The expressions of Toll-like receptor 9 and T-bet in circulating B and T cells in newly diagnosed, untreated systemic lupus erythematosus and correlations with disease activity and laboratory data in a Chinese population

Objective Hypomethylation of CD40-ligand (CD40L) in T-cells is associated with increased disease activity in systemic lupus erythematosus (SLE). We therefore investigated possible associations of dietary methyl donors and products with CD40L methylation status in SLE. Methods Food frequency questionnaires were employed to calculate methyl donor micronutrients in 61 female SLE patients (age 45.7 ± 12.0 years, disease duration 16.2 ± 8.4 years) and compared to methylation levels of previously identified key DNA methylation sites (CpG17 and CpG22) within CD40L promotor of T-cells using quantitative DNA methylation analysis on the EpiTYPER mass spectrometry platform. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Linear regression modelling was used. P values were adjusted according to Benjamini & Hochberg. Results Amongst the micronutrients assessed (g per day), methionine and cysteine were associated with methylation of CpG17 (β = 5.0 (95%CI: 0.6-9.4), p = 0.04; and β = 2.4 (0.6-4.1), p = 0.02, respectively). Methionine, choline, and cysteine were additionally associated with the mean methylation of the entire CD40L (β = 9.5 (1.0-18.0), p = 0.04; β = 1.6 (0.4-3.0), p = 0.04; and β = 4.3 (0.9-7.7), p = 0.02, respectively). Associations of the SLEDAI with hypomethylation were confirmed for CpG17 (β=-32.6 (-60.6 to -4.6), p = 0.04) and CpG22 (β=-38.3 (-61.2 to -15.4), p = 0.004), but not the mean methylation of CD40L. Dietary products with the highest impact on methylation included meat, ice cream, white bread, and cooked potatoes. Conclusions Dietary methyl donors may influence DNA methylation levels and thereby disease activity in SLE.

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CD4+Foxp3+ T cells, interleukin-35 (IL-35) and IL-10 in systemic lupus erythematosus patients: Relation to disease activity

The Egyptian Rheumatologist ◽

10.1016/j.ejr.2018.08.001 ◽

2019 ◽

Vol 41 (3) ◽

pp. 209-214 ◽

Cited By ~ 2

Author(s):

Maha Bassiouny ◽

Ahmed Sonbol ◽

Hend Eissa ◽

Amira El-Shanawany ◽

Alaa Labeeb

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

Disease Activity ◽

Lupus Erythematosus ◽

Systemic Lupus

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Increased CD4+CD25-Foxp3+ T cells in Chinese systemic lupus erythematosus: correlate with disease activity and organ involvement

Lupus ◽

10.1177/0961203318804881 ◽

2018 ◽

Vol 27 (13) ◽

pp. 2057-2068 ◽

Cited By ~ 5

Author(s):

Z-J Yin ◽

B-M Ju ◽

L Zhu ◽

N Hu ◽

J Luo ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

Disease Activity ◽

Lupus Erythematosus ◽

Cell Subset ◽

Treg Cells ◽

Organ Involvement ◽

Systemic Lupus ◽

Clinical Indicators ◽

Disease States

Objective The increment of CD4+CD25−Foxp3+T cells has been reported in systemic lupus erythematosus (SLE) patients. However, the exact identity of this T cell subset is still unclear. Thus, we analyzed CD4+CD25−Foxp3+T cells and Treg cells (CD4+CD25+Foxp3+ T cells) in a large sample of Chinese SLE patients in different disease states. Methods A total of 280 SLE patients and 38 healthy volunteers were enrolled, which included 21 patients with untreated new-onset lupus (UNOL), 13 patients with drug withdrawal more than 6 months and 246 patients with treatments. Phenotypic and functional analysis of peripheral blood CD4+CD25−Foxp3+ T cells and Treg cells were performed by flow cytometry. The correlation of CD4+CD25−Foxp3+T cells and Treg cells with disease activity, clinical indicators and organ involvement were analyzed. Results CD4+CD25−Foxp3+ T cells and Treg cells were significantly increased in SLE patients and showed significantly positive correlations with disease activity. CD4+CD25−Foxp3+ T cells were significantly increased in patients with skin and hematologic involvement as well as arthritis. Diverse changes between CD4+CD25−Foxp3+ T cells and Treg cells when faced with different medications, especially HCQ and MMF. CD4+CD25−Foxp3+ T cells expressed more IFN-γ and less CTLA-4 than CD4+CD25+Foxp3+ T cells, which were similar to CD4+CD25+Foxp3− T cells, and expressed similar IL-17, ICOS and Helios to CD4+CD25+Foxp3+ T cells. The synthesis capacity of IL-10 of CD4+CD25−Foxp3+ T cells and the expression of GITR on CD4+CD25−Foxp3+ T cells were between CD4+CD25+Foxp3+ and CD4+CD25+Foxp3− T cells. Conclusions Our results indicate that increased CD4+CD25−Foxp3+ T cells in lupus patients, which combined the features of suppression and pro-inflammatory, may serve as a biomarker for disease activity and organ involvement in SLE.

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Performance and psychometric properties of lupus impact tracker in assessing patient-reported outcomes in pediatric lupus: Report from a pilot study

Lupus ◽

10.1177/0961203320951264 ◽

2020 ◽

Vol 29 (13) ◽

pp. 1781-1789

Author(s):

Suhas K Ganguli ◽

Joyce S Hui-Yuen ◽

Meenakshi Jolly ◽

Jane Cerise ◽

Barbara Anne Eberhard

Keyword(s):

Systemic Lupus Erythematosus ◽

Pilot Study ◽

Disease Activity ◽

Lupus Erythematosus ◽

Patient Reported Outcomes ◽

Laboratory Data ◽

Damage Index ◽

Systemic Lupus ◽

Patient Reported ◽

The Mean

Objective To evaluate the reliability, validity, feasibility and psychometric performance of the Lupus Impact Tracker (LIT) as a patient reported outcome (PRO) measure tool in pediatric systemic lupus erythematosus (pSLE). Methods This is a prospective, observational, pilot study where patients aged between 12 and 25 years, fulfilling the 1997 ACR classification criteria for SLE, were enrolled. Over 3 consecutive, routine, clinical visits, the patients completed the LIT alongside the Patient-Reported Outcomes Measurement Information System-Short Forms (PROMIS-SFs), Childhood Health Assessment Questionnaire (CHAQ). Rheumatologists completed the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC-ACR) Damage Index. Demographic, clinical and laboratory data were also collected. Results Of 46 patients enrolled, 38 patients completed 2 visits and 31 completed all 3 visits. Seventy-eight percent were female, 33% African American, 28% Asian, 15% Caucasian and 17% Hispanic. The mean (SD) age was 17.2 (2.7) years, with a mean (SD) disease duration of 4.6 (3.1) years. The mean (SD) SLEDAI-2K at enrollment was 3.54 (2.96). In the 38 patients who completed two or more visits, intra-class correlation coefficient and Cronbach alpha were calculated to be 0.70 and 0.91 respectively, signifying good reliability of LIT. The LIT showed positive correlation with CHAQ-Disability Index and majority of the PROMIS-SFs parameters. Construct validity was established against clinical disease activity (SLEDAI-2K). Conclusion The preliminary results indicate that the LIT is a reliable and valid instrument to capture PRO in p-SLE. Prospective validation with a larger, multicenter cohort is the next step.

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Systemic lupus erythematosus of childhood onset: correlation between T cells expressing early and late activation antigens and disease activity

European Journal of Pediatrics ◽

10.1007/bf00441516 ◽

1989 ◽

Vol 148 (7) ◽

pp. 626-629 ◽

Cited By ~ 3

Author(s):

T. Hara ◽

S. Hisano ◽

Y. Mizuno ◽

K. Hatae ◽

M. Kurokawa ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

Disease Activity ◽

Lupus Erythematosus ◽

Childhood Onset ◽

Systemic Lupus ◽

Activation Antigens

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Associations of site-specific CD4+-T-cell hypomethylation within CD40-ligand promotor and enhancer regions with disease activity of women with systemic lupus erythematosus

Lupus ◽

10.1177/0961203320965690 ◽

2020 ◽

Vol 30 (1) ◽

pp. 45-51

Author(s):

Stefan Vordenbäumen ◽

Anna Rosenbaum ◽

Claudia Gebhard ◽

Johanna Raithel ◽

Alexander Sokolowski ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

T Cell ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Cd40 Ligand ◽

Systemic Lupus ◽

Site Specific

Objective To comprehensively assess associations of site-specific CD4+-T-cell hypomethylation of the CD40-Ligand gene ( CD40L) with disease activity of women with systemic lupus erythematosus (SLE). Methods CpG-sites within the DNA of the promotor and two enhancer regions (n = 22) of CD40L were identified and numbered consecutively. The rate of methylated DNA in isolated CD4+-T-cells of women with SLE were quantified for each methylation site by MALDI-TOF. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Associations of site-specific methylation rates with the SLEDAI scores were assessed by linear regression modelling. P values were adjusted according to Bonferroni-Holm as indicated. Results 60 female SLE patients participated in the study (age 45.7 ± 11.1 years, disease duration 17.0 ± 8.3 years). Significant associations to the SLEDAI were noted for CpG22 hypomethylation of the promotor (β = −40.1, p = 0.017, adjusted p = 0.027), trends were noted for CpG17 hypomethylation of the promotor (β = −30.5, p = 0.032, adjusted p = 0.6), and for CpG11 hypermethylation of the second enhancer (β = 15.0, p = 0.046, adjusted p = 0.8). Conclusion Site-specific hypomethylation of the CD40L promotor in CD4+-T-cells show associations with disease activity in female SLE patients.

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