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Biomarkers Predict Rituximab Response in RA

Research 1st

Severe ME, POTS & MCAS.
Messages
768

Hi.

Don't know if this of any use?

Interleukin (IL)-33 is a new member of the IL-1 superfamily of cytokines that is expressed by mainly stromal cells, such as epithelial and endothelial cells, and its expression is upregulated following pro-inflammatory stimulation. IL-33 can function both as a traditional cytokine and as a nuclear factor regulating gene transcription. It is thought to function as an 'alarmin' released following cell necrosis to alerting the immune system to tissue damage or stress. It mediates its biological effects via interaction with the receptors ST2 (IL-1RL1) and IL-1 receptor accessory protein (IL-1RAcP), both of which are widely expressed, particularly by innate immune cells and T helper 2 (Th2) cells. IL-33 strongly induces Th2 cytokine production from these cells and can promote the pathogenesis of Th2-related disease such as asthma, atopic dermatitis and anaphylaxis. However, IL-33 has shown various protective effects in cardiovascular diseases such as atherosclerosis, obesity, type 2 diabetes and cardiac remodeling. Thus, the effects of IL-33 are either pro- or anti-inflammatory depending on the disease and the model

Source: Miler, A. (2011).
Role of IL-33 in inflammation and disease

And...

IL-33 is a member of the IL-1 family of cytokines that includes IL-1α, IL-1β and IL-18. In contrast to other IL-1 related cytokines, except for IL-1α, IL-33 is primarily localized in the nucleus and it associates with chromatin where it can bind to the surface of nucleosomes and affect chromatin remodeling [94] and [95]. It is crucial for the induction of Th2 type cytokine-associated immune responses and thus has been extensively studied in the context of allergic disease where it has proinflammatory effects and in helminth infections where it is protective [96]. In models of anaphylaxis IL-33 directly induces mast cell degranulation after IgE sensitization. There appears to be an autocrine inflammatory loop induced by IL-33 in mast cells. IL-33 is produced by murine mast cells and mast cells also constitutively express ST2, a receptor subunit that together with IL-1 receptor accessory protein (IL-1RAcP) makes up the heterodimeric IL-33 receptor. Notably, similar to IL-3 and SCF, IL-33 can also directly induce cytokine and chemokine secretion from mast cells without affecting degranulation [94] and [95]. The proinflammatory activities of IL-33 and its link to mast cells make it a good candidate for studies in mast cell-dependent inflammatory autoimmune diseases.

Source: Walker et al (2012).
New insights into the role of mast cells in autoimmunity: Evidence for a common mechanism of action?

And...
We provide evidences of a specific role for IL-33 receptor signaling in nitric oxide induction through local IFN-γ modulation, suggesting that nitric oxide overproduction might have an important role in the progression of experimental viral encephalitis.

Source: Franca et al (2016).
IL-33 signaling is essential to attenuate viral-induced encephalitis development by downregulating iNOS expression in the central nervous system.

Thanks.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
@Jonathan Edwards have you seen this paper?

I had not seen it. I am not that impressed. Our own group showed that the presence of rheumatoid factor or anti-CCP antibodies or high Igs were a pretty reliable indication of response in RA. But then we expected that in advance since without these one would suspect that it was not really RA but some other ( maybe T cell mediated) disease. This group has added in IL-33. It would have been much more helpful if they simply indicated the predictive value of IL-33 alone since the others we knew about. High IL-33 is presumably part of the EFFECT of the autoantibodies in RA so there is no reason to think it would be relevant in a disease where autoantibodies had a completely different effect - like binding to neurotransmitter receptors as might be the case in ME.

So there is no conclusion here that IL-33 would be likely to be a biomarker for response in ME I think.
 

Kenny Banya

Senior Member
Messages
356
Location
Australia
Sorry to go a little off tangent, but I was certain I had RA, but none of the RA specific blood tests or even the contrast MRI suggested RA.
For the hell of it, I forced my rheumatologist to agree to give me methotrexate, because methotrexate has been shown to stall the progression of RA, if caught early. He was apprehensive, but agreed, stating that only one person in his entire career practice had responded to methotrexate, AFTER not responding to prednisone/solone/steroids.
Luckily, my CFS specialist said absolutely not to use it & that my symptoms were from CFS and it is an autoimmune response causing pain in my fingers, wrist & elbow joints.
That said, I wonder if methotrexate has ever been tried for CFS.