Article
Anti-Interleukin-6 (IL-6) and Anti-TNF-alpha treatments do not have a negative impact on the Cytomegalovirus- (CMV) specific Interferon-gamma immune response in children with Juvenile Idiopathic Arthritis (JIA) in vitro
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Published: | March 28, 2013 |
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Background: Previous studies showed lower proportions of CD28+ T-cells in Cytomegalovirus (CMV)-seropositive healthy donors (HD), which could not be shown in patients with Juvenile Idiopathic Arthritis (JIA), a T-cell-mediated autoimmune disease in children and adolescents. However, data on CMV-specific immune responses in JIA patients on anti-cytokine-treatments are missing.
Objective: This study determined the CMV-specific immune response in patients with JIA and age-matched HD using in vitro blockade of Interleukin-6(IL-6) and tumour-necrosis-factor-alpha(TNFalpha).
Methods: Peripheral blood mononuclear cells (PBMCs) and serum samples were obtained from 5 JIA patients in clinical remission on medication with non-steroidal anti-rheumatic drugs and 4 HD. CMV-specific IFNgamma-production was determined by ELISPOT following stimulation with CMV-antigens (CMVpp65,CMV-IE) in combination with monoclonal antibodies against IL-6 and TNFalpha. Results were expressed in spot forming units (SFU)/1000000 cells.
Results: CMV-seropositive JIA patients showed a significant higher number of IFNgamma-producing effector T-cells (CD4+CD45RA-CD28-) (39.03%) than CMV-seronegative JIA patients (16.55%). No differences were found in the IFNgamma-production between HD and JIA in the presence of anti-TNFalpha (JIA:27.8% vs. HD:27.3%), but a trend to lower IFNgamma-production by anti-IL-6 (JIA:13.3% vs. HD:35.0%). Within the JIA group, the IFNgammma-production following CMVpp65 stimulation was slightly lower in the presence of anti-IL-6 (CMVpp65:25.6% vs. CMVpp65+anti-IL-6:13.3.%) but not affected by anti-TNFalpha (CMVpp65:25.56% vs. CMVpp65+anti-TNFalpha:27. 8%).
Conclusion: Our preliminary findings did not reveal a significantly altered immune response in JIA patients against CMV in vitro. However, long-term aspects of chronic stimulation of the T-cell immune system by CMV as known from healthy elderly persons resulting in exhaustion of CD28- T-cells may follow in older age.