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4.4 Different phenotype of anaemia in systemic juvenile idiopathic arthritis (s-JIA) compared to anaemia in other subtypes of JIA
Pediatric Rheumatology volume 6, Article number: S8 (2008)
In previous studies of PBMC gene expression in s-JIA we noted a strong erythropoiesis signature in patients with severe anaemia, correlating with an expansion of CD34+ progenitor cells . Therefore, the origin of anaemia in s-JIA may be different from anaemia of chronic inflammation. We examined CD34+ progenitor cells and PBMC gene expression in patients with s-JIA and other types of JIA.
187 patients with JIA (21 s-JIA and 166 other subtypes) prior to DMARD treatment were studied. PBMCs were isolated using Ficoll gradient centrifugation and analyzed by flow cytometry after CD34 staining. Gene expression analysis was performed on Affymetrix HG U133 plus 2.0 arrays.
Patients with s-JIA and anaemia had a significant elevation of CD34+ cells compared to patients with other JIA subtypes and anaemia (Table 1). Comparing PBMC gene expression in patients with s-JIA and anaemia and other JIA subtypes and anaemia revealed 671 differentially expressed probes (T-test). Unsupervised hierarchical clustering revealed homogeneous clustering of the s-JIA group. Strongly divergent gene clusters were identified with overexpression of erythropoiesis-related genes in patients with s-JIA.
Patients with s-JIA and anaemia have an increased output or survival of hematopoietic progenitor cells and a specific erythropoiesis signature. This contradicts the paradigm that anaemia in s-JIA is caused by decreased erythrocyte production due to chronic inflammation. In addition, we recently showed that many patients with s-JIA have features of subclinical macrophage activation syndrome (MAS) . We hypothesize that anaemia in s-JIA may be due to hemophagocytosis and subclinical MAS.
Fall N, Barnes M, Thornton S, Luyrink L, Olson J, Ilowite NT, Gottlieb BS, Griffin , Sherry DD, Thompson S: Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome. Arthritis Rheum. 2007, 56: 3793-3804. 10.1002/art.22981.
Bleesing J, Prada A, Siegel DM, Villanueva J, Olson J, Ilowite NT, Brunner HI, Griffin T, Graham TB, Sherry DD: The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis. Arthritis Rheum. 2007, 56: 965-971. 10.1002/art.22416.
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Hinze, C., Fall, N., Barnes, M. et al. 4.4 Different phenotype of anaemia in systemic juvenile idiopathic arthritis (s-JIA) compared to anaemia in other subtypes of JIA. Pediatr Rheumatol 6, S8 (2008). https://doi.org/10.1186/1546-0096-6-S1-S8
- Progenitor Cell
- Chronic Inflammation
- Juvenile Idiopathic Arthritis
- Gene Expression Analysis
- Severe Anaemia