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2014 ; 26
(2
): 219-27
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Prospects for therapeutic tolerance in humans
#MMPMID24378931
Baker KF
; Isaacs JD
Curr Opin Rheumatol
2014[Mar]; 26
(2
): 219-27
PMID24378931
show ga
PURPOSE OF REVIEW: To provide an overview of recent advances and future
possibilities for therapeutic tolerance. RECENT FINDINGS: Allograft survival
despite complete immunosuppressant withdrawal has been demonstrated in selected
renal-transplant recipients with haematopoietic chimerism. Early clinical trials
of mesenchymal stromal cell therapy have shown promising results in several
autoimmune diseases. Regulatory T cells show potential benefit in graft versus
host disease, although challenges to ex-vivo expansion remain. Targeted
modulation of T-cell function in vivo with monoclonal antibodies has shown
beneficial effects in phase II/III trials of multiple sclerosis (alemtuzumab) and
type I diabetes mellitus (teplizumab, otelixizumab). Emerging data from animal
models suggest an important role for the commensal microbiome in the maintenance
and disruption of immune tolerance with parallels in human studies. SUMMARY:
After years of slow progress, recent research has reduced the translational gap
between animal models and clinical therapeutic tolerance. Early detection of
autoimmunity, potentially at preclinical stages, offers a window of opportunity
for tolerogenic therapy. Reliable biomarkers of tolerance are urgently needed to
provide objective measurements of the effectiveness of tolerogenic therapies, and
to allow intelligent immunosuppressant withdrawal in patients whose autoimmune
disease is stable. VIDEO ABSTRACT AVAILABLE: See the Video Supplementary Digital
Content 1 (http://links.lww.com/COR/A8).
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