Down syndrome (DS) is a common chromosomal disorder associated with a range of medical & immune abnormalities e.g. increased susceptibility to infections & a high incidence of autoimmune diseases, including Down’s Arthritis (DA). Previous work by our group suggests that the prevalence of DA is 18-21 fold greater than JIA, much higher than the previously reported DA prevalence of 8.7/1000. Children with DA most often follow a polyarticular course of disease, with erosive joint damage observed more frequently in this cohort when compared to a cohort of children with JIA. Small joint involvement is frequently observed, again in a significantly greater proportion (p<0.01) of children with DA than expected in a typical JIA cohort. These characteristics suggest that DA may be distinct from JIA, however little is known about the differences in synovial pathology or immunological regulation. Indeed no studies to date have examined immunology and synovial pathology in DA. The objectives of this study were to examine B & T-cell subsets, & cytokine profiles in children with DA & JIA; & to characterise & compare the synovial membrane immunohistochemistry.

Multicolour flow cytometry was used to analyse the phenotype of B & T cells in PBMCs from 40 children (Healthy Control (HC), JIA, DS, DA). Cells were stained with the following panels; Panel 1 B cells (CD38, CD24, CD20, CD80, CD27, IgM, CD138, CD45, CD19, MHCclassII, BCMA, CD40, CD86, IgD); Panel 2 T cell cytokines analysed after 5hours PMA/Ionomycin stimulation (CD3, CD8, CD161, IFN-γ, TNF-α, IL-17a, GM-CSF). Flow cytometry data was assessed by Flowjo software analysis.

Synovial tissue was obtained through US guided biopsy & analysed by immunohistochemistry for CD3, CD20, CD68, FVIII (DA n=3; JIA n=6). Synovial Inflammation & lining layer thickness were also scored. Analysis was performed using a semi-quantification scoring method.

Flow cytometry was performed on PBMC samples from 4 distinct groups (n=10 per group); HC (50%F, age 9.2y (2.5-15.6)), JIA (91%F, age 13.2y (8.2-16.1)), DS (45%F, age 6.5y (1-11.9)) & DA (60%F, age 11.4y (3.8-17.8)). All of the children in the DA & JIA cohorts had a polyarticular RF negative pattern of disease.

Analysis revealed that children with DA have a significantly lower number of circulating CD19+CD20+ B cells when compared to children with JIA (p<0.05) & HC (p<0.001). However, children with DA have a greater proportion of memory B cells (CD27+) when compared to children with DS & no arthritis (p<0.05).

IFN-γ & TNF-α production by CD8+/CD8- T cells was greater in DA compared to both JIA (CD8+IFNγ+ p<0.001; CD8+TNFα+ p<0.01; CD8-IFNγ+ p<0.05; CD8-TNFα p<0.05) & HC (CD8+IFNγ+ p<0.05; CD8+TNFα+ p<0.05; CD8-IFNγ+ p<0.05; CD8-TNFα p<0.01).

Examination of synovial tissue demonstrated higher levels of CD3+ cells (p<0.05), Macrophages (p<0.05), CD20+ cells & FVIII in the joints of children with DA.

There are significant differences in B cell populations, cytokine production & immunohistochemical features of synovial tissue in children with DA & JIA. More work is required to verify these results. Preliminary findings may begin to help explain the differences observed in the clinical picture of children with DA & JIA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-b-and-t-cell-subsets-cytokine-expression-and-synovial-pathology-in-downs-arthritis-da-and-juvenile-idiopathic-arthritis-jia/