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Eur J Immunol. 2016 Dec;46(12):2812-2821. doi: 10.1002/eji.201646393. Epub 2016 Oct 12.

Lymph node biopsy analysis reveals an altered immunoregulatory balance already during the at-risk phase of autoantibody positive rheumatoid arthritis.

Author information

1
Amsterdam Rheumatology and Immunology Center (ARC), Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
2
Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
3
Department of Radiology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
4
Clinical Unit Cambridge, GlaxoSmithKline, Cambridge, UK.
5
University of Cambridge, Cambridge, UK.
6
Ghent University, Ghent, Belgium.
7
GlaxoSmithKline, Stevenage, UK.

Abstract

The balance between proinflammatory and regulatory CD4+ T cells is tightly controlled in lymphoid organs. In autoimmune diseases this balance is altered in the periphery and target tissue of patients. However, not much is known about the balance initiated in lymphoid organs during the development of disease. Since systemic autoimmunity is present years before the clinical manifestations of rheumatoid arthritis (RA), it is possible to study the immunoregulatory balance during the earliest (preclinical) phases of disease. Here, we report for the first time the frequency and phenotype of proinflammatory and regulatory CD4+ T cells in lymph node biopsies obtained from autoantibody positive individuals at risk for developing RA, patients with established disease and healthy controls. The frequency of proinflammatory LN Th1 cells was increased in RA patients compared with HCs, while the frequency of regulatory T cells was lower in LN biopsies of RA-risk individuals. Upon in vitro stimulation LN CD4+ T cells produced lower levels of proinflammatory cytokines, IFN-γ and IL-17A, in both RA-risk individuals and early RA patients. This study shows that already during the earliest phases of systemic autoimmunity the immunoregulatory balance between proinflammatory and regulatory CD4+ T cells is altered in LN tissue.

KEYWORDS:

Autoimmunity; Cytokines; Lymph node; Rheumatoid arthritis; T cells; Th1; Th17

PMID:
27645315
PMCID:
PMC5157721
DOI:
10.1002/eji.201646393
[Indexed for MEDLINE]
Free PMC Article

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