桥粒芯糖蛋白抗体与天疱疮临床表型和疾病活动度的关系及其变化规律

【摘要】 目的 评估酶联免疫吸附试验（ELISA）检测桥粒芯糖蛋白1（Dsg1）、Dsg3抗体与天疱疮患者临床表型、疾病活动度的关系及变化规律。方法 收集2015年1月至2018年1月在中国医学科学院皮肤病医院就诊的天疱疮患者111例,按临床分型,采用ELISA测定患者初发时、控制阶段、维持阶段及复发时血清Dsg1、Dsg3抗体水平变化,并分析其变化规律。采用SPSS22软件,多组间比较采用单因素方差分析,组间两两比较采用LSD?t检验。结果 天疱疮初发时、控制阶段、维持阶段及复发时分别有92例、53例、33例、9例患者完成检测。92例初发患者中,36例落叶型天疱疮患者Dsg1和Dsg3抗体水平阳性率分别为100%、2.77%,10例黏膜型寻常型天疱疮分别为20%、80%,46例黏膜皮肤型寻常型天疱疮分别为97.82%、95.65%。初发时、控制阶段、维持阶段和复发时落叶型天疱疮患者Dsg1抗体水平分别为（137.43 ± 77.74）、（13.94 ± 14.81）、（21.50 ± 58.33）、（121.13 ± 86.89） U/ml;黏膜型寻常型天疱疮患者Dsg3抗体水平分别为（125.61 ± 94.81）、（34.5 ± 16.26）、0.6、258 U/ml;黏膜皮肤型寻常型天疱疮患者Dsg1抗体水平分别为（115.39 ± 70.62）、（15.74 ± 25.10）、（3.62 ± 12.09）、（78.60 ± 92.25） U/ml;Dsg3抗体水平分别为（137.98 ± 81.25）、（58.14 ± 63.46）、（29.26 ± 64.70）、（136.9 ± 101.47） U/ml。落叶型天疱疮Dsg1抗体水平和黏膜型寻常型天疱疮、黏膜皮肤型寻常型天疱疮Dsg3抗体水平在控制阶段、维持阶段均低于初发时、复发时（P < 0.05）。治疗过程中2例患者出现表位扩展现象,4例患者病情稳定期时出现Dsg抗体高滴度现象。结论 Dsg抗体谱与天疱疮临床表型相关,其ELISA值可用于监测疾病活动,并可对治疗的有效性作出评价。     

[开放获取] 米诺环素单药或联合小剂量糖皮质激素治疗红斑型天疱疮15例和疱疹样天疱疮9例疗效和安全性回顾分析

【摘要】 目的 探讨米诺环素单药或联合小剂量糖皮质激素（简称激素）治疗红斑型天疱疮（PE）和疱疹样天疱疮（PH）的疗效和安全性及对免疫指标的影响。方法 回顾性纳入2011年6月至2021年6月于北京大学第一医院皮肤科初诊、初治方案为米诺环素单独或联合小剂量激素且随访至少6个月的PE和PH患者。收集基线及不同随访时间点患者病情、自身抗体水平变化，分析疾病严重程度、诊断、自身抗体变化趋势及与疗效间的关系。采用Kaplan-Meier方法分析完全缓解情况，用卡方检验分析不同严重度和疗法下PF患者的疗效。结果 共纳入24例汉族患者，包括15例PE和9例PH，男女比例为1.4∶1，中位年龄68.8岁，中位病程为22.1个月，平均随访时间为21.8个月。24例均获得疾病控制，疾病控制时间M（Q1，Q3）为15.9（12，20.1）周。完全缓解23例 （95.8%），完全缓解时间8.7（6.4， 10）个月。米诺环素单药治疗1年完全缓解率（11/13）与联合小剂量激素疗法（9/11）差异无统计学意义（χ2 = 0.16，P = 0.692）。随访期间复发2例（8.7%），皆处于疾病控制状态，1例调整剂量后于第38周达完全缓解，另1例换用利妥昔单抗，半年后达到完全缓解。轻中度患者间疗效差异无统计学意义（χ2 = 0.28，P = 0.599）。3例发生药物相关不良反应，1例为背部体癣，2例为全身皮肤及牙龈部位色素沉着。结论 米诺环素单药或联合小剂量激素治疗轻中度PE或PH疗效显著，且无严重药物相关不良反应，但该方案的长期疗效、不良反应及患者预后需未来进一步扩大样本量，进行多中心、前瞻性研究。     

抗构象表位桥粒芯蛋白抗体和乙酰胆碱受体抗体滴度与寻常型天疱疮病情活动度的相关性研究

【摘要】 目的 研究寻常型天疱疮患者血清中相关抗体滴度与病情严重程度和病情活动度的相关性。方法 收集2012—2015年于中国医学科学院皮肤病医院首次就诊的24例活动期寻常型天疱疮（PV）患者,评估患者活动期和稳定期天疱疮疾病面积指数（PDAI）,并采集血清标本。采用酶联免疫吸附实验（ELISA）检测血清标本中具有致病作用的抗构象表位桥粒芯蛋白（Dsg）抗体滴度、总Dsg抗体滴度和乙酰胆碱受体（AChR）抗体滴度。计量资料比较采用t检验,计数资料比较采用Fisher 精确检验法,相关性比较采用Pearson分析。结果 活动期患者的Dsg1抗体滴度（611.4 ± 136.8）与抗构象表位Dsg1抗体滴度（585.5 ± 134.7）差异无统计学意义（t = 0.13,P = 0.89）,Dsg3抗体滴度（708.6 ± 130.7）高于抗构象表位Dsg3抗体滴度（297.2 ± 54.4,t = 2.90,P < 0.01）。活动期患者的Dsg1抗体滴度及抗构象表位Dsg1抗体滴度与PDAI评分均呈正相关（r = 0.54、0.54,均P < 0.01）;Dsg3抗体滴度与PDAI评分无相关性（r = 0.11,P = 0.62）,抗构象表位Dsg3抗体滴度与PDAI评分呈正相关（r = 0.53,P < 0.01）。20例稳定期患者血清中Dsg1抗体与抗构象表位Dsg1抗体滴度与首次就诊时比较均明显下降。Dsg3抗体滴度仅7例明显下降;13例仍存在较高滴度的Dsg3抗体,其中6例抗构象表位Dsg3抗体滴度明显下降,5例AChR抗体滴度由阳性转为阴性。结论 Dsg1抗体及抗构象表位Dsg1抗体滴度都可以反映病情活动度。部分患者病情活动度与Dsg3抗体滴度不一致,抗构象表位Dsg3抗体或者AChR抗体可能有助于反映病情活动度。     

抗桥粒芯蛋白抗体对天疱疮的临床诊断价值

目的研究天疱疮患者血清中抗桥粒芯蛋白(desmoglein,Dsg)1和抗Dsg3抗体水平在天疱疮的临床诊断价值。方法采用酶联免疫吸附试验(ELISA)测定62例天疱疮患者血清中抗Dsg1和抗Dsg3抗体水平;间接免疫荧光法(IIF)测定天疱疮抗体Ig G水平。结果 62例天疱疮患者中抗Dsg1抗体或抗Dsg3抗体任一阳性共50例,阳性率80.65%,与间接免疫荧光法(IIF)相比两种方法差异无统计学意义(P0.05)。因此抗Dsg抗体具有和IIF一样的临床诊断价值。34例寻常型天疱疮(PV)中抗Dsg3抗体阳性或抗Dsg1和抗Dsg3抗体均阳的28例,阳性率82.35%;24例落叶型天疱疮(PF)中抗Dsg1抗体阳性的为20例,阳性率83.33%。可见抗Dsg3抗体是PV的鉴别诊断指标,抗Dsg1抗体是PF的鉴别诊断指标。此外,通过对治疗前后抗Dsg1抗和Dsg3抗体的滴度水平的检测发现,抗Dsg1和抗Dsg3抗体还可作为天疱疮治疗监测的指标。结论采用ELISA方法测定天疱疮患者外周血抗Dsg1抗体和抗Dsg3抗体,方法简便,对患者创伤小,有一定的诊断和鉴别诊断价值。另外,抗Dsg1抗体和抗Dsg3抗体还可作为监测天疱疮治疗效果的指标。     

天疱疮或大疱性类天疱疮合并单纯疱疹病毒感染8例临床特征及治疗分析

目的回顾分析天疱疮/大疱性类天疱疮(BP)合并单纯疱疹病毒(HSV)感染的临床特征及治疗方法。方法回顾分析2016—2021年在武汉市第一医院住院治疗的天疱疮/BP合并HSV感染病例的临床特征及治疗和随访情况。结果 8例天疱疮/BP合并HSV感染患者中, 男2例, 女6例, 年龄(50.6 ± 8.3)岁, 包括5例寻常型天疱疮, 1例落叶型天疱疮, 2例BP。7例合并HSV-1感染, 1例合并HSV-2感染。8例均因天疱疮或BP接受系统糖皮质激素及免疫抑制剂治疗, 并对治疗抵抗入院, 其中7例表现为原发病灶加重或复发, 1例表现为全身皮损增加。HSV感染位于躯干4例, 口腔4例, 头皮3例, 面部2例。皮疹表现为不规则的糜烂面, 伴血痂, 部分为中央有脐凹的脓疱, 7例伴有皮疹处明显疼痛。发生HSV感染时, 6例天疱疮患者抗Dsg1抗体均下降, 5例寻常型天疱疮中4例抗Dsg3抗体下降;2例BP患者中1例抗BP180抗体降低, 1例升高。予足量足疗程抗病毒治疗(伐昔洛韦或更昔洛韦治疗7 ～ 14 d), 所有患者HSV感染均被控制, 自身免疫性大疱性皮肤病严重程度评分较抗病毒治疗前均...     

天疱疮患者皮损局部B淋巴细胞及其产生特异性抗体的功能研究

目的 检测寻常型天疱疮患者皮损局部B淋巴细胞及其产生特异性抗体的功能。方法 寻常型天疱疮患者35例,健康对照22例。取健康对照皮肤和寻常型天疱疮患者初发水疱或糜烂皮损组织,分离获得单个核细胞。流式细胞仪检测患者皮损局部淋巴细胞、CD19+ B细胞比例,以及特异性识别桥粒芯糖蛋白1（Dsg1）和Dsg3的CD19+ B淋巴细胞比例。体外培养寻常型天疱疮患者皮损局部淋巴细胞,ELISA法检测培养上清液中抗Dsg1和Dsg3抗体滴度,采用受试者工作特征曲线（ROC）分析阳性率。结果 寻常型天疱疮患者皮损局部淋巴细胞、CD19+ B细胞比例分别为17.95% ± 3.85%、4.27% ± 1.13%,高于健康对照组（7.83% ± 1.29%、0.61% ± 0.31%）,差异有统计学意义（t = 2.49,U = 13.00,均P < 0.05）。天疱疮患者皮损局部CD19+ B淋巴细胞中,表达IgG的细胞比例为（38.33 ± 5.56）%,表面识别Dsg1与Dsg3的细胞比例分别为12.87% ± 1.267%、10.42% ± 1.243%。局部淋巴细胞体外培养6 d后,培养上清液中抗Dsg1与Dsg3抗体滴度分别为（4.89 ± 1.56） U/ml、（35.45 ± 13.03） U/ml,阳性率分别为85%（17/20）和95%（19/20）。 结论 寻常型天疱疮患者皮损局部有可与Dsg1及Dsg3特异性结合的B淋巴细胞聚集,体外培养后可产生特异性抗Dsg1与抗Dsg3自身抗体。     

天疱疮患者病情与抗桥粒芯蛋白抗体水平的相关性研究

目的:研究天疱疮患者血清中抗桥粒芯蛋白(desmoglein,Dsg)1和抗Dsg3抗体水平与其皮肤、口腔黏膜损害严重程度的相关性,同时对间接免疫荧光(IIF)检测的天疱疮抗体滴度与治疗中使用皮质类固醇控制剂量的相关性进行分析。方法:采用酶联免疫吸附试验(ELISA)试剂盒测定55例天疱疮患者血清中抗Dsg1和抗Dsg3抗体水平。结果:抗Dsg1抗体水平与患者皮肤损害严重程度有显著相关性(P<0.01),抗Dsg3抗体水平与口腔黏膜损害严重程度有显著相关性(P<0.01)。天疱疮患者血清IIF滴度与抗Dsg1抗体水平相关(P<0.01),寻常型天疱疮患者IIF滴度与抗Dsg1和抗Dsg3抗体水平均有相关性(P分别<0.01和<0.05)。寻常型天疱疮患者皮质类固醇控制剂量与抗Dsg1抗体水平和IIF滴度显著相关(P<0.05)。结论:ELISA方法检测天疱疮患者抗Dsg1和抗Dsg3抗体对天疱疮的临床诊断、分型、衡量口腔黏膜和皮肤损害严重程度具有一定意义。     

ELISA技术检测寻常型天疱疮桥粒芯蛋白3抗体水平研究

目的:评价酶联免疫吸附试验(ELISA)检测抗桥粒芯蛋白(desmoglein,Dsg)3抗体在寻常型天疱疮(PV)诊断中的意义.方法:对来自不同中心的106例PV患者和106例对照人群血清标本编盲后,进行ELISA检测抗Dsg3自身抗体和间接免疫荧光(IIF)法检测血清天疱疮自身抗体.结果:ELISA法检测Dsg3抗体敏感度为77.4%,特异性为94.3%;IIF法检测抗体敏感度为79.2%,特异性为94.3%.两组间的差异无统计学意义.结论:ELISA方法检测Dsg3抗体对于寻常型天疱疮的诊断是一种较好的辅助方法.     

天疱疮特异性抗体亚型与疾病活动的相关性研究

目的 探讨天疱疮患者抗桥粒芯糖蛋白（Dsg）1和Dsg3抗体亚型与疾病活动的相关性。方法 收集47例天疱疮患者血清,ELISA检测其特异性抗Dsg1和Dsg3抗体及亚型,分析抗体滴度及亚型与疾病活动的相关性。结果 抗Dsg1和Dsg3抗体类别与天疱疮临床类型有关,17例皮肤黏膜同时受累的患者中有14例（82.4%）同时存在两种抗体;16例仅皮肤受累的患者中有15例（93.7%）存在抗Dsg1抗体,仅1例（6.3%）存在抗Dsg3抗体;6例仅黏膜受累的患者只存在抗Dsg3抗体,阳性率为100％。随着病情的加重,抗Dsg1和Dsg3抗体滴度有上升趋势,但该趋势与疾病的严重度并不完全平行。而抗体亚型则和疾病活动相关,活动期以特异性IgG4亚型为主,稳定期以IgG1亚型为主。抗Dsg1阳性者,活动期特异性IgG4和IgG1抗体吸光度（A）值分别为1.92 ± 1.21和0.60 ± 0.61,IgG4/IgG1 > 1;稳定期特异性IgG4和IgG1抗体A值分别为0.03 ± 0.02和0.22 ± 0.11,IgG4/IgG1 < 1;抗Dsg3阳性者,活动期特异性IgG4和IgG1抗体A值分别为2.35 ± 2.17和1.84 ± 1.16,IgG4/IgG1 > 1;稳定期特异性IgG4和IgG1抗体A值分别为0.15 ± 0.16和1.05 ± 0.77,IgG4/IgG1 < 1。结论 天疱疮特异性抗体亚型与疾病活动密切相关,用ELISA检测天疱疮患者血清中抗Dsg1和Dsg3抗体类型、特异性抗体亚型及滴度,可更好地辅助诊断疾病、监测疾病活动。     

抗p200类天疱疮7例临床及免疫血清学特征分析

【摘要】 目的 总结抗p200类天疱疮患者的临床和免疫血清学特征。方法 收集2015年1月至2021年10月在中国医学科学院皮肤病医院确诊为抗p200类天疱疮的患者资料，回顾性分析其临床和免疫血清学特征。结果 纳入7例抗p200类天疱疮患者，盐裂皮肤-间接免疫荧光实验显示，7例患者血清IgG抗体均结合于盐裂皮肤的真皮侧，以真皮提取物为底物的免疫印迹显示，在相对分子质量200 000蛋白处有条带。4例呈经典型大疱性类天疱疮样损害，2例初起呈湿疹样损害，1例类似线状IgA大疱性皮病。6例循环IgG抗体可识别层粘连蛋白γ1-C端重组蛋白。4例患者接受不同剂量系统糖皮质激素治疗，其中1例对高剂量系统糖皮质激素（相当于泼尼松1.4 mg·kg-1·d-1）治疗抵抗；2例对米诺环素、氨苯砜治疗反应好；1例失访。4例患者在随访平均22.5个月时达到完全缓解停药；2例在随访平均8个月时达到最小剂量治疗保持完全缓解。结论 抗p200类天疱疮临床表现多样，重组Lnγ1-C端可作为可靠的抗原底物用于检测抗p200类天疱疮患者自身抗体；部分患者最终可达到完全缓解并停药。     

Therapeutic effect of mizoribine on pemphigus vulgaris and pemphigus foliaceus

We evaluated the effectiveness of mizoribine, a newly developed immunosuppressive agent, as an adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. Eleven pemphigus patients (eight pemphigus vulgaris and three pemphigus foliaceus) received the combination therapy of prednisolone and mizoribine. Complete remission was observed in three of the eight patients with pemphigus vulgaris and in one of the three patients with pemphigus foliaceus. The four patients with complete remission had a rapid clinical response and achieved remission at a median of 11.8 months. Partial remission was achieved in two of the three patients with pemphigus foliaceus. The median time to achieve partial remission was 16.0 months. Six (55.6%) of the 11 patients with pemphigus had complete or partial remission and were able to taper their prednisolone. The cumulative probability of having a complete remission was 64.3% at 19 months of follow-up using Kaplan-Meier analysis. The effectiveness of the additional mizoribine therapy could be attributed to its corticosteroid-sparing properties as well as its immunosuppressive effects. The serum concentration titer of mizoribine was around 1.0?μg/mL 2 hours after administration. Patients who were not improved by the additional mizoribine might require a continuously higher dose of mizoribine to achieve effective therapy.     

Oral cyclophosphamide for treatment of pemphigus vulgaris and foliaceus

BACKGROUND: Cyclophosphamide is an alkylating adjuvant used in refractory cases of pemphigus. OBJECTIVE: We sought to evaluate the effectiveness and safety of oral cyclophosphamide in the treatment of patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) with refractory disease. PATIENTS: We studied 23 patients with pemphigus (20 with PV; 3 with PF) who failed to achieve clinical remissions with the use of prednisone and antimetabolites. RESULTS: Complete remission was achieved in 17 patients with PV and 2 with PF. A total of 3 patients with PV failed therapy. A partial remission was achieved in 1 patient with PF. The treatment was administered for a median duration of 17 months with a follow-up period of 27 months. The median time to complete remission was 8.5 months. A total of 9 patients who were severely affected received concomitant plasma exchange. Adverse reactions included 5 cases of hematuria, 6 nonlife-threatening infections, and the development of transitional cell carcinoma of the bladder 15 years after discontinuation of cyclophosphamide in 1 patient. No death was associated with cyclophosphamide treatment. CONCLUSION: Oral cyclophosphamide is an effective adjuvant in the treatment of severe and refractory PV and PF, but requires close monitoring.     

Treatment of pemphigus vulgaris and pemphigus foliaceus with mycophenolate mofetil

BACKGROUND: Mycophenolate mofetil is increasingly being used as a corticosteroid-sparing agent in immunosuppressive regimens. OBJECTIVE: To elucidate the effectiveness of mycophenolate as adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. DESIGN: Historical prospective study. SETTING: University hospital. PATIENTS: The study included 42 consecutive patients with pemphigus (31 with pemphigus vulgaris and 11 with pemphigus foliaceus) who had relapses during prednisone taper or had clinically significant adverse effects from previous drug therapy. RESULTS: Remission was achieved in 22 (71%) and 5 (45%) of patients with pemphigus vulgaris and pemphigus foliaceus, respectively. Partial remission was achieved in 1 (3%) and 4 (36%), respectively. The median time to achieve complete remission was 9 months (range, 1-13 months). The treatment was administered for a median of 22 months, and the median follow-up period was 22 months. Seventy-seven percent of patients had no adverse effect. Two patients had side effects severe enough to necessitate discontinuation of treatment, one because of symptomatic but reversible neutropenia and the other because of nausea. CONCLUSION: Mycophenolate is an effective and safe adjuvant in the treatment of both pemphigus vulgaris and pemphigus foliaceus.     

Treatment of severe pemphigus with a combination of immunoadsorption, rituximab, pulsed dexamethasone and azathioprine/mycophenolate mofetil: a pilot study of 23 patients

Background It has been previously shown in a relatively small group of patients that a combination of immunoadsorption (IA) and rituximab with daily use of high‐dose oral corticosteroids and azathioprine/mycophenolate mofetil may induce a rapid and durable remission in severe, treatment‐resistant pemphigus. Objectives To achieve a more rapid reduction of serum autoantibody levels by a more frequent use of IA in the initial phase of treatment and to reduce the number of severe adverse events of continuous oral corticosteroid therapy by switching to pulsed intravenous applications. Methods Twenty‐three consecutive patients with severe pemphigus were included. IA was performed at initially 3‐ and later 4‐week intervals until lesions healed by 90%; 1000 mg rituximab was given at weeks 1 and 3, and intravenous dexamethasone pulses were administered at first every 3 weeks and then at increasing intervals in addition to daily azathioprine/mycophenolate mofetil. Results Along with a fast and durable decline of circulating autoantibody levels, all patients showed improvement of pemphigus lesions within the first weeks of therapy and long‐term complete remission was induced in 19 (83%) patients. In the remaining four patients, one (4%) minimal disease and three (13%) partial remissions were observed. Over the long‐term follow‐up of 11–43 (mean 29) months, six (26%) patients had a recurrence and in two (9%) patients, severe adverse events occurred. Conclusions This novel protocol treatment induces a fast and long‐term remission in severe pemphigus and seems to offer an improved side‐effect profile compared with daily use of corticosteroids.     

Rituximab in practice: Clinical evaluation of patients with pemphigus after rituximab administration

Pemphigus Vulgaris (PV) is a rare autoimmune blistering disease, which mainly causes mucosal and/or cutaneous lesions. In June 2018, FDA approved Rituximab (RTX)—a B‐cell depleting agent—for the management of patients with moderate‐to‐severe pemphigus. Although the majority of patients respond well to this drug, some do not reach complete remission with a single cycle of RTX. In this review, following an overview of RTX and its clinical outcomes, we have focused on the possible outcomes after RTX therapy in patients with PV. The response is defined into four main categories; complete responders, partial responders, nonresponders, and paradoxical reactions, based on three possibilities of reaching the consolidation phase after 3 months, reaching remission until 6 months, and the ability of corticosteroid tapering in 6 months after RTX administration. Concerning the safety of RTX, three categories of infusion reactions, short and long‐term side effects are discussed. Additionally, we have suggested approaches for the evaluation of clinical and serological responses at different critical time‐points, including 1, 2, 3, and 6 months after RTX administration. Finally, available markers to predict the response to RTX and research gaps in the field of RTX therapy have been summarized.     

Patterns of remission in pemphigus vulgaris

BACKGROUND: The incidence of remissions in pemphigus is unclear because these are usually reported at a single point in the evolution of the disease. Thus it is uncertain whether treatment simply suppresses the manifestations of the disease and consequently must be continuously administered, or induces complete and long-lasting remissions that permit therapy to be discontinued. OBJECTIVE: To answer this question, we investigated the incidence of remission in a long-term longitudinal study. METHODS: The induction of complete and long-lasting remissions (lesion free with no systemic therapy for at least 6 months) was studied in 40 patients with pemphigus vulgaris treated conventionally and followed up for an average of 7.7 years by the same investigator. RESULTS: Five (5%) of the patients died of the disease. Complete and long-lasting remissions were induced in 25%, 50%, and 75% of patients 2, 5, and 10 years, respectively, after diagnosis. Most of the remaining patients were in partial remission or had mild disease controlled with a small dose of steroids. The course of the disease followed different patterns, with some patients rapidly entering complete and long-lasting remissions, whereas others never entered into a complete remission. The induction of complete remission was related to the initial severity and extent of disease and to early response to treatment. CONCLUSION: It is possible to eventually induce complete and durable remissions in most patients with pemphigus that permit systemic therapy to be safely discontinued without a flare in disease activity. The proportion of patients in whom this can be achieved increases steadily with time, and therapy can be discontinued in approximately 75% of patients after 10 years.     

Circulating pemphigus autoantibodies in healthy relatives of pemphigus patients: coincidental phenomenon with a risk of disease development?

Pemphigus is a severe autoimmune disease characterized by circulating and bound in vivo pemphigus autoantibodies. It was revealed that the autoantibodies occur in healthy first-degree relatives of pemphigus patients; however, their significance is not fully elucidated. Thus, the aim of the study was to assess the frequency of circulating IgG pemphigus autoantibodies in the healthy relatives of pemphigus patients and of their ability to bind in vivo in the epidermis. We also analyzed IgG subclasses distribution, both in the serum-positive relatives and in the patients. Our study included 67 healthy relatives, 50 healthy normal controls and 33 patients (25 at an active stage of the disease, 8 in clinical remission). To detect circulating pemphigus antibodies we applied indirect immunofluorescence and anti-desmoglein ELISA. Monoclonal anti-human IgG1, IgG2, IgG3, IgG4 antibodies were used to assess subclass distribution. The frequency of circulating pemphigus autoantibodies in the relatives, detected by IIF (30/67) was statistically higher (P < 0.001) than in the control group (0/50). ELISA revealed anti-desmoglein 1 and/or 3 antibodies in 13 out of 67 relatives. Direct immunofluorescence performed in 25 out of 32 seropositive relatives did not show intercellular bound in vivo IgG and/or C3 in the epidermis in any cases. Circulating IgG2 subclass was observed in 60% of the examined relatives and IgG4 was detected in 23.3% of them. In the patients at an active stage of pemphigus IgG4 and IgG1 were the dominant subclasses (96 and 76% relatively) while in clinical remission antibodies predominantly belonged to the IgG2 (75%) and IgG4 (37.5%) subclass. The obtained results confirmed polyclonal production of pemphigus autoantibodies and their different distributions dependent on the disease activity. Statistical analysis showed that the frequency of IgG1 and IgG4 subclasses was significantly higher in the patients at an active stage of the disease when compared to the patients in clinical remission (P < 0.001) or with seropositive healthy relatives (P < 0.001). The relevance of the presence of IgG4 autoantibodies in the healthy relatives' sera requires further studies that focus on their potential pathogenicity.     

Adjuvant rituximab therapy of pemphigus: a single-center experience with 31 patients

BACKGROUND We conducted a retrospective study of patients with pemphigus vulgaris (n?=?24) and foliaceus (n?=?7) treated with adjuvant rituximab to determine efficacy and adverse events. The end point for efficacy was complete remission of disease taking no or minimal therapy. OBSERVATIONS Eighteen patients (58%) achieved the study end point. Of these, 13 patients achieved complete remission off systemic therapy. Patients achieving the study end point had a median disease duration before rituximab therapy of 19 months vs 86 months in those not achieving the end point (P?=?.01). For the 18 patients achieving the end point, the median (SD) duration of remission was 19 (2) months. Eight of these 18 patients (44%) relapsed from 6 to 17 months after treatment. Serious adverse events attributed to rituximab treatment (osteomyelitis or phlegmon) occurred in 2 patients (6%). In paired serum samples from 10 patients before and after rituximab treatment, the percent change in serum desmoglein index value (median, -80%) was unrelated to the percent change in pneumococcal antibodies (median, +8%) (Spearman rank correlation coefficient r?=?-0.2). CONCLUSIONS Patients treated with rituximab earlier in the course of disease may have better outcomes. A discussion of rituximab's mechanism of action supports the rationale for early therapy. Prospective clinical studies are necessary to substantiate this observation.