Johan Rönnelid – Immune complexes and associated autoantibodies in rheumatic diseases
Body fluids contain both free autoantibodies and autoantibodies in circulating immune complexes (IC). IC bind different target organs in rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE).
Our basic hypothesis is that free autoantibodies and IC autoantibodies differ in clinical significance. Today healthcare providers only measure free autoantibodies. We develop new methods to evaluate the roles of IC and IC-associated autoantibodies in rheumatic diseases, primarily in RA and SLE.
New laboratory methods based on immune complexes
The immediate aim is to elucidate the mechanism and clinical significance of inflammation initiated by IC and IC-associated autoantibodies. This is done by relating the structure, function, autoantibody and antigen content of IC to clinical phenotype, prognosis, and treatment response in patients.
The long-term goal is to develop new IC-focused laboratory methods which better relate to the clinical phenotype of the individual patient at the time of sampling, and which can be used to predict future clinical responses to specific drug treatments.
Structure and function of immune complexes
We develop new methods to study IC structure and function: functional cell-based tests to measure IC-mediated effects on cells; and biochemical techniques to evaluate IC composition for specific autoantibodies, autoantigens and other proteins. We then relate these laboratory results to the patients' clinical phenotypes, and to clinical responses to treatment with anti-rheumatic drugs.
Clinical information from IC-bound autoantibodies
So far, our research suggests that the amount and/or content of IC-bound antibodies can explain the onset of inflammation in RA patients, as well as better predict treatment response in SLE, and why different ethnic groups differ in SLE disease activity.
In the long term, development of clinical methods to measure IC-bound autoantibodies can provide more clinical information than usual blood sample measurement. Thus, it could improve the possibilities of making the correct diagnosis, of predicting future prognosis for individual patients, and perhaps most importantly: being able to better foretell whether individual patients will respond positively to different types of pharmacological treatment.
Large collaboration project
The work is translational where we as clinically oriented immunologists work in teamwork with rheumatologists and their patient cohorts. We collaborate with a large number of Swedish and international researchers and research-focused clinical rheumatologists.