(231) Subclinical disease detection and immune profiling in siblings of patients with Enthesitis-related arthritis category of juvenile idiopathic arthritis

Introduction/Rationale: Enthesitis related arthritis (ERA) category of juvenile arthritis is a form of juvenile spondylarthritis. In many immune-inflammatory disorders a subclinical phase precedes a clinical disease. First degree relatives either due to genetic predisposition or sharing of environment have a high recurrence risk for these diseases. No data is available in siblings of ERA patients.

Methods: 38 sibling-proband pairs were evaluated after consent. Clinical examination, X-ray LS-spine, MRI of SI-joints and MSUS for enthesitis were done to detect subclinical disease in siblings. Frequency of lymphocyte and monocyte subsets, IL-17 producing NK cells, NK-T cells, γδ T cells and CD4 lymphocytes, IL-6 and TNF-α producing monocytes was measured using FACS. Faecal calprotectin levels were measured using ELISA.

Results: 38 siblings of 36 proband (13.8±3.5 years) were included. 20 of 38 siblings were HLA-B27 positive. Among siblings, none had arthritis, 1 each had inflammatory back pain and uveitis. On radiological assessment, 5 showed evidence of sacroiliitis (Grade II-4, Grade IV-1) on X-ray while 5 siblings had bone marrow edema around SI joints (one quadrant-4, four quadrants-1) on MRI. On MSUS enthesitis was seen in 2 siblings (patellar tendon-1, Tendoachillies-1). All but one with abnormalities were HLA-B27 positive.
In comparison to siblings, the probands had lower frequency of classical monocytes (p < 0.05), IL-6 producing monocytes (p < 0.01) and higher frequency of Th17 cells (p < 0.05). The faecal calprotectin levels were higher in probands (p < 0.01).
Analysing only the HLA-B27 siblings since subclinical disease was seen in only HLA-B27 siblings, the frequency of IL-17 producing CD4 T cells and γδ T cells (p < 0.01) and faecal calprotectin levels (p < 0.01) were higher in probands when compared with B27 positive siblings.

Conclusion: Subclinical disease is seen in subset of HLA-B27 siblings of patients with ERA. Gut inflammation and a pro-inflammatory state probably results in clinical disease in probands.