Abstract
Original language | English |
---|---|
Pages (from-to) | 233-246 |
Number of pages | 14 |
Journal | Allergy: European Journal of Allergy and Clinical Immunology |
Volume | 76 |
Issue number | 1 |
Early online date | 2020 |
DOIs | |
Publication status | Published - Jan 2021 |
Keywords
- Schistosoma mansoni
- asthma
- cross-reactive carbohydrate determinant
- α-1,3-fucose
- β-1,2-xylose
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In: Allergy: European Journal of Allergy and Clinical Immunology, Vol. 76, No. 1, 01.2021, p. 233-246.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Cross-reactive carbohydrate determinant-specific IgE obscures true atopy and exhibits ⍺-1,3-fucose epitope-specific inverse associations with asthma
AU - Nkurunungi, Gyaviira
AU - Mpairwe, Harriet
AU - Versteeg, Serge A.
AU - van Diepen, Angela
AU - Nassuuna, Jacent
AU - Kabagenyi, Joyce
AU - Nambuya, Irene
AU - Sanya, Richard E.
AU - Nampijja, Margaret
AU - Serna, Sonia
AU - Reichardt, Niels-Christian
AU - Hokke, Cornelis H.
AU - Webb, Emily L.
AU - van Ree, Ronald
AU - Yazdanbakhsh, Maria
AU - Elliott, Alison M.
N1 - Funding Information: We thank Koome sub-county and Entebbe municipality community members for participating in the rural (LaVIISWA) study and the urban survey, respectively. We are grateful to schoolchildren in Entebbe municipality and the surrounding areas in Wakiso District who took part in the asthma case-control study. We also thank all study staff. This work was funded by the Wellcome Trust (grant 095778 awarded to AME for the urban and rural survey, and grant 102512/Z/13/Z awarded to HM for the asthma study). GN was supported by a PhD fellowship from the African Partnership for Chronic Disease Research (APCDR). GN also received a small grant award (GR000904) from the Royal Society of Tropical Medicine and Hygiene (RSTMH) to conduct glycan microarray experiments and a short-term research fellowship from the European Academy of Allergy and Clinical Immunology (EAACI) to conduct ISAC microarray experiments. GN is an honorary fellow, and RES a PhD fellow, of the Makerere University?Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII-plus). MUII-plus is funded under the DELTAS Africa Initiative. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (grant 107743) and the UK Government. The MRC/UVRI and LSHTM Uganda Research Unit?is jointly?funded?by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 programme supported by the European Union. Funding Information: Gyaviira Nkurunungi reports grants from African Partnership for Chronic Disease Research, Royal Society of Tropical Medicine and Hygiene and European Academy of Allergy and Clinical Immunology, during the conduct of the study. Harriet Mpairwe reports a grant from the Wellcome Trust, during the conduct of the study. Alison Elliott reports grants from the Wellcome Trust and the Medical research Council, UK, during the conduct of the study. Richard Sanya reports a grant from Alliance for Accelerating Excellence in Science in Africa (AESA), outside the submitted work. Ronald van Ree reports personal fees from HAL Allergy BV and Thermo Fisher Scientific, outside the submitted work, and has consultant agreements with HAL Allergy BV, Citeq BV and Angany Inc The rest of the authors declare that they have no conflicts of interest. Funding Information: We thank Koome sub‐county and Entebbe municipality community members for participating in the rural (LaVIISWA) study and the urban survey, respectively. We are grateful to schoolchildren in Entebbe municipality and the surrounding areas in Wakiso District who took part in the asthma case‐control study. We also thank all study staff. This work was funded by the Wellcome Trust (grant 095778 awarded to AME for the urban and rural survey, and grant 102512/Z/13/Z awarded to HM for the asthma study). GN was supported by a PhD fellowship from the African Partnership for Chronic Disease Research (APCDR). GN also received a small grant award (GR000904) from the Royal Society of Tropical Medicine and Hygiene (RSTMH) to conduct glycan microarray experiments and a short‐term research fellowship from the European Academy of Allergy and Clinical Immunology (EAACI) to conduct ISAC microarray experiments. GN is an honorary fellow, and RES a PhD fellow, of the Makerere University—Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII‐plus). MUII‐plus is funded under the DELTAS Africa Initiative. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (grant 107743) and the UK Government. The MRC/UVRI and LSHTM Uganda Research Unit is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 programme supported by the European Union. Publisher Copyright: © 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Background: In high-income, temperate countries, IgE to allergen extracts is a risk factor for, and mediator of, allergy-related diseases (ARDs). In the tropics, positive IgE tests are also prevalent, but rarely associated with ARD. Instead, IgE responses to ubiquitous cross-reactive carbohydrate determinants (CCDs) on plant, insect and parasite glycoproteins, rather than to established major allergens, are dominant. Because anti-CCD IgE has limited clinical relevance, it may impact ARD phenotyping and assessment of contribution of atopy to ARD. Methods: Using an allergen extract-based test, a glycan and an allergen (glyco)protein microarray, we mapped IgE fine specificity among Ugandan rural Schistosoma mansoni (Sm)-endemic communities, proximate urban communities, and importantly in asthmatic and nonasthmatic schoolchildren. Results: Overall, IgE sensitization to extracts was highly prevalent (43%-73%) but allergen arrays indicated that this was not attributable to established major allergenic components of the extracts (0%-36%); instead, over 40% of all participants recognized CCD-bearing components. Using glycan arrays, we dissected IgE responses to specific glycan moieties and found that reactivity to classical CCD epitopes (core β-1,2-xylose, α-1,3-fucose) was positively associated with sensitization to extracts, rural environment and Sm infection, but not with skin reactivity to extracts or sensitization to their major allergenic components. Interestingly, we discovered that reactivity to only a subset of core α-1,3-fucose-carrying N-glycans was inversely associated with asthma. Conclusions: CCD reactivity is not just an epiphenomenon of parasite exposure hampering specificity of allergy diagnostics; mechanistic studies should investigate whether specific CCD moieties identified here are implicated in the protective effect of certain environmental exposures against asthma.
AB - Background: In high-income, temperate countries, IgE to allergen extracts is a risk factor for, and mediator of, allergy-related diseases (ARDs). In the tropics, positive IgE tests are also prevalent, but rarely associated with ARD. Instead, IgE responses to ubiquitous cross-reactive carbohydrate determinants (CCDs) on plant, insect and parasite glycoproteins, rather than to established major allergens, are dominant. Because anti-CCD IgE has limited clinical relevance, it may impact ARD phenotyping and assessment of contribution of atopy to ARD. Methods: Using an allergen extract-based test, a glycan and an allergen (glyco)protein microarray, we mapped IgE fine specificity among Ugandan rural Schistosoma mansoni (Sm)-endemic communities, proximate urban communities, and importantly in asthmatic and nonasthmatic schoolchildren. Results: Overall, IgE sensitization to extracts was highly prevalent (43%-73%) but allergen arrays indicated that this was not attributable to established major allergenic components of the extracts (0%-36%); instead, over 40% of all participants recognized CCD-bearing components. Using glycan arrays, we dissected IgE responses to specific glycan moieties and found that reactivity to classical CCD epitopes (core β-1,2-xylose, α-1,3-fucose) was positively associated with sensitization to extracts, rural environment and Sm infection, but not with skin reactivity to extracts or sensitization to their major allergenic components. Interestingly, we discovered that reactivity to only a subset of core α-1,3-fucose-carrying N-glycans was inversely associated with asthma. Conclusions: CCD reactivity is not just an epiphenomenon of parasite exposure hampering specificity of allergy diagnostics; mechanistic studies should investigate whether specific CCD moieties identified here are implicated in the protective effect of certain environmental exposures against asthma.
KW - Schistosoma mansoni
KW - asthma
KW - cross-reactive carbohydrate determinant
KW - α-1,3-fucose
KW - β-1,2-xylose
UR - http://www.scopus.com/inward/record.url?scp=85087619538&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/all.14469
DO - https://doi.org/10.1111/all.14469
M3 - Article
C2 - 32568414
SN - 0105-4538
VL - 76
SP - 233
EP - 246
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
IS - 1
ER -