尖锐湿疣局部细胞免疫功能状态与人乳头瘤病毒型的相关性研究

我们采用 (1)聚合酶链反应检测皮损中HPV6 11、16 18。 (2 )应用免疫组化技术对 6 1例CA患者疣体组织、疣旁“正常”组织及 2 0例对照包皮组织表皮中CD1a+ 朗格汉斯细胞 (LC)及表真皮中CD4 +T、CD8+ T细胞数目及CD4 + CD8+ 比值进行检测。探讨CA患者局部细胞免疫功能状态与HPV型的关系。结果CA疣体组织表皮CD1a+ LC细胞数量较正常对照明显降低 (P <0 .0 1) ,不同HPV亚型感染所致CA其CD1a+ LC数目差异无显著性 (P >0 .0 5 ) ;真皮中CD4 + T、CD8+ T细胞数目较正常对照升高 ,但CD4 + CD8+ 比值下降 (P <0 .0 1) ;CD4 + T、CD8+ T细胞数目及CD4 + CD8+ 比值相应的改变与不同HPV亚型无关。表皮CD1a+ LC与表皮、真皮中CD4 + T细胞及CD4 + CD8+ 比值成正相关 ,与CD8+ T细胞数目成负相关。因此 (1)CA患者皮损局部细胞免疫功能低下 ;疣体组织中CD1a+ LC细胞数目及CD4 + CD8+比值均降低。 (2 )CA患者局部免疫缺陷程度与HPV型无相关性。     

尖锐湿疣患者外周血及皮损T淋巴细胞亚群的检测

目的:了解尖锐湿疣(CA)患者系统和局部皮损细胞免疫功能的变化,以探讨细胞免疫功能对CA复发的影响。方法:通过流式细胞仪对21例初发CA患者、18例复发CA患者及23名正常人外周血进行T淋巴细胞亚群的检测,同时采用免疫组化染色方法对皮损进行CD4+/CD8+淋巴细胞染色,高倍显微镜下观察阳性细胞的数目。结果:初发CA和复发CA两组CD4+与CD8+细胞比值(1.04±0.50和1.01±0.59)均明显低于正常对照组(1.51±0.66,P<0.05),而两组间差异无显著性(P>0.05)。与正常对照组相比,两组CA局部皮损CD4+/CD8+比值(0.87±0.75和1.51±0.96)均明显降低(P<0.05),且复发CA组CD4+/CD8+比值也明显低于初发CA组,差异有显著性(P<0.05)。男女性患者不同部位皮损CD4+/CD8+比值均低于正常对照组,差异有显著性(P<0.05)。结论:CA患者存在全身和局部的细胞免疫功能低下,特别是局部细胞免疫功能低下在CA的复发中起着一定的作用。     

尖锐湿疣患者HPV感染与细胞免疫功能的相关性

目的研究尖锐湿疣初发、复发患者之间,以及不同病程患者之间T淋巴细胞亚群的表达情况。方法选择56例尖锐湿疣患者,经冷冻治疗后至疣体消失后随访3个月,未复发者计入A组(20例),再次复发者计入B组(36例),应用三色荧光抗体染色法检测各组患者外周血CD4+,CD8+T淋巴细胞的表达,比较A,B两组CD4+,CD8+T细胞百分率及CD4+/CD8+比值的差异,并与正常对照组进行比较。同时根据病程长短,病程<3个月者计入C组(37例),病程≥3个月者计入D组(19例),比较C,D两组CD4+,CD8+T细胞百分率及CD4+/CD8+比值的差异,并与正常对照组进行比较。结果①初发及复发患者组T淋巴细胞亚群的变化:A组CD4+,CD8+T细胞百分率及CD4+/CD8+比值分别为(34.61±4.98)%,(29.46±4.56)%和(1.20±0.22),B组分别为(30.33±4.84)%,(33.10±5.90)%和(0.94±0.21),正常对照组分别为(39.58±4.31)%,(25.44±3.54)%和(1.57±0.17),与正常对照组相比,A,B两组CD4+细胞百分率及CD4+/CD8+比值明显降低,CD8+T细胞百分率明显升高,差异有统计学意义(P<0.05),且B组变化更为明显,与A组差异有统计学意义(P<0.05);②不同病程患者组T淋巴细胞亚群的变化:C组CD4+,CD8+T细胞百分率及CD4+/CD8+比值分别为(33.03±4.51)%,(30.60±5.36)%和(1.11±0.23),D组分别为(29.57±5.98)%,(34.12±5.73)%和(0.89±0.22),C,D两组与正常对照组相比,CD4+细胞百分率及CD4+/CD8+比值明显降低,CD8+T细胞百分率明显升高,差异有统计学意义(P<0.01),且D组变化更为明显,与C组差异有统计学意义(P<0.05)。结论与正常对照组比较,尖锐湿疣患者存在细胞免疫功能降低,且随着病程延长、病情反复,全身细胞免疫功能降低更为明显,导致CA迁延不愈。     

间歇性应用免疫调节剂对亚临床型生殖器疱疹患者外周血淋巴细胞的影响

目的探讨影响亚临床型生殖器疱疹患者机体免疫水平的相关因素,以及予免疫调节剂治疗后机体免疫状态的改善情况。方法用荧光定量PCR检测患者带毒情况,用流式细胞仪检测患者的免疫功能。比较带毒阳性组与带毒阴性组,频发组(复发≥6次/年)与少发组(复发6次/年)以及使用免疫调节剂治疗前后患者的外周血淋巴细胞百分比。结果带毒阳性组CD3~+,CD4~+,CD4~+/CD8~+T细胞均低于带毒阴性组,差异有统计学意义(P0.05),频发组CD3~+,CD4~+,CD4~+/CD8~+,NK细胞均低于少发组,CD8~+T细胞高于少发组,差异有统计学意义(P0.05),治疗组CD3~+,CD4~+,CD4~+/CD8~+,NK细胞均低于对照组,CD8~+T细胞高于对照组,差异有统计学意义(P0.05),治疗后CD3~+,CD4~+,CD4~+/CD8~+,NK细胞均高于治疗前,CD8~+T细胞低于治疗前,差异有统计学意义(P0.05),在各种分组情况下比较B细胞数值变化,差异无统计学意义(P0.05)。结论亚临床型GH患者存在免疫功能低下的情况,带毒及频发患者的免疫抑制更为严重,而给予联合应用免疫调节剂后免疫低下较前改善。     

寻常疣和跖疣患者外周血T淋巴细胞亚群及共刺激分子CD28,CD40的检测

目的探讨寻常疣和跖疣患者外周血T淋巴细胞亚群的变化及共刺激分子CD28,CD40的表达情况。方法采用流式细胞仪检测实验组60例(寻常疣、跖疣患者各30例)和健康对照组30例的外周血T淋巴细胞亚群和CD28,CD40分子在淋巴细胞上的表达水平。结果寻常疣组、跖疣组与健康对照组相比:外周血CD4+T淋巴细胞(34.57%,35.39%,42.02%)明显减少,差异有统计学意义(P<0.01);CD4+/CD8+比值(1.38,1.44,1.72)降低,差异有统计学意义(P<0.05);淋巴细胞上CD28的表达(52.80%,51.87%,37.41%)明显增加,差异有统计学意义(P<0.01),CD40的表达(12.88%,11.94%,15.82%)减少,差异有统计学意义(P<0.05)。而寻常疣和跖疣两组间,外周血T淋巴细胞亚群及共刺激分子CD28,CD40的表达,差异无统计学意义(P>0.05)。实验组患者的疣体数量和外周血T淋巴细胞亚群及共刺激分子CD28,CD40的变化均无相关性(P>0.05)。结论寻常疣和跖疣患者体内存在T淋巴细胞亚群改变和共刺激分子CD28,CD40表达异常,可能与其免疫功能紊乱和病程慢性化有关。     

白癜风患者皮损中CD4~+,CD8~+T淋巴细胞及朗格汉斯细胞的检测

目的探讨白癜风患者皮损中CD4+,CD8+T淋巴细胞、朗格汉斯细胞(LC)及黑素细胞(MC)在白癜风发病中的作用。方法采用Envision免疫组化染色法,对12例白癜风进展期患者和9例稳定期患者皮损处CD4+,CD8+T淋巴细胞、LC及MC进行检测,并与10例正常人皮肤进行对照。结果白癜风患者皮损中CD4+,CD8+T淋巴细胞、LC表达较对照组显著增多(P<0.01),而MC表达较对照组显著减少(P<0.01)。结论白癜风患者皮损中LC,CD4+,CD8+T淋巴细胞异常表达可能参与白癜风的发病,其作用模式可能是LC抗原递呈,CD4+,CD8+T淋巴细胞浸润破坏或攻击MC,从而引起白癜风患者表皮基底层的MC减少或消失,导致白癜风的发生。     

尖锐湿疣亚临床感染转归与局部T淋巴细胞亚群检测北大核心CSCD

目的研究尖锐湿疣亚临床感染(SPI)转归与局部T淋巴细胞亚群变化的关系,进一步探讨SPI转归机制。方法对确诊的SPI患者进行:①所有患者随访8个月,每月观察1次,以临床表现和醋酸白试验判定SPI三种转归结局:发展为典型CA,SPI持续存在、SPI消失,依次分为A组、B组、C组;②免疫组织化学方法检测皮损组织和正常对照组织的T细胞亚群(CD_4^+,CD_8^+,CD_4^+/CD_8^+)的百分比,分析局部细胞免疫功能与三种转归结局的相关性。结果与正常组比较,SPI组CD_4^+细胞、CD_8^+细胞、CD_4^+/CD_8^+比值差异均有统计学意义(P<0.05)。SPI转归组中,A组与B组CD_4^+/CD_8^+比值差异无统计学意义(P>0.05),A组、B组分别与C组比较CD_4^+/CD_8^+比值差异均有统计学意义(P<0.05)。结论 SPI患者存在局部细胞免疫功能降低,局部细胞免疫功能强弱是决定SPI临床症状及转归的重要因素之一。     

尖锐湿疣亚临床感染转归与局部T淋巴细胞亚群检测

目的研究尖锐湿疣亚临床感染(SPI)转归与局部T淋巴细胞亚群变化的关系,进一步探讨SPI转归机制。方法对确诊的SPI患者进行:①所有患者随访8个月,每月观察1次,以临床表现和醋酸白试验判定SPI三种转归结局:发展为典型CA,SPI持续存在、SPI消失,依次分为A组、B组、C组;②免疫组织化学方法检测皮损组织和正常对照组织的T细胞亚群(CD_4~+,CD_8~+,CD_4~+/CD_8~+)的百分比,分析局部细胞免疫功能与三种转归结局的相关性。结果与正常组比较,SPI组CD_4~+细胞、CD_8~+细胞、CD_4~+/CD_8~+比值差异均有统计学意义(P0.05)。SPI转归组中,A组与B组CD_4~+/CD_8~+比值差异无统计学意义(P0.05),A组、B组分别与C组比较CD_4~+/CD_8~+比值差异均有统计学意义(P0.05)。结论 SPI患者存在局部细胞免疫功能降低,局部细胞免疫功能强弱是决定SPI临床症状及转归的重要因素之一。     

女阴硬化性苔藓皮损中朗格汉斯细胞及T淋巴细胞亚群的分析

目的研究女阴硬化性苔癣(lichen sclerosus,LS)皮损中朗格汉斯细胞、T淋巴细胞亚群的变化。方法采用直接免疫荧光的方法检测7例LS初期病例和8例LS后期病例表皮朗格汉斯细胞密度,真皮CD3~+T细胞、CD4~+T细胞、CD8~+T细胞密度,并与15例正常女性外阴皮肤进行对比。结果 LS后期病例表皮朗格汉斯细胞密度较正常组有明显增加(P=0.001)。LS初期病例和后期病例(真皮中下层)真皮CD3~+、CD4~+、CD8~+T细胞密度均较正常组增加(P均0.05),初期病例CD4~+/CD8~+T细胞比值与正常组差异无统计学意义(P=0.151);LS后期病例(真皮中下层)的CD4~+/CD8~+T细胞比值低于LS初期组、LS后期组(真皮浅层)及正常组,差异均有统计学意义(P均0.05)。结论随LS病情进展,表皮朗格汉斯细胞密度、真皮CD3~+、CD4~+、CD8~+T细胞密度以及CD4~+/CD8~+T细胞比值呈动态变化,说明细胞免疫在LS发病机制中起重要作用。     

阿维A联合重组人白介素-2对尖锐湿疣患者T淋巴细胞亚群及复发的影响

目的观察阿维A联合重组人白介素-2对尖锐湿疣(CA)患者外周血T淋巴细胞亚群的影响及预防复发的效果。方法入选患者随机分为两组,A组30例用微波彻底清除疣体后应用重组人白介素-2注射液20万U肌注,隔日1次,连用7次;B组34例采用微波彻底清除疣体后联合阿维A及重组人白介素-2治疗。所有患者均随访6个月。治疗前及治疗后8周抽取外周血检测T淋巴细胞亚群,并与25例健康对照组进行比较。结果治疗前CA患者与健康对照组比较,CD4+细胞百分比、CD4+/CD8+比值降低,差异有统计学意义(P<0.05),CD8+细胞百分比升高,差异亦有统计学意义(P<0.05),CD3+细胞百分比无明显变化;治疗后A,B组CD4+细胞百分比及CD4+/CD8+比值明显升高,CD8+细胞百分比降低,与治疗前相比差异均有统计学意义(P均<0.05),CD3+细胞无明显变化;治疗后A组,B组比较,A组CD4+细胞百分比、CD8+细胞百分比、CD4+/CD8+比值变化明显小于B组,差异有统计学意义(P<0.05);治疗后A组CD4+细胞百分比、CD4+/CD8+比值仍低于对照健康组,差异有统计学意义(P<0.05),治疗后B组与健康对照组相比上述指标差异无统计学意义(P>0.05)。A组复发率33.33%,明显高于B组的11.76%(P<0.05)。结论 CA患者存在细胞免疫功能异常,阿维A与重组人白介素-2可调节CA患者外周血T淋巴细胞亚群,从而调节患者细胞免疫功能;两者联合应用治疗CA可获得较好疗效,并能降低其复发率。     

An immunohistological study of spontaneous regression of condylomata acuminata.

An immunohistological study of four men whose perianal warts were undergoing spontaneous regression was undertaken, and the results compared with those obtained from non-regressing condylomata from six men. CD4+ and CD8+ cells were noted in the stroma of each wart, but there was no clear difference in the density of the infiltrate between regressing and non-regressing warts. Natural killer cells (CD16+ and CD57+) were only noted in the stroma and epidermis of regressing warts. Possible immunological mechanisms of regression of condylomata acuminata are discussed.     

不同病程尖锐湿疣患者HPV感染与T细胞亚群表达情况的关系

目的探讨不同病程尖锐湿疣(CA)患者人乳头状瘤病毒(HPV)感染与T细胞亚群表达情况的关系。方法选择2012年1月—2015年2月我院收治的151例CA患者,根据病程长短分为A、B组,A组病程≤3个月,B组病程3个月,A组97例,B组54例,另选同期体检健康的51例作为对照组。采集3组患者外周血,并使用流式细胞术检测T淋巴细胞亚群的表达情况。取脱落疣体细胞,并使用核酸快速杂交分型法检测HPV-DNA。结果 B组患者CD4~+、CD4~+/CD8~+水平显著低于A组和对照组,CD8~+水平显著高于对照组及A组患者,差异均有统计学意义(P0.05)。HPV阳性患者151例,其中包括单纯HPV6/11~+、HPV16/18~+型感染各45例、49例,HPV6/11、16/18~+混合型感染57例。HPV6/11~+、HPV16/18~+、(HPV6/11~+、16/18~+)各组患者CD3~+、CD4~+、CD4~+/CD8~+水平均低于健康组,差异有统计学意义(P0.05);而3组间CD3~+、CD4~+、CD8~+、CD4~+/CD8~+水平比较,差异均无统计学意义(P0.05)。结论病程3个月以上CA患者细胞免疫功能明显降低,且各型HPV感染患者细胞免疫功能差异无统计学意义。     

Local hyperthermia cleared multifarious viral warts in a patient with Cushing's syndrome

A female Cushing's syndrome patient had been suffering from extensive viral warts for months. She was diagnosed with flat warts, common warts and plantar warts. The plantar warts on her right foot were initially treated using local hyperthermia at 44°C for 30 min according to a defined protocol, followed by treatment targeting a common wart on her left thumb. In response to hyperthermia, the flat warts on her eyelid dissipated within 12 weeks, and when combined with a 1 week administration of imiquimod, the common warts and plantar warts completely disappeared within 8 weeks. There were no signs of recurrence and during this treatment her Cushing's syndrome was alleviated. This pioneer trial suggests that local hyperthermia may serve as an effective mean for treating multiple cutaneous warts under the conditions of a systemic immuno‐compromised disease.     

Clinical and immunohistochemical responses of plantar warts to topical immunotherapy with diphenylcyclopropenone

A 30-year-old man with bilateral plantar warts of the mosaic type which had been resistant to standard treatment modalities was treated with diphenylcyclopropenone. After 10 weeks, the treated warts had disappeared; the untreated warts, although showing some involution, still persisted. The untreated warts, serving as a control to prove the effectiveness of topical immunotherapy, responded likewise to subsequent treatment with diphenylcyclopropenone. Wart regression was reflected histopathologically by decreases in acanthosis, papillomatosis, granular vacuolation, and hyperkeratosis. Immunohistochemically, Ki-67 expression was markedly reduced, and a reversal of the CD4/CD8 ratio was seen. These findings suggest a major role of a cell-mediated immune response in the spontaneous resolution of warts.     

平阳霉素局部注射治疗多发性跖疣45例临床观察

目的评价平阳霉素局部注射治疗多发性跖疣的临床疗效。方法将入选的120例多发性跖疣患者随机分为A组（45例）、B组（35例）和C组（40例）。A组予平阳霉素注射治疗,B组予超脉冲CO2激光治疗,C组予液氮冷冻治疗,均为每4周1次,共治疗1-2次。结果治疗8周后,A组有效率为93.33%,B组为74.29%,C组为70.00%,A组显著优于B组和C组,差异均有统计学意义（P均〈0.05）。结论平阳霉素局部注射治疗多发性跖疣的疗效好,不良反应小,而且复发率低。     

Warts in primary schoolchildren: prevalence and relation with environmental factors

Background  Warts are very common in primary schoolchildren. However, knowledge on wart epidemiology and causes of wart transmission is scarce.
Objectives  To determine the prevalence of warts in primary schoolchildren and to examine the relation with environmental factors in order to provide direction for well-founded recommendations on wart prevention.
Methods  In this cross-sectional study, the hands and feet of 1465 children aged 4–12 years from four Dutch primary schools were examined for the presence of warts. In addition, the children's parents completed a questionnaire about possible environmental risk factors for warts.
Results  Thirty-three per cent of primary schoolchildren had warts (participation rate 96%). Nine per cent had hand warts, 20% had plantar warts and 4% had both hand and plantar warts. Parental questionnaires (response rate 76%) showed that environmental factors connected to barefoot activities, public showers or swimming pool visits were not related to the presence of warts. An increased risk of the presence of warts was found in children with a family member with warts [odds ratio (OR) 1·9, 95% confidence interval (CI) 1·3–2·6] and in children where there was a high prevalence of warts in the school class (OR per 10% increase in wart prevalence in school class 1·6, 95% CI 1·5–1·8).
Conclusions  One-third of primary schoolchildren have warts. This study does not find support for generally accepted wart prevention recommendations, such as wearing protective footwear in communal showers and swimming pool changing areas. Rather, recommendations should focus on ways to limit the transmission of wart viruses within families and school classes.     

Generalized warts and immune deficiency

A case of common variable hypogammaglobulinaemia with associated impairment of cell mediated immunity and severe wart virus infection is described. The defect of cell mediated immunity is thought to have predisposed this patient to the development of persistent wart infection which in turn grossly depressed the body's cellular immunity and thus allowed widespread dissemination of the warts. The rapid restoration of cell mediated immunity which followed the reduction in the antigenic load of wart virus by diathermy treatment was followed by the spontaneous regression of all the patient's warts. This unusual case may provide some insight into the complex relationship between wart virus infection and the immune system of the host.     

晕痣的免疫组化特点与自发性消退机制的研究

目的 研究晕痣自发性消退早期及晚期皮损区炎细胞表型、数目及其分布特点，探讨晕痣自发性消退的免疫机制。方法 应用免疫组化方法对晕痣皮损区、非皮损区及正常对照皮肤进行CD3、CD4、CD8、CD20、CD1a、CD56、CD68染色，用计算机图像分析系统（Image-pro PLUS 6.0）观察及定量分析。结果 晕痣早期及晚期皮损区CD4、CD8、CD20、CD1a阳性细胞数均明显高于非皮损区及正常对照皮肤（P ＜ 0.01），皮损区CD1a、CD68阳性细胞直径明显大于非皮损区及正常对照皮肤（P ＜ 0.01）。消退晚期CD8 与CD4阳性细胞数目比值（2.05 ∶ 1）高于消退早期（1.82 ∶ 1），CD8阳性细胞在痣细胞巢内大量浸润。结论 CD4、CD8、CD20、CD1a、CD56、CD68阳性细胞均参与晕痣自发性消退，CD8阳性T细胞在晕痣消退中起主要作用。     

Immunology of human warts.

Rapid advances have occurred in the characterization of human papilloma virus (HPV) types applying the new advanced techniques of restriction endonuclease analysis and molecular hybridization to human wart virus. Human papilloma virus can no longer be viewed as a single, homogeneous virus producing all varieties of clinical warts. At least three antigenically heterogeneous HPV types have been associated with common and plantar warts. Two additional HPV types have been found in patients with epidermodysplasia verruciformis. Condylomata acuminata and laryngeal papillomas contain viruses which are also distinct from the preceding viruses and may represent additional HPV types. This antigenic heterogeneity of HPV has important implications concerning the immunology of human warts which have not been taken into account in most previously published studies. Both antibody and cell-mediated responses may be seen in patients with active warts, but many patients with warts have no demonstrable immune reactions. The role of immunity in wart regression remains poorly understood. Nevertheless, the increased frequency of warts in patients receiving immunosuppressive drugs and with immune deficiency states and the immunologic alterations which occur in patients with regressing or cured warts compared to patients with active warts, particularly the increased frequency of cell-mediated responses and antibodies specific for viral antigens, support a possible role for immunity in the resolution of warts. The evidence to date, however, does not prove that immune mechanisms are directly responsible for the elimination of warts.