Many of the asexual stage Plasmodium falciparum proteins that are the targets of host protective responses are markedly polymorphic. The full repertoire of diversity is not defined for any antigen. Most studies have focused on the genes encoding merozoite surface proteins 1 and 2 (MSP1, MSP2). We explored the extent of diversity of some of the less studied merozoite surface antigens and analyzed the degree of complexity of malaria field isolates by deriving nucleotide sequences of several antigens. We have determined the genotype of apical membrane antigen 1 (AMA1) in a group of 30 field samples, collected over 29 months, from individuals living in an area of intense malaria transmission in Irian Jaya, identifying 14 different alleles. AMA1 genotyping was combined with previously determined MSP2 typing. AMA1 had the greatest power in distinguishing between isolates but methodological problems, especially when mixed infections are present, suggest it is not an ideal typing target. MSP1, MSP3, and glutamate-rich protein genotypes were also determined from a smaller group of samples, and all results were combined to derive an extended antigenic haplotype. Within this subset of 10 patients, nine different genotypes could be discerned; however, five patients were all infected with the same strain. This strain was present in individuals from two separate villages and was still present 12 months later. This strain was predominant at the first time point but had disappeared at the fourth time point. This significant change in malaria genotypes could be due to strain-specific immunity developing in this population.

Alleles↗

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Is there a relation between Chlamydia infection and primary biliary cirrhosis?

Over the past two decades, a number of studies have failed to provide direct evidence of specific microbial chronic infection in primary biliary cirrhosis (PBC). However, a recent report suggests that there is a specific association of Chlamydia pneumoniae in patients with PBC and that C. pneumoniae or similar antigens might play a role in the pathogenesis of disease. To determine if Chlamydia infection is associated with PBC, we applied a combination of immunological and molecular approaches to investigate (a) the serological reactivity against two common Chlamydia human pathogens, C. pneumoniae and C. trachomatis, by immunoblotting, (b) the presence of Chlamydia in liver samples of patients with PBC and controls by PCR amplification of Chlamydia specific 16S rRNA and (c) the presence of Chlamydia proteins in liver samples of patients with PBC and controls by immunohistochemical staining. By immunoblotting, C. trachomatis and C. pneumoniae specific serological antibodies were found in 52/57 (91.2%) AMA positive PBC, 7/33 (21/2%) of AMA negative PBC, 1/25 (4%) PSC, 0/15 (0%) Sjorgen's syndrome and 0/20 (0%) systemic lupus erythematosus patients and 0/20 (0%) healthy volunteers at 1:200 sera dilution. PBC sera reacted to Chlamydia and E. coli lysates in western blots up to a maximum of 10(-4) dilution. However, PCR amplification of the Chlamydia specific 16S rRNA gene was negative in 25/25 PBC livers but positive in 1/4 PSC liver, 3/6 in other liver disease controls and 1/4 normal liver samples. While two commercially available specific monoclonal antibodies stained positive controls (Chlamydia infected HEp-2 cells) they failed to detect Chlamydia antigens in PBC livers. The detection of Chlamydia specific antibodies but not Chlamydia rRNA gene and Chlamydia antigens in PBC suggests that Chlamydia infection is not involved in PBC.

Chlamydia↗

PubMedDate not supplied

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

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.

Animals↗