IgE deposition in brain microvessels and on parasitized erythrocytes from cerebral malaria patients.

Abstract

Abstract. Postmortem brain tissues of 21 cerebral malaria cases were obtained in Myanmar and Vietnam. The tissues were examined by light microscopy and by an immunohistochemical method. Brain microvessels (capillaries and venules) were examined for the presence of immunoglobulins IgE and IgG, Plasmodium falciparum antigen, and parasitized erythrocytes (PRBC). Deposition of IgE, IgG, and P. falciparum antigen was observed in the microvessels from all specimens examined. Sequestered PRBC in the microvessels were positive for IgG in all 21 cases and for IgE in six cases. In the latter cases, the percentage of microvessels with sequestered PRBC was Ͼ 50%, with the frequency of IgE-positive cells ranging from 42% to 52%. In contrast, in five cases that were only weakly positive for IgE, the percentage of microvessels with sequestered PRBC was remarkably low (Ͻ 1%). These data indicate that the degree of deposition of IgE in microvessels and on PRBC from cerebral malaria patients correlated with that of PRBC sequestration. As IgE-containing immune complexes are known to induce local overproduction of tumor necrosis factor-alpha (TNF-␣), a major pathogenic factor in cerebral malaria, IgE may contribute to the pathogenesis of this severe disease.

Total and functional parasite specific IgE responses in Plasmodium falciparum-infected patients exhibiting different clinical status

“…These observations are contrary to published data describing increased IgE levels that correlate with high concentrations of circulating TNF, a cytokine associated with malaria severity and also with pRBC adherence on brain capillary endothelial cells [9,10,25,26]. The results suggest that either IgE does not play an important role in CM pathogenesis, or that these antibodies may participate in the parasite sequestration into the brain or other organ capillaries [24]. …”

“…Nevertheless, it was reported that IgE levels were greatest in patients developing severe disease than in CM group (Figure 1A and 1B). When considering the percentage of patients that produce high levels of IgE per group, it was shown that IgE levels are higher in UM and SM (Figure 1C and 1D) than in CM patients who had values similar to that of the controls [8,24]. In addition, the median levels of circulating IgE in the ExCM group were close to that of the CM group.…”

The Th2 Lymphoproliferation Developing inLatY136FMutant Mice Triggers Polyclonal B Cell Activation and Systemic Autoimmunity

“…Increased IgE levels were detected in some lupus patients (58), and IgE deposits found in ϳ10% of cases in human renal disease were correlated with bad prognosis (59 -63). Similarly, diseases related to parasite infections might involve IgE immune deposits (64,65). HgCl 2 -induced allergic reactions have been associated with increased IgE production (66) In addition, there is a role for IgE deposits in Wegener's granulomatosis, as well as IgE myelomas (67,68).…”

Genetic Evidence for the Aggravation ofPlasmodium falciparumMalaria by Interleukin 4

“…If IFN-g and interleukin 12 (IL-12) have significant protective effects against SM [10,11], then cytokines that inhibit Th1 cell differentiation or that interfere with IFN-g-mediated activation of phagocytes-such as interleukin 10 and interleukin 4 (IL-4)-may increase the risk of SM. Indeed, children with SM have elevated immunoglobulin E (IgE) levels, and IgE deposits have been observed in brain vessels in which massive sequestration had occurred [12,13].…”