The impact of glucocorticoids and anti-cd20 therapy on cervical human papillomavirus infection risk in women with systemic lupus erythematosus

OBJECTIVE:

To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosus

METHODS:

This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay.

RESULTS:

A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05), and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01) and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005) compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03). In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection.

CONCLUSIONS:

The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus.     

Successful treatment of refractory thrombocytopenia with mycophenolate mofetil in a patient with systemic lupus erythematosus

While mild thrombocytopenia in systemic lupus erythematosus (SLE) is frequently seen in the context of active disease, severe thrombocytopenia causing significant bleeding is not that common. Corticosteroids are considered the first line therapy for severe thrombocytopenia in SLE. Second-line therapeutic agents or splenectomy have been reported to be effective for patients who fail to respond to steroids or those who require moderate doses of steroids to maintain the platelet counts. Recent randomized controlled studies have shown that mycophenolate mofetil (MMF) is an efficacious and safe therapeutic agent in patients with proliferative forms of lupus nephritis. However, little information has been available regarding the role of MMF in the treatment of immune thrombocytopenia complicated with SLE. Hereby I describe a patient with SLE in whom thrombocytopenia was refractory to corticosteroids, intermittent intravenous cyclophosphamide, azathioprine, cyclosporine, intravenous gamma globulin, danazol, and splenectomy, and whose platelet counts eventually normalized during therapy with MMF. In this patient, thrombocytopenia is initially thought to be associated with active SLE involving major organ. However, after immunosuppressive agents were given, the refractory nature of thrombocytopenia seems to be an isolated phenomenon, independently of SLE activity.     

Etanercept-induced systemic lupus erythematosus in a patient with rheumatoid arthritis

Tumor necrosis factor (TNF) is known to play a critical role in the pathogenesis of rheumatoid arthritis (RA). Etanercept is a recombinant soluble fusion protein of TNF alpha type II receptor and IgG, which acts as a specific TNF-alpha antagonist. Anti-TNF-alpha therapy has been an important advance in the treatment of RA. However, induction of autoantibodies in some proportion of patients treated with TNF alpha inhibitors raised concerns for development of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). Although new autoantibody formation is common with anti-TNF alpha therapy, there are only rare reports of overt SLE, most of which manifested without major organ involvement and resolved shortly after discontinuation of the therapy. We describe a 55-yr-old Korean woman who developed overt life threatening SLE complicated by pneumonia and tuberculosis following etanercept treatment for RA. This case is to our knowledge, the first report of etanercept-induced SLE in Korea.     

Cryptococcal meningitis presenting with isolated sixth cranial nerve palsy in a patient with systemic lupus erythematosus

Cryptococcal meningitis is a rare complication of systemic lupus erythematosus (SLE). The nonspecific neurologic findings associated with this infection delays accurate diagnosis because initial neuropsychiatric manifestations of SLE are in instances indistinguishable from that of crytococcal meningitis. We report a case of cryptococcal meningitis presenting with unilateral sixth cranial nerve palsy in a male patient with SLE, which was successfully treated with antifungal agents.     

Intraabdominal cryptococcal lymphadenitis in a patient with systemic lupus erythematosus

Cryptococcal infection is a rare, yet well recognized complication of systemic lupus erythematosus (SLE). We present a case of mesenteric and retroperitoneal cryptococcal lymphadenitis resulting in the obstruction of the stomach and proximal duodenum in a patient suffering from SLE, while recently she did not receive any immunosuppressive treatment. A 42-yr-old woman was admitted due to high fever and diffuse abdominal pain for three weeks. Abdominal computed tomography (CT) scan showed multiple conglomerated lymphadenopathies in the retroperitoneum and the mesentery resulting in luminal narrowing of the third portion of the duodenum. Cryptococcal lymphadenitis was proven by needle biopsy and she was treated with intravenous liposomal amphotericin B, followed by oral fluconazole. After fourteen-month antifungal therapies, the clinical symptoms and follow-up images improved. This case emphasize that the intrinsic immunological defects of SLE may be directly responsible for the predisposition to fungal infections.     

Appearance of systemic lupus erythematosus in patients with myasthenia gravis following thymectomy: two case reports

We report two cases of systemic lupus erythematosus (SLE) in myasthenia gravis (MG) patients who had undergone thymectomy. SLE developed in the patients 3 months or 13 yr after thymectomy, and polyarthritis was the main clinical manifestation of SLE. Both patients fulfilled at least four of the revised criteria for the classification of SLE. In this report, we describe two postthymectomy lupus patients and perform a comparative review of previous cases.     

A catastrophic-onset longitudinal myelitis accompanied by bilateral internuclear ophthalmoplegia in a patient with systemic lupus erythematosus

Transverse myelitis (TM) extending from midbrain to the entire spinal cord accompanied by internuclear ophthalmoplegia is extremely rare but cause serious central nervous system complications in patients with systemic lupus erythematosus. We report a case of a 28-yr-old woman with TM extending from the midbrain to the conus medullaris longitudinally and internuclear ophthalmoplegia associated with systemic lupus erythematosus. Her neurological symptoms had an abrupt catastrophic onset and rapidly progressed to respiratory failure within 24 hr. Bilateral internuclear ophthalmoplegia was also followed by TM. Brain MR images showed definite brainstem lesions, which were deeply associated with internuclear ophthalmoplegia, and diffuse signal changes in the whole spinal cord, medulla, pons and midbrain. Clinical improvement of her ophthalmoplegia and of neurological dysfunction of the upper extremities was noted after prompt and aggressive treatment with intravenous pulsed methylprednisolone and cyclophosphamide. However, the neurological dysfunction of the lower limbs and bladder and colon paralysis were almost unchanged until six months passed.     

人脐带间充质干细胞移植治疗系统性红斑狼疮

背景：系统性红斑狼疮是一种以多器官或多系统病变和血清中出现多种自身抗体为特征的自身免疫性疾病,目前缺乏有效的治疗方案,而理论上间充质干细胞可用于治疗系统性红斑狼疮。目的：观察人脐带间充质干细胞移植治疗系统性红斑狼疮小鼠的疗效。方法：分离培养人脐带间充质干细胞,并用深红色荧光DiR标记细胞。实验小鼠分5组：正常对照组(C57BL小鼠),模型对照组(C57BL/lpr小鼠),低、中、高剂量脐带间充质干细胞治疗组(C57BL/lpr小鼠),每组10只。各治疗组通过尾静脉注射低、中、高剂量(2×10⁶,1×10⁶,0.5×10⁶个)脐带间充质干细胞,每周1次,连续3周,治疗结束采血测抗核抗体、抗组蛋白抗体、抗双链DNA抗体变化,定量PCR检测OPG和Foxp3基因表达的变化。结果与结论：细胞移植3次后,外周血抗核抗体、抗组蛋白抗体、抗双链DNA抗体均明显下降,CD4⁺CD25⁺T细胞明显升高,OPG和Foxp3基因表达也明显升高,接近正常对照组,与模型对照组相比差异均有显著性意义(P < 0.01)。结果表明人脐带间充质干细胞能使C57BL/lpr小鼠的各项相关指标恢复到C57BL正常鼠水平,以高剂量治疗组效果最明显。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

系统性红斑狼疮患者血清多肽的MALDI-TOF MS分析研究

目的:本实验应用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)寻找SLE患者血清中与疾病相关及条件特异的差异性表达多肽,尝试建立SLE的多肽鉴别诊断模型。方法:将SLE患者分为活动期和非活动期两组,以健康志愿者作为正常对照组。应用弱阳离子交换磁珠分离纯化血清样本,MALDI-TOF-MS获取样本生物学信息,建立分类预测模型。结果:成功检测并鉴别出了一系列的差异性多肽,建立了具有高的预测能力和交叉验证能力诊断预测模型。盲法验证该分类模型显示,对活动期SLE组的诊断敏感性达91.7%,非活动期SLE组诊断敏感性达83.3%,对正常对照组的诊断特异性达86.7%。结论:运用多肽指纹图谱法从一个整体的角度进行疾病研究,为更好地理解SLE的发病机制和改进SLE的诊断方法进行了初步的探索。     

Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients

OBJECTIVES:

Hydroxychloroquine is an antimalarial agent that has been used in systemic lupus erythematosus and rheumatoid arthritis treatment for many years. Recently, novel mechanisms of action have been proposed, thereby broadening the therapeutic perspective of this medication. The purpose of this study was to evaluate the immunomodulatory activity of hydroxychloroquine in T helper 17 (Th17) cytokines in healthy individuals and patients.

METHODS:

Eighteen female patients with systemic lupus erythematosus (mean age 39.0±12.9 years) and 13 female patients with rheumatoid arthritis (mean age 51.5±7.7 years) were recruited from Universidade Federal de Pernambuco-Brazil. The patients were included after fulfilling four classification criteria for systemic lupus erythematosus or rheumatoid arthritis from the American College of Rheumatology. After being stimulated with phorbol 12-myristate 13-acetate and ionomycin in the absence or presence of different concentrations of hydroxychloroquine, the interleukin 6, 17 and 22 levels were quantified with an enzyme-linked immunosorbent assay in culture supernatants of peripheral blood mononuclear cells from healthy individuals and patients.

RESULTS:

We demonstrated that in peripheral blood mononuclear cells from healthy volunteers and in systemic lupus erythematosus and rheumatoid arthritis patients, there was a significant reduction in the IL-6, IL-17 and IL-22 supernatant levels after adding hydroxychloroquine.

CONCLUSIONS

Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication.     

Sera of patients with systemic lupus erythematosus react with plasmodial antigens and can inhibit the in vitro growth of Plasmodium falciparum

The acquisition of protective immunity in malaria is a slow process during which autoantibodies are produced. The present work aimed at studying a possible interference of autoimmune responses on malaria immune protection. This was done by investigating the presence of autoantibodies in the sera of malarious patients, by searching for reactivity of autoantibodies from autoimmune patients against plasmodial antigens, and by studying the effect of such antibodies on the in vitro growth of Plasmodium falciparum. Sera from systemic lupus erythematosus (SLE) and malaria patients were tested against autologous and plasmodial antigens. Out of the 109 SLE sera tested, 48 (44%) reacted against the parasite. In addition, 26 (47%) out of 55 randomly selected sera, mainly those containing anti-DNA and antinuclear autoantibodies, were able to inhibit parasite growth to some extent. Conversely, a high frequency (81%) of sera of malaria patients exhibited reactivity against autoantigens. The results show that patients with autoimmune processes can produce antibodies that recognize plasmodial antigens in the absence of plasmodial infection, that malaria patients can produce autoantibodies, that SLE sera can inhibit plasmodial growth in vitro, and that the presence of anti-DNA and antinuclear antibodies may be important in such anti-plasmodial activity. It is concluded that autoimmune responses may have influence on the protective immunity against malaria.     

宁波市妇女宫颈癌和人乳头瘤病毒感染的流行病学调查

目的 分析宁波市女性宫颈癌和感染人乳头瘤病毒(HPV)的流行病学特征.方法 收集2002-2014年宁波市女性宫颈癌发病和死亡资料,调查社区已婚妇女和妇科就诊妇女HPV感染情况,对社区妇女感染HPV相关危险因素进行分析,对检出的HPV16型病毒进行序列分析.结果 2006-2014年宁波市宫颈癌粗发病率、中标发病率、世标发病率分别为15.74/105、11.29/105和10.05/105,高发年龄为45-50岁;2002-2014年粗死亡率、中标死亡率和世标死亡率分别为3.09/105、2.26/105和2.08/105.778例社区妇女和387例妇科就诊妇女高危型HPV感染率分别为16.2％和18.3％,居前3位的亚型分别为HPV52(4.2％)、HPV16(3.0％)、HPV58(2.1％)与HPV16(4.9％)、HPV52(3.6％)和HPV58(2.6％).HPV16型病毒E6基因序列分析显示当地流行株均为lineage A组的亚洲变异株及欧洲变异株.结论 宁波市女性宫颈癌标化发病和死亡率均接近全国平均水平,社区妇女HPV感染率处于较高水平,研究结果为将来开展HPV疫苗人群预防提供基线资料.     

Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus

OBJECTIVE:

The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage.

METHODS:

The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher''s exact tests, as well as the Spearman rank correlation coefficient.

RESULTS:

Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0±163.4 IU/ml (range 3.5-9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6±699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels (r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03).

CONCLUSIONS:

The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.     

系统性红斑狼疮外周血单个核细胞CD28/B7分子mRNA的表达

目的 :探讨CD2 8 B7分子在系统性红斑狼疮 (SLE)发病机制中的作用及其临床意义。方法 :应用逆转录 聚合酶链反应 (RT PCR)检测 35例活动期SLE患者和 30例正常人外周血单个核细胞 (PBMC)中CD2 8、B7 1和B7 2mRNA的表达水平。结果 :35例活动期SLE患者PBMC中CD2 8的阳性表达率 (2 2 86 % )明显低于正常人对照组 (70 0 0 % ) ,差异非常显著 (P <0 0 0 1) ;B7 2的阳性表达率 (82 86 % )明显高于正常对照组 (5 3 33% ) ,差异显著 (P <0 0 1) ;活动期SLE组CD2 8的平均表达水平 (0 194 5± 0 2 0 74 )明显低于正常对照组 (0 4 2 38± 0 10 5 3) ,差异显著 (P <0 0 5 ) ;B7 2的平均表达水平 (0 86 75± 0 2 5 75 )明显高于正常人对照组 (0 4 898± 0 30 72 ) ,差异非常显著 (P <0 0 1) ;35例活动期SLE患者中仅有 2例B7 1呈阳性表达。结论 :CD2 8 B7分子的异常表达可能与SLE患者淋巴细胞和抗原呈递细胞 (APC)的功能变化有关。B7 1低水平与B7 2的高水平表达表明 ,SLE患者T细胞的活化可能主要是通过CD2 8与B7 2的交联传递共刺激信号 ,介导以Th2型反应为主的免疫应答反应 ;B7 2的表达水平可能与SLE疾病的活动性有一定的相关性。CD2 8mRNA的低水平表达可能与外周血CD2 8 T细胞凋亡增加或迁移到炎症部     

系统性红斑狼疮患者淋巴细胞共刺激分子异常表达的研究

目的 探讨系统性红斑狼疮(SLE)患者淋巴细胞共刺激分子的表达及意义.方法 采用流式细胞术检测SLE患者淋巴细胞CD28、CTLA-4、CD80和CD86的表达,并与对照组比较.结果 与健康对照者相比较,SLE患者CD3+细胞增加(P<0.05),CD3+CD4+细胞降低(P<0.05),CD3+CD8+细胞升高(P<0.05),CD4/CD8比例明显倒置(P<0.01),CD28表达降低,CTLA-4升高,CD86的表达显著高于正常人(P<0.01),CD80在SLE患者CD19+B细胞上的表达与正常人无异(P>0.05).结论 T细胞亚群改变及T、B淋巴细胞共刺激分子CD28、CTLA-4和CD86在SLE发病机制中起重要作用.     

脐带间充质干细胞移植对不同证型系统性红斑狼疮患者的效果分析

背景：系统性红斑狼疮按中医辨证分为热毒炽盛等4个症型,治疗以补肾养阴,清化淤毒为主,但仍有许多患者治疗效果不佳。间充质干细胞具有多向分化、造血支持和免疫调节的功能,目前已有多项研究用于治疗难治性、复发性系统性红斑狼疮,取得良好疗效。目的：探讨脐带间充质干细胞移植对不同证型系统性红斑狼疮患者的疗效。方法：系统性红斑狼疮患者21例,经中医辨证分成热毒炽盛证、肝肾阴虚证、脾肾阳虚证及气滞血瘀证4型,分别统计患者脐带间充质干细胞移植前后各型的临床及实验室指标变化。结果与结论：脐带间充质干细胞移植1,3,6个月均可有效减少系统性红斑狼疮患者实验尿蛋白含量,降低系统性红斑狼疮疾病活动指数评分(P < 0.01)。与移植前比较,移植脐带间充质干细胞后1,3,6个月可显著减少肝肾阴虚型患者尿蛋白含量(P < 0.01),移植后1,3个月对热毒炽盛及气滞血瘀型尿蛋白含量为轻度减少(P < 0.05),脾肾阳虚型患者在植后1个月时的尿蛋白含量轻度减少(P < 0.05)。脐带间充质干细胞移植可提高所有中医分型患者的血浆白蛋白含量(P < 0.01),其中对热毒炽盛型效果稍差(P < 0.05)。脐带间充质干细胞移植后各型患者外周血血小板有上升趋势,但与移植前相比差异无显著性意义。结果说明,脐带间充质干细胞移植治疗系统性红斑狼疮有效,对不同症型的系统性红斑狼疮患者的疗效有一定的差异。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Management of women with systemic lupus erythematosus

With improvements in survival rates for women with systemic lupus erythematosus (SLE) in the last few decades, the focus has now shifted towards the management of the associated complications. These include cancer, cardiovascular disease, osteoporosis and early menopause. These co-morbidities are believed to be the result of a complex interplay between the inflammatory process and disease treatment, and they complicate the management. A majority of women with SLE suffer considerable morbidity in the prime of their life. A team of multidisciplinary specialists is required to ensure aggressive and comprehensive management of risk factors, treatment of symptoms and prevention of complications to ensure successful outcomes.     

B cell elimination in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution, potentially life-threatening with considerable morbidity. The elimination of pathogenic B cells has emerged as a rational therapeutic option. Many open label studies have reported encouraging results in which clinical and serological remission have invariably been described, often enabling the reduction of steroid and immunosuppressive treatment. However, the results from randomized controlled studies have been disappointing and several questions remain to be answered. In this review we will focus on results of B cell direct depletion in the treatment of patients with systemic lupus erythematosus.     

Immunocytochemical localization of human papilloma virus and cytomorphologic correlation in smears and biopsies of cervical flat condylomata

The cytomorphologic features in cervical biopsies and smears associated with human papilloma virus antigen (Ag) expression as demonstrated by immunoperoxidase staining techniques are presented. There was good concordance between cytology and biopsy results with respect to immunoperoxidase staining for human papilloma virus Ag. Cytomorphologic scoring of low-grade lesions (cervical intraepithelial neoplasias, grades O and I) showed atypical mitoses, macronucleated koilocytes, superficial cell keratohyaline granules, and multinucleation to be more frequent in Ag+ biopsy specimens. Chronic inflammation was more evident in Ag- biopsy specimens (P less than 0.05). Parakeratosis was more frequent in Ag+ cytologic specimens. Koilocytosis was not a reliable indicator of Ag expression in either preparation. Human papilloma virus (HPV) Ag testing by immunoperoxidase techniques appears to be a useful adjunct for screening low-grade atypias of the cervix.