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R Maizels

Publications and source records attributed to R Maizels.

6 recordsLinked to original sources

Specificity of predominant IgG4 antibodies to adult and microfilarial stages of Brugia malayi.

Human infections with filarial nematodes such as Brugia malayi are accompanied by unusually high titres of parasite-specific IgG4 antibodies. We have compared the profile of antigens recognised by filarial-specific IgG1 and IgG4 isotypes by Western blotting. Serum samples were collected from 120 subjects exposed to Brugia malayi, divided into three groups of asymptomatic amicrofilaraemic (endemic normal), microfilaraemic, and elephantiasis patients. Antigen preparations were tested from both adult B. malayi parasites, and from microfilariae; 24 distinct bands were analysed from the former, and 19 from the latter. Both qualitative scoring for band reactivity, and densitometric scanning of major bands, were employed. The consistent result was one of high and preferential IgG4 reactivity to a set of low molecular weight bands, of 15, 17, 20, 31 and 33 kDa; most of the 19 other bands showed higher reactivity with IgG4. Analysis of Western blot patterns showed an overall tendency for stronger IgG4 responses in microfilaraemic cases, and higher IgG1 responses in elephantiasis patients, consistent with published studies using ELISA on unfractionated parasite extracts. This study has defined an array of filarial antigens from each stage, and relative levels of IgG4 recognition, which will be important in unravelling distinct immune responses to this complex parasite.

Animals↗

A member of the TGF-beta receptor gene family in the parasitic nematode Brugia pahangi.

The full length cDNA sequence of a Type I transforming growth factor-beta (TGF-beta) receptor has been isolated from the filarial parasitic nematode Brugia pahangi. This new gene, designated Bp-trk-1, encodes a predicted 645 amino acid sequence with an N-terminal hydrophobic stretch which may act as a signal peptide. The extracellular portion (residues 15-187) is cysteine-rich and has three potential N-glycosylation sites. At positions 250-255 the protein contains the glycine-serine rich motif characteristic of Type I receptors. The closest homologue is a Caenorhabditis elegans gene (Q09488) in cosmid C32D5.2 which shares 67% amino acid identity with Bp-trk-1 in the most conserved kinase domain (aa 259-482). Other type I receptors such as C. elegans daf-1 and Drosophila tkv show 38-53% identity in the same region. Some residues conserved in Drosophila and vertebrates are not present in the B. pahangi sequence. RT-PCR amplification has been used to show that the transcript is expressed in the three main stages of the B. pahangi life cycle: microfilariae, infective larvae and adults. The ligand remains unknown at this time but is likely to be most similar to that for C. elegans Q09488.

Amino Acid Sequence↗

Secreted and surface antigens from larval stages of Wuchereria bancrofti, the major human lymphatic filarial parasite.

Antigenic proteins of microfilariae and infective larvae of Wuchereria bancrofti have been identified by intrinsic and extrinsic radiolabelling, and specific immunoprecipitation with sera from filarial patients. From 125I surface-labelling experiments, the most prominent antigen on both stages is of relative molecular mass (Mr) 17 000, while a molecule of similar size is both synthesized and released in vitro following labelling with [35S]methionine. A second similarity between the two stages is the production and secretion of a Mr 21 000 component, which is, however, not detected on the worm surfaces. A series of additional proteins from larval W. bancrofti are described from each parasite compartment (secreted, surface and somatic) and the antigenicity and specificity of these components explored with serum from patients with filariasis due to W. bancrofti or Brugia species, and with onchocerciasis. Among additional molecules released in vitro we have found a Mr 51 000 antigen from both stages, and also several proteins which are not recognised by antibody from human filarial patients.

Animals↗