Recovery of the T-cell repertoire in CIDP by IV immunoglobulins
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Abstract
Objective: To investigate changes in the T-cell repertoire in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) without and with treatment of IV immunoglobulins (IVIg).
Methods: The T-cell receptor (TCR) repertoire of CD4+ and CD8+ T cells in the peripheral blood was analyzed using CDR3 spectratyping. Patients with CIDP were included without (n = 14) and with IVIg treatment (n = 11) cross-sectionally and longitudinally (n = 2).
Results: While the TCR length distribution of patients with CIDP was only moderately altered for most of the Vβ elements of CD4+ T cells, the CD8+ population displayed extensive oligoclonal expansions in all analyzed 24 Vβ elements. A public expansion of a distinct TCR length in one Vβ element within a majority of affected patients was not detectable. Treatment with IVIg reduced the oligoclonal expansions within both the CD4+ and CD8+ population.
Conclusions: Our data demonstrate that cytotoxic CD8+ T cells exhibit a much broader activation than CD4+ T cells, indicating a potentially crucial role of CD8+ T cells in the immunopathogenesis of CIDP. The profound oligoclonal response in T-cell activation suggests that multiple peptides may induce and propagate this autoimmune-driven disease. The observed reduction of highly activated T cells may contribute to the therapeutic effects of IVIg.
GLOSSARY
- CDR3=
- complementarity determining region 3;
- CIDP=
- chronic inflammatory demyelinating neuropathy;
- EBV=
- Epstein-Barr virus;
- HC=
- healthy controls;
- INCAT=
- inflammatory neuropathy cause and treatment;
- IVIg=
- IV immunoglobulin;
- MHC=
- major histocompatibility complex;
- NIN=
- noninflammatory neuropathy;
- TCR=
- T-cell receptor
Footnotes
↵* These authors contributed equally to this work.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received May 19, 2012.
- Accepted September 7, 2012.
- © 2012 American Academy of Neurology
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