scholarly journals FRI0171 THE CHANGES OF IMMUNE FUNCTION AND CLINICAL INDEXES WITH SYSTEMIC LUPUS ERYTHEMATOSUS AFTER IMMUNOREGULATORY COMBINATION THERAPIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 670.3-670
Author(s):  
X. Liu ◽  
X. Liu ◽  
H. Hou ◽  
X. LI
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Lupus Erythematosus ◽  
Low Dose ◽  
Remission Rate ◽  
Treg Cells ◽  
Control Group ◽  
Combination Therapies ◽  
Systemic Lupus

Background:Recent studies have reported that some drugs such as low-dose interleukin-2, rapamycin, metformin, retinoic acid and coenzyme Q10 could promote the proliferation and functional recovery of regulatory T cells (Treg) in patients with autoimmune diseases. However, the effects on the balance of Treg cells and pro-inflammatory lymphocytes and long-term efficacy have rarely been reported.Objectives:To evaluate the changes of peripheral lymphocyte subsets, conventional drugs and remission rate in patients with systemic lupus erythematosus (SLE) after immunomodulatory combination therapies.Methods:A total of 189 patients with SLE from the Second Affiliated Hospital of Shanxi Medical University from January 2016 to October 2019 were enrolled, who were divided into well-controlled group and untargeted control group taking a full consideration of the patient’s symptoms, signs and related laboratory findings. We measured the absolute counts of B, NK, CD8+T and helper T 1 (Th1), helper T 2 (Th2), helper T 17 (Th17) and Treg cells in peripheral blood of patients before immunomodulatory combination therapies and during the 3 months and 6 months of follow-up and 190 sex- and age- matched control individuals using flow cytometry. Moreover, the ratios of various cells to Treg cells were calculated.Results:Compared with healthy controls, Treg cells in SLE patients were significantly lower before the treatment with immunomodulator, while the ratios of various pro-inflammatory lymphocytes to Treg cells (such as Th2/Treg, Th17/Treg, CD8+T/Treg, etc.) were higher. After 3 months and 6 months with immunomodulatory therapy, the absolute number of Treg cells in peripheral blood of SLE patients increased obviously reaching to normal level. Accordingly, the ratios of various pro-inflammatory lymphocytes to Treg cells recovered. At the same time, the dose of glucocorticoid and disease-modifying antirheumatic drugs (DMARDs) decreased distinctly. Additionally, the well-controlled group was able to maintain a high remission rate, and the untargeted control group could achieve a higher response rate after immunomodulatory treatment.Conclusion:The imbalance between pro-inflammatory lymphocytes and Treg cells caused by the significant decrease of Treg cells may be the main cause of SLE. And immunomodulatory combination therapies we came up with may reverse the imbalance of proinflammatory lymphocytes and Treg cells, which is an potential and effective treatment for SLE.References:[1]Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory disease[J]. Autoimmun Rev, 2014, 13(6): 668-677.[2]Yu A, Snowhite I, Vendrame F, et al. Selective IL-2 responsiveness of regulatory T cells through multiple intrinsic mechanisms supports the use of low-dose IL-2 therapy in type 1 diabetes. Diabetes. 2015;64: 2172–2183.[3]Schuiveling M, Vazirpanah N, Radstake TRDJ, Zimmermann M, Broen JCA. Metformin, A New Era for an Old Drug in the Treatment of Immune Mediated Disease?[J]. Curr Drug Targets, 2017;18:1-15.Table 1.The changes of remission rate in the no-remission group during follow-up.Follow-up periodTotal patientsRemissionNo-remissionRemission rate(%)Baseline9209203 Months72333945.8a6 Months74423256.8aa: Compared with baseline; b: Compared with 3 months.Acknowledgments:We would like to express our sincere gratitude to all our coworkers and collaborators, Jing Luo, Xiangcong Zhao, Chen Zhang, Qi Wu, Congcong Liang, and Rui Fu for their technical support.Disclosure of Interests:None declared

scholarly journals SAT0181 ALTERATIONS OF PERIPHERAL LYMPHOCYTE SUBSETS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND THEIR CHANGES AFTER OUR NEW IMMUNOREGULATORY COMBINATION THERAPIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1031.2-1032
Author(s):  
J. Q. Zhang ◽  
S. X. Zhang ◽  
L. Xue ◽  
J. Qiao ◽  
M. T. Qiu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Lupus Erythematosus ◽  
Low Dose ◽  
Lymphocyte Subsets ◽  
Peripheral Lymphocyte ◽  
Combination Therapies ◽  
Systemic Lupus ◽  
T Subsets ◽  
The Absolute

Background:Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by abnormal activation of circulating lymphocytes and overproduction of autoantibodies1. Breakdown of self-tolerance is considered as a critical cause in the development of SLE2. However, the quantitative changes of lymphocyte subsets in SLE are unclear. Since low-dose IL-2 and several drugs have been used to promote the proliferation of regulatory T cells (Tregs)3, we developed immunoregulatory therapies using these drugs to rebalance effector T cells with Tregs and test whether they are benefit to remission disease activity of SLE.Objectives:To observe the different levels of peripheral lymphocyte subsets at the first laboratory examination of SLE patients with those of healthy controls (HCs) and to evaluate the effect of immunoregulatory combination therapies on levels of lymphocyte subsets in patients with SLE.Methods:From September 2014 to December 2019, a total of 985 diagnosed patients with SLE (878 females, 107 males, mean age 42.99±13.37 years) and 206 healthy adults were enrolled in this retrospective cross-sectional study. And 795 patients with SLE (711 females and 84 males, mean age 38.26±15.242 years) were received the immunomodulatory drugs (IMiDs) such as low-dose interleukin-2, rapamycin, metformin, retinoic acid, coenzymes Q10 or other immunomodulatory treatments. The absolute numbers of T, B, NK, CD4+T, CD8+T, Th1, Th2, Th17 and CD4+CD25+Foxp3+T regulatory cells (Tregs) in peripheral blood (PB) of these individuals were measured by Flow Cytometer (FCM) combined with standard absolute counting beads.Results:As compared with those of HCs, patients with SLE had lower absolute numbers of total T, NK, and CD4+T but higher proportions of all lymphocyte subpopulations except NK, CD4+T cells(P< 0.001) (Figure 1 A, C). Notably, the absolute numbers and proportions of Tregs as well as Th1 in CD4+T subsets were decreased (P<0.05) (Figure 1 B, D). Further, there was a significant increase in the ratio of Teffs/Tregs such as Th1/Tregs, Th2/Tregs and Th17/Tregs (P<0.05) (Figure 1 E). After receiving immunoregulatory combination therapies, the absolute numbers and proportions of T, NK, CD4+T, and CD8+T were increased, while the proportion of B cells was decreased (Figure 2 A, C); the absolute numbers of most CD4+T subsets as well as the proportions of only Th1 and Tregs were significantly increased (P< 0.001) (Figure 2 B, D). The ratios of Th1/Th2 and Th1/Tregs increased while that of Th17/Tregs and Th2/Tregs decreased (P<0.01) (Figure 2 E).Conclusion:Quantitative and functional alterations of peripheral lymphocyte subsets, especially reduced Tregs, play crucial roles in the pathogenesis of the patients. Immunoregulatory combination therapies mainly promote the proliferation and functional recovery of Tregs to rebalance pro- and anti-inflammatory T cells in patients with SLE for patients’ symptoms remission.References:[1]Sharabi A, Tsokos GC. T cell metabolism: new insights in systemic lupus erythematosus pathogenesis and therapy. Nat Rev Rheumatol 2020 doi: 10.1038/s41584-019-0356-x [published Online First: 2020/01/18][2]Durcan L, O’Dwyer T, Petri M. Management strategies and future directions for systemic lupus erythematosus in adults. Lancet 2019;393(10188):2332-43. doi: 10.1016/S0140-6736(19)30237-5 [published Online First: 2019/06/11][3]Spolski R, Li P, Leonard WJ. Biology and regulation of IL-2: from molecular mechanisms to human therapy. Nat Rev Immunol 2018;18(10):648-59. doi: 10.1038/s41577-018-0046-y [published Online First: 2018/08/10]Acknowledgments :None.Disclosure of Interests:None declared

scholarly journals The Impact of T Cell Vaccination in Alleviating and Regulating Systemic Lupus Erythematosus Manifestation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Liuye Huang ◽  
Yuan Yang ◽  
Yu Kuang ◽  
Dapeng Wei ◽  
Wanyi Li ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Side Effects ◽  
Lupus Erythematosus ◽  
Clinical Symptoms ◽  
Systemic Lupus ◽  
T Cell Vaccination ◽  
Dna Antibodies

Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease identified by a plethora of production of autoantibodies. Autoreactive T cells may play an important role in the process. Attenuated T cell vaccination (TCV) has proven to benefit some autoimmune diseases by deleting or suppressing pathogenic T cells. However, clinical evidence for TCV in SLE is still limited. Therefore, this self-controlled study concentrates on the clinical effects of TCV on SLE patients. Methods. 16 patients were enrolled in the study; they accepted TCV regularly. SLEDAI, clinical symptoms, blood parameters including complements 3 and 4 levels, ANA, and anti-ds-DNA antibodies were tested. In addition, the side effects and drug usage were observed during the patients’ treatment and follow-up. Results. Remissions in clinical symptoms such as facial rash, vasculitis, and proteinuria were noted in most patients. There are also evident reductions in SLEDAI, anti-ds-DNA antibodies, and GC dose and increases in C3 and C4 levels, with no pathogenic side effects during treatment and follow-up. Conclusions. T cell vaccination is helpful in alleviating and regulating systemic lupus erythematosus manifestation.

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

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2057-2068 ◽  
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.

scholarly journals Lymphocytes Tγδ in clinically normal skin and peripheral blood of patients with systemic lupus erythematosus and their correlation with disease activity

2001 ◽  
Vol 10 (4) ◽  
pp. 179-189 ◽  
Author(s):  
Ewa Robak ◽  
Hanna Niewiadomska ◽  
Tadeusz Robak ◽  
Jacek Bartkowiak ◽  
Jerzy Z. Bloński ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Normal Skin ◽  
Control Group ◽  
Systemic Lupus ◽  
Clinically Normal ◽  
Healthy Persons

Human Tγσ lymphocytes constitute from 1 to 15% of all peripheral blood lymphocytes. Recent work has demonstrated that this population plays a major role in the pathogenesis of infectious and immune diseases. Increased numbers of γσ T cells have been found in affected skin from systemic sclerosis and chronic cutaneous lupus erythematosus patients.In our study, we have determined the numbers of Tγσ lymphocytes and their subpopulations in peripheral blood from 29 patients with systemic lupus erythematosus (SLE) and in 19 healthy volunteers using flow cytometry and specific monoclonal antibodies. The same cells in uninvolved skin from SLE patients and human controls using immunohistochemical analysis were estimated. T-Cell receptor (TCR) delta chain gene rearrangement was identified with primers for Vσ1, Vσ2 and Vσ3 by the polymerase chain reaction. Statistical analysis showed a significantly decreased number of γσ T cells in SLE patients (26.4 Ī 16.9/μl) compared with the control group (55.3 Ī 20.6/μl) (p<0.001). The number of Vσ2 TCR+ and Vγ9 TCR+ subpopulations was also lower in SLE patients than in healthy persons. No statistical correlation between disease activity and the number of γσ T cells was demonstrated. The percentage of T γσ lymphocytes in clinically normal skin from SLE patients was twice (22.0 Ī 9.4%) that found in the skin from healthy persons (11.1 Ī 5.5%) (p<0.002). Higher percentages of the Vσ2 TCR+ and Vγ9 TCR+ subpopulation of lymphocytes were found in the skin from SLE patients. We have also found positive correlation between the percentage of Tγσ lymphocytes in skin and the activity of SLE (r=0.594, p<0.001), and between subpopulation Vσ3 TCR+ and disease activity (r=0.659, p<0.001). In conclusion, the results of our studies demonstrate that, in patients with SLE, accumulation of Tγσ lymphocytes can be seen in clinically normal skin, and the percentage of these cells correlates with the activity of the disease.

scholarly journals 4312Left ventricular systolic function in patients with systemic lupus erythematosus and its association with cardiovascular events

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Gegenava ◽  
T Gegenava ◽  
M Steup-Beekman ◽  
T Huizinga ◽  
J Bax ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Cardiovascular Events ◽  
Systolic Function ◽  
Control Group ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Lv Ejection Fraction ◽  
Lv Systolic Function

Abstract Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that may involve the cardiovascular system. Diagnosis of cardiac involvement, particularly at an early stage, represents challenge since symptoms in SLE patients are often atypical and current diagnostic tools are characterized by a low sensitivity to detect myocardial dysfunction. Purpose of this study was to assess left ventricular (LV) systolic function in a large cohort of SLE patients in comparison with a control group of healthy subjects and using standard echocardiographic measures and global longitudinal strain (GLS) by 2D speckle tracking analysis. Furthermore, the association between echocardiographic parameters and the occurrence of cardiovascular events was tested. Methods A total of 102 patients (87% female, 42±15 years) were analysed including echocardiography at the time of their first visit. All patients fulfilled the American College of Rheumatology (ACR 1997) and The Systemic Lupus Erythematosus International Collaborating Clinics (SLICC 2012) classification criteria for SLE. During follow-up, cardiovascular events included cerebrovascular accident or transient ischemic attack, pulmonary embolism, coronary artery interventions, hospitalisations for heart failure and development of supraventricular arrhythmias. The control group consisted of 50 age- and gender-matched healthy subjects. Results Prevalence of comorbidities, such as hypertension (8%), hypercholesterolemia (4%) and diabetes mellitus (2%) was relatively low in SLE patients. In comparison with the control group, SLE patients were characterized by worse LV systolic function as measured by LV ejection fraction (51±6% vs 62±6%, p<0.001) and by LV GLS (−15±3% vs −19±2%, p<0.001), as well as worse LV diastolic function (e' septal: SLE 9±2 cm/s vs 10±2 cm/s healthy controls, p=0.020; E/e': SLE 8±3 vs 7±2 healthy controls, p<0.001; TR velocity: SLE 2±0.6 m/s vs 1.6±0.5 m/s healthy controls, p=0.020). During a median follow up of 11 years (Interquartile range: 4–19 years), 43 (42%) patients developed cardiovascular events. Kaplan-Meier curves show that SLE patients with more impaired GLS (based on the median value of −15%) experienced higher cumulative rates of cardiovascular events as compared to patients with GLS ≤−15% (Chi-square 7.197; Log rank p=0.007). On uni- and multivariate Cox-regression models, LV GLS demonstrated significant association with cardiovascular events (HR: 2.229; 95% CI: 1.024–4.853; p=0.043), together with age (HR: 1.043; 95% CI: 1.017–1.069; p=0.014) after correcting for LV mass index and e'; in turn, LV ejection fraction was not significantly associated with cardiovascular events. LV GLS in SLE patients Conclusions In SLE patients, LV systolic function as measured by GLS is significantly impaired and independently associated with cardiovascular events. Incorporation of LV GLS in the early assessment of these patients may significantly improve risk-stratification for cardiovascular events.

Myelitis in systemic lupus erythematosus: clinical characteristics and effect in accrual damage. A single-center experience

Lupus ◽  
2016 ◽  
Vol 26 (3) ◽  
pp. 248-254 ◽  
Author(s):  
L Quintanilla-González ◽  
Y Atisha-Fregoso ◽  
L Llorente ◽  
H Fragoso-Loyo
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Characteristics ◽  
Control Group ◽  
Aggressive Treatment ◽  
Systemic Lupus ◽  
Neurologic Sequelae ◽  
One Year

Objective The purpose of this study was to describe the clinical characteristics of acute transverse myelitis, including the time of their presentation, and to evaluate their effect on accrual damage in patients with systemic lupus erythematosus (SLE). Methods Patients with SLE who were hospitalized because of incident, noninfectious myelitis at our institute between January 1997 and December 2013 were identified. As a control group, we selected for each of the patients in the study group one SLE patient hospitalized at the closest date to the case due to other severe non-neuropsychiatric (NP) SLE manifestation, with no history of NP manifestations or noninfectious disease. Clinical characteristics, laboratory results, treatment, disease activity (SLEDAI-2K), and damage (SLICC/ACR-DI) were collected from medical charts at the index hospitalization and one year after hospitalization. Results Demographics and SLE characteristics, including age at SLE diagnosis and time since SLE diagnosis to hospitalization, were comparable in patients with myelitis and controls. At hospitalization, disease activity and cumulative damage were similar in both groups. Patients with myelitis received more aggressive treatment than controls. One year after hospitalization, two of the 15 patients who completed follow-up had symptom improvement without neurologic sequelae, and 13 of them had some improvement of symptoms with neurologic sequelae. Four patients died in the myelitis group, three of them of infectious diseases, and one of alveolar hemorrhage. No patient died because of myelopathy and in the control group no patient died, although three were lost during the follow-up. Disease activity and treatment did not differ between both groups. However, cumulative damage was higher among the patients with myelitis than controls (1.9 ± 0.9 vs 0.75 ± 0.9; p = 0.003). Conclusion Patients with myelitis have clinical characteristics similar to those observed in non-NP SLE and receive more aggressive treatment. Furthermore, myelitis is associated with a significant increase in accrual damage compared with severe non-NP manifestations.

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