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Increased Macroautophagy in Interferon-Gamma-Producing T Cells from Patients with Newly Diagnosed Systemic lupus erythematosus

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Chinese Medical Journal 2018年第13期131卷 1527-1532页

作者： Xiong-Yan Luo Jia-Li Yuan Jing Liu Cai-Nan Luo Ming-Hui Yang Qin Wei Min Yang Yong Chen Yi Liu Guo-Hua Yuan Department of Rheumatology and Immunology West China Hospital Sichuan University Chengdu Sichuan 610041 China Department of Rheumatology The First People's Hospital of Jian Yang City Chengdu Sichuan 641400 China Institute of Rheumatology and Immunology Affiliated Hospital of North Sichuan Medical College Nanchong Sichuan 63700 China Department of Rheumatology People's Hospital of Xinjiang Uygur Autonomous Region Urumqi Xinjiang 830000 China Department of Rheumatology The First People's Hospital of Xinxiang Xinxiang Medical University Xinxiang Henan 453000 China

Background： Imbalance of interferon-gamma （IFN-γ）, interleukin （IL）-4, and IL-17 producing by T cells is confirmed to contribute to the pathogenesis of systemic lupus erythematosus （SLE）. Autophagy is now emerging as a core player in the development and the function of the immune system. Therefore, we investigated the autophagic behavior in I FN-γ, IL-4-, and IL-17-producing T cells from patients with SLE. Methods： Thirty patients with SLE and 25 healthy controls matched for gender and age were recruited between September 2016 and May 2017. The autophagic levels in IFN-γ T cells, IL-4＋ T cells, and IL-17＋ T cells fi＇om patients with newly diagnosed SLE and healthy controls were measured using flow cytometry. The plasma levels of IFN-y were determined by enzyme-linked immunosorbent assay in SLE patients and healthy controls. Unpaired t-tests and the nonparametric Mann-Whitney U-test were used to compare data from patients with SLE and controls. Spearman＇s rank correlation coefficient was applied for calculation of the correlation between parallel variables in single samples. Results： Our results showed increased percentage of atttophagy in IFN-γ＋ T cells from patients with SLE and healthy controls （[8.07 ± 2.72]% vs. [3.76 ± 1.671%, t=5.184, P 〈 0.001）, but not in IL-4 T cells or IL-17＋ T cells （P 〉 0.05） as compared to healthy donors. Moreover, the plasma levels of IFN-γ in SLE patients were significantly higher than those in healthy controls （[68.9 ± 29.1] pg/ml vs. [24.7 ± 17.6] pg/ml, t = 5.430, P 〈 0.001 ）. Moreover, in SLE patients, the percentage of autophagy in IFN-γ T cells was positively correlated with the plasma levels of IFN-y （r = 0.344, P = 0.046）, as well as the disease activity of patients with SLE （r = 0.379, P =0.039）. Conclusion： The restllts indicate that autophagy in IFN-γ＋ T cells from SLE patients is activated, which might contribute to the persistence ofT cells producing IFN-y, such as Thl cells, and consequently restly in the high plasma levels of I FN-γ, and then enhance the disease acti

关键词： Autophagy lupus erythematosus Systemic T Helper cells

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Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: report of three cases

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Chinese Medical Journal 2004年第4期117卷 637-640页

作者：张文尤欣董怡 Department of Rheumatology and Clinical Immunology

Systemic lupus erythematosus (SLE) is a multisystemic disease characterized by an autoimmune reaction.Thrombotic thrombocytopenic purpura (TTP) is a rare but severe syndrome with the manifestations of fever,thrombocytopenia, microangiopathic hemolysis,neurological symptoms, and renal involvement. The initial prognosis was reported to be dismal, 90% of patients dying within 3 months of onset. However, with the possibility of combined treatments, the survival rate has considerably improved. Data suggest a possible role of immune mechanisms in the development of TTP. 1,2We here report three cases of SLE complicated with TTP,and review the diagnosis, treatment, and outcome of SLE with TTP.

关键词： purpura thrombotic thrombocytopenic lupus erythematosus systemic

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Suicide risk in systemic lupus erythematosus:A narrative review

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Discussion of Clinical Cases 2021年第3期8卷 9-14页

作者： Solange Barros Jozélio Freire de Carvalho Institute for Health Sciences from Federal University of Bahia Brazil

Introduction:Despite the medical and scientific advances,the disease’s restrictions and the perception of personal and social losses related to its course reinforce fear and generate intense suffering in lupus patients.Psychiatric comorbidities,especially major depressive episodes,are highly prevalent during systemic lupus erythematosus.Among them,suicide is a behavior that is much more common than we believe.Objective:To perform a narrative review on suicidal behavior associated with systemic erythematosus lupus(SLE).Results:Studies have shown an increased risk of suicide among patients with chronic diseases and psychiatric disorders,especially depression.However,suicide cannot be attributed only to a higher prevalence of depression and other mental illnesses.Therefore,it is necessary to learn more about the suicide risk factors present in patients with lupus to work on secondary prevention and avoid the premature loss of lives and the additional suffering of families and surrounding communities.The coordination between the studies on suicidal behavior and its intricate network of individual and sociocultural factors and the studies on this multisystem autoimmune disease with a broad manifestation spectrum,lupus,creates new and essential field research.Conclusions:Non-psychiatrist office-based physicians,health clinics,or wards dedicated to the treatment of SLE should recognize and handle the suicide risk factors on their patients to reduce the suffering caused by this disease.

关键词： lupus erythematosus Systemic Nervous system diseases Mental disorders Suicidal ideation Suicide

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The five major autoimmune diseases increase the risk of cancer:epidemiological data froma large-scale cohort study in China

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Cancer Communications 2022年第5期42卷 435-446页

作者： Ziyue Zhou Huazhen Liu Yiying Yang Jingya Zhou Lidan Zhao Hua Chen Yunyun Fei Wen Zhang Mengtao Li Yan Zhao Xiaofeng Zeng Fengchun Zhang Huaxia Yang Xuan Zhang Department of Rheumatology and Clinical Immunology National Clinical Research Center for Dermatologic and Immunologic Diseasesthe Ministry of Education Key LaboratoryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730P.R.China Clinical Immunology Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730P.R.China Department of Medical Records Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730P.R.China State Key Laboratory of Difficult Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730P.R.China Department of Rheumatology National Center of GerontologyInstitute of Geriatric MedicineBeijing HospitalPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730P.R.China

Background:Cancer incidence and mortality have received critical attention during the long-term management of morbidities in patients with autoimmune diseases(AIDs).This study aimed to investigate and compare the risk of cancer associated with five major AIDs in a large-scale Chinese cohort.Methods:A total of 8,120 AID patients consecutively admitted to a national tertiary referral center in China were included and followed-up for 38,726.55 patient-years,including those with systemic lupus erythematosus(SLE),rheumatoid arthritis(RA),Sjoren’s syndrome(SS),systemic scleroderma(SSc),and idiopathic inflammatory myositis(IIM).Demographic data,cancer incidence,predilecting sites and cancer onset time were recorded and compared among the five AIDs.Results:Four hundred and thirty(5.3%)patients developed cancer.Their median agewas 57.5 years and AID durationwas 79.8 months.The estimated total standardized incidence ratio(SIR)of cancer in AIDs patients was 3.37,with the highest SIR observed in IIM(4.31),followed by RA(3.99),SSc(3.77),SS(2.88)and SLE(2.58).The increased SIR of cancers in AID patients showed a female predominance(female vs.male:3.59 vs.2.77)and younger patient involvement(age<50 vs.≥50 years:4.88 vs.3.04).Patientswith SLE had increased SIRs for developing hematologic malignancies and solid tumors located in the urinary bladder,corpus uteri and cervix uteri.Patients with SS had a significantly high SIR for developing non-Hodgkin’s lymphoma.Within 3 years of IIM diagnosis,74.6%of the patients developed cancer and they had a high risk of ovarian cancer.RA was associated with a wide distribution of scancers,including non-Hodgkin’s lymphoma,gynecologic,urinary tract,thyroid gland and lung cancers.SSc patients had increased SIRs for developing cervical uterine,lung,and breast cancers.Conclusion:Patients with five major AIDs in China had an increased risk of developing cancer,with a predominance in women and younger patients,although cancer incidence,predilection sites and cancer onset time may vary greatly in each

关键词： autoimmune disease cancer risk standardized incidence ratio lupus erythematosus rheumatoid arthritis Sjoren’s syndrome systemic scleroderma idiopathic inflammatory myositis epidemiology

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Increased serum IL-10 in lupus patients promotes apoptosis of T cell subsets via the caspase 8 pathway initiated by Fas signaling

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The Journal of Biomedical Research 2015年第3期29卷 232-240页

作者： Xiaofan Yang Bin Sun Huijuan Wang Cheng Yin Xiaole Wang Xiaohui Ji Department of Microbiology and Immunology Nanjing Medical University Department of Nephrology the First Affiliated Hospital of Nanjing Medical University

We sought to investigate the expression of Fas and FasL on T cell surface and caspase 8 involvement in T cell apoptosis promoted by serum IL-10 in systemic lupus erythematosus （SLE） patients. Cells and sera were obtained from 35 SLE patients. Apoptosis of T cells in patients with SLE was increased and associated with the SLE disease activity index （SLEDAI）. Elevated expression of Fas and FasL on T cell surface contributed to increased apoptosis of T cells. Increased IL-10 in the sera of SLE patients was capable of inducing Fas and FasL expression on CD4^＋T cell surface, promoting apoptosis of this cell subset. Decreased IL-10 serum levels and low expression of Fas were found in 5 patients of the first follow-up group after 2-month treatment. In another group with one-year treatment, the SLEDAI declined to inactive scores. Serum IL-10 was decreased significantly, and expression of Fas and FasL on T cells was also reduced. Declined apoptosis was predominant only in CD4^＋T cell subset. When sera with high level of IL-10 were used to culture PBMCs from healthy controls, activated caspase 8 was elevated in CD3^＋T, CD4^＋T and CD8^＋T cells. The study showed that serum IL-10 induced apoptosis of T cell subsets via the caspase 8 pathway initiated by Fas signaling. Increased apoptosis of T cells contributes to autoantigen burden, which is pathogenic in the development of SLE.

关键词： apoptosis T cell lupus erythematosus systemic

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High dose intravenous immunoglobulins in the treatment of encephalopathy in systemic lupus erythematosus

High dose intravenous immunoglobulins in the treatment of en...

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首届国际中西医结合风湿病学术会议

作者： Wang Jingyuan Zhao Yinhuan Department of Rheumatology Second Hospital of Harbin Medical University Harbin 150086

＜正＞bjective: To study the effect of high dose intravenous immunoglobulins （IVIg） in the treatment of encephalopathy in systemic lupus erythematous.Methods: A retrospective cohort study was employed. 80 patients diagnosed as encephalopathy were divided into three groups. Pulse therapy of methylprednisolone （MP） in 40 patients as group A, 20 （Bgroup） were treated by MP and cyclophosphamide （CTX）. 20 （Cgroup） were treated by high dose IVIg in combination with MP and CTX.Results: ①A combination of high dose IVIg can reduce disease activity（SLEDAI） more significantly than high dose MP alone （P＜0.05）;②IVIg group had better results than MP group, including a decline in the morbidity of hospital infection and mortality （P＜0.05）.Conclusion: High dose IVIg is a useful therapy in controlling SLEDAI, infection and encephalopathy itself.

关键词： lupus erythematosus systemic encephalopathy immunoglobulins infection

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SSB peptide and DNA co-immunization induces inhibition of anti-dsDNA antibody production in rabbits

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Chinese Medical Journal 2008年第3期121卷 227-230页

作者： DING Min ZHANG Jian-zhong Department of Dermatology Peking University People's HospitalBeijing 100044 China

Background Patients with systemic lupus erythematosus often have various autoantibodies. The relationship between these antibodies is still poorly understood. The aim of the present study was to observe the anti-SSB antibody and anti-dsDNA antibody production profiles following immunization with synthetic SSB peptide alone, DNA alone or co-immunization with these two antigens. Methods SSB 214-225 aa peptide was synthesized by organic chemistry solid-phase peptide synthesis. Rabbits were immunized with the following antigens： synthetic SSB peptide linked with keyhole limpet hemocyanin （KLH）, DNA, SSB plus dsDNA, KLH and PBS. Antibodies were measured by ELISA. Histopathology and direct immufluorescence assays were also applied. Results Anti-SSB and anti-dsDNA antibodies were produced following immunization with SSB peptide and DNA respectively. The level of SSB antibody in the co-immunization group was higher than that of the SSB peptide immunization group. The level of anti-dsDNA antibody in the co-immunization group was, however, lower than that in the DNA immunization group. Meanwhile, the level of anti-SSB antibody was higher than that of anti-DNA antibody in the co-immunization group. No morphological or immunological abnormalities were found in the heart, liver, kidney, spleen or skin tissues. Conclusion Inhibition of anti-dsDNA-antibody was induced by co-immunization with synthesized SSB peptide and DNA, which might explain, at least partly, the mild disease in some LE subsets associated with SSB antibody.

关键词： lupus erythematosus antibody SSB dsDNA immunization

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Current Status of Treatment for Systemic lupus Erythe matosus in China and Its Prospect

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Chinese Journal of Integrative Medicine 2002年第1期8卷 72-77页

作者：杨虎天魏强华 Shang hai Municipal First People's Hospital

CURRENT OVERALL LEVEL IN CHINA OF SLE TREATMENTSystemic lupus erythematosus (SLE) is a kind of most complicated auto-immune disease and its etiology is still not clear so far. There are at least one million patients in China. SLE was taken as an “inc urable disease” in the fifties, but recently th e understanding of SLE got gradually elevated, and the efficacy of treatment won further progresses, therefore prognosis was obviously improved. According to the re sult of an 18-year follow-up of 50 SLE patients treated by Shanghai Renji Hospital in 1999, their 5-, 10-, 15- and 18-year survival rate reached 98%, 84%, 76% and 70% respectively, and the international progressive level has been reach ed (1) , it was also discovered that 13 cases (26%) has stopped medication for 12 years (2-17 years) and did not have manifestation of SLE activation. SLE usually occurred in child-bearing women, hence pregnancy complicated with SLE was also a problem fr e quently encountered. The most frequent thought then was to take measures to stop pregnancy to save the life of the women, while at present, if a woman took small dosage of prednisone without the activation of SLE over 12 months, pregnancy can be considered; for those already pregnant women, dosage of pre dnisone could be inc reased under the guidance of rheumatologic and gynecologic specialists; during labor corticosterone (CS) intravenous dripping and other measures were added. Eighty-one new born babies by 80 cases of pregnancy complicated with SLE, have been delivered with both mot her and baby surviving: an inspiring good outcome (2) .

关键词： lupus erythematosus pregnant women survival rate small dosage

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广西壮族系统性红斑狼疮与HLA-DQA1等位基因的相关性研究

广西壮族系统性红斑狼疮与HLA-DQA1等位基因的相关性研究

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作者：刘栋华广西医科大学

学位级别：硕士

目的：探讨广西壮族系统性红斑狼疮（SLE）与HLA-DQA1等位基因相关性。方法：患者组为广西壮族SLE病人，男5例，女46例。正常对照组为无血缘关系的壮族健康者，男32例，女38例。SLE组与正常对照组双亲三代内均为壮族。应用经典的酚／氯... 详细信息

目的：探讨广西壮族系统性红斑狼疮（SLE）与HLA-DQA1等位基因相关性。方法：患者组为广西壮族SLE病人，男5例，女46例。正常对照组为无血缘关系的壮族健康者，男32例，女38例。SLE组与正常对照组双亲三代内均为壮族。应用经典的酚／氯仿抽提法提取外周血基因组DNA，用聚合酶链反应—序列特异性引物（PCR-SSP）技术，对51例SLE壮族患者的HLA-DQA1基因进行研究,以70例壮族健康者作对照。同时，采用免疫印迹技术测定SLE壮族患者自身抗体谱。结果：12对引物检出HLA-DQA1 8个亚型，HLA-DQA1*0201和HLA-DQA1*0302等位基因在两组中均未检测到。SLE组DQA1*0101频率显著高于对照组(RR=3.2727，χ2=7.321，P=0.009)，而DQA1*0104和DQA1*0301频率均显著低于对照组（RR=0.4561，χ2=3.885，P=0.049 和 RR=0.4317，χ2=4.843，P=0.028）。DQA1*0101与抗dsDNA正相关（χ2=4.488，P=0.034），DQA1*0301与抗dsDNA及抗SSA/SSB负相关（χ2=5.017，P=0.025及χ2=3.869，P=0.049）。结论：HLA-DQA1*0201和HLA-DQA1*0302等位基因空白构成了广西壮族人群的特殊性。HLA-DQA1*0101可能是广西壮族SLE易感基因，其易感性可能通过诱导抗dsDNA抗体产生实现。DQA1*0104和DQA1*0301可能通过抑制自身抗体的产生为保护基因。

关键词： lupus erythematosus systemic Human leukocyte antigen Autoantibody Genetic susceptibility Zhuang nationality.

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The risk factors for SLE patients developing central nervous system disease

The risk factors for SLE patients developing central nervous...

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The 8th International Congress on SLE

作者： Jin Wei Guo-Hua Yuan Jing-Guo Zhou Department of Rheumatology affiliated hospital of Northern Sichuan Medical College Nanchong City Sichuan Province China 637000

＜正＞Objective:To estimate the risk factors in patients with systemic lupus erythematosus（SLE）developing central nervous system（CNS）disease. Methods:The clinical features and laboratory findings in 46 SLE patient... 详细信息

关键词： lupus erythematosus systemic Central nervous system diseases Risk factors

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