Saturday, 3 November 2018

Depleting B cells inhibits MS

So this says if you keep CD19 B cell low it reduces your relapse rate...So much for T cells?


Ellrichmann G, Bolz J, Peschke M, Duscha A, Hellwig K, Lee DH, Linker RA, Gold R, Haghikia A. Peripheral CD19+ B-cell counts and infusion intervals as a surrogate for long-term B-cell depleting therapy in multiple sclerosis and neuromyelitis optica/neuromyelitis optica spectrum disorders. J Neurol. 2018. doi: 10.1007/s00415-018-9092-4. [Epub ahead of print]

BACKGROUND: With ocrelizumab another drug is available for the treatment of multiple sclerosis (MS). Little is known on the long-term use of ocrelizumab on immune cell subsets, and no surrogate markers are available. Rituximab (RTX) has been in off-label use for the treatment of MS, neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) for > 10 years.
OBJECTIVE: We evaluated the long-term depletion and repopulation rate of peripheral CD19+ B-cells as a potential surrogate for the clinical outcome, and whether it may serve for dosage and time-to-infusion decision making.
METHODS: We evaluated the CD19+ and CD4+/8+ T-cell counts in n = 153 patients treated with RTX (132 MS, 21 NMO/NMOSD). The dosages ranged from 250 to 2000 mg RTX. Depletion/repopulation rates of CD19+ B-cells as well as long-term total lymphocyte cell counts, were assessed and corroborated with EDSS, ARR (annualized relapse rate), MRI, and time to reinfusion.
RESULTS: CD19+ B-cells' repopulation rate significantly varied depending on the dosage applied leading to individualized application intervals (mean 9.73 ± 0.528 months). Low/absent CD19+ B-cell counts were associated with reduced ARR, EDSS, and GD+-MRI-lesions. Long-term B-cell-depleting therapy led to a transiently skewed CD4+/8+ T-cell ratio due to reduced CD4+ T-cells and absolute lymphocyte counts, which recovered after the second cycle.
CONCLUSION:Our data suggest that CD19+ B-cell repopulation latency may serve as surrogate marker for individualized treatment strategies in MS and NMO/NMOSD, which proved clinically equally effective in our cohort as evaluated by previous studies.

6 comments:

  1. Interesting ...
    Reading the posts here is an example of the failings of the Medical System.
    The ego-maniacs arguing about whether MS is T cell or B cell impacted is a wonderful example of the Pharma hold on the Medical Industry.
    All the arguments and their associated time wasting hides the essence of the problem. The reason, the 'why' factor is the issue with the immune system involvement in any and all chronic diseases, also in any of the atypical or spectrum of auto-immune impacts on Health and Wellness.
    The search for why the immune system is dysfunctional is sidelined by this drama. The issue is also about the assumptions that are held as Realities in Medical Research peer reviews.
    If the Medical System was to acknowledge that the tools and methods for assessing immune system functions and performance were inadequate, therefore the processes in diseases with labels such as MS are not defined or known which means that the causes of the immune system state isn't known or measurable with technology!
    Each individual with a diagnosis such as MS is not comparable with the next individual with the same label!
    Because Medical Science and Medical Research cannot map and measure the effects of diet, Lifestyle and stress management it suits the drivers of the Medical Industry, Pharma for one example profits from this, MS Industry and MS Societies also profit from the inability to search for the causes of the outcomes.
    So ... whether it is T cell or B cell activation and impact is a down stream effect ... the up stream effects, the cascades of effects are the essence that the ego-maniacs avoid and argue details in the smoke screen.
    Colin Adams the color atlas of MS!
    https://www.dropbox.com/s/x7u8zoiabxdvdgj/Colin%20Adams%20MS%20.pdf?dl=0&fbclid=IwAR3qn3Ig-0xwLFxrHOiFLw5HcdmGSirNaxlsyElkhSmgrsXMaMHBoM3Y8T4

    ReplyDelete
  2. Whilst the egos and Industry are battling out the immune system involvement ... which is after the event ... there are some credible findings being presented!
    RESULTS:
    MS plaques, which were newly detected during the study period, showed significantly higher venous volumes compared to the preplaque area 1 year before plaque detection and the corresponding NAWM regions. Venous volumes in established MS plaques, which were present already in the first scans, were significantly higher compared to the NAWM and controls.

    CONCLUSIONS:
    Our data underpin a relation of veins and plaque development in MS and reflect increased apparent venous calibers due to increased venous diameters or increased oxygen consumption in early MS plaques.
    https://www.ncbi.nlm.nih.gov/pubmed/25903703?fbclid=IwAR3rGyjtzfvMt8nAdszamHYIT_AG8tSeaMp9UT759DAa07mM4sxOVA7k0bM

    ReplyDelete
    Replies
    1. OK Now I get it...

      Veins...sounds like CCSVI orientation

      Delete
    2. "This creates a
      unifying concept centered onmemory B cells that is consistentwith therapeutic, histopathological and etiological
      aspects of MS."

      https://www.ncbi.nlm.nih.gov/pubmed/28161400

      So why monitoring cd19+ ?

      Why dont you monitor only cd27+?

      Cd19+ overshoot in Alemtuzumab and you dont get disease activation

      http://multiple-sclerosis-research.blogspot.com/2017/10/how-long-are-memory-b-cell-depleted-can.html

      "If you look at alemtuzumab, the CD19 B cell population (in green below) is back to normal levels within 3 months. But alemtuzumab is still working years later...so it can't be the B cell? Can it?"

      http://multiple-sclerosis-research.blogspot.com/2017/10/how-long-are-memory-b-cell-depleted-can.html

      This happens also with hsct

      http://multiple-sclerosis-research.blogspot.com/2017/05/blast-from-pastmemory-b-cells-depleted.html

      Also in due time memory b cells are likely to return to baseline levels

      (if you see in the hsct study using extremely lymphoablative conditioning. Transplant conditioning consisted of cyclophosphamide (120 mg/kg), total body irradiation (8 Gy))

      Memory B cells are back to baseline in 750 days

      In light of the recent study on the alemtuaumab 8 year outcomes

      Do you thing the memory b cell would be depleted for 8 years?

      Or the response rate have to had other mechanism at play ?

      Delete
  3. If the immune system responds to a trigger or a cascade of trigger events, the person also has the Medical System/Industry has given the label 'MS' and there are cells such as T cells or B cells 'seen' by Research 'persons' during pathology assessments what would their published conclusion in peer reviewed articles be?

    ReplyDelete
  4. MouseDoctor, 'the ego will land in a pile of his own'.
    Observations provided by Colin Adams may be hard for the current Medical System workers to accept.
    That bias has been observed recently when many other findings were presented such as the Lymphatic system of the brain and also the impact that diet, Lifestyle and stress management has on PwMS.
    It appears that because the Medical System cannot measure the changes occurring in PwMS nor the status and functional load of their immune system, such as when the diet has the impact of gluten/gliadins or the px has Lyme disease and co-infections or if EBV, mycoplasma's or CPn are active it is little wonder egos get out of control and arrogant.
    I guess the psycho-somatic dx is still popular with many of the Medical Professionals?

    ReplyDelete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.