Background/Purpose: Chikungunya virus (CHIKV) caused a large epidemic in Puerto Rico in 2014 with more than 30,000 reported cases. Many of the affected individuals developed chronic arthralgia and/or arthritis months or years after the infection. Animal and human studies have suggested that chronic arthralgia/arthritis is caused by unresolved inflammation responses in joints and persistent infection in macrophages. Thus, the main goal of this study was to identify factors released from macrophages of CHIKV-infected individuals that may play a role in the establishment of the chronic arthralgia/arthritis.

Methods:  A cross-sectional study was performed in patients with and without chronic arthralgia/arthritis (chronic and control groups, respectively) associated with CHIKV infection. All patients had laboratory confirmed CHIKV infection by IgG ELISA. Demographic features, health-related behaviors, clinical manifestations, comorbidities, disease activity (per Clinical Disease Activity Index [CDAI]), functional status (per Health Assessment Questionnaire [HAQ]), patient’s and physician’s global disease assessments by visual analog scales, and pharmacologic treatment were determined. Monocytes-derived macrophages were cultured for 7 days for differentiation. Cytokines and chemokines levels were determined in supernatants collected 3 days after macrophage differentiation using the Quantibody Inflammation Q3 ELISA array. Variables between chronic and control groups were compared using Fisher’s Exact and Mann-Whitney tests. Additional analyses were performed with stratified CDAI data (low < 10 and moderate or high ≥ 10) using Kruskal-Wallis tests with Dunn’s multiple comparisons.

Results:  Twenty-four patients were studied, 15 with chronic symptoms and 9 controls. The mean age was 47 ± 17 (SD) and 52 ± 11 years old in the chronic and control groups, respectively. A significantly higher proportion of women (13/15) had chronic arthralgia/arthritis than men (2/15, p=0.042). The mean time period between CHIKV infection and study visit was 18 months for both groups. Patients with chronic symptoms had significantly higher CDAI (12.5 ± 10.1 vs. 0.1 ± 0.3, p<0.001) and HAQ scores (0.9 ± 0.66 vs. 0.1 ± 0.29, p=0.002) than the controls. Patients in the chronic group had significantly (p<0.05) lower levels of MCP-1, MCSF, MIP1alpha, TIMP1, and TIMP2 than the controls. Conversely, patients with chronic arthralgias/arthritis were more likely to have significantly (p=0.003) higher levels of I309 than those without chronic symptoms. No differences in cytokine or chemokine levels were observed in chronic patients with low or moderate/high CDAI. Eotaxin, IL-4, IL-11, and IL-12p70 were not detected in any of the samples tested in this study.

Conclusion: Higher levels of chemokines, except for I309, were observed in patients without chronic arthralgia/arthritis suggesting a protective role, in particular of the metalloproteinase inhibitors TIMP1 and TIMP2. Further studies are required to define the mechanism of action of these chemokines in preventing the development of chronic arthralgia/arthritis after CHIKV infection.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/profile-of-macrophage-derived-cytokines-and-chemokines-of-patients-with-chikungunya-induced-chronic-arthralgiaarthritis/