scholarly journals Screening for hub genes and signaling pathways of CD8+ T cells in systemic lupus erythematosus using bioinformatics

2021 ◽  
Vol 271 ◽  
pp. 03034
Author(s):  
Yuefeng Wu

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, which can damage multiple organs. The adaptive immune system, including CD8+ T cells, plays an essential role in this disease. However, the pathogenesis of SLE remains unclear, and there is a lack of effective diagnosis and treatment methods for SLE. In particular, there has been little research on SLE biomarkers, which have been widely studied and used in cancer diagnosis and treatment. In this study, bioinformatics tools were used to screen for hub genes and signaling pathways involving CD8+ T cells in patients with SLE. This is the first determination of metabolic abnormalities in SLE CD8+ T cells using bioinformatics pathway enrichment analysis. The PPI network and MCC algorithm identified SKP2 as a potential biomarker for SLE.

2020 ◽  
Vol 3 (1) ◽  
pp. 34-43
Author(s):  
Jessy J Alexander ◽  
Alexander Jacob ◽  
Anthony Chang ◽  
Richard J Quigg ◽  
James N Jarvis

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease that is a challenge to diagnose and treat. There is an urgent need for biomarkers to help define organ involvement, and more effective therapies. A unique population of T cells, the CD3+CD4−CD8− (DNeg) cells, is significantly increased in lupus patients. Twenty-seven cases (53%) of pediatric SLE patients had elevated DNeg cells in their peripheral blood, which correlated with kidney function (R2 = 0.54). Significant infiltration of DNeg cells was observed in both adult and pediatric lupus kidneys by immunofluorescence. For the first time, this study provides direct evidence that DNeg cells facilitate kidney injury in preclinical 8-week-old MRL/lpr lupus mice. In lupus mice, the increase in DNeg cells tracked with worsening disease and correlated with kidney function (R2 = 0.85). Our results show that DNeg cells per se can cause kidney dysfunction, increase in number with increase in disease pathology, and could serve as a potential biomarker.


1970 ◽  
Vol 7 (3) ◽  
pp. 213-219 ◽  
Author(s):  
D Shah ◽  
R Kiran ◽  
A Wanchu ◽  
A Bhatnagar

Background: Systemic Lupus Erythematosus (SLE) is a complex chronic immunological disease characterized by increased B cell activity and altered T cell function. Objective: To investigate relationship between T lymphocyte subsets and cortisol with the disease activity of systemic lupus erythematosus patients in North India. Materials and methods: The percentage of CD4+ and CD8+ T cells in the lymphocyte of SLE patients and healthy controls were determined by flow cytometry. Serum cortisol of SLE patients and healthy controls was determined by enzyme-linked immunosorbent assay (ELISA). Results: A significant decrease in the percentage of CD4+ T cells and increase in the percentage of CD8+ T cells were found in patients with SLE compared to the healthy controls. Decrease in the ratio of CD4+/CD8+ T cell and low level of serum cortisol were found in the patients with SLE. The ratio of CD4+/CD8+ T cell was inversely correlated with systemic lupus erythematosus disease activity index (SLEDAI) score and erythrocyte sedimentation rate (ESR). A positive correlation was observed between CD8+ T cells and SLEDAI score. Furthermore, CD8+ T cells were positively correlated with ESR in the patients with SLE. Conclusion: The results showed that low level of cortisol and high percentage of CD8+ T cells in the lymphocytes could be actively involved in the pathogenesis of SLE. Key words: CD4+/CD8+ T cell ratio; cortisol; systemic lupus erythematosus; T-cell activation DOI: 10.3126/kumj.v7i3.2726 Kathmandu University Medical Journal (2009) Vol.7, No.3 Issue 27, 213-219


Lupus ◽  
2021 ◽  
Vol 30 (6) ◽  
pp. 1022-1024
Author(s):  
Tobias AW Holderried ◽  
Mareike Kruse ◽  
Michael Serries ◽  
Peter Brossart ◽  
Dominik Wolf ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 634.1-634
Author(s):  
T. Fu ◽  
Y. Yang ◽  
X. Gu ◽  
C. Dong ◽  
R. Zhao ◽  
...  

Background:SLE is an autoimmune disease characterized by the abnormal function of lymphocytes. The impairment of hematopoietic function of bone marrow participates in its pathogenesis, in which T cells play an important role. However, study on bone marrow T cells in SLE patients is very limited.Objectives:This study aims to characterize the phenotype and molecular characteristics of abnormally activated CD8+T cells in bone marrow of SLE patients and explore the mechanism of hematopoietic stem cells (HSCs) reduction caused by the abnormally activated CD8+T cells in bone marrow of patients with SLE.Methods:A total of 8 SLE patients and 5 age- and sex-matched controls were recruited in our study. Among them, 3 SLE patients and 4 donors were collected bone marrow and peripheral blood samples for Single-cell RNA sequencing (scRNA-seq) and functional studies. BM and peripheral T cell subsets were measured by flow cytometry. Plasma cytokines and secreted immunoglobulins were detected by Luminex. Disease activity of SLE patients was measured using the SLE Disease Activity Index (SLEDAI). All analyses were performed using R language and Flowjo 9.Results:In the present study, SLE patients had increased CD8+T%αβT cells and decreased CD4+T%αβT cells in bone marrow of SLE, compared to healthy controls. A large number of CD38+HLADR+CD8+T cells existed in the bone marrow and peripheral blood of SLE patients. Those patients also showed reduced number of HSCs, and with a downward trend of the numbers of peripheral red blood cells, white blood cells, neutrophils, hemoglobin, and platelets. By scRNA-seq, the CD38+HLADR+CD8+T cells contained high levels of GZMK, GZMA, PRF1, IFNG, and TNF in the bone marrow of SLE patients. the CD38+HLADR+CD8+T cells exhibited significant relationship with HSCs, white blood cells, neutrophils, and platelets.Conclusion:These findings demonstrated that the abnormally activated CD8+T cells in bone marrow can reduce the number of HSCs by the expression of killer molecules, which contributes to the impairment of hematopoietic function and the development of SLE. This project focuses on the specific bone marrow T cell subset in SLE. The completement of this project provides information for exploring the mechanism of hematopoiesis involvement.References:[1]Anderson E, Shah B, Davidson A, Furie R. Lessons learned from bone marrow failure in systemic lupus erythematosus: Case reports and review of the literature. Semin Arthritis Rheum. 2018;48(1):90-104.[2]Sun LY, Zhou KX, Feng XB, Zhang HY, Ding XQ, Jin O, Lu LW, Lau CS, Hou YY, Fan LM. Abnormal surface markers expression on bone marrow CD34+cells and correlation with disease activity in patients with systemic lupus erythematosus. Clin Rheumatol. 2007;26(12):2073-2079.Acknowledgements:We want to thank Lu Meng, Teng Li, Wei Zhou, and Jiaxin Guo for their assistance with this study.Disclosure of Interests:None declared


Rheumatology ◽  
2012 ◽  
Vol 51 (9) ◽  
pp. 1587-1594 ◽  
Author(s):  
J.-S. Kim ◽  
B.-A. Cho ◽  
J. H. Sim ◽  
K. Shah ◽  
C. M. Woo ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document