ObjectivesI aimed to investigate the prevalence and clinical associations of autoantibodies in patients with Juvenile Dermatomyositis (JDM) and Juvenile Idiopathic Arthritis (JIA). Both conditions are heterogeneous and I also aimed to explore the potential utility of such autoantibodies as biomarkers to sub-categorise patients into homogenous disease groups, inform prognosis and identify requirements for further investigations and monitoring. MethodsFor patients with JDM, autoantibodies were identified using protein radio-immunoprecipitation and ELISA. For patients with JIA indirect immunofluorescence of HEp2 cells was used and a variety of additional techniques employed in order to further characterise the antigenic target(s). The relationship between autoantibody presence and key disease characteristics was explored. ResultsAutoantibodies were common in both conditions and could be identified in 60% of those with JDM and 55% of those with JIA. Myositis specific autoantibodies were exclusively found in patients with JDM and autoantibody titre was found to correlate with disease activity measures. Relationships were identified between autoantibody subgroups and key clinical features including anti-NXP2 with calcinosis, anti-MDA5 with arthritis, interstitial lung disease and ulceration, and anti-HMGCR with severe disease poorly responsive to standard treatment.In those with JIA whilst I was unable to characterise the autoantibody further, a homogenous or dense fine speckle anti-nuclear antibody immunofluorescence pattern was found to be of greatest significance. Indeed, patients with an alternative pattern were no more likely to develop JIA associated uveitis than those who were autoantibody negative. ConclusionsAutoantibodies represent attractive biomarkers capable of facilitating diagnosis and identifying homogenous disease subgroups in both conditions studied. In those with JDM patient stratification by autoantibody status informs prognosis and directs appropriate further investigation and monitoring. Future clinical trials should adjust for autoantibody status as variations in disease severity and treatment response suggest the potential to act as confounders.
|Date of Award||24 May 2017|
|Supervisor||Neil McHugh (Supervisor) & Stephen Ward (Supervisor)|