Disease trends over time and effector memory T-cells predict atherosclerosis development in Systemic Lupus Erythematosus

2017 ◽  
Vol 27 (1) ◽  
pp. e7
Author(s):  
A. Baragetti ◽  
G.A. Ramirez ◽  
M. Magnoni ◽  
K. Garlaschelli ◽  
L. Grigore ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Lupus Erythematosus ◽  
Memory T Cells ◽  
Effector Memory ◽  
Systemic Lupus ◽  
Effector Memory T Cells ◽  
Trends Over Time ◽  
Atherosclerosis Development ◽  
Over Time

Role of Stem Cell-Like Memory T Cells in Systemic Lupus Erythematosus

2018 ◽  
Vol 70 (9) ◽  
pp. 1459-1469 ◽  
Author(s):  
Ye Ji Lee ◽  
Ji Ah Park ◽  
Hyunmi Kwon ◽  
Youn Soo Choi ◽  
Kyeong Cheon Jung ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Stem Cell ◽  
Lupus Erythematosus ◽  
Memory T Cells ◽  
Systemic Lupus

scholarly journals AB0385 TARGETING CD38 IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1493.3-1493
Author(s):  
L. Ostendorf ◽  
U. Schneider ◽  
M. Urbicht ◽  
P. Enghard ◽  
F. Heinrich ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Single Cell ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Immune Thrombocytopenia ◽  
Plasma Cells ◽  
Memory T Cells ◽  
Systemic Lupus

Background:Depletion of long-lived plasma cells (PC) resembles a novel concept for the treatment of antibody-mediated autoimmune diseases, such as systemic lupus erythematosus (SLE). Therapeutic approaches such as autologuos stem-stem cell transplantation and proteasome inhibition are limited by significant treatment-related toxicity. A novel target for PC depletion is CD38, a surface protein that is highly expressed on plasma cells (PCs) but also activated T-cells and most myeloid cells. Daratumumab is a monoclonal antibody targeting CD38 that is licensed for the treatment of multiple myeloma.Objectives:Here, we aimed to ascertain clinical safety and efficacy of Daratumumab for the treatment of refractory SLE, as well as to gain insights into effects of Daratumumab on the immune system.Methods:We treated two SLE patients with life- and organ-threatening SLE with four weekly dosis of 16 mg/kg Daratumumab. We performed integrative analyses of clinical, serological and immunological effects over a follow-up period of 6 months. Using flow cytometry and single-cell RNA and T-cell receptor sequencing we followed CD38 expression and composition of peripheral blood leukocytes with a special focus on memory T cells.Results:Patient 1, a 50-year old woman, suffered from active biopsy-proven class III lupus nephritis (LN) with nephrotic syndrome, pericarditis, arthritis and skin rash. Upon Daratumumab treatment, her glomerular filtration rate normalized within 3 months and proteinuria gradually declined from 6.4 to 1.9g/g Creatinine during the 180-day follow-up period. Pericarditis, arthritis and skin rash completely resolved. Patient 2, a 32-year-old woman, presented with autoimmune hemolytic anemia requiring blood transfusions, immune thrombocytopenia and cutaneous vasculitis. Her direct antiglobulin test normalized within 3 months and remained negative throughout follow-up with consecutive recovery of the hemolytic anemia. Immune thrombocytopenia stabilized and vasculitic skin lesions completely resolved. Infusions were well tolerated without severe adverse drug reactions. NK cells and Dendritic Cells were transiently depleted, while numbers of T cells, B cells and Monocytes in the peripheral blood remained stable. CD38+ memory T cells that were expanded prior to treatment were virtually undetectable early after treatment. Their single cell transcriptomics demonstrated an upregulation of genes associated with activation, cytotoxicity and type 1 interferon response. CD38+ CD8+ memory T-cells showed marked oligoclonality. These prominent clones persisted upon treatment but their transcription profile gradually normalized.Conclusion:Daratumumab appears to be a safe and effective treatment for refractory SLE. Further investigations are warranted to establish the efficacy in a clinical trial and to gain further insights into the pathophysiologic mechanism of action.Disclosure of Interests:Lennard Ostendorf: None declared, Udo Schneider: None declared, Marie Urbicht: None declared, Philipp Enghard: None declared, Frederik Heinrich: None declared, Pawel Durek: None declared, Gitta Heinz: None declared, Henrik Mei: None declared, Mir-Farzin Mashreghi: None declared, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Andreas Radbruch: None declared, Falk Hiepe: None declared, Tobias Alexander: None declared

scholarly journals Abnormal differentiation of memory T cells in systemic lupus erythematosus

2006 ◽  
Vol 54 (7) ◽  
pp. 2184-2197 ◽  
Author(s):  
Ruth D. Fritsch ◽  
Xinglei Shen ◽  
Gabor G. Illei ◽  
Cheryl H. Yarboro ◽  
Calman Prussin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Lupus Erythematosus ◽  
Memory T Cells ◽  
Systemic Lupus

Phenotypic Changes of Lymphocytes in Patients with Systemic Lupus Erythematosus Who Are in Longterm Remission After B Cell Depletion Therapy with Rituximab

2010 ◽  
Vol 38 (4) ◽  
pp. 633-641 ◽  
Author(s):  
SHIGERU IWATA ◽  
KAZUYOSHI SAITO ◽  
MIKIKO TOKUNAGA ◽  
KUNIHIRO YAMAOKA ◽  
MASAO NAWATA ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Memory T Cells ◽  
Memory B Cells ◽  
Systemic Lupus ◽  
Phenotypic Changes ◽  
Inducible Costimulator ◽  
Peripheral B Cells

Objective.Rituximab has recently emerged as a novel treatment strategy for systemic lupus erythematosus (SLE). We investigated longitudinally the differentiation and phenotypic changes of peripheral B cells and T cells in patients with SLE after rituximab treatment.Methods.Phenotypic changes on B cells and T cells in 10 patients with SLE treated with rituximab were analyzed before, 28 days after, and 2 years after rituximab treatment, and at relapse.Results.Rituximab rapidly depleted naive and memory B cells from the peripheral blood. In the patients with prolonged remission, the memory B cells remained depleted while naive B cells recovered within 3–9 months, and the expression levels of CD40 and CD80 remained downregulated for 2 years. There was also a decrease of memory T cells relative to naive T cells, and the expression of CD40L and inducible costimulator (ICOS) on CD4-positive T cells rapidly decreased and remained downregulated for 2 years. In 1 patient, an increase in the number of memory B cells with upregulation of CD40 and CD80 expression was noted just before relapse. In another patient with relapse, however, recovery of CD4-positive memory T cells with upregulation of ICOS expression was noted, with no change in the number of memory B cells.Conclusion.Our results suggest that the phenotypic changes of peripheral B cells result in inhibition of T cell differentiation and activation mediated by B cells and thereby bring about longterm remission of SLE. Activated memory B cells or ICOS-positive CD4-positive memory T cells reappeared in association with relapse, probably reflecting the heterogeneity of SLE.

scholarly journals AB0343 THE CHARACTERISTICS OF T CELLS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH ANXIETY BASED ON MACHINE LEARNING

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1196.2-1197
Author(s):  
X. Gu ◽  
Y. Jin ◽  
R. Li ◽  
D. Zhang ◽  
C. Dong ◽  
...  
Keyword(s):  
Machine Learning ◽  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Systemic Lupus

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease, the immune system of patients to be disordered, especially in T cell subsets1. They were prone to mental diseases, anxiety particularly, which lead to suicide2. The recent study had reported that CD4+ T cells in the peripheral blood played the key role in like anxiety behavior of mice3. Although there showed that the level of serum TNF-α in SLE patients with anxiety was higher than without anxiety4, finding the important special mediators especially in T cell subsets was still necessary for the prevention of anxiety in SLE patients.Objectives:In total, 108 SLE patients, which met the diagnostic criteria of the American Society of rheumatology (v1997), were enrolled in this study from Affilliated Hospital of Nantong University, China. Exclusion criteria included other autoimmune diseases and active infection (including hepatitis B or C virus, Epstein-Barr virus, human immunodeficiency virus or Mycobacterium tuberculosis infection).Methods:We surveyed the abundance of 74 immune cell subpopulations from 108 SLE patients using flow cytometry, and investigated their differences between patients with and without anxiety (24 versus 84). Moreover, machine learning including Lasso regression, Random forest (RF) and Sparsity partial least squares discriminant analysis (sPLS-DA) was employed to build models and futher selected important features for the classification of SLE patients with anxiety.Results:SLE patients with anxiety showed higher body mass index (BMI) and lower quality of life. In their peripheral blood, the proportion of internal cell subsets composition of Th cell and Treg cells changed. By machine learning, we finally found that BMI and PD1-CD28- Treg played important rules to developing lupus anxiety.Conclusion:In this study, machine learning was applied to build models to select the most important T cell subset in SLE patients with anxiety. These findings suggested that BMI and imbalance of PD1-CD28- Treg containing effector memory Treg cells and effector Treg cells mostly played important roles in the development of SLE anxiety.Disclosure of Interests:None declared

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