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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 1

Diversity of the antibody response patterns in chikungunya acute febrile versus chronic patients.

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Diversity of the antibody response patterns in chikungunya acute febrile...
(A) Paired analysis of CHIKV-specific plasma IgM (red circles) and IgG (blue squares) values in individual CHIKV-confirmed patients within the no antibodies, IgM-alone, or IgM and IgG antibody response patterns in the acute febrile (left, n = 133), early chronic (middle, n = 21), and late chronic (right, n = 30) phases. Within each antibody response pattern group, the patients are stratified based on increasing IgM values on the x axis. Horizontal dotted line indicates assay cutoff for IgM and IgG. The samples that were also positive for CHIKV PCR are indicated by green-filled symbols. (B) Evaluation of plasma CHIKV NT antibody activity in each of the patient groups that are described in A. Dotted gates were placed to further subgroup the patients based on a combination of IgM, IgG, and NT activity. NT assay limit of detection is indicated by the horizontal dotted line. The NT antibody titers were significantly different between the IgM-alone group and IgM and IgG group in the acute febrile patients. Statistical significance was calculated by unpaired Mann-Whitney U test. (C) Relative proportion of the patients with each of the indicated antibody response patterns shown in B among the CHIKV-confirmed patients in febrile phase (left), early chronic phase (middle), and late chronic phase (right).

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