Follistatin-like Protein 1 and the Ferritin/Erythrocyte Sedimentation Rate Ratio Are Potential Biomarkers for Dysregulated Gene Expression and Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis

• Published in: Journal of rheumatology 2013-07, Vol.40 (7), p.1191-1199
• Main Authors: GORELIK, Mark, FALL, Ndate, ALTAYE, Mekibib, BARNES, Michael G, THOMPSON, Susan D, GROM, Alexei A, HIRSCH, Raphael
• Format: Article
• Language: English
• Subjects: Arthritis, Juvenile - blood; Arthritis, Juvenile - complications; Arthritis, Juvenile - genetics; Biological and medical sciences; Biomarkers - blood; Blood Sedimentation; Child; Child, Preschool; Diseases of the osteoarticular system; Female; Ferritins - blood; Follistatin-Related Proteins - blood; Gene Expression; Hematologic and hematopoietic diseases; Humans; Inflammatory joint diseases; Macrophage Activation Syndrome - blood; Macrophage Activation Syndrome - diagnosis; Macrophage Activation Syndrome - etiology; Male; Medical sciences; Other diseases. Hematologic involvement in other diseases
• ISSN: 0315-162X; 1499-2752
• DOI: 10.3899/jrheum.121131

Follistatin-like protein 1 (FSTL-1) is a secreted glycoprotein overexpressed in certain inflammatory diseases. Our objective was to correlate FSTL-1 levels with gene expression, known biomarkers, and measures of disease activity in systemic juvenile idiopathic arthritis (sJIA), including macrophage activation syndrome (MAS). FSTL-1 serum levels were measured by ELISA in 28 patients with sJIA, including 7 patients who developed MAS, and 30 healthy controls. Levels were correlated with erythrocyte sedimentation rate (ESR), ferritin, and soluble interleukin-2 receptor-α (sIL-2Rα). Gene expression based on FSTL-1 levels was analyzed in peripheral blood mononuclear cells (PBMC). Serum levels of FSTL-1 were elevated at time of presentation of sJIA (mean 200.7 ng/ml) and decreased to normal (mean 133.7 ng/ml) over 24 months (p < 0.01). FSTL-1 levels were markedly elevated during acute MAS (mean 279.8 ng/ml) and decreased to normal following treatment (p < 0.001). FSTL-1 levels correlated with serum markers of inflammation, including sIL-2Rα and ferritin. Ferritin/ESR ratio was superior to ferritin, sIL-2Rα, and FSTL-1 in discriminating MAS from new-onset sJIA. PBMC from patients with FSTL-1 levels > 200 ng/ml showed altered expression of genes related to innate immunity, erythropoiesis, and natural killer cell dysfunction. Two patients with the highest FSTL-1 levels at disease onset (> 300 ng/ml) ultimately developed MAS. Elevated pretreatment serum FSTL-1 levels in sJIA are associated with dysregulated gene expression suggestive of occult MAS, and may have utility in predicting progression to overt MAS. Ferritin/ESR ratio may be superior to ferritin alone in discriminating overt MAS from new-onset sJIA.