Chikungunya Arthritis Mechanisms in the Americas

A Cross-Sectional Analysis of Chikungunya Arthritis Patients Twenty-Two Months After Infection Demonstrating No Detectable Viral Persistence in Synovial Fluid

Aileen Y. Chang, Karen A.O. Martins, Liliana Encinales, St Patrick Reid, Marlon Acuña, Carlos Encinales, Christian B. Matranga, Nelly Pacheco, Carlos Cure, Bhavarth Shukla, Teofilo Ruiz Arteta, Richard Amdur, Lisa H. Cazares, Melissa Gregory, Michael D. Ward, Alexandra Porras, Alejandro Rico Mendoza, Lian Dong, Tara Kenny, Ernie Brueggemann & 7 others Lydia G. Downey, Priyanka Kamalapathy, Paola Lichtenberger, Orlando Falls, Gary L. Simon, Jeffrey M. Bethony, Gary S. Firestein

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objective: To determine if chikungunya virus persists in synovial fluid after infection, potentially acting as a causative mechanism of persistent arthritis. Methods: We conducted a cross-sectional study of 38 Colombian participants with clinical chikungunya virus infection during the 2014–2015 epidemic who reported chronic arthritis and 10 location-matched controls without chikungunya virus or arthritis. Prior chikungunya virus infection status was serologically confirmed, and the presence of synovial fluid chikungunya virus, viral RNA, and viral proteins was determined by viral culture, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), and mass spectrometry, respectively. Biomarkers were assessed by multiplex analysis. Results: Patients with serologically confirmed chikungunya arthritis (33 of 38 [87%]) were predominantly female (82%) and African Colombian (55%) or white Colombian (33%), with moderate disease activity (mean ± SD Disease Activity Score in 28 joints 4.52 ± 0.77) a median of 22 months after infection (interquartile range 21–23 months). Initial symptoms of chikungunya virus infection included joint pain (97%), swelling (97%), stiffness (91%), and fever (91%). The most commonly affected joints were the knees (87%), elbows (76%), wrists (75%), ankles (56%), fingers (56%), and toes (56%). Synovial fluid samples from all patients with chikungunya arthritis were negative for chikungunya virus on qRT-PCR, showed no viral proteins on mass spectrometry, and cultures were negative. Case and control plasma cytokine and chemokine concentrations did not differ significantly. Conclusion: This is one of the largest observational studies involving analysis of the synovial fluid of chikungunya arthritis patients. Synovial fluid analysis revealed no detectable chikungunya virus. This finding suggests that chikungunya virus may cause arthritis through induction of potential host autoimmunity, suggesting a role for immunomodulating agents in the treatment of chikungunya arthritis, or that low-level viral persistence exists in synovial tissue only and is undetectable in synovial fluid.

Original languageEnglish (US)
Pages (from-to)585-593
Number of pages9
JournalArthritis and Rheumatology
Volume70
Issue number4
DOIs
StatePublished - Apr 1 2018

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Synovial Fluid
Chikungunya virus
Arthritis
Cross-Sectional Studies
Infection
Viral Proteins
Mass Spectrometry
Viral RNA
Arthralgia
Toes
Elbow
Knee Joint
Wrist
Autoimmunity
Chemokines
Ankle
Fingers
Observational Studies
Fever
Joints

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Chikungunya Arthritis Mechanisms in the Americas : A Cross-Sectional Analysis of Chikungunya Arthritis Patients Twenty-Two Months After Infection Demonstrating No Detectable Viral Persistence in Synovial Fluid. / Chang, Aileen Y.; Martins, Karen A.O.; Encinales, Liliana; Reid, St Patrick; Acuña, Marlon; Encinales, Carlos; Matranga, Christian B.; Pacheco, Nelly; Cure, Carlos; Shukla, Bhavarth; Ruiz Arteta, Teofilo; Amdur, Richard; Cazares, Lisa H.; Gregory, Melissa; Ward, Michael D.; Porras, Alexandra; Rico Mendoza, Alejandro; Dong, Lian; Kenny, Tara; Brueggemann, Ernie; Downey, Lydia G.; Kamalapathy, Priyanka; Lichtenberger, Paola; Falls, Orlando; Simon, Gary L.; Bethony, Jeffrey M.; Firestein, Gary S.

In: Arthritis and Rheumatology, Vol. 70, No. 4, 01.04.2018, p. 585-593.

Research output: Contribution to journalArticle

Chang, AY, Martins, KAO, Encinales, L, Reid, SP, Acuña, M, Encinales, C, Matranga, CB, Pacheco, N, Cure, C, Shukla, B, Ruiz Arteta, T, Amdur, R, Cazares, LH, Gregory, M, Ward, MD, Porras, A, Rico Mendoza, A, Dong, L, Kenny, T, Brueggemann, E, Downey, LG, Kamalapathy, P, Lichtenberger, P, Falls, O, Simon, GL, Bethony, JM & Firestein, GS 2018, 'Chikungunya Arthritis Mechanisms in the Americas: A Cross-Sectional Analysis of Chikungunya Arthritis Patients Twenty-Two Months After Infection Demonstrating No Detectable Viral Persistence in Synovial Fluid', Arthritis and Rheumatology, vol. 70, no. 4, pp. 585-593. https://doi.org/10.1002/art.40383
Chang, Aileen Y. ; Martins, Karen A.O. ; Encinales, Liliana ; Reid, St Patrick ; Acuña, Marlon ; Encinales, Carlos ; Matranga, Christian B. ; Pacheco, Nelly ; Cure, Carlos ; Shukla, Bhavarth ; Ruiz Arteta, Teofilo ; Amdur, Richard ; Cazares, Lisa H. ; Gregory, Melissa ; Ward, Michael D. ; Porras, Alexandra ; Rico Mendoza, Alejandro ; Dong, Lian ; Kenny, Tara ; Brueggemann, Ernie ; Downey, Lydia G. ; Kamalapathy, Priyanka ; Lichtenberger, Paola ; Falls, Orlando ; Simon, Gary L. ; Bethony, Jeffrey M. ; Firestein, Gary S. / Chikungunya Arthritis Mechanisms in the Americas : A Cross-Sectional Analysis of Chikungunya Arthritis Patients Twenty-Two Months After Infection Demonstrating No Detectable Viral Persistence in Synovial Fluid. In: Arthritis and Rheumatology. 2018 ; Vol. 70, No. 4. pp. 585-593.
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abstract = "Objective: To determine if chikungunya virus persists in synovial fluid after infection, potentially acting as a causative mechanism of persistent arthritis. Methods: We conducted a cross-sectional study of 38 Colombian participants with clinical chikungunya virus infection during the 2014–2015 epidemic who reported chronic arthritis and 10 location-matched controls without chikungunya virus or arthritis. Prior chikungunya virus infection status was serologically confirmed, and the presence of synovial fluid chikungunya virus, viral RNA, and viral proteins was determined by viral culture, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), and mass spectrometry, respectively. Biomarkers were assessed by multiplex analysis. Results: Patients with serologically confirmed chikungunya arthritis (33 of 38 [87{\%}]) were predominantly female (82{\%}) and African Colombian (55{\%}) or white Colombian (33{\%}), with moderate disease activity (mean ± SD Disease Activity Score in 28 joints 4.52 ± 0.77) a median of 22 months after infection (interquartile range 21–23 months). Initial symptoms of chikungunya virus infection included joint pain (97{\%}), swelling (97{\%}), stiffness (91{\%}), and fever (91{\%}). The most commonly affected joints were the knees (87{\%}), elbows (76{\%}), wrists (75{\%}), ankles (56{\%}), fingers (56{\%}), and toes (56{\%}). Synovial fluid samples from all patients with chikungunya arthritis were negative for chikungunya virus on qRT-PCR, showed no viral proteins on mass spectrometry, and cultures were negative. Case and control plasma cytokine and chemokine concentrations did not differ significantly. Conclusion: This is one of the largest observational studies involving analysis of the synovial fluid of chikungunya arthritis patients. Synovial fluid analysis revealed no detectable chikungunya virus. This finding suggests that chikungunya virus may cause arthritis through induction of potential host autoimmunity, suggesting a role for immunomodulating agents in the treatment of chikungunya arthritis, or that low-level viral persistence exists in synovial tissue only and is undetectable in synovial fluid.",
author = "Chang, {Aileen Y.} and Martins, {Karen A.O.} and Liliana Encinales and Reid, {St Patrick} and Marlon Acu{\~n}a and Carlos Encinales and Matranga, {Christian B.} and Nelly Pacheco and Carlos Cure and Bhavarth Shukla and {Ruiz Arteta}, Teofilo and Richard Amdur and Cazares, {Lisa H.} and Melissa Gregory and Ward, {Michael D.} and Alexandra Porras and {Rico Mendoza}, Alejandro and Lian Dong and Tara Kenny and Ernie Brueggemann and Downey, {Lydia G.} and Priyanka Kamalapathy and Paola Lichtenberger and Orlando Falls and Simon, {Gary L.} and Bethony, {Jeffrey M.} and Firestein, {Gary S.}",
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T1 - Chikungunya Arthritis Mechanisms in the Americas

T2 - A Cross-Sectional Analysis of Chikungunya Arthritis Patients Twenty-Two Months After Infection Demonstrating No Detectable Viral Persistence in Synovial Fluid

AU - Chang, Aileen Y.

AU - Martins, Karen A.O.

AU - Encinales, Liliana

AU - Reid, St Patrick

AU - Acuña, Marlon

AU - Encinales, Carlos

AU - Matranga, Christian B.

AU - Pacheco, Nelly

AU - Cure, Carlos

AU - Shukla, Bhavarth

AU - Ruiz Arteta, Teofilo

AU - Amdur, Richard

AU - Cazares, Lisa H.

AU - Gregory, Melissa

AU - Ward, Michael D.

AU - Porras, Alexandra

AU - Rico Mendoza, Alejandro

AU - Dong, Lian

AU - Kenny, Tara

AU - Brueggemann, Ernie

AU - Downey, Lydia G.

AU - Kamalapathy, Priyanka

AU - Lichtenberger, Paola

AU - Falls, Orlando

AU - Simon, Gary L.

AU - Bethony, Jeffrey M.

AU - Firestein, Gary S.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Objective: To determine if chikungunya virus persists in synovial fluid after infection, potentially acting as a causative mechanism of persistent arthritis. Methods: We conducted a cross-sectional study of 38 Colombian participants with clinical chikungunya virus infection during the 2014–2015 epidemic who reported chronic arthritis and 10 location-matched controls without chikungunya virus or arthritis. Prior chikungunya virus infection status was serologically confirmed, and the presence of synovial fluid chikungunya virus, viral RNA, and viral proteins was determined by viral culture, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), and mass spectrometry, respectively. Biomarkers were assessed by multiplex analysis. Results: Patients with serologically confirmed chikungunya arthritis (33 of 38 [87%]) were predominantly female (82%) and African Colombian (55%) or white Colombian (33%), with moderate disease activity (mean ± SD Disease Activity Score in 28 joints 4.52 ± 0.77) a median of 22 months after infection (interquartile range 21–23 months). Initial symptoms of chikungunya virus infection included joint pain (97%), swelling (97%), stiffness (91%), and fever (91%). The most commonly affected joints were the knees (87%), elbows (76%), wrists (75%), ankles (56%), fingers (56%), and toes (56%). Synovial fluid samples from all patients with chikungunya arthritis were negative for chikungunya virus on qRT-PCR, showed no viral proteins on mass spectrometry, and cultures were negative. Case and control plasma cytokine and chemokine concentrations did not differ significantly. Conclusion: This is one of the largest observational studies involving analysis of the synovial fluid of chikungunya arthritis patients. Synovial fluid analysis revealed no detectable chikungunya virus. This finding suggests that chikungunya virus may cause arthritis through induction of potential host autoimmunity, suggesting a role for immunomodulating agents in the treatment of chikungunya arthritis, or that low-level viral persistence exists in synovial tissue only and is undetectable in synovial fluid.

AB - Objective: To determine if chikungunya virus persists in synovial fluid after infection, potentially acting as a causative mechanism of persistent arthritis. Methods: We conducted a cross-sectional study of 38 Colombian participants with clinical chikungunya virus infection during the 2014–2015 epidemic who reported chronic arthritis and 10 location-matched controls without chikungunya virus or arthritis. Prior chikungunya virus infection status was serologically confirmed, and the presence of synovial fluid chikungunya virus, viral RNA, and viral proteins was determined by viral culture, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), and mass spectrometry, respectively. Biomarkers were assessed by multiplex analysis. Results: Patients with serologically confirmed chikungunya arthritis (33 of 38 [87%]) were predominantly female (82%) and African Colombian (55%) or white Colombian (33%), with moderate disease activity (mean ± SD Disease Activity Score in 28 joints 4.52 ± 0.77) a median of 22 months after infection (interquartile range 21–23 months). Initial symptoms of chikungunya virus infection included joint pain (97%), swelling (97%), stiffness (91%), and fever (91%). The most commonly affected joints were the knees (87%), elbows (76%), wrists (75%), ankles (56%), fingers (56%), and toes (56%). Synovial fluid samples from all patients with chikungunya arthritis were negative for chikungunya virus on qRT-PCR, showed no viral proteins on mass spectrometry, and cultures were negative. Case and control plasma cytokine and chemokine concentrations did not differ significantly. Conclusion: This is one of the largest observational studies involving analysis of the synovial fluid of chikungunya arthritis patients. Synovial fluid analysis revealed no detectable chikungunya virus. This finding suggests that chikungunya virus may cause arthritis through induction of potential host autoimmunity, suggesting a role for immunomodulating agents in the treatment of chikungunya arthritis, or that low-level viral persistence exists in synovial tissue only and is undetectable in synovial fluid.

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