Paediatric rheumatology/The role of HMGB1 in chronic inflammatory diseases
Around 1500-2000 swedish children have chronic joint inflammation, juvenile idiopathic arthritis (JIA). There is a great need for improved diagnostic and prognostics tools as well as new therapeutic options. In addition to joint inflammation, destruction of joint tissue and pain are hallmarks of the disease. An improved, in depth understanding of the molecular mechanisms driving these three hallmarks forms the basis for development of diagnostic/prognostic biomarker tests as well as development of new, subgroup specific therapy – precision medicine.
Alarmins is a class of endogenous molecules released from stressed, injured and dying cells with the function to initiate an inflammatory response. The protein HMGB1, a prototypic alarmin, is a nuclear protein during tissue homeostasis which when released can induce cell migration, cytokine production, cell differentiation and regeneration. All important features of the inflammatory response. Our research has clearly demonstrated HMGB1 as a mediator of inflammation. In arthritis, HMGB1 mediates inflammation, destruction and pain. Treatment targeting HMGB1 improves all three arthritis hallmarks.
Our projects are focused on expanding the molecular knowledge of the immune mechanisms active in JIA as a basis for biomarker and therapy development. To achieve this we analyse biosamples collected from children with JIA, our sample collection JABBA, and compare generated data with information retrieved from the national quality register Svenska barnreumaregistret. In a recently started project we are investigating the possible connection of JIA, neuroinflammation and its potential influence on quality of life.
How HMGB1 is contributing to inflammation, pan and destruction is studied with a translational approach using molecular and cellular functional studies, analyses of HMGB1 in patient samples and model systems.
To develop better diagnostics, prognostics and treatment for JIA. Our results will also be applicable for many other inflammatory diseases.