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Antibody response patterns in chikungunya febrile phase predict protection versus progression to chronic arthritis
Kaustuv Nayak, Vineet Jain, Manpreet Kaur, Naushad Khan, Kamalvishnu Gottimukkala, Charu Aggarwal, Rohit Sagar, Shipra Gupta, Ramesh Chandra Rai, Kritika Dixit, Mohammad Islamuddin, Wajihul Hasan Khan, Anil Verma, Deepti Maheshwari, Yadya M. Chawla, Elluri Seetharami Reddy, Harekrushna Panda, Pragati Sharma, Priya Bhatnagar, Prabhat Singh, Siva Raghavendhar B, Ashok Kumar Patel, Vinod H. Ratageri, Anmol Chandele, Pratima Ray, Kaja Murali-Krishna
Kaustuv Nayak, Vineet Jain, Manpreet Kaur, Naushad Khan, Kamalvishnu Gottimukkala, Charu Aggarwal, Rohit Sagar, Shipra Gupta, Ramesh Chandra Rai, Kritika Dixit, Mohammad Islamuddin, Wajihul Hasan Khan, Anil Verma, Deepti Maheshwari, Yadya M. Chawla, Elluri Seetharami Reddy, Harekrushna Panda, Pragati Sharma, Priya Bhatnagar, Prabhat Singh, Siva Raghavendhar B, Ashok Kumar Patel, Vinod H. Ratageri, Anmol Chandele, Pratima Ray, Kaja Murali-Krishna
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Research Article Immunology Infectious disease

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

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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.

Authors

Kaustuv Nayak, Vineet Jain, Manpreet Kaur, Naushad Khan, Kamalvishnu Gottimukkala, Charu Aggarwal, Rohit Sagar, Shipra Gupta, Ramesh Chandra Rai, Kritika Dixit, Mohammad Islamuddin, Wajihul Hasan Khan, Anil Verma, Deepti Maheshwari, Yadya M. Chawla, Elluri Seetharami Reddy, Harekrushna Panda, Pragati Sharma, Priya Bhatnagar, Prabhat Singh, Siva Raghavendhar B, Ashok Kumar Patel, Vinod H. Ratageri, Anmol Chandele, Pratima Ray, Kaja Murali-Krishna

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Figure 3

NT activity in the acute febrile phase is contributed by both IgM and IgG.

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NT activity in the acute febrile phase is contributed by both IgM and Ig...
(A) Analysis of correlation between NT antibody titers and IgM levels in plasma of patients from group I (n = 25), group II (n = 26), group III (n = 10), group IV (n = 17), and group V (n = 55). Dotted line indicates assay cutoff. Spearman’s correlation coefficient r was calculated. P values are indicated where significant. (B) Analysis of correlation between NT antibody titers and IgG levels in plasma of patients from group I (n = 25), group II (n = 26), group III (n = 10), group IV (n = 17), and group V (n = 55). Dotted line indicates assay cutoff. Spearman’s correlation coefficient r was calculated, and P values are indicated where significant. (C) NT antibody titers prior to and after IgM depletion. Plasma of group III patients (n = 5) and group V patients (n = 50) was evaluated for NT activity prior to and after IgM destruction. Dotted line indicates assay cutoff. The patients in whom NT titers decreased after IgM depletion are marked in red (100% in group III and 48% in group V). Paired 2-tailed t test was performed to evaluate statistical significance.

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