The IgG-subclass distribution of naturally acquired antibodies to<i>Plasmodium falciparum</i>, in relation to malaria exposure and severity

Ferreira, Marcelo U.; Kimura, Emı́lia A.; Katzin, Alejandro M.; Santos-Neto, Leopoldo Luiz dos; Ferrari, Julie; Villalobos, José Manuel Berruecos; Carvalho, Maria Esther de

doi:10.1080/00034983.1998.11813287

Cited by 22 publications

(21 citation statements)

References 33 publications

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“…Another aspect of particular note concerns the detection of the anti-VSA antibodies of all four IgG isotypes, in the case of some isolates at very similar levels, which is consistent with an earlier report (23). The antibody response to crude parasite antigen preparations commonly comprises a mixture of all four IgG isotypes, but the response to defined P. falciparum asexual-stage antigens is usually more restricted and is dominated by cytophilic isotypes (4,18,41,57). In the profile that we observed here, IgG3 antibodies did predominate, although they were equivalent to IgG4 in children in terms of magnitude and equivalent to IgG2 in adults in terms of the IRR.…”

Section: Discussionsupporting

confidence: 69%

Immunoglobulin G Isotype Responses to Variant Surface Antigens ofPlasmodium falciparumin Healthy Gabonese Adults and Children during and after Successive Malaria Attacks

et al. 2004

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We assessed immunoglobulin G (IgG) isotype responses with specificity for the variant surface antigens (VSA) of heterologous Plasmodium falciparum isolates by using flow cytometry and plasma from healthy Gabonese adults and from children during and after two consecutive malaria episodes. The individual isolate-specific antibody profiles differed markedly in terms of their isotype content but were similar for healthy adults and healthy uninfected children. In healthy adults, IgG3 and IgG2 responses were the highest, while in healthy children, IgG3 and IgG4 predominated. A transiently elevated IgG1 response was observed during the second of two successive malaria episodes in children, signaling P. falciparum infection-induced cross-reactive anti-VSA responses. Our findings highlight the prominence of IgG3 in the overall profile of these responses but also indicate a marked age-related increase in the prevalence of anti-VSA antibodies of the classically noncytophilic IgG2 isotype, possibly reflecting the high frequency of the histidine-131 variant of Fc␥RIIA in the Gabonese population.

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Section: Discussionsupporting

confidence: 69%

Immunoglobulin G Isotype Responses to Variant Surface Antigens ofPlasmodium falciparumin Healthy Gabonese Adults and Children during and after Successive Malaria Attacks

et al. 2004

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“…Unexpectedly, these assays also indicated that human IgG3 may be a poor inducer of respiratory bursts despite possessing the highest affinity for Fc␥Rs of all of the human IgG subclasses (6,31). Since antigen-specific antimalarial Abs from clinically immune individuals can belong to the human IgG3 subclass (12,30), these data suggest that the effectiveness of human IgG3 (and indeed human neutrophils) in controlling malaria parasites may not be mediated via respiratory bursts but through alternative modes of action. Neutrophils are abundant in blood, and products of their respiratory bursts have been shown to kill merozoites, although the exact mechanisms are unclear (18).…”

Section: Discussionmentioning

confidence: 85%

Inhibition of Erythrocyte Invasion andPlasmodium falciparumMerozoite Surface Protein 1 Processing by Human Immunoglobulin G1 (IgG1) and IgG3 Antibodies

et al. 2009

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Antigen-specific antibodies (Abs) to the 19-kDa carboxy-terminal region of Plasmodium falciparum merozoite surface protein 1 (MSP1 19 ) play an important role in protective immunity to malaria. Mouse monoclonal Abs (MAbs) 12.10 and 12.8 recognizing MSP1 19 can inhibit red cell invasion by interfering with MSP1 processing on the merozoite surface. We show here that this ability is dependent on the intact Ab since Fab and F(ab) 2 fragments derived from MAb 12.10, although capable of binding MSP1 with high affinity and competing with the intact antibody for binding to MSP1, were unable to inhibit erythrocyte invasion or MSP1 processing. The DNA sequences of the variable (V) regions of both MAbs 12.8 and 12.10 were obtained, and partial amino acid sequences of the same regions were confirmed by mass spectrometry. Human chimeric Abs constructed by using these sequences, which combine the original mouse V regions with human ␥1 and ␥3 constant regions, retain the ability to bind to both parasites and recombinant MSP1 19 , and both chimeric human immunoglobulin G1s (IgG1s) were at least as good at inhibiting erythrocyte invasion as the parental murine MAbs 12.8 and 12.10. Furthermore, the human chimeric Abs of the IgG1 class (but not the corresponding human IgG3), induced significant NADPHmediated oxidative bursts and degranulation from human neutrophils. These chimeric human Abs will enable investigators to examine the role of human Fc␥ receptors in immunity to malaria using a transgenic parasite and mouse model and may prove useful in humans for neutralizing parasites as an adjunct to antimalarial drug therapy.

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“…Since particular IgG subclass responses were found to be associated with resistance to malaria (1,4,6,10,14,17,29), genes controlling such responses may affect the resistance or the susceptibility to malarial infection or disease in humans. In this study, we evaluated familial correlation of IgG subclass responses against RESA, MSP-1, and MSP-2 conserved B epitopes and crude P. falciparum antigens in two populations living in differently exposed areas in Burkina Faso.…”

Section: Discussionmentioning

confidence: 99%

Familial Correlation of Immunoglobulin G Subclass Responses to Plasmodium falciparum Antigens in Burkina Faso

et al. 2001

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Host genes are thought to determine the immune response to malaria infection and the outcome. Cytophilic antibodies have been associated with protection, whereas noncytophilic antibodies against the same epitopes may block the protective activity of the protective ones. To assess the contribution of genetic factors to immunoglobulin G (IgG) subclass responses against conserved epitopes and Plasmodium falciparum bloodstage extracts, we analyzed the isotypic distribution of the IgG responses in 366 individuals living in two differently exposed areas in Burkina Faso. We used one-way analysis of variance and pairwise estimators to calculate sib-sib and parent-offspring correlation coefficients, respectively. Familial patterns of inheritance of IgG subclass responses to defined antigens and P. falciparum extracts appear to be similar in the two areas. We observed a sibling correlation for the IgG, IgG1, IgG2, IgG3, and IgG4 responses directed against ringinfected-erythrocyte surface antigen, merozoite surface protein 1 (MSP-1), MSP-2, and P. falciparum extract. Moreover, a parent-offspring correlation was found for several IgG subclass responses, including the IgG, IgG1, IgG2, IgG3, and IgG4 responses directed against conserved MSP-2 epitopes. Our results indicated that the IgG subclass responses against P. falciparum blood-stage antigens are partly influenced by host genetic factors. The localization and identification of these genes may have implications for immunoepidemiology and vaccine development.

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The IgG-subclass distribution of naturally acquired antibodies toPlasmodium falciparum, in relation to malaria exposure and severity

Cited by 22 publications

References 33 publications

Immunoglobulin G Isotype Responses to Variant Surface Antigens ofPlasmodium falciparumin Healthy Gabonese Adults and Children during and after Successive Malaria Attacks

Immunoglobulin G Isotype Responses to Variant Surface Antigens ofPlasmodium falciparumin Healthy Gabonese Adults and Children during and after Successive Malaria Attacks

Inhibition of Erythrocyte Invasion andPlasmodium falciparumMerozoite Surface Protein 1 Processing by Human Immunoglobulin G1 (IgG1) and IgG3 Antibodies

Familial Correlation of Immunoglobulin G Subclass Responses to Plasmodium falciparum Antigens in Burkina Faso

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