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Tissue-resident memory T cells break tolerance to renal autoantigens and orchestrate immune-mediated nephritis

Cellular & Molecular Immunology 2024年第9期21卷 1066-1081页

作者： Frederic Arnold Laurence Kupferschmid Philipp Weissenborn Lukas Heldmann Jonas F.Hummel Paulina Zareba Sagar Manuel Rogg Christoph Schell Yakup Tanriver Department of Medicine IV Medical CenterFaculty of MedicineUniversity of FreiburgFreiburgGermany Institute of Microbiology and Hygiene Medical CenterFaculty of MedicineUniversity of FreiburgFreiburgGermany Institute of Pathology Medical CenterFaculty of MedicineUniversity of FreiburgFreiburgGermany Department of Medicine II Medical CenterFaculty of MedicineUniversity of FreiburgFreiburgGermany

Immune-mediated nephritis is a leading cause of acute kidney injury and chronic kidney *** the role of B cells and antibodies has been extensively investigated in the past,the advent of immune-checkpoint inhibitors has led to a reappraisal of the role of T cells in renal ***,it remains elusive how T cells with specificity for renal autoantigens are activated and participate in immune-mediated ***,we followed the fate and function of pathogen-activated autoreactive CD8 T cells that are specific for a renal *** demonstrate that recently activated splenic CD8 T cells developed a hybrid phenotype in the context of renal autoantigen cross-presentation,combining hallmarks of activation and T cell *** circulating memory T cells rapidly disappeared,tissue-resident memory T cells emerged and persisted within the kidney,orchestrating immune-mediated ***,T cells infiltrating kidneys of patients with interstitial nephritis also expressed key markers of tissue *** study unveils how a tissue-specific immune response can dissociate from its systemic counterpart driving a compartmentalized immune response in the kidneys of mice and ***,targeting tissue-resident memory T cells emerges as a promising strategy to control immune-mediated kidney disease.

关键词： T cell response Tissue residency Renal autoimmunity nephritis CD8

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Successful treatment of tubulointerstitial nephritis in immunoglobulin G4-related disease with rituximab: A case report

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World Journal of Clinical Cases 2019年第16期7卷 2309-2315页

作者： Eray Eroglu Murat Hayri Sipahioglu Soner Senel Sule Ketenci Ertas Seyma Savas Figen Ozturk Ismail Kocyigit Bulent Tokgoz Oktay Oymak Division of Nephrology Department of Internal MedicineErciyes University School of MedicineKayseri 38039Turkey Division of Rheumatology Department of Internal MedicineErciyes University School of MedicineKayseri 38039Turkey Department of Internal Medicine Erciyes University School of MedicineKayseri 38039Turkey Department of Pathology Erciyes University School of MedicineKayseri 38039Turkey

BACKGROUND Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition that consisted of disorders that share particular clinical,serologic and pathologic *** common presentation of disease includes tumor-like swelling of involved organs and the histopathological findings are a lymphoplasmacytic infiltrate enriched with IgG4-positive plasma cells,and a variable degree of fibrosis that has a characteristic "storiform" pattern in biopsy specimens of tumorlike *** presentations of this disease,which often affects more than one organ,include autoimmune pancreatitis,salivary gland disease (sialadenitis),orbital disease and retroperitoneal *** steroid treatment is essential for the treatment of the disease however,other immunosuppressive drugs including cyclophosphamide or rituximab could be an option in resistant *** SUMMARY Herein,we reported a 34-year-old woman whom previously had diagnosed with asthma,rheumatoid arthritis and Sj?gren’s syndrome (SS) referred our nephrology department due to acute kidney failure development at the last rheumatology *** kidney biopsy she has been diagnosed with IgG4-RD and tubuluointerstitial *** had been accepted resistant to steroid,mycophenolate mofetil,methotrexate and azathioprine therapies due to receiving in last two *** refused to receive cyclophosphamide due to potential gonadotoxicity of the ***,rituximab therapy was *** received 1000 mg infusion,15 d apart and 6 mo later it has been administered same *** one year from the last rituximab dose serum creatinine decreased from 4.4 mg/dL to 1.6 mg/dL,erythrocyte sedimentation rate decreased from 109 mm/h to 13 mm/h [reference range (RR) 0-20],and Creactive protein decreased from 55.6 mg/L to 5 mg/L (RR 0–6).All pathologic lymph nodes and masses were also *** Patients with IgG4-RD usually misdiagnosed with rheumatologic diseases including systemic lupus erythem

关键词： Immunoglobulin G4-related disease Tubulointerstitial nephritis Rituximab Case report

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Henoch-Schönlein purpura nephritis in children:incidence,pathogenesis and management

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World Journal of Pediatrics 2015年第1期11卷 29-34页

作者： Jun-Yi Chen Jian-Hua Mao Department of Nephrology Children's HospitalZhejiang University School of MedicineHangzhou 310003China

Background:Henoch-Schönlein purpura(HSP)is one of the most common vasculitides in *** is manifested by skin purpura,arthritis,abdominal pain,renal involvement,***,HSP is considered to be self-limiting,although renal involvement(HSP purpura nephritis,HSPN)is the principal cause of morbidity from this *** this reason,it is important to clarify the mechanism of onset and clinical manifestations of HSPN and to ascertain the most appropriate treatment for *** this article,we review the updated pathophysiology and treatment strategies for *** sources:We searched databases including PubMed,Elsevier and Wanfang for the folowing key words:Henoch-Schönlein purpura,nephritis,mechanism and treatment,and we selected those publications written in English that we judged to be relevant to the topic of this ***:Based on the data present in the literature,we reviewed the following topics:1)the possible pathogenesis of HSPN:several studies suggest that immunoglobulin A immune complexes deposit in the mesangium and induce renal injury;2)multiple-drug treatment for HSPN:although there have been few evidence-based treatment strategies for HSPN,several studies have suggested that immunosuppressive drugs and multiple drug combination therapy were effective in ameliorating proteinuria and histological ***:HSPN is a severe disease of *** better understand this disease,detailed investigations into the pathogenesis of HSPN and prospective randomized controlled treatment studies on children with severe HSPN are needed.

关键词： Henoch-Schönlein purpura immunosuppressive drug nephritis pathogenesis treatment

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Tripterygium wilfordii Hook F is efficacious in the treatment of Henoch-Schönlein purpura nephritis in children

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World Journal of Pediatrics 2016年第3期12卷 375-375,376页

作者： Shu-Jiong Mao Xian-Mei Huang Department of Pediatrics Hangzhou First People's HospitalHangzhouChina

I read with interest the recently published article by Huang et al.[1]The article is very informative and has brought an utmost important insight on chronic glomerulonephritis in *** is an interesting issue,because glomerulonephritis such as Schonlein-Henoch nephritis(HSPN)may lead to renal failure in children and *** well-presented clinical features and histopathological changes described in the article are valuable for pediatricians in diagnosing HSPN in the high-risk population.

关键词： nephritis Tripterygium al.

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Tripterygium wilfordii Hook F is efficacious in the treatment of Henoch-Schönlein purpura nephritis in children

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World Journal of Pediatrics 2016年第3期12卷 376-379页

作者： Yan-Jie Huang Xiao-Qing Yang Wen-Sheng Zhai Xian-Qing Ren Yuan Sun Ying Ding The First Affiliated Hospital of Henan University of Traditional Chinese Medicine 19 Renmin road Zhengzhou 450000China

Our retrospective study was aimed to define the clinical manifestations,pathological features and prognosis of children with grade VI HSPN,our results also showed that tripterygium glycosides(T glycosides)alone or com... 详细信息

关键词： protective nephritis Tripterygium

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The　prognosis　of　biopsy-proven　lupus　nephritis　in 　Chinese　patients: long-term　follow-up　of　86　cases

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Chinese Medical Journal 1997年第7期 6-11页

作者：沈克勤俞雨生唐政刘志红黎磊石

Objective To investigate the prognosis of lupus nephritis (LN) and its influencing factors in patients with lupus nephritis in China. Methods A retrospective study was carried out in 86 patients followed up for at least 5 years. Clinical features, serological and immunological tests were investigated. Renal biopsies were performed at the beginning of the study and repeated in some cases during the follow up period. All the 86 patients had serum creatinine (Scr) level less than 132.6 μmol/L at the inital presentation and were divided into three groups according to the level of Scr at the end of the study. Group Ⅰ: the patients with normal renal function (Scr<132.6 μmol/L); Group Ⅱ: the patients with mild～moderate renal insufficiency (132.6 μmol/L≤Scr≤530.4 μmol/L); Group Ⅲ: the patients with end stage real failure (ESRF) (Scr≥ 530.4 μmol/L). Results Forty seven patients reached clinical remission with normal renal function, 11 had with stabilization of renal function although the systemic lupus erythematosis (SLE) acti vity relapsed repeatedly, while 28 subjects developed renal insufficiency after 60～170 (mean 88.12±28.23) months of observation. ESRF rate was 11.6% in this group of patients. Eight patients died (2 died of infections and 6 died of ESRF) during the follow up period. At the beginning of the study the rates of hypertension, persistent anemia and hematuria in Group Ⅲ were 50%, 70% and 70% respectively, being much higher than those in Group I. The calculation of AI and CI in 60 patients revealed that there were 65% of patients with AI ≥7 and 70% of patients with CI≥3 in Groups Ⅱ and Ⅲ, while in Group I there were only 32% of patients with AI≥7 and 19% of patients with CI≥3. Sixteen cases had pathologic class changed in 48 repeated biopsies. Seven cases changed to Class Ⅳ, 5 to Class Ⅱ, 3 to Class Ⅴ from other classes and one to class Ⅲ from Class Ⅱ. Conclusions Factors associated with the development of renal insufficiency in the

关键词： biopsy-proven prognosis The nephritis follow-up long-term patients 克勤 Chinese

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CLINICAL OBSERVATION ON TREATMENT OF RENAL FUNCTION DAMAGE DUE TO CHRONIC nephritis WITH BLOOD CIRCULATION INVIGORATING AND BLOOD STASIS REDUCING REGIMEN

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Journal of Traditional Chinese Medicine 1989年第1期9卷 18-20页

作者：洪淑云李仁康陈思源刘德元刘建国肖荣华杜绪胜 Department of TCM Union HospitalTongji Medical UniversityWuhan

Chronic nephritis is a frequently seen disease,but difficult to treat,from which the restora-tion of damaged renal functions is even more *** clinical practice,the authors

关键词： nephritis noted stasis Radix vomiting nausea diarrhea 高凝状态活血化疲 belonged

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TUBULORETICULAR STRUCTURE AND CYLINDRICAL CONFRONTING CISTERNAE IN LUPUS nephritis

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Chinese Medical Sciences Journal 1998年第3期13卷 166-169页

作者：陈振斌梁平余英豪谢福安陈莲云

*** investigate the pathological significance of tubuloreticular structure(TRS) and cylindri- cal confronting cisternae(CCC) in patients with lupus nephritis. Methods. An electron microscopical study of 24 renal biopsy specimens from patients with lupus nephritis was carried out, with particular emphasis on two endoplasmic reticulum(ER)-related structures. Result. TRS was found in 18 cases, and CCC in 10 of them. TRS often appeared in the capillary en- dothelium,and did not correlate well with the activity index of lupus nephritis. CCC appeared frequently in monocyte/macrophage and lymphocyte, and correlated well with both the activity index and the amount of interstitial immune deposits. *** and CCC derived from inward "budding" of ER membrane were suggested and the morphogenesis and morphologic variations of CCC were discussed. Both TRS and CCC are pathognomonic, though not specific changes. They may be helpful in pathologic diagnosis of lupus nephritis, when properly combined with certain clinical and pathological features.

关键词： sytemic lupus erythematosus ultrastructure nephritis

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Role of p300 in the pathogenesis of Henoch-Schonlein purpura nephritis and as a new target of glucocorticoid therapy in mice

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Chinese Medical Journal 2019年第16期132卷 1942-1950页

作者： Ming-Yu Jiang Wei Li Xiang-Ping Xu Jie-Qing Zhou Hong Jiang Department of Pediatrics The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110001China Department of Pediatrics The First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiang 150001China

Background: Henoch-Schonlein purpura nephritis (HSPN) is a very common secondary kidney disease of childhood. Its pathogenesis and the treatment mechanism of glucocorticoid have not been fully elucidated. The aim of this study was to determine the relationship between p300 and the pathogenesis, glucocorticoid therapy in mice with HSPN, respectively. Methods: Forty-eight C57BL/6N male mice, weighing 18 to 20 g, were selected (3–4 weeks old, n = 8 per group). The mice in the normal control group (Group I) were given normal solvent and the HSPN model group (Group II) were given sensitizing drugs. The mice in Group III were injected intraperitoneally with dexamethasone after being given sensitizing drugs. Meanwhile, mice in Groups IV, V and VI with conditional knockout of p300 were also given normal solvent, sensitizing drugs and dexamethasone. The levels of serum IgA, creatinine, and circulating immune complex (CIC) concentrations, 24 h urinary protein and urinary erythrocyte in C57 wild mice, and p300 conditional knockout mice in each group were measured. The expression of p300 in renal tissues and the expression of glucocorticoid receptor (GR)α and β, transforming growth factor (TGF)-β1, and activator protein (AP)-1 after dexamethasone treatment were determined by real-time polymerase chain reaction and Western blotting. Results: Compared with the normal solvent control group (Group I), the expression of p300 mRNA in the model group (Group II) was significantly up-regulated. Western blotting further confirmed the result. Urinary erythrocyte count, 24 h urinary protein quantification, serum IgA, CIC, and renal pathologic score in Group V were distinctly decreased compared with non-knockout mice in Group II (9.7 ± 3.8 per high-power field [/HP] vs. 18.7 ± 6.2/HP, t = 1.828, P = 0.043;0.18 ± 0.06 g/24 h vs. 0.36 ± 0.08 g/24 h, t = 1.837, P = 0.042;18.78 ± 0.85 mg/mL vs. 38.46 ± 0.46 mg/mL, t = 1.925, P = 0.038;0.80 ± 0.27 μg/mL vs. 1.64 ± 0.47 μg/mL, t = 1.892, P = 0.04

关键词： p300 Henoch-Schonlein purpura nephritis Pathogenesis Glucocorticoid treatment

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Mycophenolate mofetil plus prednisone for inducing remission of Henoch-Sch?nlein purpura nephritis: a retrospective study

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2015年第9期16卷 772-780页

作者： Fei HAN Liang-liang CHEN Ping-ping REN Jing-yun LE Pei-jing CHOONG Hong-ju WANG Ying XU Jiang-hua CHEN Kidney Disease Center the First Affiliated Hospital School of Medicine Zhejiang University /Key Laboratory of Kidney Disease Prevention and Control TechnologyZhejiang Province /the Third Grade Laboratory under the National State Administration of Traditional Chinese Medicine

Objective： The treatment of Henoch-Schonlein purpura （HSP） with moderate proteinuria remains con- troversial. We retrospectively analyzed the efficacy of immune suppressants, with a particular emphasis on myco- phenolate mofetil （MMF）. Methods： Ninety-five HSP patients with moderate proteinuria （1.0-3.5 g/24 h） after at least three months of therapy with angiotensin-converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） were divided into three groups： an MMF group （n=33） that received MMF 1.0-1.5 g/d combined with prednisone （0.4-0.5 mg/（kg.d））, a corticosteroid （CS） group （n=31） that received full-dose prednisone （0.8-1.0 mg/（kg.d））, and a control group （n=31）. Patients in the MMF and CS groups continued to take ACEI or ARB at the original dose. The patients in the control group continued to take ACEI or ARB but the dose was increased by （1.73±0.58）-fold. The patients were followed up for 6-78 months （median 28 months）. Results： The baseline proteinuria was higher in the MMF group （（2.1±0.9） g/24 h） than in the control group （（1.6±0.8） g/24 h）（P=0.039）. The proteinuria decreased sig- nificantly in all groups during follow-up, but only in the MMF group did it decrease significantly after the first month. At the end of follow-up, the proteinuria was （0.4±0.7） g/24 h in the MMF group and （0.4±0.4） g/24 h in the CS group, significantly lower than that in the control group （（0.9±1.1） g/24 h）. The remission rates in the MMF group, CS group, and control group were respectively 72.7%, 71.0%, and 48.4% at six months and 72.7%, 64.5%, and 45.2% at the end of follow-up. The overall number of reported adverse events was 17 in the MMF group, 30 in the CS group, and 6 in the control group （P〈0.001）. Conclusions： MMF with low-dose prednisone may be as effective as full-dose prednisone and tend to have fewer adverse events. Therefore, it is probably superior to conservative treatments of adult HSP patients with moderate proteinuria.

关键词： Henoch-Schonlein purpura nephritis Mycophenolate mofetil Remission

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