Obtaining a greater understanding of the causes of Juvenile Idiopathic Arthritis (JIA) and developing new therapies.
What was already known?
Juvenile idiopathic arthritis (JIA) is a term used to describe a collection of childhood onset arthritic diseases and as such includes a diverse group of diseases. A classification system has been established by the International League of Associations for Rheumatology (ILAR) in which seven subtypes have been defined.
However, long-term outcome and response to treatment varies not only between subtypes but also within the subtypes suggesting that these subgroups do not yet represent uniform groups of patients. This current classification is largely based on clinical data and it is proposed that the addition of genetic data could improve classification.
In the last few years there have been huge advances in the knowledge of the genetic basis of JIA, however one region which stands out as the biggest risk factor for the disease is the major histocompatibility region (MHC) on chromosome 6.
There are multiple variants in the human leukocyte antigen (HLA) genes in this region. Previous methods aimed at detecting these different variants were costly so previous studies of this region have been small. However new cost-effective methods for typing these variants have been developed allowing larger and more powerful studies to be performed.
Our aim was to use these methods to screen a large number of cases and controls in order to refine HLA associations within each JIA subtype, compare them across the subtypes and also to compare the associations with those seen in adult musculoskeletal diseases.
What was discovered?
We identified a number of HLA associations which are specific to JIA ILAR subgroups, but also found that the two most common, and clinically similar, subgroups (Oligoarthritis and Rheumatoid Factor (RF) negative polyarthritis) shared the same genetic variants across the HLA region.
After comparing our findings with adult-onset musculoskeletal diseases we found shared HLA associations between RF positive polyarticular JIA and seropositive Rheumatoid Arthritis (RA). We also found shared HLA associations between the combined oligoarthritis and RF negative polyarthritis subtypes and seronegative RA.
Why is this important?
We have shown different HLA associations between some subtypes and this may in the future help to refine the classification for this disease. There were shared HLA associations within the two most common subtypes of JIA and also with some of the subtypes of adult musculoskeletal diseases.
These shared HLA associations may highlight shared disease mechanisms and enable us to have a greater understanding of the causes of this disease and ultimately, help us to develop new therapies.
(Hinks A. et al. (2016). Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases. Ann Rheum Dis, PMID:27998952| DOI:10.1136/annrheumdis-2016-210025)