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J Neurol Neurosurg Psychiatry. 2015 Jun;86(6):686-91. doi: 10.1136/jnnp-2014-307708. Epub 2014 Jul 29.

Effective treatment with intravenous immunoglobulins reduces autoreactive T-cell response in patients with CIDP.

Author information

1
Department of Neurology, University Hospital Charité, Berlin, Germany.
2
Institute of Medical Immunology, Charité, Berlin Department of Immunology, Labor Berlin Charité
3
Department of Neurology, St. Josefs Krankenhaus Potsdam, Potsdam, Germany.

Abstract

OBJECTIVE:

To investigate changes in autoreactive T-cell responses against PMP-22 and P2 antigen as well as a T-cell memory repertoire in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) induced by repeated intravenous immunoglobulin (IVIg) treatment.

METHODS:

In an observational trial, we prepared cryopreserved human peripheral blood monocytes from blood from 34 patients with CIDP (18 treatment naïve and 16 maintenance IVIg treatment) and from 14 healthy controls (non-immune neuropathy and healthy control). Treatment response was defined by clinical evaluation. The autoantigen-specific T-cell response was analysed by enzyme linked immunosorbent spot (ELISPOT) assay before IVIg start (baseline) and at follow-up. The T-cell memory subsets were analysed by using flow cytometric analysis.

RESULTS:

Myelin-derived P2-specific and PMP-22-specific IFN-γ producers were increased in IVIg responders compared with non-responders before treatment, which decreased by repeated IVIg infusion cycles. Treatment responders but not non-responders showed higher frequencies of CD4 T effector memory (TEM) and T central memory frequencies at baseline compared with maintenance IVIg treatment patients and controls. In addition, IVIg treatment was associated with a significant reduction in CD8 TEM at follow-up.

CONCLUSIONS:

Our data demonstrate that immunomodulatory treatment with IVIgs on a long-term basis reduces the autoreactive T-cell response against PMP-22 and P2-antigens, which may be influenced by the altered maintenance of CD8 and CD4 effector/memory T-cell subsets towards a more anti-inflammatory immune status. Elevated PMP-22 and P2-specific T-cell responses may serve as predictors for treatment responsiveness to IVIgs warranting validation in larger studies.

KEYWORDS:

Neuropathy

PMID:
25074566
DOI:
10.1136/jnnp-2014-307708
[Indexed for MEDLINE]

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