风湿性心脏病细胞免疫及调控失衡初探

目的 :探讨风湿性心脏病 (RHD)细胞免疫是否存在异常及其特点 ,为 RHD的早期免疫诊断及今后的免疫疗法提供依据。方法 :对 41例 RHD和 44例 RHD伴风湿活动 (RF)患者的 T淋巴细胞亚群、淋巴细胞转化率、自然杀伤 (NK)细胞数量及活性 ,HL A- DR抗原遗传位点进行了测定 ,并与正常对照组 (5 0例 )比较。结果 :RHD和 RF组细胞免疫功能活性增强 ,表现为 CD4数量增加 ,CD8数量减少 ,CD4/ CD8比值增大 ,与正常对照组比较 P <0 .0 5和 P <0 .0 1;RF组淋巴细胞转化率较正常对照组和 RHD组高 (P <0 .0 1) ,NK细胞数量增加 ,但活性降低 (P <0 .0 1和 P <0 .0 5 ) ;RF和 RHD组 HL A- DR4抗原呈高频分布 (5 3.6 %和 47.7% ) ,DR5 呈低频分布(14.6 %和 15 .9% ) (P <0 .0 1)。结论 :RHD存在细胞免疫功能异常 ,且发生自身免疫趋式 ,其机制可能是细胞免疫调控失衡。 DR4的高频分布 ,可作为 RHD早期诊断的危险度估计     

风湿性心脏病HLA-DR抗原表达异常

近年来,国内外学者发现风湿性心脏病(RHD)有自身免疫反应,如细胞免疫功能亢进,CD_4细胞显著增加,自然杀伤细胞活性增强。在免疫活性细胞的相互作用中,人类白细胞抗原(HLA)起限制性作用。弄清RHD有无HLA的异常表达,对RHD发病机制探讨、     

风湿性心脏病患者的免疫功能变化

目的探讨风湿性心脏病(RHD)患者免疫功能的变化及其特点。方法对RHD患者54例(A组),正常对照组30例(B组),用流式细胞仪检测外周血T淋巴细胞亚群。用液相终点散射免疫沉淀法检测血清免疫球蛋白G(IgG)、免疫球蛋白A(IgA)、免疫球蛋白M(IgM)、补体3(C3)、补体4(C4)。用聚乙二醇法测血清循环免疫复合物(CIC)。A组与B组比较。结果A组细胞免疫功能低下,表现CD3、CD4、CD8数量减少,CD4/CD8降低,CD19数量减少,与B组比较P<0.01。而IgG、C4、CIC高于B组P<0.01有显著性差异。结论RHD者T淋巴细胞数量减少其细胞免疫功能低下且受抑制,而B细胞数量明显减少,表明RHD的发病过程中存在免疫功能异常。     

风心病患者伴心房颤动与不伴心房颤动者免疫功能的变化

目的风湿性心脏病（RHD）患者伴心房颤动（Af）可引起心房附壁血栓,血栓脱落会导致患者身体重要脏器栓塞而致残。RHD者的细胞免疫功能CD3、CD4、CD8减少,CD4／CD8降低与正常人有明显的差异。本文探讨RHD者伴Af与不伴Af者细胞免疫功能的变化及其特点。方法RHD伴Af31例（A组）不伴Af23例（B组）。用流式细胞仪检测外周血T淋巴细胞亚群。用液相终点散射免疫沉淀法检测血清免疫球蛋白G（IgG）、免疫球蛋白A（IgA）、免疫球蛋白M（IgM）、补体3（C3）、补体4（C4）。用聚乙二醇法测血清循环免疫复合物（CIC）两组间比较。结果A组CD3、CD8、CD4／CD8较B组低但无统计学意义,CD4明显较B组减低（P〈0．05）。A组CD3与CD4正相关r=0．354;P〈0．05;CD3与CD8正相关r=0．459;P〈0．01。结论A组细胞免疫功能低于B组,尤以CD4为低下,RHD伴AfCD3与CD4、CD8呈正相关。     

风心病患者组织相容性白细胞抗原系统和淋巴细胞亚群功能改变

风心病患者HLA-DR4阳性率较高(72%),且有遗传倾向;HLA-DR6阳性率很低,不易患风心病,两者均有重要的临床流行病学意义.患者辅助性T淋巴细胞和杀伤性T淋巴细胞增多,但其后者功能活性降低,提示细胞免疫反应增强.慢性风湿性心瓣膜病即使临床无风湿活动依据,B淋巴细胞数仍然持续增高,表明体内异常的免疫反应并未静止.被乙型A族链球菌M型蛋白质激活的人体T杀伤细胞能攻击人体心肌细胞,这是风心病心脏病变的免疫病理学基础.     

风湿性心脏病患者二尖瓣轻度狭窄与二尖瓣重度狭窄者免疫功能的变化

目的 探讨风湿性心脏病(RHD)者二尖瓣轻度狭窄与重度狭窄者细胞免疫功能的变化及特点.方法 分为二尖瓣轻度狭窄者32例(A组),重度狭窄者22例(B组).用流式细胞仪检测患者外周血T淋巴细胞亚群.用液相终点散射免疫沉淀法检测RHD血清免疫球蛋白G(IgG)、免疫球蛋白A(IgA)、免疫球蛋白M(IgM)、补体3(C3)、补体4(C4).用聚乙二醇法测血清循环免疫复合物(CIC)两组间比较.结果 B组CD3、CD4、CD8、CD19较A组明显低下(P＜0.01).B组IgG、IgA、IgM、C3、C4、CIC较A组高,但无统计学差异.结论 B组细胞免疫功能低于A组.     

风湿性心脏病细胞免疫的初步探讨

风湿性心脏病(RHD)是由A族链球菌感染诱发的自身免疫性疾病,国内外学者对RHD患者的细胞免疫进行了研究,但结果差异大.为深入探讨细胞免疫在RHD中的变化与意义,我们检测了44例RHD患者外周血清可溶性白细胞介素2受体(SIL- 2R)、T淋巴细胞亚群及自然杀伤细胞(NK)活性.现报告如下.1 对象和方法     

Treg细胞和Th17细胞的研究进展

正CD+4T淋巴细胞是一类在免疫反应中发挥重要作用的细胞,它在激活后可分化为辅助性T细胞1(T helper cells,Th细胞)、Th2细胞、辅助性滤泡T细胞(Follicular T helper cells)、Th17细胞和调节性T细胞(regulatory T cells,Treg细胞)。不同类型CD+4T淋巴细胞有不同的功能,如激活细胞免疫和非细胞免疫、直接溶细胞活性和抑制免疫反应     

阻断共刺激通路对风湿免疫性疾病进行免疫干预的研究

风湿免疫性疾病属多因素相互作用下机体免疫调节功能紊乱而引起的一组慢性炎症性疾病。由于T、B细胞的过度活化,前炎症细胞因子和自身抗体大量合成分泌而致全身多个部位慢性炎症反应,其基础机制是机体细胞免疫和体液免疫功能异常,而细胞免疫中的核心效应细胞——T淋巴细胞的异常活化又成为该机制中关键环节之一。在T细胞活化的共刺激分子途径中,研究最为广泛和深入的是CD28/CTLA4B7、     

风湿性心脏病二尖瓣组织Th17细胞轴相关细胞因子表达水平

目的探讨慢性风湿性心脏病(RHD)患者心脏二尖瓣瓣膜上Th17细胞轴相关细胞因子白细胞介素(IL)-17、IL-21、IL-6、IL-23表达水平的改变。方法选择20例RHD患者及12例非RHD对照组二尖瓣瓣膜组织(NRHD组),应用苏木素-伊红(HE)染色和免疫组化法对IL-17、IL-21、IL-6、IL-23表达水平进行检测。结果 RHD组HE染色可见瓣膜组织部分出现纤维化和钙化,局灶性散在的慢性炎性细胞浸润,以淋巴细胞、浆细胞为主。免疫组织化学染色可见慢性炎性细胞、成纤维细胞、血管内皮细胞存在IL-17、IL-21、IL-6、IL23的表达且定位于细胞质中,炎性细胞主要位于血管旁。RHD组IL-17、IL-21、IL-6、IL23表达阳性细胞比例及其乘积评分均明显高于NRHD组(P0.05)。结论 RHD患者瓣膜中Th17细胞相关细胞因子的表达明显增高,高Th17表达可能是引起RHD持续瓣膜损害的一个潜在机制。     

The natural history of rheumatic fever and rheumatic heart disease in the Orient.

Studies published in the past 10 years suggest that group A streptococcal infections are frequent in the Orient and lead to a high incidence of rheumatic fever (RF) and rheumatic heart disease (RHD). In the present study, streptococcal infections were found to be more prevalent in Japan and Taiwan, whereas RF and RHD were more common and severe in the Philippines, Thailand, and Indonesia, particularly among the socioeconomically less privileged populations. The pattern of childhood RF varied: Carditis was the most common manifestation, occurring in 57% to 94% of the patients; polyarthritis was generally atypical and less common in the tropics; chorea minor and erythema marginatum were much more common in Japan, less common in Taiwan and rare in the tropics. RF recurrences were quite common and led to the development of new carditis, and deterioration or persistence of the pre-existing heart disease. The 5 year mortality rates differed greatly, ranging from zero to 42%. There was disappearance of the heart murmur in 16.5% to 37.5% of patients. Such apparent recovery was related to adherence to chemoprophylaxis. The major risk factors adversely affecting survival were the severity of carditis, inadequacy of medical service, non-compliance to chemoprophylaxis, RF recurrence, poor socioeconomic status, and high prevalence of group A streptococci. It is concluded that there is no uniform "Oriental-type" of natural history of RF and RHD. The natural history varies greatly among countries as is true in other parts of the world.     

Prevalence of rheumatic fever and rheumatic heart disease in school children in a rural community of the hill region of Nepal

A survey of school children aged 5 to 16 years living in a rural community of the hill region of Nepal, situated about 15-22 km outside Kathmandu city, was conducted to determine the prevalence of rheumatic fever (RF) and rheumatic heart disease (RHD). Of the 4,816 eligible children enrolled in the selected schools, 4,452 (92.4%) were examined. WHO expert committee criteria (1966) was used for the diagnosis and classification of rheumatic fever. Chest x-ray, electro-cardiography, echocardiography and Doppler study were done in all suspected cases of rheumatic heart disease. Six cases of RHD (1 pure mitral stenosis, 3 mitral regurgitation and 2 combined mitral stenosis and regurgitation) were identified giving overall prevalence rate of 1.35 per thousand. No case with active rheumatic fever could be identified. This is the first study on prevalence of RF/RHD in Nepal. The prevalence rate is lower than that reported from neighbouring countries.     

Compartmentalization of cells bearing "rheumatic" cell surface antigens in peripheral blood and tonsils in rheumatic heart disease

Monoclonal antibodies that recognize "rheumatic" antigens of peripheral blood non-T cells were used to study the compartmentalization of such cells in peripheral blood and tonsils of individuals with rheumatic heart disease (RHD) and suitable control subjects. The peripheral blood of most (71%) of the 42 individuals with RHD contained cells reacting with monoclonal antibody 83S19.23 or 256S.10, whereas these cells were present in only 17% of the 41 control subjects (P less than .02). However, none of 21 individuals with RHD had such cells in their tonsils, although they were present in the tonsils of 50% of the 40 control subjects (P less than .03). These results may reflect a failure in RHD or organ-specific homing of cells with the epitopes recognized by the antibodies. The presence of these cells in tonsils may be important in the immune response to streptococcal pharyngeal infection, and their absence in RHD may be involved in the unusual immune responses characteristic of this disease.     

A correlative study of serum zinc and in vivo cell mediated immune status in rheumatic heart disease.

This study was conducted to determine the zinc status and assess relationship between serum zinc and in vivo cell mediated immunity (CMI) in patients with rheumatic heart disease (RHD). The study comprised 22 patients with active rheumatic heart disease (ARHD), 15 patients with chronic rheumatic heart disease without activity (CRHD) (selection based on Jone's Criteria--Revised), and 15 age and sex matched healthy control. Zinc estimation was done by atomic absorption spectrophotometer. To assess CMI in vivo, phytohaemagglutinin skin test and skin window test were done. Serum zinc and in vivo CMI in patients with ARHD and CRHD compared with controls. Mean serum zinc was significantly decreased in patients with ARHD and CRHD, more pronounced in the former (P less than 0.001); and mean 24 h urinary zinc was significantly increased in patients with ARHD (P less than 0.001) as compared to controls. A significant depression in CMI in vivo was observed in patients with ARHD and CRHD (P less than 0.001). A significant positive correlation was seen among serum zinc and markers of in vivo CMI (P less than 0.001). In conclusion, depletion of zinc, observed in RHD, probably causes immune alterations and suggest role of zinc in immunopathogenesis of RHD. Zinc supplementation may alter the course of rheumatic fever and RHD.     

Distribution of cells bearing "rheumatic" antigens in peripheral blood of patients with rheumatic fever/rheumatic heart disease

Cell surfaces of some peripheral blood cells from individuals with a history of rheumatic fever/rheumatic heart disease (RHD) have been demonstrated by the use of monoclonal antibodies to be antigenically distinct from the majority of the population. Our study examines the distribution of cells bearing these "rheumatic" antigens in 23 subjects with rheumatic fever/RHD of Maori, Polynesian and Caucasian ancestry and 182 members of their families (rheumatic fever/RHD families) as well as in 46 members of families in which no member had been demonstrated to have had rheumatic fever/RHD (control families). Mononuclear cells from the blood of all cooperating family members were prepared and non-T cells isolated by sheep red blood cell rosette depletion. The binding of monoclonal antibodies 83S19.23 and D8103 to non-T cells was measured using an immunoperoxidase technique. Subjects with rheumatic fever/RHD had a significantly higher proportion of cells binding the antibodies than the unaffected members of all families. Unaffected members of rheumatic fever/RHD families had significantly higher levels of such rheumatic cells than control families. An increase in the proportion of rheumatic cells with age was noted in unaffected members of rheumatic fever/RHD families but not in rheumatic fever/RHD subjects of control families. A level of 13% 83S19.23 positive non-T cells optimally discriminated between rheumatic and nonrheumatic individuals. The relative risk for rheumatic fever/RHD with 13% or greater positive cells was 9.48. The negative predictive value of having less than 13% positive cells was 98.3%. In the population studied, 83S19.23 seems especially capable of identifying those with low risk for rheumatic fever/RHD.     

Study of antibody response to 4 streptococcal antigens in rheumatic fever and Kawasaki disease with or without cardiovascular lesions

Patients with rheumatic fever (RF) and Kawasaki disease (MCLS) were divided into two groups, one with and the other without cardiovascular lesions, and their sera were examined for antibodies to 4 streptococcal antigens: anti-streptococcal polysaccharide (ASP), anti-deoxyribonuclease B (ADN-B), anti-streptolysin O (ASO) and anti-streptokinase (ASK) in order to clarify the relationship between group A streptococci and these two diseases. In RF the frequency of positive levels of ASP at its early stage was lower than those of the other 3 antibodies, but the ASP titer tended to persist at elevated levels. The frequency of ADN-B in patients with rheumatic heart disease (RHD) was higher than that in those without RHD, but with regard to the other antibodies no difference was found between the two. Of the 4 antibodies the frequency of at least one positive level was 100% in all the sera of RF patients within 3 months from onset. The differences in the frequencies of positive levels of all 4 antibodies in both MCLS and the controls did not prove to be significant. The frequencies of ASP, ADN-B and ASO in the sera of patients without cardiovascular lesions tended to be slightly higher than those in patients with cardiovascular lesions.     

老年冠心病患者外周血T、B淋巴细胞亚群的变化

本文报告34例老年冠心病患者应用抗人T、B淋巴细胞单克隆抗体检测外周血单个核细胞(PBMC)中T、B淋巴细胞亚群的变化,同时测定血清IgG、IgA、IgM、C_3及Fn含量,并与28例老人进行对比。结果表明,老年冠心病患者CD~(1/3)、CD~(1/4)、CD~(1/8)细胞均比对照组减少;而CD~(1/4)/CD~(1/8)比值增高,CD~(1/20)、SmIgG~ 阳性细胞增多。老年冠心病患者血清IgG明显高于对照组,而IgA、IgM无差异;补体C_3高于对照组,Fn则低于对照组。上述结果提示老年冠心病患者存在明显的免疫异常。免疫也与衰老、冠心病的发病有密切关系。本文还讨论了免疫损伤对冠心病发病的作用。     

Rheumatic heart disease occurrence, patterns and clinical correlates in children aged less than five years

BACKGROUND AND AIM OF THE STUDY: Rheumatic fever (RF) and chronic rheumatic heart disease (RHD) are common in developing countries. Two-thirds of RHD patients are school-children aged between 5 and 15 years. Pre-schoolers aged <5 years are not immune to RF however, and to date RHD patterns in this very young age group have not been studied systematically. METHODS: Records of all RHD patients seen at the authors' institution between January 1999 and December 2000 were retrospectively reviewed. A special analysis was conducted among pre-school children aged <5 years. RESULTS: Thirty-eight (6.8%) of the RF/RHD admissions were aged <5 years, and 28 of these patients (20 males, 8 females) presented with acute RF. The mean age of acute RF diagnosis was 4 years. All RF/RHD patients aged <5 years were in normal sinus rhythm. Joint pain and swelling (25 cases; characteristic migratory polyarthritis in six, monoarthritis in five) and fever (24 cases) were the most frequent symptoms. Arthritis, carditis and chorea occurred in 75%, 50% and 4% respectively, with no instances of erythema marginatum or subcutaneous nodules. Effort intolerance, chest discomfort and palpitations were reported by nine, five and three cases, respectively. Mitral regurgitation was the most common valvular lesion in RF. The youngest case of confirmed acute RF was an 18-month-old male. The only patient with mitral stenosis in the present series was a 4-year-old girl. None of the patients required surgical intervention, and there were no deaths. CONCLUSION: RHD is common in very young age groups of <5 years. Pre-schoolers account for a significant proportion of acute RF and chronic RHD admissions among children. Mitral regurgitation is the most common cardiac manifestation, but obstructive valve disease is distinctly rare in this age group. Aortic regurgitation, left ventricular dysfunction and pulmonary hypertension may complicate the course of RF in these very young children.     

风湿性心脏病患者红细胞免疫功能的初步探讨

应用红细胞Ｃ３ｂ（ＲＢＣ－Ｃ３ｂ）受体花环试验及红细胞免疫复合物（ＲＢＣ－ＩＣ）花环试验，对６０例风湿性心脏病（简称风心病）患者及７１例正常人的红细胞免疫功能进行了对照研究。结果表明，风心病患者ＲＢＣ－Ｃ３ｂ受体花环率明显低于正常人（Ｐ＜０．０１），ＲＢＣ－ＩＣ花环率明显高于正常人（Ｐ＜０．００１），提示风心病发病与红细胞免疫功能异常有密切关系。风心病患者ＲＢＣ－Ｃ３ｂ受体花环率及ＲＢＣ－ＩＣ花环率与瓣膜损害的数量，无明显关系（Ｐ＞０．０５）。ＲＢＣ－ＩＣ花环率在中至重度心力衰竭组明显高于心功能正常及轻度心力衰竭组（Ｐ＜０．００１），ＲＢＣ－Ｃ３ｂ受体花环率两组无明显差异（Ｐ＞０．０５）。     

Prevalence of rheumatic fever and rheumatic heart disease in rural Bangladesh

A community-based study was done on 5923 rural Bangladeshi children aged 5-15 years to determine the prevalence of rheumatic fever (RF) and rheumatic heart disease (RHD). The prevalence was found to be 1.2 (95% confidence interval 0.3-2.1) per 1000 for RF defined by revised Jones criteria and 1.3 (0.4-2.2) per 1000 for Doppler echocardiography-confirmed RHD.