Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro studies have shown that inhibition of Plasmodium falciparum blood-stage parasite growth by antibody-dependent cellular inhibition is mediated by cooperation between malaria-specific IgG1 and IgG3, but not IgG2, and monocytes via the Fcgamma receptor II (FcgammaRII). A single amino acid substitution at position 131 in FcgammaRIIa is critical in the binding of human IgG subclasses. The hypothesis that the FcgammaRIIa-Arg/Arg131 genotype, which does not bind to IgG2, is a host genetic factor for protection against high-density P. falciparum infection was tested. One hundred eighty-two infants from a large community-based birth cohort study in western Kenya were selected for an unmatched case-control study. Results showed that the infants with the FcgammaRIIa-Arg/Arg131 genotype were significantly less likely to be at risk for high-density falciparum infection, compared with infants with the FcgammaRIIa-His/Arg131 genotype (adjusted odds ratio, 0.278; 95% confidence interval, 0.123-0.627; P=.0021). This finding supports the hypothesis.
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PMID:Fcgamma receptor IIa (CD32) polymorphism is associated with protection of infants against high-density Plasmodium falciparum infection. VII. Asembo Bay Cohort Project. 1139 18

Merozoite surface protein 4 (MSP4) of Plasmodium falciparum is a glycosylphosphatidylinositol-anchored integral membrane protein that is being developed as a component of a subunit vaccine against malaria. We report here the measurement of naturally acquired antibodies to MSP4 in a population of individuals living in the Khanh-Hoa region of Vietnam, an area where malaria is highly endemic. Antibodies to MSP4 were detected in 94% of the study population at titers of 1:5,000 or greater. Two forms of recombinant MSP4 produced in either Escherichia coli or Saccharomyces cerevisiae were compared as substrates in the enzyme-linked immunosorbent assay. There was an excellent correlation between reactivity measured to either, although the yeast substrate was recognized by a higher percentage of sera. Four different regions of MSP4 were recognized by human antibodies, demonstrating that there are at least four distinct epitopes in this protein. In the carboxyl terminus, where the single epidermal growth factor-like domain is located, the reactive epitope(s) was shown to be conformation dependent, as disruption of the disulfide bonds almost completely abolished reactivity with human antibodies. The anti-MSP4 antibodies were mainly of the immunoglobulin G1 (IgG1) and IgG3 subclasses, suggesting that such antibodies may play a role in opsonization and complement-mediated lysis of free merozoites. Individuals in the study population were drug-cured and followed up for 6 months; no significant correlation was observed between the anti-MSP4 antibodies and the absence of parasitemia during the surveillance period. As a comparison, antibodies to MSP1(19), a leading vaccine candidate, were measured, and no correlation with protection was observed in these individuals. The anti-MSP1(19) antibodies were predominantly of the IgG1 isotype, in contrast to the IgG3 predominance noted for MSP4.
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PMID:Naturally acquired antibody responses to Plasmodium falciparum merozoite surface protein 4 in a population living in an area of endemicity in Vietnam. 1140 78

Two hundred thirteen mother-baby pairs in The Gambia were studied to determine the influence of placental malaria infection and maternal hypergammaglobulinemia on transplacental antibody transfer. Antibody transfer for herpes simplex virus 1 (HSV-1), respiratory syncytial virus (RSV), and varicella-zoster virus (VZV) was significantly reduced by placental malaria infection by 69%, 58%, and 55%, respectively. Maternal hypergammaglobulinemia was associated with a significant reduction in antibody transfer for HSV-1, RSV, VZV, and pneumococcus by 89%, 90%, 91%, and 88%, respectively. In addition, placental malaria infection was associated with a significant reduction in transfer of IgG1, IgG2, and IgG4 (P<.01, P=.01, and P=.03, respectively) but not of IgG3 (P=.59). Maternal hypergammaglobulinemia significantly impaired the transfer of IgG1 and IgG2 (P=.01) but not of IgG3 or IgG4 (P=.62 and P=.59, respectively). Placental malaria infection and maternal hypergammaglobulinemia were associated with reduction in the transplacental transfer of these specific antibodies, IgG1, and IgG2 in this Gambian population.
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PMID:The influence of placental malaria infection and maternal hypergammaglobulinemia on transplacental transfer of antibodies and IgG subclasses in a rural West African population. 1149 68

Antibodies against three long synthetic peptides (LSPs) derived from the glutamate-rich protein (GLURP) of Plasmodium falciparum were analyzed in three cohorts from Liberia, Ghana, and Senegal. Two overlapping LSPs, LR67 and LR68, are derived from the relatively conserved N-terminal nonrepeat region (R0), and the third, LR70, is derived from the R2 repeat region. A high prevalence of antibody responses to each LSP was observed in all three areas of endemic infection. Levels of cytophilic immunoglobulin G (IgG) antibodies against both GLURP regions were significantly correlated with protection from clinical P. falciparum malaria. Protected children from the Ghana cohort possessed predominantly IgG1 antibodies against the nonrepeat epitope and IgG3 antibodies against the repeat epitope. T-cell proliferation responses, studied in the cohort from Senegal, revealed that T-helper-cell epitopes were confined to the nonrepeat region. When used as immunogens, the LR67 and LR68 peptides elicited strong IgG responses in outbred mice and LR67 also induced antibodies in mice of different H-2 haplotypes, confirming the presence of T-helper-cell epitopes in these constructs. Mouse antipeptide antisera recognized parasite proteins as determined by immunofluorescence and immunoblotting. This indicates that synthetic peptides derived from relatively conserved epitopes of GLURP might serve as useful immunogens for vaccination against P. falciparum malaria.
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PMID:Selection of glutamate-rich protein long synthetic peptides for vaccine development: antigenicity and relationship with clinical protection and immunogenicity. 1150 Mar 89

The immunoglobulin G (IgG) subclass antibodies to Plasmodium falciparum blood stage antigens in the sera of 181 individuals living in malaria endemic area in Kanchanaburi Province, western Thailand, were determined by enzyme-linked immunosorbent assay (ELISA). In this study, IgG3 and IgG1 were shown to be the predominant subclasses. Generally, IgG2 were coexpressed with IgG1 and IgG3 while IgG4 was found to coexpress with other three IgG subclasses. The levels of specific IgG1, IgG2, and IgG3 increased significantly with age (r = 0.295, p = 0.000; r = 0.416, p = 0.000; r = 0.320, p = 0.000, respectively). The data indicate that the higher antibody production required continuous stimulation under natural condition. Furthermore, the levels of specific IgG1, IgG2 and IgG3 increased in immune individuals without clinical malaria, reported in adolescents and adults, were associated with malaria resistance. Similar results were found in children with different patterns of IgG subclasses in which the specific IgG2 and IgG3, but not IgG1 was related to resistance.
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PMID:Natural human IgG subclass antibodies to Plasmodium falciparum blood stage antigens and their relation to malaria resistance in an endemic area of Thailand. 1155 72

The merozoite surface protein-2 (MSP-2) is a major vaccine candidate for the asexual blood stage of Plasmodium falciparum. MSP-2 is essentially dimorphic, and allelic families are named after the representative isolates FC27 and IC1. The polymorphic central region contains immunodominant repeats, which vary in number, length, and sequence within and between allelic families. We have examined the antibody recognition of repeat regions from both MSP-2 allelic families expressed as recombinant fusion peptides. The results are summarized as follows. (1) Immunization of mice with the fusion peptides elicited IgG antibodies that cross-reacted with the native MSP-2 molecule in an allelic family-specific manner. (2) These mouse antibodies recognized the recombinant proteins in both a variant-specific and a family-specific manner, as shown in inhibition immunoassays. Antibodies raised against the peptide FC27 seemed to be essentially variant-specific, since the soluble form of the S20 antigen (a member of FC27 family) had relatively little inhibitory effect on them. (3) The overall pattern of human IgG antibody responses to MSP-2 in Karitiana Indians, a population continuously exposed to hypoendemic malaria in the Brazilian Amazon Region, differs from that described in hyperendemic areas in Africa and Papua New Guinea in two important features: there was no clear age-dependent increase in the prevalence and mean concentration of specific IgG antibodies, and there was no skewing towards the IgG3 subclass in antibody responses. (4) The relatively poor correlation between concentrations of IgG antibodies that are specific for members of the same allelic family suggests that recognition of MSP-2 peptides by naturally acquired antibodies was largely variant-specific in this population. The potential role of naturally acquired variant-specific antibodies in immune evasion, by selecting mutant parasites carrying insertions or deletions of repeat sequences, is briefly discussed.
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PMID:Differential antibody recognition of four allelic variants of the merozoite surface protein-2 (MSP-2) of Plasmodium falciparum. 1159 20

Serum samples from Ugandan residents of a malaria-hyperendemic region were tested by enzyme-linked immunosorbent assay for reactivity against recombinant constructs of the 47 (SE47')- and 50 (SE50A)-kDa fragments of Plasmodium falciparum serine repeat antigen (SERA). Immunoglobulin (Ig) G3 and IgG1 were the predominant subclass responses to SE47' and SE50A, respectively. The geometric mean optical density (OD) for IgG3 anti-SE47' was significantly lower in children < 15 years compared with adults > or = 15 years (P < 0.0001). By contrast, the geometric mean IgG1 anti-SE50A was slightly higher in children compared with adults (P < 0.01). The proportion of high responders (ODs > 0.5) to SE47' was significantly lower in children compared with adults (P < 0.001), whereas the proportion of high responders to SE50A was comparable in children and adults (P = 0.07). This first detailed study of SERA in a malaria-hyperendemic region suggests that natural human IgG3 anti-SE47' might be associated with immunity to malaria.
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PMID:Natural human immunoglobulin G subclass responses to Plasmodium falciparum serine repeat antigen in Uganda. 1179 98

In this study, we investigated the role of endogenous IL-12 in protective immunity against blood-stage P. chabaudi AS malaria using IL-12 p40 gene knockout (KO) and wild-type (WT) C57BL/6 mice. Following infection, KO mice developed significantly higher levels of primary parasitemia than WT mice and were unable to rapidly resolve primary infection and control challenge infection. Infected KO mice had severely impaired IFN-gamma production in vivo and in vitro by NK cells and splenocytes compared with WT mice. Production of TNF-alpha and IL-4 was not compromised in infected KO mice. KO mice produced significantly lower levels of Th1-dependent IgG2a and IgG3 but a higher level of Th2-dependent IgG1 than WT mice during primary and challenge infections. Treatment of KO mice with murine rIL-12 during the early stage of primary infection corrected the altered IgG2a, IgG3, and IgG1 responses and restored the ability to rapidly resolve primary and control challenge infections. Transfer of immune serum from WT mice to P. chabaudi AS-infected susceptible A/J mice completely protected the recipients, whereas immune serum from KO mice did not, as evidenced by high levels of parasitemia and 100% mortality in recipient mice. Furthermore, depletion of IgG2a from WT immune serum significantly reduced the protective effect of the serum while IgG1 depletion had no significant effect. Taken together, these results demonstrate the protective role of a Th1-immune response during both acute and chronic phases of blood-stage malaria and extend the immunoregulatory role of IL-12 to Ab-mediated immunity against Plasmodium parasites.
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PMID:IL-12 is required for antibody-mediated protective immunity against blood-stage Plasmodium chabaudi AS malaria infection in mice. 1180 75

There is longstanding evidence for a role of immunoglobulin (Ig)G in protection against malarial disease and infection. IgG1 and IgG3 have been shown to be particularly efficient at associating with monocytes in potentially protective mechanisms (i.e. antibody-dependent cellular inhibition, opsonization and phagocytosis). Conversely, there is some evidence that IgG2 (and possibly IgG4) antibodies may be antagonistic to this protection. The protective effect of IgG subclass antibody activity present before the beginning of a malaria transmission season (preseason antibody levels) against severe malaria has not been tested in longitudinal studies. We measured IgG class and subclass antibody levels specific to crude Plasmodium falciparum lysates by enzyme linked immunosorbent assay in a case-control study of 76 children on the coast of Kenya. The mean optical density values for both IgG class and subclass antibodies were not significantly different between the children who developed severe malaria and those who remained healthy during an observation period of two malaria transmission seasons. However, elevated levels of IgG1 in relation to levels of IgG2 and IgG4 antibodies were associated with protection from severe malaria (P = 0.02). Conversely, elevated levels of IgG2 in relation to IgG1 and IgG3 antibodies were associated with a higher risk of developing severe malaria (P = 0.006).
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PMID:Naturally acquired immunoglobulin (Ig)G subclass antibodies to crude asexual Plasmodium falciparum lysates: evidence for association with protection for IgG1 and disease for IgG2. 1187 62

A primary infection with Plasmodium chabaudi chabaudi (AS) is characterized by an expansion of gammadelta cells after the acute phase of infection in mice. This is particularly marked during chronic infections in B cell-deficient mice. Infections in gammadelta T cell-deficient mice suggest that, although these cells play some role in the control of parasitaemia and can produce interferon-gamma, they do not appear to be involved in the development of hypoglycaemia, loss of weight and temperature during a P. c. chabaudi infection. However, gammadelta T cells do influence the nature of the CD4+ T cell response during infection since, in their absence, Th2-like responses, such as interleukin (IL)-4 production and help for malaria-specific antibody responses, are more pronounced. This alteration in CD4+ T cells is reflected in a more rapid and greater immunoglobulin (Ig)G1 and IgG3 antibody response to the parasite. The large gammadelta T cell expansion normally observed in infected B cell-deficient mice did not take place in the absence of IL-2, and double-knockout mice lacking both B cells and functional IL-2 were highly susceptible to lethal infection with P. c. chabaudi. The majority of the single IL-2 knockout mice, in contrast, were able to control and clear a primary infection, suggesting that for the CD4+ T cell and antibody response, IL-2 could be replaced by other cytokines.
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PMID:The influence of gammadelta T cells on the CD4+ T cell and antibody response during a primary Plasmodium chabaudi chabaudi infection in mice. 1198 58


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