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Statins markedly potentiate aminopeptidase inhibitor activity against(drug-resistant)human acute myeloid leukemia cells

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Cancer Drug Resistance 2023年第3期6卷 430-446页

作者： Gerrit Jansen Marjon Al Yehuda G.Assaraf Sarah Kammerer Johan van Meerloo Gert J.Ossenkoppele Jacqueline Cloos Godefridus J.Peters Department of rheumatology and Clinical Immunology Amsterdam Rheumatology and immunology CenterAmsterdam University Medical Centerlocation VUmcAmsterdam 1081 HVThe Netherlands The Fred Wyszkowsky Cancer Research Laboratory Faculty of BiologyThe Technion-Israel Institute of TechnologyHaifa 3200003Israel Department of Medical Oncology Amsterdam University Medical Centerlocation VUmcAmsterdam 1081 HVThe Netherlands institute of Biotechnology Molecular Cell BiologyBrandenburg University of Technology Cottbus-SenftenbergSenftenberg 01968Germany Department of Hematology Amsterdam University Medical Centerlocation VUmcAmsterdam 1081 HVThe Netherlands Department of Biochemistry Medical University of GdanskGdansk 80-210Poland

Aim: This study aimed to decipher the molecular mechanism underlying the synergistic effect of inhibitors of the mevalonate-cholesterol pathway (i.e., statins) and aminopeptidase inhibitors (APis) on APi-sensitive and -resistant acute myeloid leukemia (AML) cells.Methods: U937 cells and their sublines with low and high levels of acquired resistance to (6S)-[(R)-2-((S)-Hydroxy-hydroxycarbamoyl-methoxy-methyl)-4-methyl-pentanoylamino]-3,3 dimethyl-butyric acid cyclopentyl ester (CHR2863), an APi prodrug, served as main AML cell line models. Drug combination effects were assessed with CHR2863 and in vitro non-toxic concentrations of various statins upon cell growth inhibition, cell cycle effects, and apoptosis induction. Mechanistic studies involved analysis of Rheb prenylation required for mTOR activation.Results: A strong synergy of CHR2863 with the statins simvastatin, fluvastatin, lovastatin, and pravastatin was demonstrated in U937 cells and two CHR2863-resistant sublines. This potent synergy between simvastatin and CHR2863 was also observed with a series of other human AML cell lines (e.g., THP1, MV4-11, and KG1), but not with acute lymphocytic leukemia or multiple solid tumor cell lines. This synergistic activity was: (i) specific for APis (e.g., CHR2863 and Bestatin), rather than for other cytotoxic agents;and (ii) corroborated by enhanced induction of apoptosis and cell cycle arrest which increased the sub-G1 fraction. Consistently, statin potentiation of CHR2863 activity was abrogated by co-administration of mevalonate and/or farnesyl pyrophosphate, suggesting the involvement of protein prenylation;this was experimentally confirmed by impaired Rheb prenylation by simvastatin.Conclusion: These novel findings suggest that the combined inhibitory effect of impaired Rheb prenylation and CHR2863-dependent mTOR inhibition instigates a potent synergistic inhibition of statins and APis on human AML cells.

关键词： Aminopeptidase statins mevalonate pathway carboxyl esterase Rheb mTOR

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Natural biopolymers derived hydrogels with injectable,self-healing,and tissue adhesive abilities for wound healing

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Nano Research 2023年第2期16卷 2798-2807页

作者： Bin Kong Rui Liu Yi Cheng Xiaodong Cai Junying Liu Dagan Zhang Hui Tan Yuanjin Zhao Department of rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210002China Respiratory department Shenzhen Children's HospitalShenzhen 518038China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325001China

Developing a biocompatible and multifunctional adhesive hydrogel with injectability and self-healing ability for promoting wound healing is highly anticipated in various clinical applications.In this paper,we present a novel natural biopolymer-derived hydrogel based on the aldehyde-modified oxidized guar gum(OGG)and the carboxymethyl chitosan(CMCS)for efficiently improving wound healing with the encapsulation of vascular endothelial growth factor(VEGF).As the hydrogels are synthesized via the dynamically reversible Schiff base linkages,it is imparted with excellent self-healing ability and good shear thinning behavior,which make the hydrogel be easily and conveniently injected through a needle.Besides,the physiochemical properties,including porous structure,mechanical strength and swelling ratio of the hydrogel can be well controlled by regulating the concentrations of the OGG.Moreover,the hydrogel can attain strong adhesion to the tissues at physiological temperature based on the Schiff base between the aldehyde group on the hydrogel and the amino group on the tissue.Based on these features,we have demonstrated that the VEGF encapsulated hydrogel can adhere tightly to the defect tissue and improve wound repair in the rat model of defected skin by promoting cell proliferation,angiogenesis,and collagen secretion.These results indicate that the multifunctional hydrogel is with great scientific significance and broad clinical application prospects.

关键词： hydrogel self-healing injectability tissue adhesive wound healing

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Leflunomide,a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase Ⅱ clinical trial

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Chinese Medical Journal 2003年第8期116卷 1228-1234页

作者：鲍春德陈顺乐顾越英劳志英倪立青於强徐建华李向培刘嘉玲孙凌云何培根马骥良徐淑云丁长海 Department of Clinical Immunology Shanghai Renji Hospital Shanghai Second Medical University Shanghai 200001 China Department of rheumatology Shanghai Guanghua Hospital Shanghai 200000 China Department of rheumatology Shanghai Zhongshan Hospital Shanghai Medical University Shanghai 200032 China Department of Clinical Immunology Affiliated Hospital of Anhui Medical University Hefei 230022 China Department of rheumatology Anhui Provincial Hospital Hefei 230001 China Department of rheumatology Affiliated Hospital of Nanjing Medical University Nanjing 210029 China Department of rheumatology Nanjing Gulou Hospital Nanjing 210008 China Department of rheumatology Tongji Hospital Tongji Medical University Wuhan 430003 China Department of rheumatology Beijing Friendship Hospital Beijing 100050 China institute of Clinical Pharmacology Anhui Medical University Hefei 230022 China

Objective To evaluate the efficacy and safety of leflunomide in comparison with methotrexate (MTX) on patients with rheumatoid arthritis (RA) in China.Methods Five hundred and sixty-six patients with active rheumatoid arthritis were randomly assigned to receive leflunomide at 20 mg once daily or MTX at 15 mg once weekly in a controlled trial. Five hundred and four patients completed the 12-week treatment and some patients continued the treatment for 24 weeks. Results Both leflunomide and MTX could improve the symptoms,signs,and joint function,but there were no changes in X-ray observations of patients with rheumatoid arthritis. In the leflunomide group,the overall rates of effectiveness at 12 weeks and 24 weeks were 86.94% and 92.31% respectively; the rates of remarkable improvement were 64.95% and 79.81% respectively. In the MTX group,the overall rates of effectiveness at 12 weeks and 24 weeks were 84.04% and 83.15% respectively; the rates of remarkable improvement were 56.81% and 75.28% respectively. According to intent-to-treat analysis,the ACR 20% response rates at 12 weeks and 24 weeks in the leflunomide group were 62.54% and 67.18% respectively,compared with 60.08% and 61.32% respectively in MTX group. No statistical differences were shown in the efficacy between the two groups ( P >0.05). The adverse events in the leflunomide group were gastrointestinal symptoms,skin rash,alopecia,nervous system symptoms,decreased leukocyte count,and elevation of alanine aminotransferase (ALT). Most of these side effects were mild and transient. The incidence of adverse events in the leflunomide group was 16.84%,significantly lower than that in MTX group (28.17%,P =0.002).Conclusions Leflunomide is effective in the treatment of RA with less adverse events than MTX. Its efficacy is similar to MTX,but the incidence of adverse events and the rate of withdrawal due to adverse events were lower in the leflunomide group than in MTX group.

关键词： leflunomide rheumatoid arthritis·methotrexate·clinical trial

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Phase II study of novel orally PI3Kα/δinhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2193-2201页

作者： Huaqing Wang Jifeng Feng Yanyan Liu Zhengzi Qian Da Gao Xuehong Ran Hui Zhou Lihong Liu Binghua Wang Meiyun Fang Hebing Zhou Zhenqian Huang Shi Tao Zhuowen Chen Liping Su Hang Su Yu Yang Xiaobao Xie Huijing Wu Ping Sun Guoyu Hu Aibin Liang Zhiming Li Department of Oncology Tianjin Union Medical Center of Nankai UniversityTianjin 300121PR China The institute of Translational Medicine Tianjin Union Medical Center of Nankai UniversityTianjin 300121PR China Department of Medical Oncology Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009PR China Department of Medical Oncology Henan Cancer HospitalThe Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003PR China Department of Medical Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Hematology The Affiliated Hospital of Inner Mongolia Medical College010050 HohhotPR China Department of Hematology Weifang People’s HospitalThe First Affiliated Hospital of Weifang Medical University261000 WeifangPR China Department of Lymphoma&Hematology Hunan Cancer HospitalThe Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University410013 ChangshaPR China Department of Hematology The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital050011 ShijiazhuangPR China Department of Lymphoma Weihai Central Hospital264400 WeihaiPR China Department of Hematology and rheumatology The Affiliated Zhongshan Hospital of Dalian University116001 DalianPR China Department of Hematology Beijing Luhe Hospital101199 BeijingPR China Department of Hematology The First Affiliated Hospital of Guangzhou Medical University510120 GuangzhouPR China Department of Hematology The First Affiliated Hospital of Hainan Medical College570102 HaikouPR China Department of Hematology The First People’s Hospital of Foshan528000 FoshanPR China Department of Hematology Shanxi Cancer Hospital030013 TaiyuanPR China Department of Lymphoma Senior Department of HematologyThe Fifth Medical Center of Chinese PLA General Hospital100039 BeijingPR China Department of Lymphoma and Head and Neck Cancer Fujian Cancer Hospital350014 FuzhouPR China Department of Hematology The First People’s Hospit

This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(ClinicalTrials.gov NCT04324879.Registered March 27,2020)comprised run-in stage and stage 2.R/R FL patients after≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression.Primary endpoint was independent review committee(IRC)-assessed objective response rate(ORR).Based on results(ORR,88.0%;duration of response[DOR],11.8 months;progression-free survival[PFS],12.0 months)in 25 patients at run-in stage,second stage study was initiated and included 82 patients for efficacy/safety analysis.Patients received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at baseline.At stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete responses.Disease control rate was 95.1%due to 7(8.5%)stable diseases.Median time to response was 1.8 months.Among 71 responders,median DOR was not reached;18-month DOR rate was 51.6%.with median follow-up of 13.3 months,median PFS was 18.5(95%CI,10.2-not estimable)months.Median overall survival(OS)was not reached by cutoff date;24-month OS rate was estimated as 86.1%.Response rates and survival data were consistent across all subgroups.Grade 3 or higher treatment-related adverse events were observed in 63(76.8%)cases,with neutropenia(22.0%),hyperglycemia(19.5%),and diarrhea(13.4%)being common.TQ-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.

关键词： lymphoma assessed initiated

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Endoscopy is of low yield in the identification of gastrointestinal neoplasia in patients with dermatomyositis: A cross-sectional study

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World Journal of Gastroenterology 2017年第26期23卷 4788-4795页

作者： Trilokesh D Kidambi Gabriela Schmajuk Andrew J Gross James W Ostroff Jonathan P Terdiman Jeffrey K Lee Division of Gastroenterology University of California Division of rheumatology University of California Division of rheumatology San Francisco Veterans Affairs Medical Center

AIM To determine the prevalence of gastrointestinal neoplasia among dermatomyositis patients who underwent an esophagogastroduodenoscopy and/or colonoscopy.METHODS A cross-sectional study examining the results of upper endoscopy and colonoscopy in adults with dermatomyositis at an urban, university hospital over a ten year period was performed. Chart review was performed to confirm the diagnosis of dermatomyositis. Findings on endoscopy were collected and statistical analyses stratified by age and presence of symptoms were performed.RESULTS Among 373 adult patients identified through a code based search strategy, only 163 patients had dermatomyositis confirmed by chart review. Of the 47 patients who underwent upper endoscopy, two cases of Barrett's esophagus without dysplasia were identified and there were no cases of malignancy. Of the 67 patients who underwent colonoscopy, no cases of malignancy were identified and an adenoma was identified in 15% of cases. No significant differences were identified in the yield of endoscopy when stratified by age or presence of symptoms.CONCLUSION The yield of endoscopy is low in patients with dermatomyositis and is likely similar to the general population; we identified no cases of malignancy. A code based search strategy is inaccurate for the diagnosis of dermatomyositis, calling into question the results of prior population-based studies. Larger studies with rigorously validated search strategies are necessary to understand the risk of gastrointestinal malignancy in patients with dermatomyositis.

关键词：内视镜检查法 Dermatomyositis 结肠癌屏蔽

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IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling

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Cellular & Molecular Immunology 2023年第6期20卷 651-665页

作者： Holly Bachus Erin McLaughlin Crystal Lewis Amber M.Papillion Etty N.Benveniste Dave Durell Hill Alexander F.Rosenberg AndréBallesteros-Tato Beatriz León Department of Medicine Division of Clinical Immunology and RheumatologyUniversity of Alabama at BirminghamBirminghamALUSA Department of Microbiology University of Alabama at BirminghamBirminghamALUSA Department of Cell Developmental and Integrative BiologyUniversity of Alabama at BirminghamBirminghamALUSA informatics institute University of Alabama at BirminghamBirminghamALUSA Alexion Pharmaceuticals Inc.New HavenCTUSA

Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house dust mite (HDM)-induced Th2 cell differentiation and allergic airway inflammation, we showed that IL-6 signaling in allergen-specific T cells was required to prevent Th2 cell differentiation and the subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. We found that IL-6 turned off IL-2 signaling during early T-cell activation and thus inhibited Th2 priming. Mechanistically, IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of Suppressor Of Cytokine Signaling 3 (SOCS3). This mechanism could be mimicked by pharmacological Janus Kinase-1 (JAK1) inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.

关键词： Th2 cell polarization IL-6 IL-2 SOCS3 JAK1 inhibitor

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Expression of CC Chemokine Ligand 5 in Patients with Rheumatoid Arthritis and Its Correlation with Disease Activity and Medication

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Chinese Medical Sciences Journal 2009年第1期24卷 50-54页

作者： Ming-hui Yang Feng-xia Wu Chuan-mei Xie Yu-feng Qing Guang-rong Wang Xiao-lan Guo Zhong Tang Jing-guo Zhou Guo-hua Yuan institute of rheumatology and Immunology Affiliated Hospital of North Sichuan Medical College Nanchong Sichuan 637000 China

Objective To determine the levels of CC chemokine ligand 5 (CCL5) in serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and their relations with disease activity and medication. Methods CCL5 in serum and SF was quantified by enzyme-linked immunosorbent assay (ELISA) in 28 RA patients and 21 osteoarthritis (OA) patients. In RA patients, the correlations of CCL5 levels in serum and SF with disease activity were analyzed. Meanwhile, the serum CCL5 levels among RA patients treated with disease-modifying antirheumatic drugs (DMARDs), Tripterygium Glucosides, and other Chinese herbs without disease-modifying effects were also compared. Results CCL5 levels in both serum and SF of RA patients were significantly higher than those of OA patients (P<0.05). Moreover, the level of CCL5 was higher in SF than that in serum of RA patients (P<0.01). Serum CCL5 level was correlated significantly with the number of swollen joints (r=0.3329, P<0.05), erythrocyte sedimentation rate (r=0.4001, P<0.05), and C reactive protein (r=0.3735, P<0.01). In addition, the level of CCL5 had a trend of lower in patients treated with DMARDs or Tripterygium Glucosides than those treated with other Chinese herbs, although the difference was not significant among those patients due to the small number of patients in each group. Conclusions In RA patients, the expression of CCL5 increases and correlates with some clinical and laboratory parameters of RA, which indicate that CCL5 plays an important role in RA and may serve as a useful marker of disease activity. DMARDs and Tripterygium Glucosides might exert their clinical effects through reducing CCL5 production in RA.

关键词：类风湿关节炎疾病活动性趋化因子配体关节炎患者药物治疗酶联免疫吸附试验雷公藤多甙 RA患者

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Expression of FLICE-inhibitory Protein in Synovial Tissue and Its Association with Synovial Inflammation in Juvenile Idiopathic Arthritis

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Chinese Medical Sciences Journal 2010年第1期25卷 20-26页

作者： Feng-xia Wu Li-jun Wu Xiong-yan Luo Ming-hui Yang Zhong Tang Chuan-mei Xie Jing-guo Zhou Jian-long Guan Guo-hua Yuan institute of rheumatology and Immunology Affiliated Hospital of North Sichuan Medical College Nanchong Sichuan 637000 China Department of rheumatology People＇s Hosptial of Xinjiang Uygur Autonomus Region Urumchi 830001 China Department of rheumatology and Immunology Changhai Hospital Second Military Medical University Shanghai 200433 China

Objective To examine the expression of FLICE-inhibitory protein (FLIP) in juvenile idiopathic arthritis (JIA) and analyze its correlation with synovial inflammation. Methods The expression of FLIP was assessed in 11 JIA and 3 normal synovial tissue samples by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The cell types expressing FLIP were further characterized,and the correlation of FLIP expression with the degree of synovial inflammation,as well as the activity of caspase 8 was then analyzed. Results RT-PCR revealed the expression of FLIP mRNA in all 11 JIA samples,but not in 3 normal synovial tissues. In JIA,FLIP expression could be found in both the lining and sublining layers,mainly in the macrophage-like cells. Moreover,the expression of FLIP in JIA synovial tissues was positively correlated with the degree of synovial inflammation (r=0.563,P<0.05). Conclusion The expression of antiapoptotic FLIP in JIA synovial tissue and its correlation to accumulation of inflammatory cells in synovial tissue suggests that FLIP potentially extends the lifespan of synovial cells and thus contributes to the progression of joint destruction.

关键词：抑制蛋白膜组织关节炎滑膜逆转录聚合酶链反应 FLIP caspase 幼年

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Impact of frailty on endoscopic retrograde cholangiopancreatography outcomes in nonagenarians:A United States national experience

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World Journal of Gastrointestinal Endoscopy 2024年第3期16卷 148-156页

作者： Sanket Dhirubhai Basida Dushyant Singh Dahiya Muhammad Nadeem Yousaf Brinda Basida Bhanu Siva Mohan Pinnam Manesh Kumar Gangwani Hassam Ali Sahib Singh Yash R Shah Daksh Ahluwalia Mihir Prakash Shah Saurabh Chandan Neil R Sharma Shyam Thakkar Department of Internal Medicine University of Missouri-ColumbiaColumbiaMO 65212United States Division of Gastroenterology Hepatology&MotilityThe University of Kansas School of MedicineKansas CityKS 66160United States Division of Gastroenterology and Hepatology University of MissouriColumbiaMO 65212United States Department of rheumatology Medical College of GeorgiaAugusta UniversityNorth AugustaGA 30912United States Department of Internal Medicine John H.Stroger Hospital of Cook CountyChicagoIL 60612United States Department of Internal Medicine The University of ToledoToledoOH 43606United States Division of Gastroenterology and Hepatology East Carolina University/Brody School of MedicineGreenvilleNC 27858United States Department of Internal Medicine Sinai HospitalBaltimoreMD 21215United States Department of Internal Medicine Trinity Health Oakland/Wayne State UniversityPontiacMI 48341United States Division of Gastroenterology and Hepatology Creighton University School of MedicineOmahaNE 68131United States Division of Interventional Oncology&Surgical Endoscopy GI Oncology Tumor Site TeamParkview Cancer InstituteParkview HealthFort WayneIN 46845United States Section of Gastroenterology&Hepatology West Virginia University School of MedicineMorgantownWV 26505United States

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is an essential therapeutic tool for biliary and pancreatic diseases.Frail and elderly patients,especially those aged≥90 years are generally considered a higher-risk population for ERCP-related complications.AIM To investigate outcomes of ERCP in the Non-agenarian population(≥90 years)concerning Frailty.METHODS This is a cohort study using the 2018-2020 National Readmission Database.Patients aged≥90 were identified who underwent ERCP,using the international classification of diseases-10 code with clinical modification.Johns Hopkins’s adjusted clinical groups frailty indicator was used to classify patients as frail and non-frail.The primary outcome was mortality,and the secondary outcomes were morbidity and the 30 d readmission rate related to ERCP.We used univariate and multivariate regression models for analysis.RESULTS A total of 9448 patients were admitted for any indications of ERCP.Frail and non-frail patients were 3445(36.46%)and 6003(63.53%)respectively.Indications for ERCP were Choledocholithiasis(74.84%),Biliary pancreatitis(9.19%),Pancreatico-biliary cancer(7.6%),Biliary stricture(4.84%),and Cholangitis(1.51%).Mortality rates were higher in frail group[adjusted odds ratio(aOR)=1.68,P=0.02].The Intra-procedural complications were insigni-ficant between the two groups which included bleeding(aOR=0.72,P=0.67),accidental punctures/lacerations(aOR=0.77,P=0.5),and mechanical ventilation rates(aOR=1.19,P=0.6).Post-ERCP complication rate was similar for bleeding(aOR=0.72,P=0.41)and post-ERCP pancreatitis(aOR=1.4,P=0.44).Frail patients had a longer length of stay(6.7 d vs 5.5 d)and higher mean total charges of hospitalization($78807 vs$71392)compared to controls(P<0.001).The 30 d all-cause readmission rates between frail and non-frail patients were similar(P=0.96).CONCLUSION There was a significantly higher mortality risk and healthcare burden amongst nonagenarian frail patients undergoing ERCP compared to non-frail.Larger studies are warranted to in

关键词： Endoscopic retrograde cholangiopancreatography Nonagenarians Frailty Mortality Healthcare burden

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HLA-DQ and-DR alleles in patients with SLE:A tertiary hospital-based case–control study in Bangladesh

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rheumatology & Autoimmunity 2023年第1期3卷 43-49页

作者： Muhammad S.A.Khan Shamim Ahmed Iftekhar H.Bandhan Farhana Zaman MdKamrul H.Sajib Shirin Tarafder Minhaj R.Choudhury Syed A.Haq Mohammad M.Zaman Sheikh Hasina National institute of Burn and Plastic Surgery DhakaBangladesh Department of rheumatology Bangabandhu Sheikh Mujib Medical UniversityDhakaBangladesh Upazilla Health Complex BancharampurB-BariaBangladesh Department of Community Medicine Universal Medical CollegeDhakaBangladesh Department of rheumatology Dhaka Medical College HospitalDhakaBangladesh Green Life Center for Rheumatic Care and Research DhakaBangladesh World Health Organization DhakaBangladesh

Background:Systemic lupus erythematosus(SLE)is a systemic autoimmune disease characterized by the involvement of multiple organs and autoantibody production.This study aimed to determine the association of human leukocyte antigen(HLA)-DQ and-DR alleles with SLE at a tertiary hospital in Bangladesh.Methods:This case-control study was conducted in the Department of rheumatology,Bangabandhu Sheikh Mujib Medical University(BSMMU),Dhaka,Bangladesh.The patients who fulfilled the 1997 revised American College of rheumatology classification criteria for SLE were considered cases(n=41).The controls(n=32)were selected from the hospital staff of BSMMU,including doctors and nurses who did not suffer from any known rheumatic diseases,and there was no such disease in their first-degree relatives.Polymerase chain reaction using a sequence-specific primer(PCRSSP)in a low-resolution typing method was carried out on blood samples collected for HLA-DQ and-DR allele typing.Results:The cases and controls had comparable mean ages(31 vs.32 years),and most cases were female(95.1%vs.34.4%).The most frequent clinical manifestations were mucocutaneous(85.4%),followed by musculoskeletal(70.7%)and constitutional symptoms(58.5%).The cases had a significantly higher frequency of HLA-DR2 allele compared with healthy controls(70.7%vs.43.8%;odds ratio:3.1;95%confidence interval:1.2-8.2).In addition,HLADQ6 allele was found to have a significant association with mucocutaneous manifestations of the cases(88.9%,P=0.03).Conclusions:Bangladeshi adults having HLA-DR2 may be more susceptible to SLE.HLA-DQ6 allele might be associated with mucocutaneous manifestations of SLE.

关键词： alleles Bangladesh HLA-DQ HLA-DR systemic lupus erythematosus

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