Children with Down’s syndrome (a genetic disorder caused by the presence of an extra chromosome 21) are at increased risk of developing arthritis. The early diagnosis and treatment of arthritis in children is critical for long-term joint health and normal growth. However, the diagnosis of arthritis in children with Down’s syndrome (termed Down’s Arthritis or DA) is extremely challenging. As a result, it is rarely recognised at onset, and has been under-diagnosed in the past.
Recent research by Dr. Charlene Foley/Dr. Orla Killeen (Pubmed) demonstrated that the prevalence of DA was 1 in 50. This is 20 times higher than the prevalence of arthritis in children without Down Syndrome, known as juvenile idiopathic arthritis (JIA). In many cases, the diagnosis of DA was delayed and there was increased evidence of joint erosion, indicating irreversible joint damage.
The lack of information and awareness regarding the clinical and epidemiological characteristics of this inflammatory arthritis, increased risk of arthritis in children with Down Syndrome, suggests that children with DA are potentially at a greater risk of long-term complications. Up until now there was little information on its unique immunological features, which hindered effective treatment.
New research published this week, led by Prof. Ursula Fearon/Dr. Achilleas Floudas (Molecular Rheumatology, Trinity Biomedical Sciences Institute, TCD), with Dr. Charlene Foley/Dr. Orla Killeen (National Children’s Research Centre, Crumlin), and Prof. Douglas Veale (St Vincent’s University Hospital & UCD), has identified an underlying immune system dysregulation in children with DA that is distinct from that of JIA.
This is the first detailed study to examine immune cell responses in these children, which demonstrated that a specific cell type of the immune system is significantly activated in children with DA, paralleled by a decrease in anti-inflammatory cells. This was associated with an increase in the migration of immune cells to the joint, which promotes further inflammation and invasiveness of joint cells. The altered immune profile observed in children with DA was associated with a more aggressive, erosive and damaging form of arthritis, emphasising the need for early diagnoses. Further studies and support for this condition will lead to improved diagnostic and prognostic outcomes for patients.
Prof. Ursula Fearon explains “This work represents a significant advance in our understanding of the disease and identifies for the first time distinct immunological dysregulation in children with Down syndrome-associated Arthritis (DA) compared to JIA, suggesting they are distinct arthropathies. It also demonstrates the importance of translational research, and the involvement of patients with research, we would like to thank the children and their parents as this study could not have been performed without them”.
This research was published this week in the international peer-reviewed journal ‘Arthritis & Rheumatology’*, and was funded by the National Children’s Research Centre, Crumlin, Arthritis Ireland, Down Syndrome Ireland, and the Health Research Board.
The complete publication can be found through the following link:
Foley C, Floudas A*, Canavan M, Biniecka M, MacDermott EJ, Veale DJ, Mullan RH, Killeen OG, Fearon U. Increased T cell plasticity with dysregulation of T follicular helper, T peripheral helper and T regulatory cell responses in children with JIA and Down syndrome-associated arthritis. Arthritis Rheumatol. 2019 Oct 27 (Pubmed).