T cells, fibroblast-like synoviocytes, and granzyme B+ cytotoxic cells are associated with joint damage in patients with recent onset rheumatoid arthritis

Background CD8+ T cells and natural killer (NK) cells are cytotoxic cells that use granzyme B (GrB) and perforin. Defective cytotoxic function is known to play a role in dysregulated immune response as seen in chronic sinusitis, also referred to as chronic rhinosinusitis (CRS). However, to our knowledge, in the United States, neither GrB or perforin expression has been reported in patients with CRS. Objective The aim of this study was to investigate sinonasal cytotoxic cells, their mediators, and cell-specific distribution of these mediators in patients with CRS with nasal polyp (CRSwNP) and in patients with CRS without nasal polyp (CRSsNP). Methods Blood and sinus tissue samples were taken from patients with CRSsNP (n = 8) and CRSwNP (n = 8) at the time of surgery. Control subjects (n = 8) underwent surgery for cerebrospinal fluid leak repair or to remove non-hormone-secreting pituitary tumors. The cells were analyzed via flow cytometry by using CD8 expression to identify cytotoxic T cells and CD56 expression to identify NK cells. Intracellular GrB and perforin expression were analyzed with flow cytometry. Results We observed no significant differences in plasma or peripheral blood immune cell numbers or specific levels of GrB or perforin among the groups. In the sinonasal mucosa of the patients with CRSsNP and the patients with CRSwNP, there was a significant decrease in GrB and perforin levels (p <0.05) despite similar or increased numbers of cytotoxic cells when compared with the controls. The overall decrease in GrB and perforin in the sinonasal mucosa of the patients with CRSsNP and the patients with CRSwNP was due to decreased T cell production. There was no difference in total NK cell count or expression of perforin or GrB among all the groups. Conclusion Total levels of sinonasal GrB and perforin were decreased in the sinonasal mucosa of both the patients with CRSwNP and the patients with CRSsNP compared with the controls, whereas sinonasal CD8+ T cells, (but not NK cells,), intracellular stores of GrB and perforin were reduced in the patients with CRSwNP compared with the controls.

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DAS-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2008.097683 ◽

2009 ◽

Vol 69 (01) ◽

pp. 65-69 ◽

Cited By ~ 85

Author(s):

Y P M Goekoop-Ruiterman ◽

J K de Vries-Bouwstra ◽

P J S M Kerstens ◽

M M J Nielen ◽

K Vos ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Disease Activity Score ◽

Controlled Trial ◽

Joint Damage ◽

Routine Care ◽

Activity Score ◽

Recent Onset ◽

Group A ◽

Group B

Objectives:To compare the efficacy of Disease Activity Score (DAS)-driven therapy and routine care in patients with recent-onset rheumatoid arthritis.Methods:Patients with recent-onset rheumatoid arthritis receiving traditional antirheumatic therapy from either the BeSt study, a randomised controlled trial comparing different treatment strategies (group A), or two Early Arthritis Clinics (group B) were included. In group A, systematic DAS-driven treatment adjustments aimed to achieve low disease activity (DAS ⩽2.4). In group B, treatment was left to the discretion of the treating doctor. Functional ability (Health Assessment Questionnaire (HAQ)), Disease Activity Score in 28 joints (DAS28) and Sharp/van der Heijde radiographic score (SHS) were evaluated.Results:At baseline, patients in group A (n = 234) and group B (n = 201) had comparable demographic characteristics and a mean HAQ of 1.4. Group A had a longer median disease duration than group B (0.5 vs 0.4 years, p = 0.016), a higher mean DAS28 (6.1 vs 5.7, p<0.001), more rheumatoid factor-positive patients (66% vs 42%, p<0.001) and more patients with erosions (71% vs 53%, p<0.001). After 1 year, the HAQ improvement was 0.7 vs 0.5 (p = 0.029), and the percentage in remission (DAS28 <2.6) 31% vs 18% (p<0.005) in groups A and B, respectively. In group A, the median SHS progression was 2.0 (expected progression 7.0), in group B, the SHS progression was 1.0 (expected progression 4.4).Conclusions:In patients with recent-onset rheumatoid arthritis receiving traditional treatment, systematic DAS-driven therapy results in significantly better clinical improvement and possibly improves the suppression of joint damage progression.

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A8.9 Rheumatoid arthritis synovial IL-21 + CD4+ t cells specifically induce matrix metalloproteinase production by fibroblast-like synoviocytes

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2013-205124.183 ◽

2014 ◽

Vol 73 (Suppl 1) ◽

pp. A79.2-A79 ◽

Cited By ~ 1

Author(s):

M Cristina Lebre ◽

Pedro L Vieira ◽

Saida Aarrass ◽

Thomas Newsom-Davis ◽

Paul P Tak ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

Matrix Metalloproteinase ◽

Cd4 T Cells ◽

Fibroblast Like Synoviocytes

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Associations of Alcohol Use with Radiographic Disease Progression in African Americans with Recent-onset Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.121325 ◽

2013 ◽

Vol 40 (9) ◽

pp. 1498-1504 ◽

Cited By ~ 3

Author(s):

Marshall L.R. Davis ◽

Kaleb Michaud ◽

Harlan Sayles ◽

Doyt L. Conn ◽

Larry W. Moreland ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

African Americans ◽

Alcohol Consumption ◽

Alcohol Use ◽

Disease Progression ◽

Joint Damage ◽

Alcoholic Beverages ◽

Recent Onset ◽

Increased Risk ◽

Radiographic Disease

Objective.To investigate the associations of alcohol consumption and radiographic disease progression in African Americans with recently diagnosed rheumatoid arthritis (RA).Methods.Patients with RA included in the study were participants in the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) registry. Patients were categorized based on self-reported alcohol consumption; those consuming < 15 beverages per month versus those with ≥ 15 per month. Association of radiographic disease progression over a 1-year to 3-year period of observation with alcohol consumption was evaluated using multivariate generalized estimating equations.Results.Of 166 patients included in the study, 39% reported that they had never consumed alcohol. Of the 61% who had consumed alcohol, 73% reported that they consumed on average < 15 alcoholic beverages per month and 27% reported consuming ≥ 15 per month. In multivariate analysis, consumption of ≥ 15 alcoholic beverages per month was associated with an increased risk of radiographic disease progression (p = 0.017). There was no evidence of a relationship in those consuming < 15 beverages per month (p = 0.802).Conclusion.There appears to be a dose-dependent relationship between alcohol use and radiographic disease progression in RA. Individuals who consume 15 or more alcoholic beverages per month may have faster rates of radiographic joint damage than those with lower levels of consumption.

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Genetic Polymorphisms of Foxp3 in Patients with Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.131381 ◽

2014 ◽

Vol 42 (2) ◽

pp. 170-180 ◽

Cited By ~ 14

Author(s):

Agnieszka Paradowska-Gorycka ◽

Monika Jurkowska ◽

Anna Felis-Giemza ◽

Katarzyna Romanowska-Próchnicka ◽

Malgorzata Manczak ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

Gene Polymorphisms ◽

Multiple Testing ◽

Joint Damage ◽

Phenotype Analysis ◽

Laboratory Variables ◽

Polymorphic Variants ◽

Polymerase Chain ◽

Extraarticular Manifestation

Objective.The aim of the study was to identify 2 polymorphic variants in the promoter region of the Foxp3 gene and their possible association with susceptibility to and severity of rheumatoid arthritis (RA). The association between genetic factors and pathogenesis suggests that T cells take part in the induction of RA. The CD4+CD25highFoxp3+ subset of regulatory T cells plays an essential role in preventing autoimmunity and maintaining immune homeostasis.Methods.Patients with RA (n = 274) and healthy individuals (n = 295) were examined for −3279 C/A and −924 A/G Foxp3 gene polymorphisms by the polymerase chain reaction–restriction fragment-length polymorphism method. Serum Foxp3 levels in patients with RA and controls were measured with ELISA.Results.Foxp3 −3279 A and −924 G alleles were associated with significantly elevated risk of RA in the population tested (p = 0.003 and p = 0.004, respectively) compared to the wild-type alleles. Overall, −3279 C/A and −924 A/G Foxp3 gene polymorphisms were in indistinct linkage disequilibrium with D′ = 0.481 and r2 = 0.225. From 4 possible haplotypes, frequencies of 2 (AG and CA) showed significant differences between both examined groups (respectively, p < 0.001 and p = 0.007). After appropriate adjustment of Bonferroni correction for multiple testing, the genotype-phenotype analysis showed no significant correlation of the Foxp3 −3279 C/A and −924 A/G polymorphisms with the disease activity, joint damage, laboratory variables, and extraarticular manifestation in patients with RA. Serum Foxp3 level was significantly higher in patients than in controls (p < 0.0001).Conclusion.Current findings indicated that the Foxp3 genetic polymorphism and the Foxp3 protein level may be associated with susceptibility to RA in the Polish population.

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