572例系统性红斑狼疮住院患者临床病例分析
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摘要
目的了解系统性红斑狼疮(SLE)的流行病学、临床表现、常规实验室检查的特点及用药情况,评估常规实验室检查指标在SLE的诊断、判断病情活动程度中的意义,同时探讨各因素对首发症状的影响及使用激素治疗的影响。以便从中吸取经验教训,找出其临床共性与特性,利于早诊断、早治疗、提高疗效、延长患者生存期和提高患者生活质量。
方法对1997年1月～2007年12月间在蚌埠医学院附属医院住院的572例SLE患者的临床资料进行回顾性研究,了解患者的一般情况、职业、首发症状、临床表现、实验室检查指标、家族史和预后等,对患者的病情进行计分和分类,利用统计学方法得出相关结论。
结果
1、一般情况: 572例患者中,男32例,女540例,男女比例为1:16.88,城市患者153例,农村及城郊患者419例,城乡比例为1:2.7。年龄最小7岁,最大者80岁,平均年龄33.55岁。平均发病年龄18.67岁。病程最短0月,最长144月,平均病程20.37月。平均住院时间为16.50天。所有统计病例中活动期患者463例,稳定期患者109例;首次发病患者215例,再发患者357例。
2、临床表现:在首发症状中,关节痛是最常见的,占58.6%,其次分别是皮疹、红斑36.7%、发热34.8%、其它21.3%、浮肿8.4%、肌肉酸痛,腰背痛6.6%。重要脏器损害包括:泌尿系统受累最多42.1%,以狼疮肾炎37.9%为主,其次为尿路感染5.6%,再次为慢性肾衰竭2.3%;呼吸系统受累占21.2%,包括肺部感染占9.8%,上呼吸道感染占7.7% ;血液系统受累占19.8%,包括败血症5.1%,高血压3.3%;免疫系统受累占7.9%,包括干燥综合症4.2%,糖尿病1.2%;消化系统受累占7.3%,包括肝功能损伤2.4%,肝炎和胆囊炎分别为1.2%;神经系统受累占7.2%,包括狼疮脑病3.7%,神经精神狼疮2.3%;运动系统和生殖系统受累较少,分别为5.1%,0.3%,其他10.3%。
3、常规实验室检查:
3.1 572例患者中血液系统异常113例(19.76%),血小板减少发生率按病情活动来分析,其水平轻度活动组比基本无活动组和中度活动组高(P<0.05)。各组间白细胞的减少发生率差异无显著性(P>0.05)。
3.2尿常规中尿蛋白和尿潜血阳性率分别为50.7%,26.2%,而24小时尿蛋白异常率为89.5%。(57人做了此检查,51人异常)
3.3 ESR和CRP升高发生率分别为73.1%,55.1%;在各病情活动组间ESR差异有显著性(P<0.05),而各组间ESR水平差异也有显著性(P<0.05),其水平随病情活动度增加而有升高的趋势。
3.4抗ds-DNA,抗Sm阳性率分别为56.0%,56.4%,C3降低、C4降低的发生率分别是36.6%,18.7%。其中在各病情活动组间抗ds-DNA阳性率和C3降低差异有显著性(P<0.05)。
4、治疗根据572例患者的用药情况发现,激素使用率高达97.0%,其次是抗感染药,所占比例为49.1%,非甾体类抗炎药物、环磷酰胺、抗疟药及雷公藤所占比例分别为20.3%,12.6%,9.4%和7.9%。
结论
1、育龄妇女是SLE多发群体。
2、关节炎或关节痛是SLE患者最主要的首发症状,可作为SLE重要临床特征之一。
3、重要脏器损害以肾脏受累最多,多数为狼疮肾炎,其次为呼吸系统和血液系统,而神经系统和运动,生殖系统受累较少。
4、白细胞水平与SLE病情活动度未见明显关联,SLE既可出现白细胞下降,也可出现白细胞升高。
5、CRP升高发生率、C4降低发生率及抗Sm阳性率与SLE病情活动度未见明显关联。
6、ESR升高发生率、C3降低的发生率及抗ds-DNA阳性率与SLE病情活动度有明显关联,其中ESR水平也与SLE病情活动度有明显关联,可以作为判断SLE病情活动度的参考指标。
7、在住院病人的治疗用药中发现,激素的使用率高达97.0%,其次是抗感染药,所占比例为49.1%,提示激素迄今仍是治疗SLE的主要药物,但要恰当使用,否则会增加患者发生感染的概率。
Objective To summarize the characteristics of Epidemiology,clinical manifestation and regular laboratory examination and medication situation.And to assess the utility of measurement of laboratory parameters in the diagnosis,evaluating the disease activity and exploring the influence of hormonal therapy.Then to draw experiences and lessons from the summary of SLE,seek the clinical commonness and characteristics of SLE beneficial to the earlier diagnosis and therapy,raise curative effect, prolong the survival period and improve the life quality of the patients.
Methods Retrospective epidemiological survey was used on 572 hospitalized SLE patients in the affiliated hospital of Bengbu Medical College from January 1997 to December 2007. Their general condition ,career, the first symptom,clinical manifestation, index of laboratory examination, family history ,prognosis and the degree of disease activity were collected and then made a related conclusion by statistical analysis.
Results
1. Demographic details: The study cohort comprised 540 female and 32 male patienis,the ratio of women to men was l:16.88.The number of city patients was 153,and the number of countryside patients was 419,the city and countryside proportion is 1:2.7.The average age was 33.55 years.The average age of the onset of the disease was 18.67,a mean follow-up of 20.37 months.The mean duration in hospital was 16.50 days.The number of the patients with active-stage was 463,the number of the patients with inactive-stage was 100.The number of the patients of first morbidity was 215 and the number of the patients of once more morbidity was 357.
2. Clinical features: The onset maniefstation was arthritic ache,its frequence was 58.6%.The cumulative frequeneies of organic involvement were: urinary system 42.1% was in the first place,respiratory system 21.2%,haematological 19.8%,digesting system 7.3% and neurological 7.2%.
3. Laboratory data:
3.1 The frequence of hematological exceptionally was 19.76%. The PLT of different case groups showed significant difference in its incidence rate of decrease, its formation rate in the slightly active group was higher than the basically inactive group and medially active group(P<0.05). The WBC of different case groups showed no obvious difference in its incidence rate of decrease.
3.2 The positive rates of the Urine protein and Urine occult blood(OB)in the urine RT respectively were 50.7%,26.2%.Abnormity rate of the 24 hours Urine protein(24hUPr) was 89.5%.
3.2 The increase incidence rates of the ESR and CRP respectively were 73.1%,26.2%;it was showed obvious difference in the increase incidence rate of the ESR was shown in different groups (P<0.05),and the ESR level in different groups was significant different (P<0.05),too, its level increased with the degree of the disease activity.
3.4 The positive rate of the anti-dsDNA and anti-Sm respectively were 56.0%, 56.4%,;The incidence rate of the C3 decrease and C4 decrease respectively were 36.6%, 18.7%. The C3 in its decrease incidence rate and anti-dsDNA in its positive rate in different groups were significantly different(P<0.05).
4. Treatment: Hormone is the best curative thearpy strategis: The total number of the patients with hormone was 554,its percentage was 97.0%.
Conclusion
1. The male/female ratio in the hospital and patients age accords with disease disciplinarian.
2. The main initial symptoms were arthrodynia and arthritis.They can be used as the significant clinical characteristics.
3. The most important organ damage is kidney,Next came respiratory system and hematological system.
4. There were no statistically significant difference in the correlation of the level of leucocyte and the activity degree of SLE.
5. The incidence of the CRP increase, the incidence of the C4 decrease and the positive rate of the anti-Sm have no obvious correlation with the disease activity degree of SLE.
6. It was showed obvious difference in the incidence of the ESR increase, the incidence of the C3 decrease and the positive rate of the anti-dsDNA was shown in different groups (P<0.05),and the ESR level in different groups was significant different (P<0.05),too.So the ESR level may be an index in the judgement of the disease activity in SLE.
7. The main drugs for treatment still was hormone, its usage rate was 97.0%. Hormone should be used properly to prevent the infection of the patients.
方法对1997年1月～2007年12月间在蚌埠医学院附属医院住院的572例SLE患者的临床资料进行回顾性研究,了解患者的一般情况、职业、首发症状、临床表现、实验室检查指标、家族史和预后等,对患者的病情进行计分和分类,利用统计学方法得出相关结论。
结果
1、一般情况: 572例患者中,男32例,女540例,男女比例为1:16.88,城市患者153例,农村及城郊患者419例,城乡比例为1:2.7。年龄最小7岁,最大者80岁,平均年龄33.55岁。平均发病年龄18.67岁。病程最短0月,最长144月,平均病程20.37月。平均住院时间为16.50天。所有统计病例中活动期患者463例,稳定期患者109例;首次发病患者215例,再发患者357例。
2、临床表现:在首发症状中,关节痛是最常见的,占58.6%,其次分别是皮疹、红斑36.7%、发热34.8%、其它21.3%、浮肿8.4%、肌肉酸痛,腰背痛6.6%。重要脏器损害包括:泌尿系统受累最多42.1%,以狼疮肾炎37.9%为主,其次为尿路感染5.6%,再次为慢性肾衰竭2.3%;呼吸系统受累占21.2%,包括肺部感染占9.8%,上呼吸道感染占7.7% ;血液系统受累占19.8%,包括败血症5.1%,高血压3.3%;免疫系统受累占7.9%,包括干燥综合症4.2%,糖尿病1.2%;消化系统受累占7.3%,包括肝功能损伤2.4%,肝炎和胆囊炎分别为1.2%;神经系统受累占7.2%,包括狼疮脑病3.7%,神经精神狼疮2.3%;运动系统和生殖系统受累较少,分别为5.1%,0.3%,其他10.3%。
3、常规实验室检查:
3.1 572例患者中血液系统异常113例(19.76%),血小板减少发生率按病情活动来分析,其水平轻度活动组比基本无活动组和中度活动组高(P<0.05)。各组间白细胞的减少发生率差异无显著性(P>0.05)。
3.2尿常规中尿蛋白和尿潜血阳性率分别为50.7%,26.2%,而24小时尿蛋白异常率为89.5%。(57人做了此检查,51人异常)
3.3 ESR和CRP升高发生率分别为73.1%,55.1%;在各病情活动组间ESR差异有显著性(P<0.05),而各组间ESR水平差异也有显著性(P<0.05),其水平随病情活动度增加而有升高的趋势。
3.4抗ds-DNA,抗Sm阳性率分别为56.0%,56.4%,C3降低、C4降低的发生率分别是36.6%,18.7%。其中在各病情活动组间抗ds-DNA阳性率和C3降低差异有显著性(P<0.05)。
4、治疗根据572例患者的用药情况发现,激素使用率高达97.0%,其次是抗感染药,所占比例为49.1%,非甾体类抗炎药物、环磷酰胺、抗疟药及雷公藤所占比例分别为20.3%,12.6%,9.4%和7.9%。
结论
1、育龄妇女是SLE多发群体。
2、关节炎或关节痛是SLE患者最主要的首发症状,可作为SLE重要临床特征之一。
3、重要脏器损害以肾脏受累最多,多数为狼疮肾炎,其次为呼吸系统和血液系统,而神经系统和运动,生殖系统受累较少。
4、白细胞水平与SLE病情活动度未见明显关联,SLE既可出现白细胞下降,也可出现白细胞升高。
5、CRP升高发生率、C4降低发生率及抗Sm阳性率与SLE病情活动度未见明显关联。
6、ESR升高发生率、C3降低的发生率及抗ds-DNA阳性率与SLE病情活动度有明显关联,其中ESR水平也与SLE病情活动度有明显关联,可以作为判断SLE病情活动度的参考指标。
7、在住院病人的治疗用药中发现,激素的使用率高达97.0%,其次是抗感染药,所占比例为49.1%,提示激素迄今仍是治疗SLE的主要药物,但要恰当使用,否则会增加患者发生感染的概率。
Objective To summarize the characteristics of Epidemiology,clinical manifestation and regular laboratory examination and medication situation.And to assess the utility of measurement of laboratory parameters in the diagnosis,evaluating the disease activity and exploring the influence of hormonal therapy.Then to draw experiences and lessons from the summary of SLE,seek the clinical commonness and characteristics of SLE beneficial to the earlier diagnosis and therapy,raise curative effect, prolong the survival period and improve the life quality of the patients.
Methods Retrospective epidemiological survey was used on 572 hospitalized SLE patients in the affiliated hospital of Bengbu Medical College from January 1997 to December 2007. Their general condition ,career, the first symptom,clinical manifestation, index of laboratory examination, family history ,prognosis and the degree of disease activity were collected and then made a related conclusion by statistical analysis.
Results
1. Demographic details: The study cohort comprised 540 female and 32 male patienis,the ratio of women to men was l:16.88.The number of city patients was 153,and the number of countryside patients was 419,the city and countryside proportion is 1:2.7.The average age was 33.55 years.The average age of the onset of the disease was 18.67,a mean follow-up of 20.37 months.The mean duration in hospital was 16.50 days.The number of the patients with active-stage was 463,the number of the patients with inactive-stage was 100.The number of the patients of first morbidity was 215 and the number of the patients of once more morbidity was 357.
2. Clinical features: The onset maniefstation was arthritic ache,its frequence was 58.6%.The cumulative frequeneies of organic involvement were: urinary system 42.1% was in the first place,respiratory system 21.2%,haematological 19.8%,digesting system 7.3% and neurological 7.2%.
3. Laboratory data:
3.1 The frequence of hematological exceptionally was 19.76%. The PLT of different case groups showed significant difference in its incidence rate of decrease, its formation rate in the slightly active group was higher than the basically inactive group and medially active group(P<0.05). The WBC of different case groups showed no obvious difference in its incidence rate of decrease.
3.2 The positive rates of the Urine protein and Urine occult blood(OB)in the urine RT respectively were 50.7%,26.2%.Abnormity rate of the 24 hours Urine protein(24hUPr) was 89.5%.
3.2 The increase incidence rates of the ESR and CRP respectively were 73.1%,26.2%;it was showed obvious difference in the increase incidence rate of the ESR was shown in different groups (P<0.05),and the ESR level in different groups was significant different (P<0.05),too, its level increased with the degree of the disease activity.
3.4 The positive rate of the anti-dsDNA and anti-Sm respectively were 56.0%, 56.4%,;The incidence rate of the C3 decrease and C4 decrease respectively were 36.6%, 18.7%. The C3 in its decrease incidence rate and anti-dsDNA in its positive rate in different groups were significantly different(P<0.05).
4. Treatment: Hormone is the best curative thearpy strategis: The total number of the patients with hormone was 554,its percentage was 97.0%.
Conclusion
1. The male/female ratio in the hospital and patients age accords with disease disciplinarian.
2. The main initial symptoms were arthrodynia and arthritis.They can be used as the significant clinical characteristics.
3. The most important organ damage is kidney,Next came respiratory system and hematological system.
4. There were no statistically significant difference in the correlation of the level of leucocyte and the activity degree of SLE.
5. The incidence of the CRP increase, the incidence of the C4 decrease and the positive rate of the anti-Sm have no obvious correlation with the disease activity degree of SLE.
6. It was showed obvious difference in the incidence of the ESR increase, the incidence of the C3 decrease and the positive rate of the anti-dsDNA was shown in different groups (P<0.05),and the ESR level in different groups was significant different (P<0.05),too.So the ESR level may be an index in the judgement of the disease activity in SLE.
7. The main drugs for treatment still was hormone, its usage rate was 97.0%. Hormone should be used properly to prevent the infection of the patients.
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37.Fureder W,Firbas U,Nichol JL.Serum thrombopoietin levels and antithrombopoietin antibodies in systemic lupus erythematosus.Lupus,2002,11(4):221-226.
38.冉立伟,惠艳,谭升顺,等.系统性红斑狼疮患者血清及脑脊液中C-反应蛋白的水平及临床意义.中国皮肤性病学杂志,2003,17(6):369-370.
39.王兰兰.临床免疫学及免疫学检验. 3版.北京:人民卫生出版社, 2003.
40.刘鸿林,杜志勋.抗核抗体和抗双链DNA检测在系统性红斑狼疮诊断中的意义.中国医药导报,2008,5(1).
41 .徐平.系统性红斑狼疮血清自身抗体检测临床意义.宁夏医学院学报,1988,10(3):93-95.
42.Belmont HM,Buyon J,Giorno R,et al.Up-regulation of endothelial cell adhesion molecules characterizes disease activity in systemic lupus erythematosus.Arthritis Rheum, 1994,37:376-383.
43.谢红付,张慧,陈翔,等.SLE疾病活动性与补体及免疫球蛋白水平相关性的探讨.中国麻风皮肤病杂志,2004,20(2):100-102.
44.张文,李向红,俞春霞.系统性红斑狼疮患者合并重症感染的危险因素分析.临床内科杂志,2003,20(10):534-536.
1.Stewart JJ .Theory and treatment of the Xinactivation chimera in female prevalent autoimmune disease.Arch Immunol Ther Exp(Warsz),1999,47 (6):355-359.
2.Shirai T, Hirose S. Preface and overview: genetics of SLE; a sine quanon for identification. Int Rev Immunol,2000,19:289-295.
3.ZHU Yi min, LAI Mao de .Role of DNA methylation in the occurrence of tumor. Journal of Zhejiang University(Medical Sc ience) ,2003,32 (2):162-166.
4.LU Q ,KAPLAN M, RAY D, et al. Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupuserythematosus. Arthritis Rheum,2002,46 (5) : 1 282-1 291.
5. Cheng J, Zhou T, Liu C, et al. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science,1994,263(5 154):1 759-1 762.
6. Wu J, Metz C, Xu X, et al. A novel polymorphic CAAT/ enhancer-binding protein beta element in the FasL gene promoter alters Fas ligand expression : a candidate background gene in African American systemic lupus erythematosus patients. J Immunol,2003,170(1):132-138.
7.Goerg S. The association between systemic lupus erythematosus and deficiencies of the complement system.Cell Mol Biol ( Noisy-legrand),2002,48(3) :237-245.
8. Rafnar BO, Traustadottir KH, Sigfusson A, et al. An enzyme based assay for the measurement of complement mediated binding of immune complexes to red blood cells. J Immunol Methods, 1998,211(1-2):171-181.
9.Nielsen CH , Leslie RG. Complement’s participation in acquired immunity. J Leukoc Biol, 2002,72(2) :249-261.
10.Tsao BP. An update on genetic studies of systemic lupus erythematosus.Curr Rheumatol Rep, 2002,4(4) :359-367.
11.Marzocchi-Machado CM, Alves CM, Azzolini AE,et al. Fcgamma and complement receptors : expression, role and co-operation in mediating the oxidative burst anddegranulation of neutrophils of Brazilian systemic lupus erythematosus patients.Lupus,2002,11(4):240-248.
12.Traynor AE , Barr WG, Rosa RM, et al. Hematopoietic stem cell transplantation for severe and refractory lupus. Analysis after five years and fifteen patients.Arthritis Rheum,2002,46 (11) :1 917 -1 923.
13.Blanco P , Palucka AK, Gill M , et al.Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science,2001,294 (5 546) :1 540-1 543.
14.Baechler EC, Batliwalla FM, Karypis G. Interferon- inducible gene expression signature in peripheral blood cells of patients with severe lupus.PNAS,2003,5:2 610-2 615.
15.Bennett L, Palucka AK, Arce E. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med,2003,197: 711-723.
16.Crow MK, Kirou KA, Wohlgemuth J. Microarray analysis of interferon-regulated genes in SLE. Autoimmunity,2003,36: 481-490.
17.Han GM, Chen SL, Shen N. Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray.Genes Immun,2003, 4: 177-186.
18.Ye S, Pang H, Gu YY. Protein interaction for an interferon- inducible systemic lupus associated gene, IFIT1. Rheumatology(Oxford),2003, 42: 1 155-1 163.
19.Pogue SL, Preston BT, Stalder J.The receptor for type I IFNs is highly expressed on peripheral blood B cells and monocytes and mediates a distinct profile of differentiation and activation of these cells. J Interferon Cytokine Res, 2004, 24: 131-139.
20.Herrman M, Voll RE , Zoller OM, et al . Impaired phagocytosis of apoptotic cell material by monocyte2derived macrophages frompatients with systemic lupus erythematosus. Arthritis Rheum, 1998 ,41:1 241–1 250.
21.Lorenz HM,Grunke M,Hieronymus T,et al.Invitro apoptosis and expression of apoptosis-related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases. Arthritis Rheum, 1997,40:306-317.
22.Yu D , Zhu FG, Bhagat L , et al . Potent CpGoligonucleotides containing phosphodiester linkages : in vitro and in vivo immunostimulatory properties. Biochem Biophys Res Commun , 2002 ,297 :83 - 90.
23. Messina JP , Gilkeson GS , Pisetsky DS , et al . The influence of DNA structure on the in vitro stimulation of murine lymphocytes by natural and synthetic polynucleotide antigens. Cell Immunol , 1993 ,147 :148 - 157.
24. Gantner F , Hermann P , Nakashima K, et al . CD40-dependent and independent activation of human tonsil B cells by CpG oligodeoxynucleotides. Eur J Immunol , 2003 ,33 :1 576–1 585.
25.Bennett RM, Peller JS , Merritt MM, et al . Detective DNA-receptor function in systemic lupus erythematosus and related diseases : evidence for an autoantibody influencing cell physiology. Lancet , 1986 ,1 :186 -188.
26.Krieg AM. CpG DNA: a pathogenic factor in systemic lupus erythematosus ?J Clin Immunol , 1995 ,15 :284 - 292.
27.Yung RL , Quddus J , Chrisp CE , et al . Mechanismof drug-induced lupus. I. cloned The cells modified with DNA methylation inhibitors in vitro cause autoimmunity in vivo. J Immunol , 1995 ,154 :3025 - 3035.
28.RICHARDSON BC.Role of DNA methylation in the regulation of cell function : auto immunity,aging and cancer.J Nutr,2002,132 ( 8Supp l): 2 401S-2 405S.
29.ZHU Yi min, LAI Mao de .Role of DNA methylation in the occurrence of tumor. Journal of Zhejiang University(Medical Sc ience) ,2003, 32 (2): 162-166.
30.CORNACCH IA E,GOLBUS J ,MAYBAUM J,et al. Hydralazine and procainam ide inhibit T cell DNA methylation and induce auto reactivity .J Immunol,1988,140 (7) :2 197-2 200.
31.YUNG RL,CHAN GS,HEMATI N,et al.Mechanisms of drug-induced lupus Ⅳ.Comparison of procainam ide and hydralazine with analogs invitro and invivo.Arthritis Rheum,1997,40(8) : 1 436-1 443.
32.RICHARDSON B.DNA methylat ion and auto immune disease.Clin Immunol,2003,109(1) : 72-79.
33.Hughes JF, Coffin JM. Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nat Genet ,2001 ,29 :487 - 489.
34.Sekigawa I, Ogasawara H, Kaneko H, et al. Retroviruses and autoimmunity. Intern Med, 2001 ,40:80 - 86.
35.Urnovitz HB, Murphy WH. Human endogenous retroviruses : nature ,occurrence , and clinical implications in human diseases. Clin Microbiol Rev,1996,9 :72 - 99.
36.Herrmann M, Kalden JR. PCR and reverse dot hybridization for the detection of endogenous retroviral transcripts. J Virol Methods,1994,46:333 - 348.
37.Oldstone MB. Molecular mimicry and autoimmune disease. Cell,1987,50 :819 - 820.
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15.Tsao BP.An update on genetic studies of systemic lupus erythematosus. Curr Rheumatol ReP,2002,4(4):359-367.
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29.程秀峰,谭魁麟.伴血细胞减少的系统性红斑狼疮患者临床及骨髓学特点.临床皮肤科杂志,2004,33(1):20-21.
30.Lorenzh M,Grunke M,Hieronymus T,et al.Invitro apoptosis and expression of apoptosis-related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases.Arthritis Rheum,1997,40(2):306-317.
31.Tolusso B,Fabrism,Gremese E,et al.Platelet GPIIb/IIIa(PIA1/2) Polymorphism in SLE:clinical and laboratory association.Ann Rheum Dis,2003,62(8):781-782.
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34.徐亮,王元,陈顺乐,等.系统性红斑狼疮血小板减少患者巨核祖细胞分化障碍.上海医学,2004,27(10):739-742.
35.李娟,尹培达,罗绍凯,等.系统性红斑狼疮患者骨髓造血干/祖细胞体外培养及其发病机制的研究.中华风湿病学杂志,2000,4(5):143-145.
36.Shiozaki H,Miaywaki S,Kuwaki T,et al.Autoantibodies neutralizing thrombopoieti in a patient with a megakaryocytic thrombocytopenic purpura.Blood,2000,95(6):2 187-2 188.
37.Fureder W,Firbas U,Nichol JL.Serum thrombopoietin levels and antithrombopoietin antibodies in systemic lupus erythematosus.Lupus,2002,11(4):221-226.
38.冉立伟,惠艳,谭升顺,等.系统性红斑狼疮患者血清及脑脊液中C-反应蛋白的水平及临床意义.中国皮肤性病学杂志,2003,17(6):369-370.
39.王兰兰.临床免疫学及免疫学检验. 3版.北京:人民卫生出版社, 2003.
40.刘鸿林,杜志勋.抗核抗体和抗双链DNA检测在系统性红斑狼疮诊断中的意义.中国医药导报,2008,5(1).
41 .徐平.系统性红斑狼疮血清自身抗体检测临床意义.宁夏医学院学报,1988,10(3):93-95.
42.Belmont HM,Buyon J,Giorno R,et al.Up-regulation of endothelial cell adhesion molecules characterizes disease activity in systemic lupus erythematosus.Arthritis Rheum, 1994,37:376-383.
43.谢红付,张慧,陈翔,等.SLE疾病活动性与补体及免疫球蛋白水平相关性的探讨.中国麻风皮肤病杂志,2004,20(2):100-102.
44.张文,李向红,俞春霞.系统性红斑狼疮患者合并重症感染的危险因素分析.临床内科杂志,2003,20(10):534-536.
1.Stewart JJ .Theory and treatment of the Xinactivation chimera in female prevalent autoimmune disease.Arch Immunol Ther Exp(Warsz),1999,47 (6):355-359.
2.Shirai T, Hirose S. Preface and overview: genetics of SLE; a sine quanon for identification. Int Rev Immunol,2000,19:289-295.
3.ZHU Yi min, LAI Mao de .Role of DNA methylation in the occurrence of tumor. Journal of Zhejiang University(Medical Sc ience) ,2003,32 (2):162-166.
4.LU Q ,KAPLAN M, RAY D, et al. Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupuserythematosus. Arthritis Rheum,2002,46 (5) : 1 282-1 291.
5. Cheng J, Zhou T, Liu C, et al. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science,1994,263(5 154):1 759-1 762.
6. Wu J, Metz C, Xu X, et al. A novel polymorphic CAAT/ enhancer-binding protein beta element in the FasL gene promoter alters Fas ligand expression : a candidate background gene in African American systemic lupus erythematosus patients. J Immunol,2003,170(1):132-138.
7.Goerg S. The association between systemic lupus erythematosus and deficiencies of the complement system.Cell Mol Biol ( Noisy-legrand),2002,48(3) :237-245.
8. Rafnar BO, Traustadottir KH, Sigfusson A, et al. An enzyme based assay for the measurement of complement mediated binding of immune complexes to red blood cells. J Immunol Methods, 1998,211(1-2):171-181.
9.Nielsen CH , Leslie RG. Complement’s participation in acquired immunity. J Leukoc Biol, 2002,72(2) :249-261.
10.Tsao BP. An update on genetic studies of systemic lupus erythematosus.Curr Rheumatol Rep, 2002,4(4) :359-367.
11.Marzocchi-Machado CM, Alves CM, Azzolini AE,et al. Fcgamma and complement receptors : expression, role and co-operation in mediating the oxidative burst anddegranulation of neutrophils of Brazilian systemic lupus erythematosus patients.Lupus,2002,11(4):240-248.
12.Traynor AE , Barr WG, Rosa RM, et al. Hematopoietic stem cell transplantation for severe and refractory lupus. Analysis after five years and fifteen patients.Arthritis Rheum,2002,46 (11) :1 917 -1 923.
13.Blanco P , Palucka AK, Gill M , et al.Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science,2001,294 (5 546) :1 540-1 543.
14.Baechler EC, Batliwalla FM, Karypis G. Interferon- inducible gene expression signature in peripheral blood cells of patients with severe lupus.PNAS,2003,5:2 610-2 615.
15.Bennett L, Palucka AK, Arce E. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med,2003,197: 711-723.
16.Crow MK, Kirou KA, Wohlgemuth J. Microarray analysis of interferon-regulated genes in SLE. Autoimmunity,2003,36: 481-490.
17.Han GM, Chen SL, Shen N. Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray.Genes Immun,2003, 4: 177-186.
18.Ye S, Pang H, Gu YY. Protein interaction for an interferon- inducible systemic lupus associated gene, IFIT1. Rheumatology(Oxford),2003, 42: 1 155-1 163.
19.Pogue SL, Preston BT, Stalder J.The receptor for type I IFNs is highly expressed on peripheral blood B cells and monocytes and mediates a distinct profile of differentiation and activation of these cells. J Interferon Cytokine Res, 2004, 24: 131-139.
20.Herrman M, Voll RE , Zoller OM, et al . Impaired phagocytosis of apoptotic cell material by monocyte2derived macrophages frompatients with systemic lupus erythematosus. Arthritis Rheum, 1998 ,41:1 241–1 250.
21.Lorenz HM,Grunke M,Hieronymus T,et al.Invitro apoptosis and expression of apoptosis-related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases. Arthritis Rheum, 1997,40:306-317.
22.Yu D , Zhu FG, Bhagat L , et al . Potent CpGoligonucleotides containing phosphodiester linkages : in vitro and in vivo immunostimulatory properties. Biochem Biophys Res Commun , 2002 ,297 :83 - 90.
23. Messina JP , Gilkeson GS , Pisetsky DS , et al . The influence of DNA structure on the in vitro stimulation of murine lymphocytes by natural and synthetic polynucleotide antigens. Cell Immunol , 1993 ,147 :148 - 157.
24. Gantner F , Hermann P , Nakashima K, et al . CD40-dependent and independent activation of human tonsil B cells by CpG oligodeoxynucleotides. Eur J Immunol , 2003 ,33 :1 576–1 585.
25.Bennett RM, Peller JS , Merritt MM, et al . Detective DNA-receptor function in systemic lupus erythematosus and related diseases : evidence for an autoantibody influencing cell physiology. Lancet , 1986 ,1 :186 -188.
26.Krieg AM. CpG DNA: a pathogenic factor in systemic lupus erythematosus ?J Clin Immunol , 1995 ,15 :284 - 292.
27.Yung RL , Quddus J , Chrisp CE , et al . Mechanismof drug-induced lupus. I. cloned The cells modified with DNA methylation inhibitors in vitro cause autoimmunity in vivo. J Immunol , 1995 ,154 :3025 - 3035.
28.RICHARDSON BC.Role of DNA methylation in the regulation of cell function : auto immunity,aging and cancer.J Nutr,2002,132 ( 8Supp l): 2 401S-2 405S.
29.ZHU Yi min, LAI Mao de .Role of DNA methylation in the occurrence of tumor. Journal of Zhejiang University(Medical Sc ience) ,2003, 32 (2): 162-166.
30.CORNACCH IA E,GOLBUS J ,MAYBAUM J,et al. Hydralazine and procainam ide inhibit T cell DNA methylation and induce auto reactivity .J Immunol,1988,140 (7) :2 197-2 200.
31.YUNG RL,CHAN GS,HEMATI N,et al.Mechanisms of drug-induced lupus Ⅳ.Comparison of procainam ide and hydralazine with analogs invitro and invivo.Arthritis Rheum,1997,40(8) : 1 436-1 443.
32.RICHARDSON B.DNA methylat ion and auto immune disease.Clin Immunol,2003,109(1) : 72-79.
33.Hughes JF, Coffin JM. Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nat Genet ,2001 ,29 :487 - 489.
34.Sekigawa I, Ogasawara H, Kaneko H, et al. Retroviruses and autoimmunity. Intern Med, 2001 ,40:80 - 86.
35.Urnovitz HB, Murphy WH. Human endogenous retroviruses : nature ,occurrence , and clinical implications in human diseases. Clin Microbiol Rev,1996,9 :72 - 99.
36.Herrmann M, Kalden JR. PCR and reverse dot hybridization for the detection of endogenous retroviral transcripts. J Virol Methods,1994,46:333 - 348.
37.Oldstone MB. Molecular mimicry and autoimmune disease. Cell,1987,50 :819 - 820.