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Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment.

Chalmers IW, Fitzsimmons CM, Brown M, Pierrot C, Jones FM, Wawrzyniak JM, Fernandez-Fuentes N, Tukahebwa EM, Dunne DW, Khalife J, Hoffmann KF - PLoS Negl Trop Dis (2015)

Bottom Line: To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment.Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively) when compared to rising IgG1 levels against sub-surface SmTAL1.Collectively, these results expand the number of SmLy6 proteins found within S. mansoni and specifically demonstrate that surface-associated SmLy6A and SmLy6B elicit immunological responses during infection in endemic communities.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological, Environmental & Rural Sciences (IBERS), Aberystwyth University, Aberystwyth, United Kingdom.

ABSTRACT

Background: The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29) containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study). While vaccination with SmLy6A (SmCD59a) and SmLy6D (Sm29) induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored.

Methodology/principal findings: Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K). Our examination extends the number of members to eleven (including three novel proteins) and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D) is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively), these values are both higher than IgG1 prevalence (2.7%) for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively) when compared to rising IgG1 levels against sub-surface SmTAL1.

Conclusions/significance: Collectively, these results expand the number of SmLy6 proteins found within S. mansoni and specifically demonstrate that surface-associated SmLy6A and SmLy6B elicit immunological responses during infection in endemic communities.

No MeSH data available.


Related in: MedlinePlus

SmLy6A and SmLy6B are differentially recognised in a cohort of S. mansoni infected males from a Ugandan fishing community.Recombinant SmLy6A and SmLy6B were used in ELISA to measure antigen-specific IgG1 (SmLy6A—Panel A, SmLy6B—Panel D), IgG4 (SmLy6A—Panel B and SmLy6B—Panel E) and IgE (SmLy6A—Panel C and SmLy6B—Panel F) responses in the plasma of 216 males infected with S. mansoni prior to praziquantel treatment. The cohort is divided into 5 age groups, 7–9 (n = 36), 10–13 (n = 37), 14–23 (n = 41), 24–32 (n = 42) and 33+ (n = 60) and the antibody levels of each group is presented as box plots.
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pntd.0003920.g004: SmLy6A and SmLy6B are differentially recognised in a cohort of S. mansoni infected males from a Ugandan fishing community.Recombinant SmLy6A and SmLy6B were used in ELISA to measure antigen-specific IgG1 (SmLy6A—Panel A, SmLy6B—Panel D), IgG4 (SmLy6A—Panel B and SmLy6B—Panel E) and IgE (SmLy6A—Panel C and SmLy6B—Panel F) responses in the plasma of 216 males infected with S. mansoni prior to praziquantel treatment. The cohort is divided into 5 age groups, 7–9 (n = 36), 10–13 (n = 37), 14–23 (n = 41), 24–32 (n = 42) and 33+ (n = 60) and the antibody levels of each group is presented as box plots.

Mentions: Antibody responses against rSmLy6A and rSmLy6B were measured in the plasma of a S. mansoni infected male (aged 7–70 yrs) cohort [43] from a high transmission area in Uganda at two time-points—before and 9 weeks after PZQ treatment (Fig 4). To assess the age profiles of the responses, anti-rSmLy6A and rSmLy6B IgG1, IgG4 and IgE levels were plotted for five age groups (7–9, 10–13, 14–23, 24–32 and 33+ years) and positive responders (seropositive) were defined as those individuals exhibiting mean anti-rSmLy6 titers above the mean level observed from uninfected European/North American samples + 3x standard deviation (Fig 4).


Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment.

Chalmers IW, Fitzsimmons CM, Brown M, Pierrot C, Jones FM, Wawrzyniak JM, Fernandez-Fuentes N, Tukahebwa EM, Dunne DW, Khalife J, Hoffmann KF - PLoS Negl Trop Dis (2015)

SmLy6A and SmLy6B are differentially recognised in a cohort of S. mansoni infected males from a Ugandan fishing community.Recombinant SmLy6A and SmLy6B were used in ELISA to measure antigen-specific IgG1 (SmLy6A—Panel A, SmLy6B—Panel D), IgG4 (SmLy6A—Panel B and SmLy6B—Panel E) and IgE (SmLy6A—Panel C and SmLy6B—Panel F) responses in the plasma of 216 males infected with S. mansoni prior to praziquantel treatment. The cohort is divided into 5 age groups, 7–9 (n = 36), 10–13 (n = 37), 14–23 (n = 41), 24–32 (n = 42) and 33+ (n = 60) and the antibody levels of each group is presented as box plots.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492491&req=5

pntd.0003920.g004: SmLy6A and SmLy6B are differentially recognised in a cohort of S. mansoni infected males from a Ugandan fishing community.Recombinant SmLy6A and SmLy6B were used in ELISA to measure antigen-specific IgG1 (SmLy6A—Panel A, SmLy6B—Panel D), IgG4 (SmLy6A—Panel B and SmLy6B—Panel E) and IgE (SmLy6A—Panel C and SmLy6B—Panel F) responses in the plasma of 216 males infected with S. mansoni prior to praziquantel treatment. The cohort is divided into 5 age groups, 7–9 (n = 36), 10–13 (n = 37), 14–23 (n = 41), 24–32 (n = 42) and 33+ (n = 60) and the antibody levels of each group is presented as box plots.
Mentions: Antibody responses against rSmLy6A and rSmLy6B were measured in the plasma of a S. mansoni infected male (aged 7–70 yrs) cohort [43] from a high transmission area in Uganda at two time-points—before and 9 weeks after PZQ treatment (Fig 4). To assess the age profiles of the responses, anti-rSmLy6A and rSmLy6B IgG1, IgG4 and IgE levels were plotted for five age groups (7–9, 10–13, 14–23, 24–32 and 33+ years) and positive responders (seropositive) were defined as those individuals exhibiting mean anti-rSmLy6 titers above the mean level observed from uninfected European/North American samples + 3x standard deviation (Fig 4).

Bottom Line: To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment.Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively) when compared to rising IgG1 levels against sub-surface SmTAL1.Collectively, these results expand the number of SmLy6 proteins found within S. mansoni and specifically demonstrate that surface-associated SmLy6A and SmLy6B elicit immunological responses during infection in endemic communities.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological, Environmental & Rural Sciences (IBERS), Aberystwyth University, Aberystwyth, United Kingdom.

ABSTRACT

Background: The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29) containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study). While vaccination with SmLy6A (SmCD59a) and SmLy6D (Sm29) induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored.

Methodology/principal findings: Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K). Our examination extends the number of members to eleven (including three novel proteins) and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D) is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively), these values are both higher than IgG1 prevalence (2.7%) for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively) when compared to rising IgG1 levels against sub-surface SmTAL1.

Conclusions/significance: Collectively, these results expand the number of SmLy6 proteins found within S. mansoni and specifically demonstrate that surface-associated SmLy6A and SmLy6B elicit immunological responses during infection in endemic communities.

No MeSH data available.


Related in: MedlinePlus