Antibody response patterns in chikungunya febrile phase predict protection versus progression to chronic arthritis

• Type of Material: Article
• Authors: Kaustuv Nayak, International Center for Genetic Engineering and Biotechnology, India; Vineet Jain, Hamdard Institute of Medical Sciences and Research; Manpreet Kaur, Int Ctr Genet Engn & Biotechnol; Naushad Khan, Hamdard Institute of Medical Sciences and Research; Kamalvishnu Gottimukkala, International Center for Genetic Engineering and Biotechnology, India; Rohit Sagar, Hamdard Institute of Medical Sciences and Research; Shipra Gupta, Hamdard Institute of Medical Sciences and Research; Ramesh Chandra Rai, International Centre for Genetic Engineering and Biotechnology; Kritika Dixit, International Centre for Genetic Engineering and Biotechnology; Mohammad Islamuddin, Hamdard Institute of Medical Sciences and Research; Wajihul Hasan Khan, Hamdard Institute of Medical Sciences and Research; Anil Verma, All India Institute of Medical Sciences; Deepti Maheshwari, International Center for Genetic Engineering and Biotechnology, India; Yadya M. Chawla, International Center for Genetic Engineering and Biotechnology, India; Elluri Seetharami Reddy, International Center for Genetic Engineering and Biotechnology, India; Harekrushna Panda, International Center for Genetic Engineering and Biotechnology, India; Pragati Sharma, International Center for Genetic Engineering and Biotechnology, India; Priya Bhatnagar, International Center for Genetic Engineering and Biotechnology, India; Prabhat Singh, International Center for Genetic Engineering and Biotechnology, India; Siva Raghavendhar B., Indian Institute of Technology; Ashok Kumar Patel, Indian Institute of Technology; Vinod H. Ratageri, Karnataka Institute of Medical Science; Anmol Chandele, Emory University; Pratima Ray, Hamdard Institute of Medical Sciences and Research; Kaja Murali-Krishna, Emory University
• Language: English
• Date: 2020-04-09
• Publisher: American Society for Clinical Investigation Inc.
• Publication Version: Final Published Version
• Copyright Statement: © 2020, American Society for Clinical Investigation.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1172/jci.insight.130509
• Title of Journal or Parent Work: JCI Insight
• Volume: 5
• Issue: 7
• Grant/Funding Information: This work was supported by Department of Biotechnology, Government of India, and National Institutes of Health Indo-U.S. Vaccine Action Program BT/MB/Indo-US/VAP/06/2013; Department of Science and Technology EMR/2016/002475.; National Institutes of Health International Collaborations in Infectious Disease Research 1U01AI115651
• Keywords: Vaccine; Life Sciences & Biomedicine; Epidemiology; Fever; Pathogenesis; Medicine, Research & Experimental; India; Infected patients; Emergence; Research & Experimental Medicine; Science & Technology; Virus infection
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Immunology; Engineering, Biomedical

Abstract

Chikungunya virus (CHIKV) infection causes acute febrile illness in humans, and some of these individuals develop a debilitating chronic arthritis that can persist for months to years for reasons that remain poorly understood. In this study from India, we characterized antibody response patterns in febrile chikungunya patients and further assessed the association of these initial febrile-phase antibody response patterns with protection versus progression to developing chronic arthritis. We found 5 distinct patterns of the antibody responses in the febrile phase: no CHIKV binding or neutralizing (NT) antibodies but PCR positive, IgM alone with no NT activity, IgM alone with NT activity, IgM and IgG without NT activity, and IgM and IgG with NT activity. A 20-month follow-up showed that appearance of NT activity regardless of antibody isotype or appearance of IgG regardless of NT activity during the initial febrile phase was associated with a robust protection against developing chronic arthritis in the future. These findings, while providing potentially novel insights on correlates of protective immunity against chikungunya-induced chronic arthritis, suggest that qualitative differences in the antibody response patterns that have evolved during the febrile phase can serve as biomarkers that allow prediction of protection or progression to chronic arthritis in the future.