Tuesday, 30 August 2016

ResearchSpeak: low lymphocyte counts in MSers

Do you have a normal lymphocyte count? Do you know your lymphocyte counts? #ResearchSpeak #MSBlog #MSResearch

"The retrospective study below found that 1 in 10 DMT-naive MSers had low lymphocyte counts and in the majority of these no obvious cause could be found. The authors' suggest the lymphopaenia is due to autoimmunity, or is stress-induced through increased cortisol production or Epstein-Barr activation."

"I live and learn something new every day of the week about MS. I had no idea that ~10% of MSers had idiopathic (no apparent cause found) lymphopaenia. What is interesting that in this study low lymphocyte counts at baseline predicted low lymphocyte counts on treatment. Clearly these findings needs to be confirmed and explained. Who knows it may provide interesting insights into the pathogenesis of MS. I like the suggestion that it may be linked to stress and/or EBV reactivation."

"Lymphopaenia is one of the key battlegrounds in the marketing of DMTs. Low lymphocyte counts are an important risk factor for several serious adverse events on DMTs. Understanding MS-related lymphopaenia may help de-risk some of these DMTs. I am interested to know how many of you know what your latest lymphocyte counts are? If you don't you should find out and keep a record of it for yourself."

A lymphocyte: image source Wikipedia


Lim et al. Lymphopenia in treatment-naive relapsing multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2016 Aug 12;3(5):e275. doi: 10.1212/NXI.0000000000000275. eCollection 2016.

Background: Lymphopenia accompanies some autoimmune diseases. Several studies, but not others, have suggested that lymphopenia occurs in treatment-naive multiple sclerosis (MS), so the issue remains unresolved.

Methods: Data were collected retrospectively during an institutionally approved service evaluation of blood test monitoring of patients with relapsing MS in a regional MS service in Southampton, UK, over a 2-year period (2012–2014). Control lymphocyte data were derived from preoperative blood counts of age- and sex-matched individuals undergoing septoplasty in the same hospital for structural reasons, excluding neoplastic and infective operative indications.

Results:  Seven hundred sixty-four patients were identified with blood test data (table). Baseline and post-treatment blood tests were available in 466 and 247 patients, respectively. Average blood test frequency was 4 per year. Lymphocyte counts were relatively stable with time, with a coefficient of variation of 7.5%. The mean lymphocyte count in treatment-naive patients with MS was 2.18 × 109/L with an SD of 0.66 × 109. Lymphopenia was present in 10% (48 patients; 46 grade I, one grade II, one grade III). In only 3 cases steroids were administered in the month before lymphopenia. There was no association between pretreatment lymphocyte count and any patient characteristic or month or season. 

Discussion: Since the lymphocyte reference range covers 95% of values in a healthy population, lymphopenia is expected in 2.5%. In our treatment-naive relapsing MS population, we found lymphopenia in 10%. Moreover, lymphopenia was not associated with relapsing activity. Hence, the lymphopenia in patients with MS is unlikely to be related to autoimmunity. A more likely explanation is stress-induced lymphopenia in both cohorts, through cortisol or Epstein-Barr activation.

7 comments:

  1. I am one of those cases where my lymphocytes count before starting DMTs had been already below normal.

    When I started taking DMTs and read about PML I checked the lymphos again and they were even lower so I stopped the drugs.

    Now I am not taking anything just because of this problem which my docs underestimate.

    ReplyDelete
  2. I have had PPMS for 16+ years now and have never taken any DMT. About 10 years ago, I had a blood test to check for anaemia and was told that my white blood cell count was low. It's interesting to read that this is not unusual amongst MSers.

    ReplyDelete
  3. Re. "Because of this study's retrospective nature, lymphocyte subsets were not available, and these are important."
    I was wondering about this too and also if it could be an idea to ask for the 3 monthly Tec blood monitoring to include subsets.

    ReplyDelete
  4. That's interesting to me. Mine were only 1.4 at baseline and after 16 months of tecfidera have dropped to 0.7. So now I'm on monthly tests to keep a closer eye on it. I'm not entirely sure what happens if they drop lower as it won't be because a DMT failed for efficacy so I guess I can't escalate, just switch. And although I would have been able to access Alemtuzumab after my first recognised relapse, I'm not sure whether I qualify any more as I haven't had a relapse since starting Tecfidera. And CRAB drugs aren't of interest.

    ReplyDelete
  5. I get my blood tested regularly since my pulmonary embolism in November- here are my figures:

    Nov 2015 Lymph%auto 42.0
    Mar 2016 lymph%auto 42.8
    Aug 2016 lymph%auto 52.2

    I had thought this related to MS and clotting.

    ReplyDelete
    Replies
    1. If MS is a question of lack of balance in a system; would the symptom be low or high rather than only low?

      Delete
  6. Not directly related, but this reminded me of an interesting point from one of Prof Muraro's papers on HSCT, which I'd meant to ask you about on here.

    In it, he refers to (treatment naïve) MS'ers having age-inappropriate TREC levels, suggesting an intrinsic impairment of thymic export.

    Compared to gender & age-matched healthy patients, TREC expressing CD4s & CD8s in MS'ers were at levels equivalent to 30-years-older healthy controls.

    Interestingly, post-therapy, the TREC levels doubled at 2yrs vs pre-therapy - suggesting HSCT can correct the pre-existing deficiency and normalize naive T cell homeostasis.

    Is this something you're familiar with and see elsewhere? Found another reference to it in the paper below, but have not seen it mentioned elsewhere... Pretty old paper to be fair. Is this still a thing, or debunked?

    http://www.ncbi.nlm.nih.gov/pubmed/12817027

    Thanks
    Matt

    ReplyDelete

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