Role of Burkholderia pseudomallei–Specific IgG2 in Adults with Acute Melioidosis,Thailand |
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Authors: | Panjaporn Chaichana Kemajittra Jenjaroen Suchintana Chumseng Manutsanun Sumonwiriya Patpong Rongkard Barbara Kronsteiner Prapit Teparrukkul Direk Limmathurotsakul Nicholas P.J. Day Narisara Chantratita Susanna J Dunachie |
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Affiliation: | Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand (P. Chaichana, K. Jenjaroen, S. Chumseng, M. Sumonwiriya, P. Rongkard, D. Limmathurotsakul, N.P.J. Day, N. Chantratita, S.J. Dunachie);University of Oxford, Oxford, England (P. Rongkard, B. Kronsteiner, D. Limmathurotsakul, N.P.J. Day, S. Dunachie);Sunpasithiprasong Hospital, Ubon Ratchathani, Thailand (P. Teparrukkul) |
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Abstract: | Melioidosis is a life-threatening infectious disease caused by the gram-negative bacillus Burkholderia pseudomallei. An effective vaccine is needed, but data on protective immune responses in human melioidosis are lacking. We used ELISA and an antibody-dependent cellular phagocytosis assay to identify the major features of protective antibodies in patients with acute melioidosis in Thailand. We found that high levels of B. pseudomallei–specific IgG2 are associated with protection against death in a multivariable logistic regression analysis adjusting for age, diabetes, renal disease, and neutrophil count. Serum from melioidosis survivors enhanced bacteria uptake into human monocytes expressing FcγRIIa-H/R131, an intermediate-affinity IgG2-receptor, compared with serum from nonsurvivors. We did not find this enhancement when using monocytes carrying the low IgG2–affinity FcγRIIa-R131 allele. The findings indicate the importance of IgG2 in protection against death in human melioidosis, a crucial finding for antibody-based therapeutics and vaccine development. |
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Keywords: | bacteria, antimicrobial resistance, melioidosis, Burkholderia pseudomallei, antibodies, IgG subclasses, IgG2 subclass, Fcγ RIIA, H131, R131, polymorphism, bacterial infection, melioidosis, Thailand |
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