Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease

AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.

Prevalence and clinical significance of antiphospholipid antibodies among hospitalized COVID-19 patients

Objective:To describe the prevalence of antiphospholipid antibodies in coronavirus disease-19(COVID-19)and to find potential associations between antiphospholipid antibody positivity and clinical outcomes.Methods:From September to November 2020,clinical and laboratory data were collected from 50 COVID-19 patients hospitalized at Saiful Anwar General Hospital in Malang,Indonesia.Antiphospholipid antibodies were measured by finding Ig M anti-β2 glycoprotein,lupus anticoagulant,and Ig M/Ig G anticardiolipin.Clinical characteristics,thrombotic events,ICU admission,and mortality during hospitalization were recorded.Disease severity was defined by the Guidelines for the Prevention and Control of COVID-19,Indonesia.Results:Among 50 patients,5 patients(10.0%)were positive for antiphospholipid antibodies:4 patients(80.0%)had Ig M anti-β2 glycoprotein and 1 patient had Ig G anti-cardiolipin(20.0%)and Ig M anti-cardiolipin(20.0%),none of lupus anticoagulant was detected.Antiphospholipid antibodies were associated with anosmia(OR 8.1;95%CI 1.1-57.9;P=0.018),nausea and vomiting(OR 12.4;95%CI 1.2-122.6;P=0.010),diarrhea(OR 9.8;95%CI 1.3-70.9;P=0.010),cardiovascular disease(OR 1.4;95%CI 1.0-1.9;P=0.001),chronic kidney disease(OR 12.0;95%CI 1.6-90.1;P=0.05),acute coronary syndrome(OR 29.3;95%CI 2.0-423.7;P=0.001),moderate(OR 0.11;95%CI 0.01-1.10;P=0.031)and severe(OR 18.5;95%CI 1.8-188.4;P=0.002)disease severity,and in-hospital mortality(OR 8.1;95%CI 1.1-57.9;P=0.018).However,there is no correlation between the presence of antiphospholipid antibody and ICU admission.Conclusions:In summary,the prevalence of antiphospholipid antibodies in COVID-19 patients is low,mainly against Ig M anticardiolipin,and is associated with an acute coronary syndrome,gastrointestinal manifestations,moderate and severe disease severity,and increased risk of mortality.

THE STUDY OF PRODUCTION AND MECHANISM OF ANTIPHOSPHOLIPID ANTIBODIES IN PATIENTS WITH CORONARY HEART DISEASE

Objective To assess whether there was strong association between antiphospholipid antibodies and coronary heart disease, to study the environmental factors of APA production and APA pathogenic mechanism in patients with CHD.Methods Blood samples from 76 patients with CHD and 30 controls were tested for anticardiolipin antibodies IgG,human cytomegalovirus IgG,IgM by enzyme link immunosorbant assay and 6 keto PGF 1a ,endothelin by radioimmunoassay.Results A total of 27 patients were ACA positive in 76, as compared to 2 of 30 healthy individuals, P <0.05. There was no difference in ACA among acute myocardial infarction, old myocardial infarction, unstable angina pectoris, P >0.05. The number of ACA positive subjects was higher in HCMV infection patients with CHD than no HCMV infectious patients with CHD. There was no PGI 2 and ET level difference between ACA IgG positive and negative CHD.Conclusion There are strong association between APA and CHD. The HCMV infection may be an environmental factor of APA production in CHD patients with raised ACA. The alteration of PGI 2 and ET are not the pathogenic mechanism of ACA in patients with CHD.

Pathogenetic mechanisms of antiphospholipid antibody production in antiphospholipid syndrome

Antiphospholiipid syndrome(APS) is an autoimmune disease characterized by the pathological action of antiphospholipid antibodies(a PL),that leads to recurrent pregnancy loss and thrombosis.Despite limited evidence,it is clear that there are both inherited and acquired components of the ontogeny of these antibodies.Animal genetic studies and human familial and population studies highlight the influence of genetic factors in APS,particularly human leukocyte antigen associations.Similarly,both animal and human studies have reported the importance of acquired factors in APS development and infectious agents in particular have a great impact on a PL production.Bacterial and viral agents have been implicated in the induction of autoimmune responses by various mechanisms including molecular mimicry,cryptic autoantigens exposure and apoptosis.In this review we highlight the latest updates with regards to inherited and acquired factors leading to the manufacturing of pathogenic antibodies and APS.

Study of the Effect of Intralipid Infusion during Pregnancy as an Additive Treatment for Reducing Pregnancy Complications Caused by Antiphospholipid Antibody Syndrome

Aim: To evaluate the safety and efficacy of intralipid infusion in addition to other lines of treatment in reduction of complications caused by antiphospholipid antibody syndrome. Methods: This study was held in the period from June 1, 2016, to December 1, 2019. This study was conducted in the Department of Obstetrics and Gynecology, Tanta University on patients attending the antenatal care clinic and also on patients attending the researcher’s private clinics for antenatal care, 105 patients were enrolled after application of strict inclusion and exclusion criteria. They were randomized into 2 groups. In group A (study group 1) the patients received in addition to the conventional basic treatment of APS, intralipid 20% (Frezenius, Clayton, NC, USA) in a dose of 4 ml diluted in 250 ml 0.9% regular saline IV and to be repeated every 2 weeks. In group B (control group 2) the patients received the conventional basic treatment of APS. The outcome measures were the incidence of pregnancy complications of APS namely fetal loss, premature delivery, IUGR and preeclampsia. Results: 49 patients were enrolled in the study group, and 48 patients were enrolled in the control group, after exclusion of the skipped cases. The demographic data and the gestational age at the beginning of the study show insignificant differences. There were insignificant differences as regard the gestational age at which the pregnancy was terminated and fetal birth weight in patients with positive ACL test, positive LA test and positive B2 however the mean gestational age at which pregnancy was terminated was higher in study group. Also, there was insignificant difference as regards no of patients who complicated with abortion or who completed to full term. But had significant decrease number of case who complicated with preeclampsia (8, 21 patients in study and control group respectively). Conclusion: Intralipid infusion is a promising treatment option for control and prevention of problems caused by antiphospholipid antibody syndrome.

Antiphospholipid Antibody and Antiphospholipid Syndrome

Antiphospholipid antibodies(APA)APA is a big category for all kinds of negative charge phospholipid or lecithin- a protein complex autoantibodies or the same antibody,through its recognition of antigen(target protein) different,and

Myocardial infarction in antiphospholipid antibody syndrome

A 52-year-old man was admitted to hospital with chest pain after physical activity. Emergency coronary angiography showed multiple throm-boembolic occlusions in the anterior descen-ding coronary artery and in the right coronary artery. Further testing revealed anticardiolipin and ?2-glicoprotein antibodies (the patient had been diagnosed for ulcerative colitis and poly-myalgia rheumatica). Heparin and nitrate were administered intravenously in addition to oral aspirin and metoprolol. Soon after, the patient referred a withdrawal of chest oppression, and his general clinical condition rapidly stabilised. A follow-up examination was performed 9 months later the discharge: he had resumed most of his activities and sieric concentration of lupus anticoagulant antibodies and anticardiolipin an- tibodies, IgM isotype, were decreased.

糖脂代谢指标联合抗磷脂抗体对动脉粥样硬化患者预后的预测价值

目的探讨糖脂代谢指标联合抗磷脂抗体与动脉粥样硬化患者预后的相关性。方法选取2021年4月至2023年3月在河北省人民医院进行治疗128例动脉粥样硬化患者分为观察组,另外选取48例体检健康者作为对照组,对比两组糖脂代谢指标、抗磷脂抗体水平,ROC分析糖脂代谢指标、抗磷脂抗体及联合检测对动脉粥样硬化患者预后的预测价值。结果观察组TC、TG、ACL、抗β2-GP1水平高于对照组(P<0.05)。观察组动脉粥样硬化患者预后不良组TC、TG、ACL、抗β2-GP1表达水平高于预后良好组(P<0.05)。TC、TG、ACL、抗β2-GP1水平与动脉粥样硬化患者预后不良呈正相关(P<0.05)。ROC曲线显示,6项联合检测对动脉粥样硬化患者预后的预测价值高于TC、TG、ACL、抗β2-GP1单项预测价值(P<0.05)。结论TC、TG、ACL、抗β2-GP1联合检测对动脉粥样硬化患者预后的预测价值较高。

抗磷脂抗体损害子宫蜕膜血管内皮细胞血管形成的机制研究

目的:研究抗磷脂抗体(aPL)对蜕膜组织血管内皮细胞(DVEC)增殖、迁移与血管形成能力的影响。方法:采用细胞免疫荧光鉴定DVEC细胞;CCK-8法检测aPL对DVEC细胞增殖的影响;细胞划痕实验与血管形成实验检测aPL对DVEC细胞迁移与血管生成的影响;实时荧光定量PCR(RT-PCR)检测aPL对DVEC细胞基质金属蛋白酶2(MMP-2)和血管内皮生长因子(VEGF)mRNA表达的影响;Western blot检测aPL对DVEC细胞中p-ERK、t-ERK、VEGF与MMP-2蛋白表达的影响。结果:aPL能抑制DVEC细胞增殖、迁移与血管形成能力;aPL能抑制DVEC细胞中p-ERK、VEGF与MMP-2表达水平,加ERK激动剂后DVEC细胞中p-ERK、VEGF与MMP-2表达水平明显升高。结论:aPL可通过调控ERK通路减少DVEC细胞中VEGF与MMP-2表达,进而抑制DVEC的增殖、迁移与血管形成能力。

抗磷脂综合征相关心血管疾病的表现及新进展

抗磷脂综合征(APS)是以反复发生血栓事件和妊娠并发症以及抗磷脂抗体持续阳性为特点的一种系统性自身免疫性疾病。APS可以影响包括心血管系统在内的多个器官和系统,APS相关心血管疾病会给患者生命造成严重威胁。在2023年更新的美国风湿病学会(ACR)联合欧洲抗风湿病联盟(EULAR)APS分类标准中,将瓣膜病变纳入了APS的临床标准,这也提示应该重视APS合并的心血管疾病。本文将对APS合并的常见心血管疾病的表现及机制进行综述。

胱抑素C及抗磷脂抗体与系统性红斑狼疮肾损伤病理类型的相关性

目的 探讨胱抑素C(CysC)、抗磷脂抗体及其他指标与系统性红斑狼疮(SLE)肾损伤病理类型的相关性,进一步研究SLE发生肾损伤的危险因素,为临床诊治提供依据。方法 选取75例单纯SLE患者和55例狼疮性肾炎(LN)患者,及同期到医院体检的健康对照者52例。行穿刺活检术的31例LN患者再分为LN-III/IV组19例和LN-II/V组12例。收集一般资料(D-二聚体、PLR、C3、C4、IgM、IgG、ESR、抗ds DNA抗体、Cysc、抗磷脂抗体、抗β2糖蛋白1抗体及肾脏穿刺病理资料)。比较Cysc等SLE疾病相关指标及抗磷脂抗体在三组之间的差异,探讨抗磷脂抗体与SLE肾损伤病理类型的相关性。结果 SLE组和LN组Cysc、IgG、PLR、D-二聚体、ESR、CRP水平高于健康对照组,C3、IgM、C4水平低于健康对照组,LN组Cysc水平高于SLE组,C3、IgG、IgM水平低于SLE组(P<0.05)。LN患者中抗β2糖蛋白1抗体、抗磷脂抗体的阳性率明显高于SLE患者(P<0.05)。LN-Ⅲ型/Ⅳ型组抗磷脂抗体(ACA)的阳性率较LN-Ⅱ/Ⅴ型组的显著升高(P=0.043)。CysC、C3、IgM、IgG是SLE发生肾损伤的危险因素。结论 抗磷脂抗体阳性可能提示肾损伤病理类型有更高的活动性,CysC、C3、IgM、IgG水平是SLE发生肾损伤的危险因素。

抗磷脂抗体在小鼠激素性股骨头坏死中的作用

目的探讨抗磷脂抗体在C3H/HeN小鼠激素性股骨头坏死中的作用。方法纯化抗磷脂抗体综合征(APS)患者的血清抗β2GPI抗体,建立实验性APS C3H/HeN小鼠动物模型。随机分为对照组、对照+激素组、模型组及模型+激素组,每组10只。于第8周末处死所有小鼠,对血标本及股骨头病理组织学标本进行分析。结果至实验结束(第8周末),对照组、对照+激素组、模型组及模型+激素组各有9、7、8、8只小鼠存活,APTT指标模型+激素组、模型组、对照+激素组及对照组依次升高(P<0.05),NO指标模型+激素组、对照+激素组、模型组及对照组依次降低(P<0.05);股骨头坏死发生率及空骨陷窝率比较,对照组、模型组、对照+激素组、模型+激素组依次升高,骨小梁面积占比对照组、模型组、对照+激素组、模型+激素组依次下降(P<0.01)。结论抗磷脂抗体可能通过加剧血管内皮损伤及高凝状态在激素性股骨头坏死中起作用。

超声检测妊娠早期子宫动脉频谱预测抗磷脂抗体综合征患者妊娠结局的价值

目的探讨早孕期彩色多普勒超声检测子宫动脉频谱在预测妊娠合并抗磷脂抗体综合征(APS)妊娠结局中的价值。方法选取本院收治的妊娠合并APS患者115例临床及超声检查资料为观察组,选取同期在本院就诊的临床及超声检查资料完整的健康孕妇100例为对照组。所有孕妇均接受早孕期子宫动脉超声检查。统计分析两组间妊娠早期子宫动脉RI、S/D、PI以及不良妊娠发生率,分析子宫动脉超声检查判定妊娠合并APS妊娠结局的效能。结果观察组孕妇子宫动脉血流参数PI、RI、S/D均>对照组,差异均有统计学意义(P<0.05)。观察组子宫动脉频谱异常发生率及不良妊娠发生率均高于对照组。结论孕早期子宫动脉彩色多普勒超声血流参数可预测妊娠合并APS结局的价值,并为临床及早诊疗提供客观的参考依据。

育龄期健康孕妇抗磷脂抗体正常参考区间的建立及不同孕周变化规律

目的:建立育龄期健康孕期女性抗磷脂抗体(aPL)的正常参考区间,并探讨不同孕周aPL水平的变化规律。方法:选取2023年1月至2023年12月在佛山市南海区第六人民医院进行检查的200例育龄期健康孕期女性作为研究对象。采用化学发光免疫分析法(CLIA)检测研究对象不同孕周抗心磷脂抗体(aCL)、抗β_(2)–糖蛋白Ⅰ抗体(aβ_(2)GPI)的免疫球蛋白(Ig)A、IgM、IgG水平,并用非参数法计算各百分位值。结果:育龄期健康孕期女性aCL IgA、IgM、IgG和aβ_(2)GPI IgA、IgM、IgG水平呈偏态分布(P<0.001);不同孕周孕期女性体内aCL IgA、IgM、IgG和aβ_(2)GPI IgA、IgM、IgG水平比较,差异均无统计学意义(P>0.05);育龄期健康孕期女性血清中aCL IgA、IgM、IgG和aβ_(2)GPI IgA、IgM、IgG的参考区间P99值分别为8.49 PL–U·mL^(-1)、12.58 PL–U·mL^(-1)、5.68 PL–U·mL^(-1)、20.17 RU·mL^(-1)、36.79 RU·mL^(-1)和8.37 RU·mL^(-1),P95值分别为5.16 PL–U·mL^(-1)、6.10 PL–U·mL^(-1)、3.39 PL–U·mL^(-1)、17.48 RU·mL^(-1)、25.60 RU·mL^(-1)和6.53 RU·mL^(-1)。结论:不同孕周孕期女性体内aCL、aβ_(2)GPI水平较为稳定,本研究初步建立了aCL、aβ_(2)GPI的参考区间,可为筛查和诊断APS提供一定参考。

羟氯喹联合低分子肝素钠、小剂量阿司匹林治疗抗磷脂抗体相关性复发性流产的效果及对凝血功能、免疫平衡的影响

目的探讨羟氯喹联合低分子肝素钠、小剂量阿司匹林治疗抗磷脂抗体相关性复发性流产(RSA)的效果及对凝血功能、免疫平衡的影响。方法选取2022年5月至2023年5月收治的106例抗磷脂抗体相关性RSA患者为研究对象,随机将其分为对照组和观察组,每组58例。对照组采用低分子肝素钠、小剂量阿司匹林治疗,观察组在对照组基础上加羟氯喹治疗。比较两组的治疗效果。结果观察组的治疗总有效率高于对照组(P<0.05)。治疗后,观察组凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)长于对照组,D-二聚体(D-D)、纤维蛋白原(FIB)水平低于对照组(P<0.05)。治疗后,观察组的白细胞介素-2(IL-2)、白细胞介素-1(IL-1)水平低于对照组,白细胞介素-10(IL-10)水平高于对照组(P<0.05)。观察组的不良反应总发生率低于对照组(P<0.05)。结论羟氯喹联合低分子肝素钠、小剂量阿司匹林治疗抗磷脂抗体相关性RSA效果显著,能够改善患者的凝血功能和免疫平衡,降低不良反应发生率,值得推广。

Bilateral Choroidal Occlusion in Antiphospholipid Syndrome Associated with Systemic Lupus Erythematosus

This article reports a rare case of bilateral choroidal occlusion that occurred in a 24-year-old woman with antiphospholipid syndrome (APS) associated with systemic lupus erythematosus (SLE). This young lady concurred with aorta ventralis thrombosis and bilateral iliac artery occlusion when presented, and experienced a rapid deterioration of vision. She also has a history of recurrent miscarriage. Corticosteroid,immunosuppression and anticoagulation therapy were administered. Patients with APS associated with SLE are at risk for thrombotic phenomena, which may affect the ocular vessels of all sizes, including choroidal vessel.Our case alerts ophthalmologists and rheumatologists that bilateral choroidal occlusion may indeed be developed in patients with APS associated with SLE, and is a potential cause of visual morbidity.

Antiphospholipid syndrome and its role in pediatric cerebrovascular diseases: A literature review

Antiphospholipid syndrome(APS)or Hughes syndrome is an acquired thromboinflammatory disorder.Clinical criteria of APS diagnosis are large-and small-vessel thrombosis as well as obstetric problems;laboratory criteria are the presence of antiphospholipid antibodies(lupus anticoagulant,anticardiolipin antibodies and anti-β2-glycoprotein-1).The presence of at least 1 clinical and 1 laboratory criterion allows definitive diagnosis of APS.Primary APS is diagnosed in patients without features of connective tissue disease;secondary APS is diagnosed in patients with clinical signs of autoimmune disease.A high frequency of catastrophic APS as well as a high tendency to evolve from primary APS to secondary syndrome during the course of lupus and lupus-like disease is a feature of pediatric APS.The most characteristic clinical presentation of APS in the pediatric population is venous thrombosis,mainly in the lower limbs,and arterial thrombosis causing ischemic brain stroke.Currently,no diagnostic criteria for pediatric APS exist,which probably results in an underestimation of the problem.Similarly,no therapeutic procedures for APS specific for children have yet been established.In the present literature review,we discussed data concerning APS in children and its role in cerebrovascular diseases,including pediatric arterial ischemic stroke,migraine and cerebral venous thrombosis.

Segmental small bowel necrosis associated with antiphospholipid syndrome:A case report

Antiphospholipid syndrome is a multi-system disease characterized by the formation of thromboembolic complications and/or pregnancy morbidity, and with persistently increased titers of antiphospholipid antibodies. We report the case of a 50-year-old, previously healthy man who presented with fever and new-onset, dull abdominal pain. A contrast-enhanced computed tomography scan showed segmental small bowel obstruction, for which an emergency laparotomy was performed. Histopathologic examination of resected tissues revealed multiple intestinal and mesenteric thromboses of small vessels. Laboratory tests for serum antiphospholipid(anticardiolipin Ig M) and anti-β2-glycoprotein I antibodies were positive. Despite proactive implementation of anticoagulation, steroid, and antibiotic therapies, the patient's condition rapidly deteriorated, and he died 22 d after admission. This case highlights that antiphospholipid syndrome should be suspected in patients with unexplainable ischemic bowel and intestinal necrosis presenting with insidious clinical features that may be secondary to the disease, as early diagnosis is critical to implement timely treatments in order to ameliorate the disease course.

A successful birth of severe secondary recurrent miscarriage case after a decline of phosphatidylserine-dependent anti-prothrombin antibody by intravenous immunoglobulin administration

A 33 years old woman was referred to our hospital since her sixth pregnancy had been revealed. In fact, at 19 years of age she had diagnosed as having systemic lupus erythematosus without organ failure. In addition, she had a past history of uncontrollable severe pregnancy-induced hypertension occurred during the second pregnancy, resulting in extremely premature delivery and following postpartum HELLP syndrome. It was so severe that we employed administration of dexamethasone and plasma exchange to ameliorate a life-threatening situation. In the course of her recovery it was revealed that she had been complicated with antiphospholipid antibodies, and at the same time we observed that phosphatidylserine-dependent anti-prothrombin antibody IgG levels were declining as her condition was getting better. There-after, she became pregnant three times, but all pregnancies ended in miscarriage despite administration of prednisolone and anticoagulant therapy. Therefore, we realized that her recurrent miscarriages could not be prevented with generally acceptable therapies, so we tried intravenous immunoglobulin shortly after fetal heart beats were detected. In fact, her sixth pregnancy was going well, but we had to terminate it at the 35th week of gestation due to the onset of HELLP syndrome-like condition. However, she could achieve an almost intact pregnancy outcome without neonatal complications or persistently worsening postpartum HELLP syndrome-like condition. Considering the etiologic relation overlapping between systemic lupus erythematosus, antiphospholipid syndrome and recurrent miscarriage, intravenous immunoglobulin can be one of the treatment options for severe secondary recurrent miscarriage, although the evidence of the treatment is always certain. In addition, a decline of phosphatidylserine-dependent anti-prothrombin antibody IgG levels we observed in this case may represent its therapeutic immunomodulatory effects.