CD4 T-cell transcriptome analysis reveals aberrant regulation of STAT3 and Wnt signaling pathways in rheumatoid arthritis: evidence from a case–control study

Abstract Background T cell cytokines play important roles in the development and progression of rheumatoid arthritis (RA). Loss of Th1/Th2 and Th17/Treg balance has been reported in several inflammatory autoimmune diseases. However, their role in RA within the Ghanaian context has not been explored. Here, we evaluated the intracytoplasmic CD4 + T cell cytokine patterns in rheumatoid arthritis patients in Ghana and determined their relationship with disease activity. Methods This case-control study included 48 newly-diagnosed RA patients and 30 healthy controls from two major hospitals in Ghana. Validated structured questionnaires were administered to obtain demographic data; blood samples were collected and processed for flow cytometric analysis. Results IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17A, IL-6/IL-4 and IL-17/IL-10 expression were significantly higher in RA cases compared to the healthy controls. The expression of IL-6 (0.00 (0.00-0.98) vs 0.82 (0.34–1.10) vs 1.56 (1.39–1.68), p < 0.0001), IL-17A (0.00 (0.00-0.02) vs 0.19 (0.09–0.30) vs 0.99 (0.64–1.25), p < 0.0001) and IL-17A/IL-10 (0.00 (0.00-0.39) vs 0.15 (0.09–0.26) vs 0.88 (0.41–1.47), p < 0.0001) increased significantly from the healthy controls through RA patients with low DAS scores to RA patients with moderate DAS scores. IL-6 (β = 0.681, r2 = 0.527, p < 0.0001), IL-17A (β = 0.770, r2 = 0.593, p < 0.0001) and IL-17A/IL-10 (β = 0.677, r2 = 0.452, p < 0.0001) expression were significantly directly associated with DAS28 scores. IL-6 (Cutoff = 1.32, Sensitivity = 100.0%, Specificity = 100.0%, Accuracy = 100.0%, AUC = 1.000) and IL-17A (Cutoff = 0.58, Sensitivity = 100.0%, Specificity = 100.0%, Accuracy = 100.0%, AUC = 1.000) presented with the best discriminatory power in predicting moderate DAS scores from low DAS scores. Conclusion Th1 and Th17 related cytokines predominate in the pathophysiology of RA; with IL-6 and IL-17 being principally and differentially expressed based on the severity of the disease. IL-6 and IL-17A could serve as useful prognostic and disease-monitoring markers in RA in the African context.

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Intracytoplasmic Expression of IL-6 and IL-17A in Circulating CD4+ T Cells Are Strongly Associated with and Predict Disease Activity in Rheumatoid Arthritis: A Case-Control Study in Ghana

International Journal of Rheumatology ◽

10.1155/2020/2808413 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Samuel Asamoah Sakyi ◽

Tonnies Abeku Buckman ◽

Daniel Antwi-Berko ◽

Kwame Yeboah-Mensah ◽

Dzifa Dey ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

Disease Activity ◽

Case Control Study ◽

Demographic Data ◽

Flow Cytometric Analysis ◽

Case Control ◽

Healthy Controls ◽

Severity Of The Disease ◽

Control Study

Background. T cell cytokines play important roles in the development and progression of rheumatoid arthritis (RA). Loss of Th1/Th2 and Th17/Treg balance has been reported in several inflammatory autoimmune diseases. However, their role in RA within hitherto rare Ghanaian context has not been explored. Here, we evaluated the intracytoplasmic CD4+ T cell cytokine patterns in rheumatoid arthritis patients in Ghana and determined their relationship with disease activity. Methods. This case-control study included 48 newly diagnosed RA patients and 30 apparent healthy controls from two major hospitals in Ghana. Validated structured questionnaires were administered to obtain demographic data; blood samples were collected and processed for flow cytometric analysis. Results. IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17A, IL-6/IL-4, and IL-17/IL-10 expressions were significantly higher in RA cases compared to the healthy controls. The expression of IL-6 (0.00 (0.00-0.98) vs. 0.82 (0.34-1.10) vs. 1.56 (1.39-1.68), p<0.0001), IL-17A (0.00 (0.00-0.02) vs. 0.19 (0.09-0.30) vs. 0.99 (0.64-1.25), p<0.0001), and IL-17A/IL-10 (0.00 (0.00-0.39) vs. 0.15 (0.09-0.26) vs. 0.88 (0.41-1.47), p<0.0001) increased significantly from the healthy controls through RA patients with low DAS scores to RA patients with moderate DAS scores. IL-6 (β=0.681, r2=0.527, p<0.0001), IL-17A (β=0.770, r2=0.593, p<0.0001), and IL-17A/IL-10 (β=0.677, r2=0.452, p<0.0001) expressions were significantly directly associated with DAS28 scores. IL-6 (cutoff=1.32, sensitivity=100.0%, specificity=100.0%, accuracy=100.0%, and AUC=1.000) and IL-17A (cutoff=0.58, sensitivity=100.0%, specificity=100.0%, accuracy=100.0%, and AUC=1.000) presented with the best discriminatory power in predicting moderate DAS scores from low DAS scores. Conclusion. Th1- and Th17-related cytokines predominate in the pathophysiology of RA, with IL-6 and IL-17 being principally and differentially expressed based on the severity of the disease. IL-6 and IL-17A could serve as useful prognostic and disease-monitoring markers in RA in the African context.

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Low CD4 T cell count predicts radiological progression in severe and critically ill COVID-19 patients: a case control study

Journal of Thoracic Disease ◽

10.21037/jtd-20-1848 ◽

2021 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Qingqing Wang ◽

Yumeng Yao ◽

Zheyong Huang ◽

Jiatian Cao ◽

Chouwen Zhu ◽

...

Keyword(s):

T Cell ◽

Cell Count ◽

Critically Ill ◽

Case Control Study ◽

Case Control ◽

Cd4 T Cell ◽

Radiological Progression ◽

Cd4 T Cell Count ◽

Control Study

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Predictors of Late HIV Diagnosis among Adult People Living with HIV/AIDS Who Undertake an Initial CD4 T Cell Evaluation, Northern Ethiopia: A Case-Control Study

PLoS ONE ◽

10.1371/journal.pone.0140004 ◽

2015 ◽

Vol 10 (10) ◽

pp. e0140004 ◽

Cited By ~ 7

Author(s):

Melkamu Bedimo Beyene ◽

Habtamu Bedimo Beyene

Keyword(s):

T Cell ◽

Case Control Study ◽

Case Control ◽

Cd4 T Cell ◽

People Living With Hiv ◽

Northern Ethiopia ◽

Hiv Diagnosis ◽

Late Hiv Diagnosis ◽

Living With Hiv ◽

Control Study

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Serum Complement C3 and Type 2 Diabetes in Rheumatoid Arthritis: A Case-Control Study

Reviews on Recent Clinical Trials ◽

10.2174/1574887113666180314092757 ◽

2018 ◽

Vol 13 (3) ◽

pp. 215-221 ◽

Cited By ~ 3

Author(s):

Francesco Ursini ◽

Salvatore D`Angelo ◽

Emilio Russo ◽

Giorgio Ammerata ◽

Ludovico Abenavoli ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Type 2 Diabetes ◽

Case Control Study ◽

Case Control ◽

Complement C3 ◽

Serum Complement ◽

Control Study

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TNF-α Blockers Showed Prophylactic Effects in Preventing COVID-19 in Patients with Rheumatoid Arthritis and Seronegative Spondyloarthropathies: A Case–Control Study

Rheumatology and Therapy ◽

10.1007/s40744-021-00342-8 ◽

2021 ◽

Author(s):

Mansour Salesi ◽

Behrokh Shojaie ◽

Ziba Farajzadegan ◽

Naghmeh Salesi ◽

Erfan Mohammadi

Keyword(s):

Rheumatoid Arthritis ◽

Case Control Study ◽

Case Control ◽

Tnf Α ◽

Seronegative Spondyloarthropathies ◽

Control Study

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SAT0077 CARDIOVASCULAR RISK ASSESSMENT WITH CAROTID ULTRASONOGRAPHY IN ADDITION TO THE TRADITIONAL CARDIOVASCULAR RISK FACTORS IN RHEUMATOID ARTHRITIS PATIENTS: A CASE CONTROL STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6420 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 973-973

Author(s):

R. Gonzalez Mazario ◽

J. J. Fragio-Gil ◽

P. Martinez Calabuig ◽

E. Grau García ◽

M. De la Rubia Navarro ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Risk Factor ◽

Cardiovascular Risk ◽

Disease Duration ◽

Case Control Study ◽

Case Control ◽

Healthy Controls ◽

Carotid Ultrasonography ◽

Control Study

Background:Cardiovascular disease (CV) is the most frequent cause of death in rheumatoid arthritis (RA) patients. It is well known that RA acts as an independent cardiovascular risk factor.Objectives:To assess the CV risk in RA patients using carotid ultrasonography (US) additionally to the traditional CV risk factors.Methods:A prospective transversal case control study was performed, including adult RA patients who fulfilled ACR/EULAR 2010 criteria and healthy controls matched according to CV risk factors. Population over 75 years old, patients with established CV disease and/or chronic kidney failure (from III stage) were excluded. The US evaluator was blinded to the case/control condition and evaluated the presence of plaques and the intima-media thickness. Statistical analysis was performed with R (3.6.1 version) and included a multivariate variance analysis (MANOVA) and a negative binomial regression adjusted by confounding factors (age, sex and CV risk factors).Results:A total of 200 cases and 111 healthy controls were included in the study. Demographical, clinical and US data are exposed in table 1. Not any difference was detected in terms of CV risk factors between the cases and controls. In both groups a relationship between age, BMI and high blood pressure was detected (p<0.001).Table 1.Table 2.RA basal characteristicsDisease duration (years)16,98 (11,38)Erosions (X-Ray of hands/feet)163 (81,5%)Seropositive (RF/anti-CCP)146 (73%)Extra-articular symptoms44 (22%)Intersticial difusse lung disease10 (5%)Rheumatoid nodules14 (7%)Prednisone use103 (51,5%)Median dose of Prednisone last year (mg)2,34 (2,84)sDMARDsMethotrexate104 (52%)Leflunomide29 (14,5%)Hydroxycloroquine9 (4,5%)bDMARDs89 (44,5%) TNFi41 (20,5%) Abatacept15 (7,5%) IL6i22 (11%) RTX11 (5,5%)JAKi26 (13%) Baricitinib11 (5,5%) Tofacitinib15 (7,5%)DAS 28-ESR3,1 (2,3, 3,9)SDAI7,85 (4,04, 13,41)HAQ0,88 (0,22, 1,5)RF (U/mL)51 (15, 164,25)Anti-CCP (U/mL)173 (22, 340)Patients showed higher intima-media (both right and left) thickness compared to controls (p<0.006). Moreover it was also related to the disease duration and DAS28 score (p<0.001). A higher plaque account was noted in cases(p<0.004) and it was also related to the disease duration (p<0.001).Conclusion:RA implies a higher CV risk. Traditional CV risk factors explains only partially the global risk. These findings support that RA acts as an independent cardiovascular risk factor.Disclosure of Interests:None declared

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