ABSTRACTS â ORAL PRESENTATIONS - AMCA, spol. s r.o.
ABSTRACTS â ORAL PRESENTATIONS - AMCA, spol. s r.o.
ABSTRACTS â ORAL PRESENTATIONS - AMCA, spol. s r.o.
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Acknowledgements<br />
This work was supported by a grants from the Slovak Grant Agency VEGA (No.2/0041/10),<br />
(No.2/0134/13) and Grant NFM/EEA SK0095. The authors acknowledge the physicians<br />
(Peter Švec, MD PhD., Halina Vargová, PhD.) from the Department of Pediatric Oncology<br />
of University Children’s Hospital, Bratislava, Slovakia, for submitting patient bone marrow<br />
samples and referrals.<br />
References<br />
Wood, B. Cytometry, 4th Edition New Developments. Elsevier Academic Press 2004;<br />
Methods in Cell Biology 75:559–76.<br />
Fajtova, M., et al. Leuk Lymphoma. 2013 Apr 23. [Epub ahead of print]<br />
Malcovati, L., et al. Leukemia 2005; 19:776–783.<br />
Matarraz, S., et al. Cytometry Part B. 2010; 78B:154–168.<br />
42. EFFECTS OF NATALIZUMAB ON CD4+CD25HIGH LYMPHOCYTES<br />
Helena Mareckova 1 , Zdenka Hruskova 1 , Lucia Skacikova 1 , Eva Havrdova 2<br />
1<br />
Inst. Immunology and Microbiology, 1 st Medical Faculty, Charles University, Prague<br />
2<br />
MS Centrum Neurology Clinic, 1 st Medical Faculty, Charles University, Prague<br />
Background: Natalizumab is a humanized monoclonal antibody directed against very<br />
late activation antigen 4 (VLA-4) and has a potent effect on disease activity in multiple<br />
sclerosis (MS). Blockade of VLA-4 with natalizumab may not only interfere<br />
with autoimmune mechanisms but also with central nervous system immune surveillance.<br />
Methods: Longitudinal study (follow-up between 2 and 5 years) to determine the<br />
effect of natalizumab on the frequency of CD4+CD25high regulatory T cells (Tregs) in<br />
peripheral blood (PB) and in cerebrospinal fluid (CSF). We examined 58 patients with MS<br />
treated with Tysabri (Biogen, Idec) at baseline and during therapy. Using flow cytometry<br />
with six-color imaging (Canto, BD Biosciences) following markers were assessed: CD4,<br />
CD8, CD25, CD28, CCR5 (BD) and CXCR3 (RD) in CSF and PB.<br />
Results: There was a gradual increase in circulating CD4+CD25high lymphocytes in PB<br />
during whole follow-up and marked increase in all patients in CSF between baseline and<br />
control examination. Results from CSF analysis revealed that natalizumab blocks CD4+<br />
more than CD8+ T cells from transmigration<br />
Conclusion: The evidence for the use of natalizumab in MS from clinical trials is strong,<br />
but knowledge on effects on different immune cell populations is limited, especially for<br />
CSF. Impairment of the inhibitory function of Tregs seems to play a role in MS disease<br />
pathogenesis. Direct effects of natalizumab on T cell function have been proposed to<br />
promote some of the effects in MS, and VLA-4 blockade has been reported to modulate<br />
the activation state of CD4+ T cells. Thus, natalizumab may positively influence frequency<br />
of Tregs.<br />
Supported by IGA MZ NT / 13108 – 4<br />
Analytical Cytometry VII 63