Humoral immune responses of Solomon Islanders to the merozoite surface antigen 2 of Plasmodium falciparum show pronounced skewing towards antibodies of the immunoglobulin G3 subclass

Rzepczyk, Christine M.; Hale, Kate; Woodroffe, Nick; Bobogare, Albino; Csurhes, Peter A.; Ishii, Akira; Ferrante, A

doi:10.1128/iai.65.3.1098-1100.1997

Cited by 66 publications

(30 citation statements)

References 19 publications

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“…Imbalance of antibody subclass distribution in antibodies to other P. falciparum blood-stage antigens has been reported. For example, antibody responses to MSP2 are mainly of IgG3 subclass (25,26) and responses to MSP1 19 and rhoptry-associated antigen 1 are mainly of the IgG1 subclass (15,20,30). Little is known about the parameters that regulate human isotype responses and the consequences of such responses in malaria.…”

Section: Discussionmentioning

confidence: 99%

Naturally acquired antibody responses to the components of the Plasmodium falciparum merozoite surface protein 1 complex

Wang

Crouch

Richie

et al. 2003

Parasite Immunology

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Merozoite surface protein 6 (MSP6) and 7 (MSP7) of Plasmodium falciparum are peripheral membrane proteins whose cleaved products, MSP636, MSP722 and MSP719, are found on the merozoite surface as components of a non-covalently bound complex which also contains four polypeptides derived from merozoite surface protein 1 (MSP1). We have expressed both the precursor regions and the processed mature products of MSP6 and MSP7 in Escherichia coli and showed that these recombinant proteins react with human immune sera. In a set of sera collected from individuals living in malaria-endemic areas of Southern-central Vietnam, antibodies to the mature polypeptides of MSP636 and MSP722 were detected in 50.6 and 85.6% of the serum samples, whereas antibodies to the precursor regions of MSP6 and MSP7 were detected in only 12.1 and 42.5% of the serum samples, respectively. The predominant subclass of anti-MSP6 antibodies was IgG1, whereas the predominant subclass of anti-MSP7 antibodies was IgG3. In the same set of serum samples, the antibody responses to MSP119 are predominantly IgGI, whereas antibodies to merozoite surface protein 4 (MSP4) are mainly IgG3. This data is consistent with the proposition that, during malaria infection, variable proteins induce responses that are predominantly of the IgG3 isotype, and conserved proteins induce responses that are predominantly IgG1. The antibodies to MSP6, MSP7 and MSP119 all decreased at the time of infection, but increased during the convalescent period. No correlation was observed between the antibodies at the commencement of the study and absence of parasitaemia during surveillance in this population.

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Section: Discussionmentioning

confidence: 99%

Naturally acquired antibody responses to the components of the Plasmodium falciparum merozoite surface protein 1 complex

Wang

Crouch

Richie

et al. 2003

Parasite Immunology

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“…The significance of IgG3 specificity in visceral leishmaniasis is not clearly understood. IgG3 in malaria is associated with recovery from the fatal disease (33), and skewing of the response toward the IgG3 subclass is merozoite surface antigen 2 specific (30). In leprosy, disease progression is correlated with selective increases in IgG3, along with IgG1 responses (20).…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin Subclass Distribution and Diagnostic Value ofLeishmania donovaniAntigen-Specific Immunoglobulin G3 in Indian Kala-Azar Patients

Anam

Afrin

Banerjee

et al. 1999

Clin Diagn Lab Immunol

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Visceral leishmaniasis, or kala-azar, a fatal tropical disease, remains problematic, as early diagnosis is difficult and treatment often results in drug resistance and relapse. We have developed a sensitive enzyme-linked immunosorbent assay (ELISA), using leishmanial membrane antigenic extracts (LAg) to detect specific antibody responses in 25 untreated Indian visceral leishmaniasis patients. To investigate the pathogenetic significance of isotype markers in kala-azar, relative levels of specific immunoglobulin G (IgG), IgM, IgA, IgE, and IgG subclasses were analyzed under clinically established diseased conditions. Since LAg showed higher sensitivity for specific IgG than lysate, the immunoglobulin isotype responses were evaluated, with LAg as antigen. Compared to 60 controls, which included patients with malaria, tuberculosis, leprosy, and typhoid and healthy subjects, visceral leishmaniasis patients showed significantly higher IgG (100% sensitivity, 85% specificity), IgM (48% sensitivity, 100% specificity), and IgE (44% sensitivity, 98.3% specificity) responses. Low levels of IgA in visceral leishmaniasis patients contrasted with a 13-fold-higher reactivity in sera from patients with leprosy. Among IgG subclasses, IgG1, -3, and -4 responses were significantly higher in visceral leishmaniasis patients than in the controls. IgG2 response, however, was significantly higher (twofold) in leprosy than even visceral leishmaniasis patients. The rank orders for sensitivity (IgG = IgG1 = IgG3 = IgG4 > IgG2 > IgM > IgE > IgA) and specificity (IgM = IgG3 > IgE > IgG4 > IgG2 > IgG > IgG1 > IgA) for LAg-specific antibody responses suggest the potentiality of IgG3 as a diagnostic marker for visceral leishmaniasis.

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“…Furthermore, the predominant subclass of MSP2-specific antibody was IgG3, a finding that has recently been confirmed in Solomon Islanders. 13 Merozoite surface protein 2-specific polyclonal and monoclonal antibodies, defining variable, linear epitopes, have been shown to inhibit in vitro parasite invasion and growth. 14,15 Mice immunized with peptides from conserved regions of MSP2 were protected from challenge with asexual parasites of the murine malaria P. chabaudi 16 but the protective capacity of these peptides has not been confirmed in other models of infection.…”

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confidence: 99%

IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria.

Taylor¹,

Allen²,

Greenwood³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

205

166

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In a cross-sectional survey carried out in west Africa (The Gambia), where Plasmodium falciparum malaria is endemic with seasonal transmission, 178 individuals 1-75 years of age were assessed for their antibody response to the malaria vaccine candidate, merozoite surface protein 2 (MSP2). Total IgG to recombinant antigens representing full-length, repetitive, and group-specific domains of both allelic families of MSP2 was determined by ELISA. The IgG-subclass profile of IgG-positive sera was assessed. Antibody prevalence was age-dependent, reaching a peak during adolescence. In MSP2-seropositive individuals, there was a predominance of cytophilic antibodies (IgG1 and IgG3); IgG1 antibodies were prevalent in children less than 10 years of age, whereas in adolescents and adults MSP2-specific antibodies were predominantly IgG3. In parallel, we conducted a longitudinal study of children (3-8 years of age) from the same community; sera collected before the malaria transmission season were tested for the presence of anti-MSP2 antibodies. The subsequent susceptibility of these children to clinical malaria was monitored and the association between anti-MSP2 antibodies of different IgG subclasses and resistance to clinical malaria was tested. The presence of IgG3 antibodies to MSP2 serogroup A was negatively associated with the risk of clinical malaria whereas IgG1 antibodies to MSP2 serogroup B were associated with an increased risk of clinical infection. Our data suggest that age/exposure-related acquisition of IgG3 antibodies to MSP2 may contribute to the development of clinically protective immunity to malaria.

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Humoral immune responses of Solomon Islanders to the merozoite surface antigen 2 of Plasmodium falciparum show pronounced skewing towards antibodies of the immunoglobulin G3 subclass

Cited by 66 publications

References 19 publications

Naturally acquired antibody responses to the components of the Plasmodium falciparum merozoite surface protein 1 complex

Naturally acquired antibody responses to the components of the Plasmodium falciparum merozoite surface protein 1 complex

Immunoglobulin Subclass Distribution and Diagnostic Value ofLeishmania donovaniAntigen-Specific Immunoglobulin G3 in Indian Kala-Azar Patients

IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria.

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