Johan Rönnelid's research projects on immune complexes and associated autoantibodies in rheumatic diseases

Anti-collagen II antibodies in rheumatoid arthritis

Eleftheria Pertsinidou, Christine Möller Westerberg, Anna Svanqvist, Johan Rönnelid

The two most important autoantibodies defining rheumatoid arthritis (RA), rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), are found in the majority of RA. Having these antibodies at the time of diagnosis is associated with more inflammation in the following years, and antibody serology is used both for diagnostic purposes and to prognosticate the response to treatment with anti-rheumatic drugs.

Anti-collagen II antibodies as potential biomarkers

Anti-collagen II antibodies on the other hand can be detected in a small subset of RA patient at the time of diagnosis, but levels drop sharply during the first year after arthritis onset. We have shown mechanisms by which these antibodies can induce inflammation by forming surface-bound immune complexes in joint cartilage, and how, as the anti-collagen II antibody levels drop, the corresponding inflammation decreases. Consequently, this RA subgroup has high levels of inflammation at the time of disease onset, but a comparatively good long-term prognosis. As opposed to RF and ACPA, anti-collagen II antibodies seem to be a prognostically beneficial biomarker.

At present, measurement of anti-collagen II antibodies is not commonly used for evaluation of RA patients by healthcare providers. In this project we examine the molecular mechanisms whereby anti-collagen II antibodies induce inflammation, as well as investigate large RA cohorts from different countries to evaluate whether analysis of this antibody can be a useful biomarker in the evaluation of newly diagnosed RA patients.

Quantification of autoantibodies and antigens in soluble immune complexes

Sahwa Elbagir, Anna Svanqvist, Christine Möller Westerberg, Johan Rönnelid

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 hypothesis is that free autoantibodies and IC-bound autoantibodies differ in clinical significance, and that IC autoantibodies might have a special importance. Today healthcare providers only measure free antibodies.

My group develops new methods to evaluate the roles of circulating IC and IC-associated autoantibodies in rheumatic diseases, primarily RA and SLE, focusing on two lines of enquiry:

1. Intact IC is purified and then used to stimulate human cells in the laboratory, to evaluate the function of intact circulating IC.
2. We have developed a technique to first isolate IC and then dissociate it into its components, which we then measure the amount and qualities of.

Both the functional responses to intact IC and the measurements of components in dissolved IC are then related to clinical data from large groups of patients with mainly rheumatic diseases, in collaboration with rheumatologists.

By such means we have, for example, shown how the autoantibody content in RA IC purified from the fluid of inflamed joints associate both with inflammation and radiological destruction (measured with X-ray), how levels of antibodies against DNA in circulating IC in the blood can be used to forecast how well SLE patients will respond to a modern anti-cytokine treatment, and how SLE patients from Sudan have higher levels of antibodies in their IC when compared to Swedish SLE patients.

These are findings that might explain why SLE patients with African ancestry have more active disease than those with European ancestry.

Comparative studies of rheumatic diseases in Sweden and Sudan

Sahwa Elbagir, Amir Elshafie, Johan Rönnelid

Rheumatic diseases in Africa are yet under-investigated. Currently, most available studies are conducted in African American populations. We investigate RA and SLE in Sudanese patients showing higher disease activity and more organ damage respectively, as compared to Swedish patients. Different patterns of autoantibodies also characterise Sudanese compared to Swedish population.

The World’s highest rates of stillbirths are found in sub-Saharan Africa. The anti-phospholipid syndrome (APS) is characterised by thromboses and severe pregnancy complications. APS is associated with anti-phospholipid antibodies, and often related to systemic lupus erythematosus (SLE) a disease with a very strong female preponderance and increased pregnancy risk. We perform comparative studies between Sudanese and Swedish patients with APS.

In all Sudanese projects we compare clinical manifestations, autoantibody profiles, and genes (HLA and Genome Wide Association Studies).