Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

CD49d blockade by natalizumab therapy in patients with multiple sclerosis increases immature B-lymphocytes

Bone Marrow Transplantation volume 46, pages 1489–1491 (2011)Cite this article

Subjects

We read with interest the paper of Jing et al.1 dealing with CD49d blockade by natalizumab in patients with multiple sclerosis (MS) resulting in mobilization of progenitors with a distinct phenotype and function. Compared with healthy controls and untreated MS patients, natalizumab treatment increased CD34+ cells in the peripheral blood and in the BM. Moreover, the CD34+ cells of natalizumab-treated patients expressed lower levels of adhesion molecules (L-selectin, LFA-1 and PECAM-1) than G-CSF-mobilized CD34+ cells. Natalizumab is an anti-α4 integrin humanized IgG4 MoAB that blocks α4β1-(also referred as very late activation Ag (VLA)-4 integrin or CD49d) mediated leukocyte migration. It consequently prevents extravasation of all leukocytes except polymorphonuclears that do not express VLA-4.2 Secondary effects of natalizumab include mild leukocytosis with lymphocytosis and decreased numbers of B and T lymphocytes in the cerebrospinal fluid,3 but have been poorly investigated.4 We checked the peripheral blood lymphocytes of seven patients (from a series of 10)5 before and during Natalizumab treatment and demonstrated an increase of immature B cells with a particular pattern of adhesion molecules.

In conclusion, our data validate those previously generated by Jing et al.1 and further study the side effects of natalizumab on lymphopoiesis of MS patients. The peripheral blood lymphocytosis observed after natalizumab therapy in MS patients appeared as an immediate side effect. The immunophenotypic profile CD5–, CD10–, CD27–, IgMdim and IgDbright is consistent with an immature ‘naive’ B-cell subset, recently egressed from the BM and not activated (CD25–, CD38low). Upregulation of CD4+ and CD8+ T cells was less convincing suggesting a different effect of natalizumab on the medullary and thymic environments. The adhesion molecule profile seems to be favorable for the patients, protecting them from progressive multifocal leukoencephalopathy in preventing damaging immune cells from crossing the blood–brain barrier.8

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Jing D, Oelschlaegel U, Ordemann R, Hölig K, Ehninger G, Reichmann H et al. CD49d blockade by natalizumab in patients with multiple sclerosis affects steady-state hematopoiesis and mobilizes progenitors with a distinct phenotype and function. Bone Marrow Transplant 2010; 45: 1489–1496.

    Article  CAS  PubMed  Google Scholar 

  2. Stüve O . The effects of natalizumab on the innate and adaptive immune system in the nervous system. J Neurological Sci 2008; 274: 39–41.

    Article  Google Scholar 

  3. Stüve O, Marra CM, Jerome KR, Cook L, Cravens PD, Cepok S et al. Immune surveillance in multiple sclerosis patients treated with natalizumab. Annal Neurol 2006; 59: 743–747.

    Article  PubMed  Google Scholar 

  4. Krumbholz M, Meinl I, Kumpfel T, Hohleld R, Meinl E . Natalizumab disproportionately increases circulating pre-B and B cells in multiple sclerosis. Neurology 2008; 71: 1350–1354.

    Article  CAS  PubMed  Google Scholar 

  5. Lesesve JF, Debouverie M, Decarvalho M, Pittion-Vouyovitch S, Grégoire MJ, Béné MC . Peripheral blood lymphocytosis characterization after Natalizumab therapy in patients with multiple sclerosis (submitted).

  6. Leclerc M, Lesesve JF, Gaillard B, Troussard X, Tourbah A, Debouverie M et al. Binucleated lymphocytes in multiple sclerosis patients treated with natalizumab. Leuk Lymphoma (accepted).

  7. Le Naour F, André M, Boucheix C, Rubinstein E . Membrane microdomains and proteomics: lessons from tetraspanin microdomains and comparison with lipid rafts. Proteomics 2006; 6: 6447–6454.

    Article  CAS  PubMed  Google Scholar 

  8. Stüve O, Eagar TN . B cells, antibodies, and tertiary lymphoid tissue in MS brains. Lancet Neurol 2008; 7: 766–767.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Hematology, University Hospital, Nancy, France

    J-F Lesesve

  2. Neurology department, University Hospital, Nancy, France

    M Debouverie

  3. Laboratory of Immunology, University Hospital, Nancy, France

    M Decarvalho Bittencourt & M-C Béné

Authors
  1. J-F Lesesve
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Debouverie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Decarvalho Bittencourt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M-C Béné
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J-F Lesesve.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lesesve, JF., Debouverie, M., Decarvalho Bittencourt, M. et al. CD49d blockade by natalizumab therapy in patients with multiple sclerosis increases immature B-lymphocytes. Bone Marrow Transplant 46, 1489–1491 (2011). https://doi.org/10.1038/bmt.2010.328

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.328

This article is cited by

Search

Advanced search

Quick links