RT Journal Article
SR Electronic
T1 Alemtuzumab long-term immunologic effect
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e194
DO 10.1212/NXI.0000000000000194
VO 3
IS 1
A1 De Mercanti, Stefania
A1 Rolla, Simona
A1 Cucci, Angele
A1 Bardina, Valentina
A1 Cocco, Eleonora
A1 Vladic, Anton
A1 Soldo-Butkovic, Silva
A1 Habek, Mario
A1 Adamec, Ivan
A1 Horakova, Dana
A1 Annovazzi, Pietro
A1 Novelli, Francesco
A1 Durelli, Luca
A1 Clerico, Marinella
YR 2016
UL http://nn.neurology.org/content/3/1/e194.abstract
AB Objective: To analyze changes in T-helper (Th) subsets, T-regulatory (Treg) cell percentages and function, and mRNA levels of immunologically relevant molecules during a 24-month follow-up after alemtuzumab treatment in patients with relapsing-remitting multiple sclerosis (RRMS).Methods: Multicenter follow-up of 29 alemtuzumab-treated patients with RRMS in the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I and CARE-MS II trials. Peripheral blood (PB) samples were obtained at months 0, 6, 12, 18, and 24. We evaluated (1) mRNA levels of 26 immunologic molecules (cytokines, chemokines, chemokine receptors, and transcriptional factors); (2) Th1, Th17, and Treg cell percentages; and (3) myelin basic protein (MBP)–specific Treg suppressor activity.Results: We observed 12 relapses in 9 patients. mRNA levels of the anti-inflammatory cytokines interleukin (IL)–10, IL-27, and transforming growth factor–β persistently increased whereas those of proinflammatory molecules related to the Th1 or Th17 subsets persistently decreased after alemtuzumab administration throughout the follow-up period. PB CD4+ cell percentage remained significantly lower than baseline while that of Th1 and Th17 cells did not significantly change. A significant increase in Treg cell percentage was observed at month 24 and was accompanied by an increase in Treg cell suppressive activity against MBP-specific Th1 and Th17 cells.Conclusions: The long-lasting therapeutic benefit of alemtuzumab in RRMS may involve a shift in the cytokine balance towards inhibition of inflammation associated with a reconstitution of the PB CD4+ T-cell subsets that includes expansion of Treg cells with increased suppressive function.BBB=blood–brain barrier; CARE-MS=Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CCL=C-C motif ligand; CCR=C-C chemokine receptor; CXCL=C-X-C motif ligand; CXCR=C-X-C chemokine receptor; EDSS=Expanded Disability Status Scale; ELISPOT=enzyme-linked immunospot; FACS=fluorescence-activated cell sorting; FoxP3=forkhead box P3; IFN=interferon; IL=interleukin; mAb=monoclonal antibodies; MBP=myelin basic protein; MS=multiple sclerosis; PB=peripheral blood; PBMC=peripheral blood mononuclear cells; PPD=purified protein derivative of tuberculin; RORC=retinoid-related orphan receptor γ; RR=relapsing-remitting; Tbet=T-box expressed in T cells; TGF=transforming growth factor; Th=T-helper; TNF=tumor necrosis factor; Treg=T-regulatory cells; VLA=very late antigen