Johan Rönnelid's research projects on immune complexes

Characterization of immune complexes

Vivek Anand Manivel, Azita Sohrabian, Amir Elshafie, Linda Mathsson, Mohammed Mullazehi, Sahwa Elbagir, Johan Rönnelid
The project relies on close collaboration between basic immunological and clinical research, mostly within rheumatology. The basic research concerns characterization of IC-induced immune/inflammatory reactions and development of new techniques to measure effects of IC and IC-associated autoantibodies. The measurement outcomes are then related to the clinical situation for the individual patients at the time of sampling (pathogenetic issues) or later (prognostic issues).

Our present interest is to evaluate the prognostic impact of autoantibody levels within IC. We have shown that these levels show changes over time that fundamentally differ from the changes in serum. We are currently investigating whether such changes have prognostic impact by analysing serum and IC levels over time in SLE patients treated with antibodies depleting all B cells (Rituximab) and neutralizing B-cell activating factor (Belimumab) as well as in RA patients treated with intra-articular steroids.

The role of IC in disease

Vivek Anand Manivel, Azita Sohrabian, Amir Elshafie, Linda Mathsson, Mohammed Mullazehi, Johan Rönnelid
At the clinical level we investigate the importance of IC-triggered mechanisms for the development and maintenance of disease activity in RA, SLE and chronic infections. One of our main interests is currently to describe in detail the group of RA patients with high levels of circulating autoantibodies reacting with collagen type II in joint cartilage. We have shown that these antibodies, which show the highest levels very early (at the time of RA diagnosis) are found in patients which also have maximum inflammation and joint destruction at this early time point; these patients on the other hand have a good long-term prognosis

With two in vitro models reflecting anti-collagen containing IC in the joints, we have shown that these IC induce the production of inflammation-promoting and joint-degrading substances. Thereby we have explained the link between the early appearance of anti-collagen antibodies and the simultaneously appearing inflammation and joint destruction in anti-collagen antibody positive RA patients.

We purify IC from blood or inflamed joints, whereupon these IC are used to stimulate cells in vitro. In other in vitro systems, we create artificial IC with human components, and use these IC to stimulate different cell types. In these experiments, we aim to mimic immune reactions that take place in specific target organs in patients, e.g. RA cartilage or in the soft tissues in close vicinity to bone/cartilage erosion in RA joints. This work is done in close collaboration with researchers from many rheumatology centres in Sweden, Holland, United Kingdom, USA, Malaysia, and Sudan.

We believe that a greater functional understanding of IC-mediated mechanisms can lead to new principles of treatment in IC-associated diseases like RA and SLE. Such knowledge will also lead to better understanding and distinguishing of pathogenetically separate subgroups of patients in traditional criterion-based diseases like RA and SLE. Thereby it will be possible to treat each phenotypical patient subgroup in an individually and biologically adequate way.

Comparative studies of rheumatic diseases in Sweden and Sudan

Sahwa Elbagir, Amir Elshafie, Johan Rönnelid
Little is today known about the natural history of rheumatoid arthritis in third world countries, and nothing has been published from Sudan. We investigate Sudanese RA patient and have reported very high disease activity and severe joint destructions among Sudanese RA patients.

The world’s highest rates of stillbirths are found in sub-Saharan Africa. The anti-phospholipid syndrome (APS) is characterized 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 SLE and APS.

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