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IL-22 as a Prognostic Biomarker: Predictability of Disease Progression for Rheumatoid Arthritis

According to a recent study, a new biomarker may make it possible to make a prognosis regarding the progression of the autoimmune disease rheumatoid arthritis (RA).

The results of the study, which was carried out at the University of Munich Clinics, were recently published in the Annals of the Rheumatic Diseases, The EULAR Journal. At the centre of this study lies an analysis of the cell hormone interleukin-22, IL-22, and its significance as a prognostic marker for RA. The researchers examined the relationship between the serum levels of interleukin-22 and the risk of bone erosion and joint damage in RA patients.

This project in the division of rheumatology of the clinic was initially motivated by the observation that for reasons not yet understood, the onset of RA is associated with increased immunological activity and increased secretion of certain CD4 T cell cytokines. This increased immunological activity results in a CD4 T-cell-mediated persistent inflammatory reaction that leads to joint damage within a short period for two thirds of patients.

Desperately seeking: prognostic marker for RA

For researchers in the field of rheumatic diseases, the identification of molecules involved in the development of inflammation, joint erosion, and bone destruction represents a major challenge. Of particular interest are those biomarkers that allow an individualized prognosis of when a specific patient will develop joint erosion or destruction in the course of the disease. The primary goal of modern treatments is to hinder looming joint destruction with systematic treatment.

In this latest study from the research group led by Dr. med. Jan Leipe, the Munich scientists have now found that some patients with RA have significantly elevated serum levels of proinflammatory cytokine IL-22. Interestingly, these elevated IL-22 serum levels correlate significantly with the occurrence of joint erosion in the early stages of rheumatoid arthritis.

Interleukin-22 in the pathogenesis or rheumatoid arthritis

IL-22 is a cytokine produced primarily by CD4 T cells. The receptor for IL-22 is expressed in various joint tissues. Earlier studies demonstrated that IL-22 activates synovial fibroblasts. These in turn secrete cartilage-destroying proteinases that immediately participate in the destruction of cartilage. In addition, interleukin-22 promotes the formation of osteoclasts, which are substantially involved in bone erosion and joint destruction.

In the study Interleukin 22 serum levels are associated with radiographic progression in rheumatoid arthritis now published in the Annals of the Rheumatic Diseases, the significance of IL-22 in the occurrence of joint erosions was thoroughly investigated in a homogeneous, clinically well-defined cohort of RA patients. In order to ensure an unbiased analysis of IL-22 production at the beginning of the disease, only patients with an average symptom duration of less than three months were included in the study. In addition, the patients must have had no previous immunomodulator treatment. About half of the RA patients (49%) exhibited IL-22 values significantly above the norm at the beginning of the disease, while the other half had values in the normal range.

IL-22 serum levels are associated with radiographic progression in RA

Interestingly, up to 33% of the patients in the group with elevated interleukin-22 levels already exhibited joint damage at this early stage of the disease. In the group of patients with low IL-22 serum levels, this was only the case for a single patient (corresponding to 4%).

All patients were subsequently examined regularly over a period of two years. It was found that another quarter of the patients with elevated IL-22 values exhibited new joint erosion. In contrast, no damage was found in any of the patients with normal IL-22 values. The predictive value of IL-22 was independent of other parameters associated with more aggressive RA.

The measurement of IL-22 serum levels thus makes it possible to predict the risk of early joint destruction, the Munich scientists conclude. In addition, the results of this study also indicate that IL-22 plays an important role in the pathogenesis of joint destruction in rheumatoid arthritis.

Author of this article:  Tobias Stolzenberg

Literature:

Leipe J., Schramm MA, Grunke M., Baeuerle M., Dechant C., Nigg A.P., Witt M.N., Vielhauer V., Reindl C.S., Schulze-Koops H., Skapenko A. Interleukin 22 serum levels are associated with radiographic progression in rheumatoid arthritis. Ann Rheum Dis. 2011 Aug;70(8):1453-7. Epub 2011 May 18. – link opens the abstract

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