Later-onset rheumatoid factor negative polyarticular juvenile idiopathic arthritis (JIA): a unique patient group?

OBJECTIVES: To determine the two-year outcome of patients with later-onset polyarticular rheumatoid factor (RF) negative (-) juvenile idiopathic arthritis (JIA), and predictors of outcome. METHODS: All patients ages 10 to16 years diagnosed and followed in the Rheumatology Clinic at SickKids Hospital with the diagnosis of polyarticular RF- JIA were eligible for study. A retrospective chart analysis was performed and number of active joints, medications, laboratory information and childhood health assessment questionnaire scores were recorded at diagnosis, and 6, 12, and 24 months following diagnosis. RESULTS: As early as 6 months after diagnosis the mean number of active joints decreased from 16 to < 10, with 50% of the patients having < 5 active joints. The predominant joints affected were the wrist, knee, and small joints of the hand. The only predictor of active joint count at the 2-year follow-up was initial presenting active joint count as classified as mild, moderate, or severe. Sex, age, and laboratory results at presentation did not show any correlation with active joint count at 2 years. Majority of patients were treated with non-steroidal anti-inflammatory drugs (98%) and at least one disease-modifying anti-rheumatic drug (56%). CONCLUSIONS: The two-year outcome of patients with late-onset RF- polyarticular JIA was very good with the majority of patients having minimally active disease at last follow-up. Presence of significant polyarthritis at presentation was the only feature associated with long-term joint activity. Sex and lab results did not show any correlation with active joint in this cohort of RF-JIA patients.

Galectin-3-mediated xenoactivation of human monocytes.

BACKGROUND: Delayed xenograft rejection (DXR) remains a roadblock to successful xenotransplantation. A feature of DXR is early recruitment of monocytes to the xenograft. Naïve human monocytes can recognize and adhere to unstimulated porcine aortic endothelial cells (PAEC) more than human aortic endothelial cells, partly due to endothelial expression of the xenoantigen galactose-alpha(1,3)galactose-beta(1,4)GlcNAc-R (alpha-gal). Previous work from our laboratory has implicated galectin-3 as a candidate molecule on monocytes involved in initial recognition and adhesion of human monocytes to PAEC. METHODS: Flow cytometry was used to analyze monocyte activation and galectin-3 accumulation in PAEC. Reactive oxygen intermediate production was analyzed using dihydrorhodamine measured in a fluorescence plate reader. Western blotting was performed to determine galectin-3 secretion and expression by human monocytes. Immunofluorescence staining for the tight junction protein zona occludens-1 was used as a measure of PAEC monolayer integrity. RESULTS: We demonstrate that galectin-3 can be secreted from monocyte intracellular stores on contact with alpha-gal. Soluble galectin-3 binds PAEC partly by expression of alpha-gal. Binding is reduced on endothelium derived from alpha-gal knockout animals, but not completely. Competing terminal sugars expressed on human aortic endothelial cells such as sialic acid, may block galectin-3 binding. Furthermore, soluble galectin-3 activates monocytes in an autocrine/paracrine manner. Blocking galectin-3 reduces the activation of human monocytes. Finally, the inhibition of galectin-3 reduces monocyte-mediated endothelial injury on co-culture with PAEC. CONCLUSION: Galectin-3 plays a role in human monocyte activation and adhesion in the presence of PAEC, which may contribute to DXR. Additional transgenic strategies targeting galectin-3 ligands on porcine endothelium may be required to achieve optimal xenograft survival.