ABSTRACT
Chikungunya, caused by the chikungunya virus (CHIKV) mostly presents as acute and chronic articular inflammatory manifestations. Interleukin 1 receptor antagonist (IL-1RN) is a potent endogenous competitive inhibitor of IL-1α and 1ß and has an anti-inflammatory role. The present study evaluated the possible association of IL1RN variable number tandem-repeat (VNTR) alleles and genotypes, and CHIKV stimulated IL-1RN cytokine production with resistance and/or susceptibility to chikungunya infection and disease state in 224 patients with chikungunya (61 patients with acute chikungunya and 163 patients with chronic chikungunya) and 355 healthy controls. Polymerase chain reaction, CHIKV stimulated cytokine assay and luminex platform were used for assessing polymorphism and protein levels respectively. The study revealed a significant association of IL1RN*1/*1 genotype under recessive genetic model with the risk of developing chikungunya infection. Our findings also indicated that IL1RN *2 allele under dominant mode was associated with protection to chronic chikungunya. The results also revealed a higher production of IL-1 RN protein in patients with chronic chikungunya. To conclude, the results suggest the association of ILRN VNTR polymorphism and IL-RN protein levels with chronic chikungunya.
Subject(s)
Chikungunya Fever/genetics , Genetic Association Studies , Interleukin 1 Receptor Antagonist Protein/genetics , Minisatellite Repeats , Polymorphism, Genetic , Adolescent , Adult , Aged , Alleles , Chikungunya Fever/immunology , Child , Child, Preschool , Chronic Disease , Cytokines/immunology , Female , Genetic Predisposition to Disease , Genotype , Humans , India , Male , Middle Aged , Young AdultABSTRACT
The role of natural killer (NK; CD3-CD56+)/NKT (CD3+CD56+)-like cells in chikungunya virus (CHIKV) disease progression/recovery remains unclear. Here, we investigated the expression profiles and function of NK and NKT-like cells from 35 chronic chikungunya patients, 30 recovered individuals, and 69 controls. Percentage of NKT-like cells was low in chronic chikungunya patients. NKp30+, CD244+, DNAM-1+, and NKG2D+ NK cell percentages were also lower (MFI and/or percentage), while those of CD94+ and NKG2A+ NKT-like cells were higher (MFI and/or percentage) in chronic patients than in recovered subjects. IFN-γ and TNF-α expression on NKT-like cells was high in the chronic patients, while only IFN-γ expression on NK cells was high in the recovered individuals. Furthermore, percentage of perforin+NK cells was low in the chronic patients. Lower cytotoxic activity was observed in the chronic patients than in the controls. CD107a expression on NK and NKT-like cells post anti-CD94/anti-NKG2A blocking was comparable among the patients and controls. Upregulated inhibitory and downregulated activating NK receptor expressions on NK/NKT-like cells, lower perforin+ and CD107a+NK cells are likely responsible for inhibiting the NK and NKT-like cell function in the chronic stage of chikungunya. Therefore, deregulation of NKR expression might underlie CHIKV-induced chronicity.
Subject(s)
Chikungunya Fever/immunology , Killer Cells, Natural/immunology , Natural Killer T-Cells/immunology , Receptors, Natural Killer Cell/physiology , Adolescent , Adult , Aged , Child , Female , Humans , Interferon-gamma/metabolism , Killer Cells, Natural/metabolism , Male , Middle Aged , Natural Killer T-Cells/metabolism , Tumor Necrosis Factor-alpha/metabolism , Young AdultABSTRACT
AIM: 1) To study clinical features and laboratory findings in patients of post chikungunya chronic arthritis (PCCA). 2) To study effectivity of disease modifying antirheumatic drugs (DMARDs) in treatment of post-chikungunya chronic arthritis. MATERIALS AND METHODS: Sixteen Chikungunya IgM positive patients having arthritis lasting more than 3 months in spite of NSAIDs and Hydroxychloroquine therapy were selected. Their clinical, laboratory and radiological features were noted. Disease activity was assessed by clinical parameters and Disease Activity Score System (DAS 28). Functional status was assessed by HAQ Questionnaire on follow-up visits over next 2 years. Effectivity of treatment with Sulfasalazine and Methotrexate was assessed. RESULTS: Chronic inflammatory polyarthritis does occur following chikungunya infection. It involves large and small joints of hands and feet and is erosive and deforming. It is rheumatoid factor negative. AntiCCP antibody was positive in majority. Synovial biopsy revealed nongranulomatous chronic synovitis with infiltration with lymphocytes and plasma cells. It was negative for chikungunya RNA. Treatment with Sulfasalazine with and without methotrexate produced good response in 71.4 % and 12.5% respectively. CONCLUSIONS: Chronic inflammatory, erosive and rarely deforming polyarthritis does occur after acute chikungunya infection in some (5.6%). It is seronegative and AntiCCP positive in majority. DMARDs like sulfasalazine and methotrexate are required and effective in treatment of PCCA.
