[Research] 2017/09/21

Novel biomarkers pave the way of precision medicine in predicting antibody response to drug

   Many drugs are conjugated with polyethylene glycol (PEG) to increase their solubility, extension of circulation half-lives and reduction in immunogenicity. However, the presence of anti-PEG antibodies in some patients has been shown to affect the therapeutic efficacy and safety of PEGylated drugs. The mechanism of the variable antibody response to PEG is not clear. A team led by Dr. Jer-Yuarn Wu, Dr. Steve Roffler, and Dr. Yuan-Tsong Chen at the Institute of Biomedical Sciences (IBMS) in Academia Sinica identified the immunoglobulin heavy chain (IGH) locus to be associated with anti-PEG IgM response at genome-wide significance. The research was published in the journal Nature Communications on September 12th, 2017.

    The team performed genome-wide association studies for anti-PEG IgM and IgG responses in adult healthy subjects with 177 and 140 individuals, defined as positive for anti-PEG IgM and IgG responses, respectively, and with 492 subjects without either anti-PEG IgM or IgG as controls. The team validated the association results in the replication cohort, consisting of 211 and 192 subjects with anti-PEG IgM and anti-PEG IgG, respectively, and 596 controls. The team eventually identified the immunoglobulin heavy chain (IGH) locus to be associated with anti-PEG IgM response at genome-wide significance. The risk allele of the most significant SNP (P = 2.23 × 10-22; odds ratio (OR) = 2.36), rs12590237, was associated with higher prevalence and concentrations of anti-PEG IgM in the plasma.

    This is the first time a susceptibility locus for predisposing individuals toward inducing antibody response to PEG. is identified. The results shed new light on the genetic basis for the immunogenicity of PEG and reveal novel markers likely used for PEGylated drug therapeutics’ efficacy prediction, paving the way for precision medicine.

 

Authors and Institutions
 

Dr. Chia-Jung Chang, Postdoctoral Research Fellow, Institute of Biomedical Sciences, Academia Sinica

Dr. Chien-Hsiun Chen, Associate Research Scientist, Institute of Biomedical Sciences, Academia Sinica

Ms. Bing-Mae Chen, Research Assistant, Institute of Biomedical Sciences, Academia Sinica

Dr. Yu-Cheng Su, Postdoctoral Research Fellow, Institute of Biomedical Sciences, Academia Sinica

Ms. Ying-Ting Chen, Research Assistant, Institute of Biomedical Sciences, Academia Sinica

Dr. Michael S. Hershfield, Professor, Department of Medicine, Duke University Medical Center

Dr. Ming-Ta Michael Lee, Associate Professor & Associate Director, Geisonger Biobank, Genomic Medicine Institute, Geisinger Health System

Dr. Tian-Lu Cheng, Professor, Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University

Dr. Yuan-Tsong Chen, Distinguished Research Fellow, Institute of Biomedical Sciences, Academia Sinica

Dr. Steve R. Roffler, Research Fellow, Institute of Biomedical Sciences, Academia Sinica

Dr. Jer-Yuarn Wu, Research Fellow, Institute of Biomedical Sciences, Academia Sinica


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