THU0539 SERUM SOLUBLE CD25: AN USEFUL BIOMARKER OF MACROPHAGE ACTIVATION SYNDROME IN SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS

Abstract

Background Systemic juvenile idiopathic arthritis (SJIA) is an auto-inflammatory disorder secondary to innate immune dysfunction with a propensity to develop macrophage activation syndrome (MAS), a life-threatening condition (1). sCD25 has been used as a sensitive biomarker for the diagnosis of Hemophagocytic lymphohistiocytosis which has similarities in clinical features and pathogenesis to MAS (2). Objectives To assay serum soluble CD25 in children with systemic juvenile idiopathic arthritis (SJIA) and to compare levels of sCD25 in children with inactive disease, active disease and those with macrophage activation syndrome (MAS). Methods This prospective study was conducted in a tertiary care referral centre in North India from January 2017 to June 2018. All patients fulfilling the International League of Associations for Rheumatology (ILAR) 2001 criteria for SJIA were eligible for enrolment. At enrolment, all patients were examined clinically for signs of disease activity. Appropriate investigations were carried out and sCD25 was analyzed by using commercially available sCD25/IL-2R ELISA kit. Results A total of 35 children (1-18 years) with 43 events were included in the study. Mean age at enrolment in the study was 7.3±3.59 years with male to female ratio of 2.5. Based on clinical features and investigations, events were categorized into 3 groups; SJIA with inactive disease (15; 34.9%), SJIA with active disease (15; 34.9%) and SJIA with MAS (13; 30.2%). Mean sCD25 levels in the study population were 10,966.02 ± 10,854.93 pg/ml. Children with inactive disease, active disease and disease with MAS had mean ± SD serum sCD25 levels of 4710.6 ± 1817.04 pg/ml, 7604 ± 2376.24 pg/ml, and 22062.9 ± 14335.97 pg/ml respectively. Although, Mean level of sCD25 in children with active disease was higher than those with inactive disease, but no significant difference could be found. sCD25 levels significantly (p value 0.0001) varied between MAS and other 2 groups. sCD25 cut off level of 10,385 pg/ml was found to have sensitivity of 100% and specificity of 96.7% in differentiating MAS in SJIA from disease flare and inactive disease. There was no significant correlation of sCD25 with demographic parameters, Total leucocyte count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet counts, urea, creatinine, prothrombin time, activated partial prothrombin time and fibrinogen levels. A correlation of sCD25 was found with levels of haemoglobin (p-value .01), ferritin (p-value .001), aspartate aminotransferase (AST) (p-value .000), alanine aminotransferase (ALT) (p-value .000), alkaline phosphatase (ALP) (p-value .005) and triglycerides (p-value .001). Higher sCD25 levels were found in patients who had low Hb, elevated ferritin, elevated AST, ALT, ALP and serum triglyceride levels. Conclusion: sCD25 is a useful biomarker in differentiating MAS in SJIA from disease flare and inactive disease with sensitivity and specificity of 100% and 96.7% respectively at a cut off level of 10,385 pg/ml. Coupling sCD25 with other laboratory parameters may be useful for early diagnosis of MAS in SJIA.