of protective IgM during experimental malaria

“…Alternatively, the prevalence and accumulation of IgM did not prevent parasite persistence in CD28KO mice, which could indicate that the parasite evolved mechanisms that can subvert the immune response into a less effective type in certain circumstances. The notion of malaria-induced autoantibodies is not new; in humans, autoantibodies are produced during malaria infection [ 27 ]. A logical prediction would be that the recognition of auto-antigens by malaria-induced IgM could induce autoimmunity at some extent in chronically infected mice.…”

Malaria and COVID-19: unmasking their ties

“…Also, SARS-CoV-2 has various glycoproteins (GPs): membrane GPs, spike GPs and GPs that have acetyl esterase and haemagglutination features. These GPs could be identified by the anti-GPI antibodies resulting in protection against virus infection or inducing a milder disease pattern [20].…”

Diametrical diseases reflect evolutionary-genetic tradeoffs

“…As such, levels of inflammation, and self-foreign recognition thresholds, should be subject to tradeoffs between (i) efficacy in recognition and clearance of pathogens and (ii) degrees of damage to one’s own tissues [ 374 , 375 ]. Indeed, some level of autoimmune (autoantibody) response appears to provide protection against malaria [ 376 , 377 ].…”