Three years ago I’ve published a blog post on IL-33 here (link: see below); as inhibition of IL-33 could be a potential therapeutic and/or diagnostic approach. Let’s look for the studies on IL-33, which have emerged during the past three years.
There has been a study by S. Tang and colleagues in 2013: “Increased : L-33 in synovial fluid and paired serum is associated with disease activity and autoantibodies in rheumatoid arthritis.” In results the authors found: “SF IL-33 was significantly higher in RA than in OA, which was correlated with disease activity score 28, erythrocyte sedimentation rate, rheumatoid factor (RF)-IgM, RF-IgG, glucose phosphate isomerase (GPI), and immunoglobulin. …” So they concluded that IL-33 played an important role in the local pathogenesis of rheumatoid arthritis.
J. Shen and colleagues presented a study at the 2014 ACR/ARHP Annual Meeting [Abstract No. 374]: “IL-33 and Soluble ST2 Levels As Novel Predictors for Remission and Progression of Carotid Plaque in Early Rheumatoid Arthritis: A Prospective Study.” The authors want to identify predictors for treatment response, which may help to develop a form of personalized medicine. In conclusion they tell us: “Lower baseline sST2 levels independently predict disease remission and baseline detectable IL-33 independently predicts carotid plaque progression in ERA patients. This study suggests that inflammation induced by the IL-33/ST2 axis may play a significant role in the development of cardiovascular disease in RA.” This may seem far from a personalized medicine, but it’s a step towards this goal.
J. Sellam and colleagues published a study at the 2014 ACR/ARHP Annual Meeting [Abstract No. 2928]: “Serum IL-33 Level Is Increased in Rheumatoid Arthritis and Predicts Response to Rituximab in Combination with High Serum IgG Level and Autoantibody Positivity: An Open-Label, Prospective, Multicentre Biological Trial. “ Conclusion: “Serum IL-33 level, intrinsically increased in RA, represents a simple marker predicting accurately clinical response to RTX, independently of and synergistically with auto-antibodies and serum IgG level.” Does this help us right now? No. We don’t have a commercially IL-33 test, which is reimbursed to use it. But I find the result “Using ROC curve analyze, 249 pg/mL was the optimal serum IL-33 level cut-off to discriminate responders from non-responders.” intriguing. It would tell us more, when not to use rituximab, than, when to use it.
F. Rivellese and colleagues published a stuy: “Ability of Interleukin-33- and Immune Complex-Triggered Activation of Human Mast Cells to Down-Regulate Monocyte-Mediated Immune Responses.” Conclusion: “When human mast cells are activated by IL-33, an immunomodulatory phenotype develops, with human mast cells gaining the ability to suppress monocyte activation via the release of IL-10 and histamine. These findings, together with the presence of synovial mast cell-monocyte interactions and the inverse association between the expression of mast cell genes at the synovial level and disease activity, suggest that these newly described mast cell-mediated inhibitory pathways might have a functional relevance in the pathogenesis of RA.” This is a more basic study and therefore it isn’t clear to what it might mean to gain more control on disease activity. IL-33 is upregulated in RA patients to suppress monocyte activation.
These studies show that we still have a lot to learn about the role of IL-33 in rheumatoid arthritis. I’m sure that there will be a useful tool, if commercially test of IL-33 will be available. But I also hope for a breakthrough to use IL-33 (or IL-10) as a target to treat rheumatoid arthritis and/or other inflammatory rheumatic diseases.
Links:
IL-33 at the EULAR 2013 - http://rheumatologe.blogspot.de/2013/07/il-33-at-eular-2013.html
S. Tang: Increased : L-33 in synovial fluid - http://www.ncbi.nlm.nih.gov/pubmed/24106520
J. Shen and colleagues: IL-33 and Soluble ST2 Levels As Novel Predictors for Remission and Progression of Carotid Plaque in Early Rheumatoid Arthritis: A Prospective Study. Abstract 374 at the 2014 ACR/ARHP Annual Meeting. http://acrabstracts.org/abstract/il-33-and-soluble-st2-levels-as-novel-predictors-for-remission-and-progression-of-carotid-plaque-in-early-rheumatoid-arthritis-a-prospective-study/
J. Sellam and colleagues: Serum IL-33 Level Is Increased in Rheumatoid Arthritis and Predicts Response to Rituximab in Combination with High Serum IgG Level and Autoantibody Positivity: An Open-Label, Prospective, Multicentre Biological Trial. Abstract 2928 at the 2014 ACR/ARHP Annual Meeting. http://acrabstracts.org/abstract/serum-il-33-level-is-increased-in-rheumatoid-arthritis-and-predicts-response-to-rituximab-in-combination-with-high-serum-igg-level-and-autoantibody-positivity-an-open-label-prospective-multicentre/
F. Rivellese and colleagues: Ability of Interleukin-33- and Immune Complex-Triggered Activation of Human Mast Cells to Down-Regulate Monocyte-Mediated Immune Responses. Arthritis Rheumatol. 2015 Sep;67(9):2343-53. doi: 10.1002/art.39192. http://www.ncbi.nlm.nih.gov/pubmed/25989191
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