Rituximab

Jonathan Edwards, Emeritus Professor of Connective Tissue Medicine at University College London, provided these insights to readers of the Phoenix Rising website earlier this week:

I need to look at the paper in detail but I think these are important findings.

The only caveat to flag up is that muscarinic ACh receptor antibodies have a reputation for being a bit of a pain in terms of reproducibility but I would not worry too much about that.

It is good to see dynamic results – i.e. changing with treatment.

It is also great to see the Norwegian/German collaboration bearing fruit.

There is a lot more work to do but this is very promising.

It is hard to answer the question about implications specifically.

However, if it proves possible to select cases for rituximab based on data like this then that makes a huge difference to getting a therapeutic programme of the ground.

One of the most important brakes on the programme is the worry that treatments like rituximab would have to be used hit and miss in a condition that is hard to pin down diagnostically and that may include people for whom this is the wrong approach.

Take away that worry and treating ME by B cell targeting begins to look much more similar to lots of other diseases.

Antibodies to ß adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome

sciencedirect.com/science/a...

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  • Promising made it through the fog

  • Can't say a word of it got through so I am holding onto promising.

  • Targeting elevated antibody levels as a means of predicting treatment responders increases possibility of wider use than first thought.

  • Hit and miss treatment hasn't concerned medics treating M.E in over 20 years why start now is my question.

  • Abstract

    Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in CFS point to an autoimmune disease directed against neurotransmitter receptors. Autoantibodies against G-protein coupled receptors were shown to play a pathogenic role in several autoimmune diseases. Here, serum samples from a patient cohort from Berlin (n= 268) and from Bergen with pre- and post-treatment samples from 25 patients treated within the KTS-2 rituximab trial were analysed for IgG against human α and ß adrenergic, muscarinic (M) 1-5 acetylcholine, dopamine, serotonin, angiotensin, and endothelin receptors by ELISA and compared to a healthy control cohort (n=108). Antibodies against ß2, M3 and M4 receptors were significantly elevated in CFS patients compared to controls. In contrast, levels of antibodies against α adrenergic, dopamine, serotonin, angiotensin, and endothelin receptors were not different between patients and controls. A high correlation was found between levels of autoantibodies and elevated IgG 1-3 subclasses, but not with IgG 4 . Further patients with high ß2 antibodies had significantly more frequently activated HLA-DR+ T cells and more frequently thyreoperoxidase and anti-nuclear antibodies. In patients receiving rituximab maintenance treatment achieving prolonged B-cell depletion, elevated ß2 and M4 receptor autoantibodies significantly declined in clinical responder, but not in non-responder. We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and ß adrenergic receptors which are potential biomarkers for response to B-cell depleting therapy. The association of autoantibodies with immune markers suggests that they activate B and T cells expressing ß adrenergic and M acetylcholine receptors. Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS.

    Potential biomarkers for treatment wow !

  • Evidence towards approving the first medical treatment the NHS have ever given targeted at more than symptom management.

  • Side effects of treatment would worry me

    Headache, fever, chills, nausea, heartburn, flushing, weakness, or dizziness may occur.

    If any of these effects persist or worsen, contact your doctor or pharmacist promptly. Many people using this medication have serious side effects.

    A patient information leaflet warning that things that are everyday are also side effect warnings worth contacting a doctor or pharmacist.

  • Treats Leukaemia and Lymphoma when non treatment is a fatal alternative to side effects. Agree it would not be my first choice of treatment with any other options proven as effective.

  • Maybe I'm being naïve, but I've pinned so much hope on this treatment working that I don't care if it makes my hair fall out or I have to sell the family silver (not that we have any - but you know what I mean!) to pay for it privately. At this point I'd do anything to get my life back. Got to admit I'm worried I'll be in the subset that it doesn't work for though...

    Does anybody know of any UK trials looking for volunteers?

  • First results published in 2017 helse-bergen.no/en/OmOss/Av...