Rheumatoid Arthritis is an inflammatory disease, what are the pathways that are involved in its parthenogenesis?
The interventions aimed at specific targets that have major impact in RA are TNF blockade, IL6 blockade, B cell depletion and costimulation blockade. B cell depletion produces benefit that follows the kinetics of autoantibody so it seems fairly certain that autoantibody is driving inflammation (complete normalisation of CRP can occur with B cell depletion alone). Antibodies generate TNF and IL6 though interactions with Fc receptors and there is evidence for FcRIII being critical since it occurs specifically in the tissues affected by the disease. B cell survival involves costimulation-related interactions (and IL6). There is a vast amount more information in the literature but this is the summary.
Check this link:
http://rheumatology.oxfordjournals.org/content/51/suppl_5/v3.full
The pdf of the article is available
Why check that out Alfonso? This is just Ernest rehashing the received T cell wisdom based on no evidence. Let's stick to facts. I don't know of any good evidence for TH17 or CD4 cells being important in joints. Blockade and depletion of these did not work if a remember rightly.
I came across that article recently and it seems to me an good summary of inflammatory pathways in RA for clinicians (that´s what I am).
Trying to help in aswering your question, although I am not an expert, in a fast search in Pubmed I have found an small study published in 2010 (Leipe J, et al. Role of Th17 cells in human autoimmune arthritis. Arthritis Rheum 2010;62 (10): 2876-85. doi: 10.1002/art.27622) about the role of Th17 cells in autoimmune arthritis, and some data about intervention on Th17 response in murine models of arthritis (Wu S, et al. Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine. Eur J Pharmacol 2014 Apr 19; 735C: 97-104. doi: 10.1016/j.ejphar.2014.04.019. [Epub ahead of print]). However, as it is stated in a recent review (Kobezda T et al. Of mice and men: how animal models advance our understanding of T-cell function in RA. Nat Rev Rheumatol 2014; 10 (3): 160-70. doi: 10.1038/nrrheum.2013.205. Epub 2014 Jan 7) RA and murine models of arthritis differ in T-cell subsets and functions. Specifically "local expansion of type 17 T-helper (TH17) cells is observed in some animal models, but not in RA". I will get the pdf of this article in a couple of days.
It may seem like a good summary Alfonso but the question is whether it is based on evidence. As you may realise I was both a clinician and worked on the inflammatory pathways in the lab. We managed to show that B cells are essential - and by clinical benefit in real human RA (NEJM 2004). Others managed to show that removing T cells makes more or less no difference. It is fairly simple, but people like to stick to ideas even when after thirty years there is not a shred of evidence. Th17 cells became popular because they were new and good for getting grants on - not because they had anything to do with RA as far as I can see. Do they even exist in humans in a meaningful sense?
The problem is that everyone just repeats what everyone else says. Did you really have good reason to refer to this paper other than that it 'seemed' reasonable? I answered because I spent thirty five years in the middle of this research field and actually got somewhere! My opinion is based on having been involved in the clinical experiments addressing the various pathways and seeing which worked and which did not.
Nullis in verba - always a good motto.
You are right, great motto, I agree.
Of course, the paper I cited seems reasonable; although as you point, there are other views of the subject and probably your opinion is one of the most authorized in this field.
As the motto suggests, it is very important not to accept without questions the information we receive; however, busy clinicians do not have time to keep up to date about every aspect of every clinical condition we see, so these summaries are welcome. Time to check the evidence-based condition of everything we read is scanty, and we have to use it judiciously in decisions that have a direct impact on our patients.
I just tried to give you an "easy" answer that, obviously you do not need.
Faciam ut potero - this is the motto of my town's medical academy and fits perfectly in my reflection.
I am looking forward to other colleagues' opinions about this subject
Do not argue, gentlemen! You're both right! Veritas - ut semper in medio. ambo sunt recti.
Rheumatoid arthritis - it is not nosological unit, it is - a condition to which various curves and deaf trails may lead.
Sory!
Something like that (see the attached file) with some clauses.
Dear Marina,
I think Gary's analysis is wrong, a muddle. He even confuses stochastic with environmental. He has not addressed the maths of the causality - even to the extent that Paul Stastny did. The tired old T cell cross reactivity idea is still there. The fact that lots of approaches provide effective treatment is merely an indication of the seriality of the pathways involved. Not impressed I fear.
"He even confuses stochastic with environmental" - YES!! But the main idea and some of the arguments are absolutely correct. Although the review is rather weak and not all-embracing. You're right. "The tired old T cell cross reactivity idea is still there" - I do not think that we should unequivocally reject the idea. Simply, this mechanism is not the only and perhaps not the most important.
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