Soluble cytotoxic T-lymphocyte antigen-4 (sCTLA-4) in children with immune cytopenia: relation to disease activity

Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is a costimulatory receptor exhibiting a potent inhibitory signal on antigen-activated immune responses. A soluble form, sCTLA-4, has been identified and was found to be increased in several autoimmune diseases. We aimed to evaluate serum levels of sCTLA-4 in different immune cytopenias, and to determine its possible relation to the disease activity. We measured serum levels of sCTLA-4 in 47 patients with immune cytopenias and compared them to 47 age- and sex-matched healthy controls. sCTLA-4 levels were significantly higher in patients with immune cytopenias compared to healthy controls (<i>p</i> < 0.001), however, levels were comparable between different groups of immune cytopenias (<i>p</i> = 0.084). Serum sCTLA-4 inversely correlated with age at diagnosis and hemoglobin level (<i>p</i> = 0.048, and <i>p</i> = 0.039 respectively), while it directly correlated with disease duration (<i>p</i> = 0.023) as well as markers of hemolysis including reticulocyte count, serum LDH and indirect bilirubin (<i>p</i> = 0.025; <i>p</i> = 0.019; <i>p</i> = 0.004 respectively). In the AIHA group, serum sCTLA-4 levels were significantly lower in patients in remission compared to patients with active disease (<i>p</i> = 0.026). Children with immune cytopenia exhibit significantly higher levels of circulating sCTLA-4 which correlated with disease activity, yet the prognostic significance and its use to tailor treatment regimen require additional studies.