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

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.

SUBMITTER: Nayak K

PROVIDER: S-EPMC7205261 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Nayak Kaustuv K Jain Vineet V Kaur Manpreet M Khan Naushad N Gottimukkala Kamalvishnu K Aggarwal Charu C Sagar Rohit R Gupta Shipra S Rai Ramesh Chandra RC Dixit Kritika K Islamuddin Mohammad M Khan Wajihul Hasan WH Verma Anil A Maheshwari Deepti D Chawla Yadya M YM Reddy Elluri Seetharami ES Panda Harekrushna H Sharma Pragati P Bhatnagar Priya P Singh Prabhat P Raghavendhar B Siva S Patel Ashok Kumar AK Ratageri Vinod H VH Chandele Anmol A Ray Pratima P Murali-Krishna Kaja K

JCI insight 20200409 7

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 ...[more]

PMID: 32155134

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Project description:The development of cancer is a multistep process in which cells increase in malignancy through progressive alterations. Such altered cells compete with wild-type cells and have to establish within a tissue in order to induce tumor formation. The range of this competition and the tumor-originating cell type which acquires the first alteration is unknown for most human tissues, mainly because the involved processes are hardly observable, aggravating an understanding of early tumor development. On the tissue scale, one observes different progression types, namely with and without detectable benign precursor stages. Human epidemiological data on the ratios of the two progression types exhibit large differences between cancers. The idea of this study is to utilize data of the ratios of progression types in human cancers to estimate the homeostatic range of competition in human tissues. This homeostatic competition range can be interpreted as necessary numbers of altered cells to induce tumor formation on the tissue scale. For this purpose, we develop a cell-based stochastic model which is calibrated with newly-interpreted human epidemiological data. We find that the number of tumor cells which inevitably leads to later tumor formation is surprisingly small compared to the overall tumor and largely depends on the human tissue type. This result points toward the existence of a tissue-specific tumor-originating niche in which the fate of tumor development is decided early and long before a tumor becomes detectable. Moreover, our results suggest that the fixation of tumor cells in the tumor-originating niche triggers new processes which accelerate tumor growth after normal tissue homeostasis is voided. Our estimate for the human colon agrees well with the size of the stem cell niche in colonic crypts. For other tissues, our results might aid to identify the tumor-originating cell type. For instance, data on primary and secondary glioblastoma suggest that the tumors originate from a cell type competing in a range of 300 - 1,900 cells.

Dataset Information

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

Publications

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

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