Therapy with CTLA4-Ig and an antiviral monoclonal antibody controls chikungunya virus arthritis.
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.
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jonathan J
JJ
Miner
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Lindsey E
LE
Cook
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jun P
JP
Hong
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Amber M
AM
Smith
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Justin M
JM
Richner
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Raeann M
RM
Shimak
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Alissa R
AR
Young
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kristen
K
Monte
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Subhajit
S
Poddar
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.|Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.|Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
James E
JE
Crowe
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. diamond@borcim.wustl.edu dlenschow@wustl.edu.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Deborah J
DJ
Lenschow
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. diamond@borcim.wustl.edu dlenschow@wustl.edu.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA.
Michael S
MS
Diamond
D000069594:Abatacept / Q000627:therapeutic use*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D001170:Arthritis, Infectious / Q000188:drug therapy* / Q000821:virology; D018925:Chemokines / Q000276:immunology; D065632:Chikungunya Fever / Q000188:drug therapy*; D016207:Cytokines / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019562:Viral Load
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000998:Antiviral Agents; D018925:Chemokines; D016207:Cytokines; D000069594:Abatacept