THU0111 T-Cell Subsets in Lymph Node Biopsies of Autoantibody Positive Subjects at Risk of Rheumatoid Arthritis (RA) and Early RA Patients

Rheumatoid arthritis (RA) is a chronic, inflammatory disease of the synovium of uncertain pathogenesis. A number of phenotypic and functional T-cell defects have been described in RA, including abnormal clonal expansions and suppressed proliferative responses, which suggest a defect in T-cell differentiation. Here, we show that RA patients possess fewer naive CD4+ T cells than healthy controls. Furthermore, a smaller proportion of these cells contains a T-cell receptor excision circle (TREC). Patients with RA also have unusual populations of T cells. These include immature cells characterized as CD45RBbrightCD45RA+CD62L− by flow cytometry and a large population that coexpresses CD45RA and CD45RO. These cells are hyperresponsive to mitogen and TCR stimulation when compared to naive cells. Additionally, an unusual putative central memory subset expressing CD62L, but not CD45RA, appears in RA patients at the expense of more typical cells. Levels of C-reactive protein correlate inversely with the TREC content of naive T cells and positively with the sizes of naive and immature atypical T-cell subsets. These data suggest that inflammation drives proliferation of naive T cells in RA and encourages their differentiation into atypical, hyperresponsive progeny. TREC content of individual naive and atypical T-cell subsets suggests an ontogeny consistent with this hypothesis. These studies provide further evidence of a T-cell differentiation defect in RA, which could explain some of the well-characterized immunologic features of the disease.

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The Effect of Low Doses of Prednisolone on T-Cell Subsets in Rheumatoid Arthritis

Protides of the Biological Fluids ◽

10.1016/b978-0-08-030764-0.50158-0 ◽

1984 ◽

pp. 687-690

Author(s):

G. VERBRUGGEN ◽

E.M. VEYS ◽

PH. HERMANNS ◽

J. DELANGHE ◽

M. VAN STEENKISTE

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

T Cell Subsets ◽

Low Doses

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Dysbiosis in the oral microbiomes of anti-CCP positive individuals at risk of developing rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-216972 ◽

2020 ◽

pp. annrheumdis-2020-216972

Author(s):

Zijian Cheng ◽

Thuy Do ◽

Kulveer Mankia ◽

Josephine Meade ◽

Laura Hunt ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

At Risk ◽

Risk Group ◽

Orthologous Gene ◽

Oral Microbiome ◽

Periodontal Pathogen ◽

P Value ◽

Illumina Hiseq ◽

Early Ra ◽

Taxonomic Profile

ObjectivesAn increased prevalence of periodontitis and perturbation of the oral microbiome has been identified in patients with rheumatoid arthritis (RA). The periodontal pathogen Porphyromonas gingivalis may cause local citrullination of proteins, potentially triggering anti-citrullinated protein antibody production. However, it is not known if oral dysbiosis precedes the onset of clinical arthritis. This study comprehensively characterised the oral microbiome in anti-cyclic citrullinated peptide (anti-CCP) positive at-risk individuals without clinical synovitis (CCP+at risk).MethodsSubgingival plaque was collected from periodontally healthy and diseased sites in 48 CCP+at risk, 26 early RA and 32 asymptomatic healthy control (HC) individuals. DNA libraries were sequenced on the Illumina HiSeq 3000 platform. Taxonomic profile and functional capability of the subgingival microbiome were compared between groups.ResultsAt periodontally healthy sites, CCP+at risk individuals had significantly lower microbial richness compared with HC and early RA groups (p=0.004 and 0.021). Microbial community alterations were found at phylum, genus and species levels. A large proportion of the community differed significantly in membership (523 species; 35.6%) and structure (575 species; 39.1%) comparing CCP+at risk and HC groups. Certain core species, including P. gingivalis, had higher relative abundance in the CCP+at risk group. Seventeen clusters of orthologous gene functional units were significantly over-represented in the CCP+at risk group compared with HC (adjusted p value <0.05).ConclusionAnti-CCP positive at-risk individuals have dysbiotic subgingival microbiomes and increased abundance of P. gingivalis compared with controls. This supports the hypothesis that the oral microbiome and specifically P. gingivalis are important in RA initiation.

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Relevance of involvement of tofacitinib in T cell subsets to clinical courses and adverse events in patients with rheumatoid arthritis

Japanese Journal of Clinical Immunology ◽

10.2177/jsci.38.443 ◽

2015 ◽

Vol 38 (6) ◽

pp. 443-447 ◽

Cited By ~ 1

Author(s):

Koshiro SONOMOTO ◽

Yohisya TANAKA

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

Adverse Events ◽

T Cell Subsets

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Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial)

Annals of the Rheumatic Diseases ◽

10.1136/ard.2009.119016 ◽

2009 ◽

Vol 69 (3) ◽

pp. 510-516 ◽

Cited By ~ 147

Author(s):

P Emery ◽

P Durez ◽

M Dougados ◽

C W Legerton ◽

J-C Becker ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

Early Stage ◽

Imaging Study ◽

Serious Adverse Events ◽

Double Blind ◽

Early Ra ◽

Acr Criteria ◽

Very Early Ra ◽

The Impact

BackgroundSeveral agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA.ObjectiveTo determine the impact of T-cell costimulation modulation in patients with UA or very early RA.MethodsIn this double-blind, phase II, placebocontrolled, 2-year study, anti-cyclic citrullinated peptide (CCP)2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of two or more joints were randomised to abatacept (∼10 mg/kg) or placebo for 6 months; the study drug was then terminated. The primary end point was development of RA (by ACR criteria) at year 1. Patients were monitored by radiography, MRI, CCP2, rheumatoid factor and 28 joint count Disease Activity Score (DAS28) over 2 years.ResultsAt year 1, 12/26 (46%) abatacept-treated versus 16/24 (67%) placebo-treated patients developed RA (difference (95% CI) −20.5% (−47.4% to 7.8%)). Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients, respectively, were 0 versus 1.1 for total score, and 0 versus 0.9 for erosion score. Mean changes from baseline to year 1 in MRI erosion, osteitis and synovitis scores were 0, 0.2 and 0.2, respectively, versus 5.0, 6.7 and 2.3 in the abatacept versus placebo groups. Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group.ConclusionAbatacept delayed progression of UA/very early RA in some patients. An impact on radiographic and MRI inhibition was seen, which was maintained for 6 months after treatment stopped. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease.Trial registration numberNCT00124449.

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