James Crowe
Faculty Member
Last active: 3/31/2019

Therapy with CTLA4-Ig and an antiviral monoclonal antibody controls chikungunya virus arthritis.

Miner JJ, Cook LE, Hong JP, Smith AM, Richner JM, Shimak RM, Young AR, Monte K, Poddar S, Crowe JE, Lenschow DJ, Diamond MS
Sci Transl Med. 2017 9 (375)

PMID: 28148840 · PMCID: PMC5448557 · DOI:10.1126/scitranslmed.aah3438

In 2013, chikungunya virus (CHIKV) transmission was documented in the Western Hemisphere, and the virus has since spread throughout the Americas with more than 1.8 million people infected in more than 40 countries. CHIKV targets the joints, resulting in symmetric polyarthritis that clinically mimics rheumatoid arthritis and can endure for months to years. At present, no approved treatment is effective in preventing or controlling CHIKV infection or disease. We treated mice with eight different disease-modifying antirheumatic drugs and identified CLTA4-Ig (abatacept) and tofacitinib as candidate therapies based on their ability to decrease acute joint swelling. CTLA4-Ig reduced T cell accumulation in the joints of infected animals without affecting viral infection. Whereas monotherapy with CTLA4-Ig or a neutralizing anti-CHIKV human monoclonal antibody provided partial clinical improvement, therapy with both abolished swelling and markedly reduced levels of chemokines, proinflammatory cytokines, and infiltrating leukocytes. Thus, combination CTLA4-Ig and antiviral antibody therapy controls acute CHIKV infection and arthritis and may be a candidate for testing in humans.

Copyright © 2017, American Association for the Advancement of Science.

MeSH Terms (13)

Abatacept Animals Antibodies, Neutralizing Antibodies, Viral Antiviral Agents Arthritis, Infectious Chemokines Chikungunya Fever Cytokines Leukocytes Mice Mice, Inbred C57BL Viral Load

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