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Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus, 2020, Ostendorf et al.

Discussion in 'Other health news and research' started by sveinnb, Jan 28, 2021.

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  1. sveinnb

    sveinnb Established Member (Voting Rights)

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    Summary

    Daratumumab, a human monoclonal antibody that targets CD38, depletes plasma cells and is approved for the treatment of multiple myeloma. Long-lived plasma cells are implicated in the pathogenesis of systemic lupus erythematosus because they secrete autoantibodies, but they are unresponsive to standard immunosuppression. We describe the use of daratumumab that induced substantial clinical responses in two patients with life-threatening lupus, with the clinical responses sustained by maintenance therapy with belimumab, an antibody to B-cell activating factor. Significant depletion of long-lived plasma cells, reduction of interferon type I activity, and down-regulation of T-cell transcripts associated with chronic inflammation were documented.

    https://www.nejm.org/doi/full/10.1056/NEJMoa2023325

    I personally think this is a major breakthrough and could have implications for ME/CFS
     
    Last edited by a moderator: Jan 28, 2021
    Sid, voner, ME/CFS Skeptic and 5 others like this.
  2. sveinnb

    sveinnb Established Member (Voting Rights)

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    See also:

    Is There a Future for Anti-CD38 Antibody Therapy in Systemic Autoimmune Diseases?

    CD38 is a type II glycoprotein highly expressed on plasmablasts, short-lived and long-lived plasma cells, but weakly expressed on other lymphoid cells, myeloid cells and non-hematopoietic cells. This expression pattern makes CD38 an interesting target for a targeted therapy aiming to deplete antibody-producing plasma cells. We present data suggesting that anti-CD38 therapy may be effective for the prevention at the preclinical stage and for the treatment of established autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Given the high unmet need for efficacious disease-modifying treatment in these diseases, studies are warranted to determine if anti-CD38 antibody-based therapies may delay or prevent the disease progression of systemic autoimmune diseases.

    https://pubmed.ncbi.nlm.nih.gov/31892266/
     
    Sid, Amw66, Hutan and 2 others like this.
  3. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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  4. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Thanks for posting this. We had talked about using anti-~CD38 back in the 2000s after initial success with rituximab. The idea was shelved because `CD~38 was found on cardiac cells and people thought it would be toxic. From what I see this is a double case report. That may be enough to show the potential. If Radbruch is involved it is worth taking seriously. My main concern would be that it turns out not to take things that much further than anti-CD20 in terms of long term remission.

    I am due to give a presentation on B cell targeting to the British Society for Rheumatology this April. This is about the first new story I have seen since 2004! I agree that potentially it could be a major step forward.

    But I fear it is unlikely to be relevant to ME.
     
    Aroa, FMMM1, Amw66 and 6 others like this.

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