Extensive genetic polymorphism in the human tumor necrosis factor region and relation to extended HLA haplotypes

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Parasitology Today, vol. 8, no. 2, 1992

Fine Structure of a New Human Microsporidian, Encephalitozoon hellem, in Culture P.J. Didier, E.S. Didier, J.M. Orenstein and J.A. Shadduck J. Protozool. 38,502-507

The phylum Microspora consists of unicellular obligate intracellular parasites that have a polar tubule. They have been described commonly in invertebrates and fish, but only sporadically in humans. However, the incidence of human microsporidiosis has increased with the incidence of AIDS: Enterocytozoon bieneusi is associated with diarrhoea and weight loss; E. cuniculi is reported in AIDS patients with hepatic

lesions and peritonitis and an E. cuniculilike microsporidian has been observed in ocular tissue from AIDS patients that was morphologically similar to, but biochemically distinct from, E. cuniculi, as assessed by SDS-PAGE, dot-ELISA and western blotting. The differences highlighted by these techniques may represent qualitative differences in the protein components, or quantitative differences in the amount of glycosyl-

Extensive Genetic Polymorphism in the Human Tumor Necrosis Factor Region and Relation to Extended HLA Haplotypes C.V. Jongeneel, L. Briant, I.A. Udalova, A. Sevin, S.A, Nedospasov and A. Cambon-Thomsen Proc. Natl Acad. Sci. USA 88, 9717-9721 Tumour necrosis factor (TNF) is now known to be involved in several immunopathological phenomena linked to parasitic diseases (compare the rote of TNF in severe malaria in the light of the recent work by Hill et al. on the correlation between severe malaria and HLA). The TNF locus consists of TNF-0c (the major macrophage-monocytederived form) and TiNIF-13 (produced exclusively by lymphocytes) and is located within the MHC of mouse and

human. Hitherto, a lack of genetic markers for this locus has impeded the study of the role of TNF alleles in the etiology of MHC-linked diseases, but these authors have previously used a technique known as 'microsatellite mapping' to define multiallelic polymorphisms in the mouse TNF locus; this paper extends the work to humans. In this technique, a repeat number of a simple sequence (CA or CT dinucleotide) occurring at a unique location

Recombinant Pfs25 Protein of Plasmodium falciparum Elicits Malaria Transmission-blocking Immunity in Experimental Animals PJ Barr K.M. Green, H.L. Gibson, I.C. Bathurst, I.A. Quakyi and D.C. KaslowJ. Exp. Med. 174, 1203-1208 The search for an effective malaria vaccine goes on with increasing urgency, in the face of mounting resistance to chemotherapy of Plasmodium species that are responsible for human malaria. Subunit vaccines have focussed primarily on the immunization of the human host against asexual forms of the parasite. Another approach for the control of endemic malaria is to develop a vaccine that prevents the transmission of sexual forms of Plasmodium from humans to mosquitoes. The P. falciparurn 25 kDa seXU~LIstage antigen, Pfs25, is expressed on the surface of zygote and ookinete forms of the parasite, and monoclonal antibodies (mAbs) directed against it can completely block the development of oocysts in the mosquito midgut. The appropriate conformation of B-cell epitope (required for immunological activity), in vivo, togethe.r with recom-

binant Pfs25 protein, makes possible a human vaccine. The gene for Pfs25 that encodes for amino acids 22-190 of the natural 217 amino acid precursor protein has been chemically synthesized; the NH2 terminal that contains the secretory signal sequence and the COOH terminal that signals the attachment of a glycosylphosphatidylinositol membrane anchor

ation of the subcomponents of the different parasites. In a 1991 paper inJ. Inf. Dis. these authors identified this new human microsporidian as E. hellem, and in this paper they report immunological evidence that E. hellern and E. cuniculi are different organisms, and discuss the ultrastructure of E. hellern. The only deviation from the structure of E. cuniculi would seem to be a variability in the number of coils in the polar tubule (4-9 coils in E. hellem). Microsporidia from human infections will allow for further definition of the phylogenetic relationships among microsporidia using biochemical techniques. •

within the genome is measured after amplification by PCR and used as an allelic marker. These authors have identified three polymorphic microsatellites, TNFa, TNFb and TNFc, within the 12 kilobase (kb) sequence of the human MHC that includes the TNF locus. TNFc, with two alleles, is in the TNF-~ gene, and TNFa (13 alleles) and TNFb (seven alleles) are located 33.5 kb upstream from TNFc. These microsatellites are in linkage disequilibrium with alleles at other MHC loci. This identification of TNF polymorphisms will allow a thorough genetic analysis of the involvement of TNF in MHC-linked pathologies. •

are excluded. This gene is expressed in yeast, and the secreted protein purified and analysed by immunoblotting using rabbit polydonal antisera to Pfs25 or with the monoclonal antibody (mAb) IC7, a transmission-blocking mAb that has been shown to recognize natural Pfs25 only under nonreducing conditions. The recombinant Pfs25 reacts with conformation-dependent mAbs, and elicits transmission-blocking antibodies when used in conjunction with MTP-MF59 (a muramyl tripeptide adjuvant that has been shown to be safe and efficacious in humans)to immunize mice and monkeys. •

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