Background Inflammatory process in bone marrow (BM) observed on MRI scans of rheumatoid arthritis (RA) patients (called bone marrow oedema) was shown to proceed joint destruction in RA. Our previous studies supported the concept that BM actively participate in the pathogenesis of RA by TLR triggered B cell activity (1), increased number of activated T cells and increased level of proinflammatory cytokines (2,3). Cytokines play a key role in the bone destruction of rheumatoid arthritis.
Objectives To investigate the levels of IL-21 and IL-22 in RA BM plasma and their association with bone destruction.
Methods BM samples were obtained from RA and osteoarthritis (OA) patients during total hip replacement surgery. Levels of IL-17AF, IL-21, IL-22, RANKL and cathepsin K in BM plasma were determined by specific ELISA tests. We analyzed pelvic radiographs of 22 patients with RA admitted to the NIGRR and subjected to total hip replacement. Radiographs were taken a day or two before surgery. In our study we assessed hip joint changes semi-quantitatively with the use of the proposed scoring system including primary RA (juxta-articular osteoporosis, axial joint space narrowing, inflammatory cyst presence, bony erosion) and late RA changes (axial migration of the femoral head, femoral head deformation, avascular necrosis of femoral head, femoral head subluxation).
Results We found increased levels of activated T cell associated cytokines IL-21 (924.8 pg/ml vs 688.6 pg/ml, p<0.05) and IL-22 (94.5 pg/ml vs 65.8 pg/ml, p<0.05) in BM plasma of RA patients in comparison to osteoarthritis (OA) patients. Interestingly levels of both of these cytokines strongly correlated positively with concentration of osteoclastogenesis/osteoclast activity marker RANKL and cathepsin K. Surprisingly level of IL-17AF did not correlate with RANKL or cathepsin K. Furthermore, concentration of IL-21 was statistically significantly higher in patients with more severe radiologically assessed bone destruction. Median value of concentration of IL-21 in RA patients with small bone destruction was 797.4 pg/ml, with mild bone destruction was 1037.8 pg/ml, with severe bone destruction (1079.0 pg/ml).
Conclusions Our results show an association between BM plasma levels of IL-21 and IL-22 and bone destruction, supporting the hypothesis that IL-21 and IL-22 are important pathogenic factors of this disease. Therapy targeting IL-21 and IL-22 may be of value in preventing bone erosions in patients with RA.
W Rudnicka et al.: Eur J Immunol 2009; 12.
E Kuca-Warnawin et al.: Ann Rheum Dis Jan;70(1):227–33.
E Kuca-Warnawin et al.: Reumatologia 2016;54(2):51–3.
Acknowledgements This work was sponsored by grant No UMO-2011/03/B/NZ6/05035 from National Science Centre, Poland.
Disclosure of Interest None declared
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