Johan Rönnelid – Autoantibodies in rheumatic diseases

We are studying how levels of autoantibodies in the blood and in immune complexes control clinical disease phenotypes and predict treatment response in rheumatic diseases.

Autoantibodies directed against cell nuclei (anti-nuclear antibodies or ANA) constitute a group of autoantibodies that are important in the diagnosis and prognosis assessment of patients with rheumatic diseases.

Very high and very low levels of autoantibodies

Disease-specific ANA can often be detected several years before patients develop rheumatic diseases. This can be used to identify risk groups early with the aim of treating the individuals even before the disease becomes clinically manifest. In these situations, the levels of antibodies are often low.

Many autoantibodies associated with specific diagnoses are also linked to specific clinical symptoms in these patients. In such cases, the cut-off point between the groups is often at high antibody levels.

Today’s routine methods are mostly used to determine whether ANA can be detected or not. However, the methods are not adapted to measure very low or very high antibody levels. We develop methods to measure ANA accurately both in very low and high ranges where current routine methods do not provide any information.

Autoantibodies in circulating immune complexes

Bodily fluids contain both free autoantibodies and autoantibodies that are part of circulating immune complexes (IC). These IC can cause damage by binding to different target organs in patients with rheumatic diseases.

We hypothesize that free antibodies and antibodies in IC have different clinical significance. Only free antibodies are measured in hospital laboratories today. My group develops new methods to measure the amount and biological function of IC and IC-associated autoantibodies in rheumatic diseases.

Antibodies to joint collagen (collagen type II) in rheumatoid arthritis

Anti-collagen II antibodies are detected early in connection with diagnosis in some patients with rheumatoid arthritis. We have shown that these autoantibodies cause inflammation, and described the mechanisms for how this occurs.

After rheumatoid arthritis diagnosis, the initially high levels decrease during the first year. Consequently, this group of patients has much inflammation at the time of diagnosis but a comparatively good long-term prognosis, which we were the first to show.

Our research

We develop quantitative methods for measuring autoantibodies, including ANA and anti-collagen II. We study IC with functional cell-based tests to measure IC function on cells in test tubes, and biochemical techniques to evaluate IC content of specific autoantibodies and their target proteins.

We then evaluate our laboratory results in relation to the patients’ clinical symptoms at the time of examination and to symptoms and signs that develop in the future. Our autoantibody findings are also related to future response to treatment with different antirheumatic drugs.

The work is translational where we are responsible for the immunological knowledge and our clinical rheumatology colleagues for the knowledge about the investigated patients. We collaborate with a large number of Swedish and international clinical rheumatologists and basic researchers.

New methods for prognosis and predicting treatment results

The long-term goal is to develop new autoantibody-focused laboratory methods that better than today describe the individual patient's condition when the sample is taken, what future prognosis the patient has, and whether she or he can be expected to improve after treatment with specific drugs.