Impact of infliximab therapeutic drug level monitoring on outcomes of patients with inflammatory bowel disease: A real-world experience from a Middle Eastern cohort

Background and study aimTherapeutic drug monitoring (TDM) through measurement of infliximab (IFX) trough levels and antibodies to infliximab (ATI) is performed to guide IFX intensification strategies and improve its efficacy. We conducted this study to explore the relationship between clinical and endoscopic/radiological remission and IFX and ATI levels in patients with inflammatory bowel disease (IBD) treated with IFX and to evaluate the appropriateness of treatment decision post TDM.Patients and methodsThis was a cross-sectional study of a cohort of adult patients with IBD. Serum IFX trough concentrations and ATI were measured.ResultsA total of 129 patients [104] with ulcerative colitis (UC) and 25 with Crohn’s disease (CD)] were included in this study, of whom 61.2% were men. The mean disease duration was 6.7 years, and 72% of patients with UC had extensive colitis. The mean serum IFX trough level was 4.1 µg/mL; the IFX trough levels were subtherapeutic in 75 patients (58%), therapeutic in 37 patients (29%), and supratherapeutic in 17 patients (13%). Positivity to ATI was found in 16 patients (12.4%). Only 43 patients (33.3%) underwent an appropriate change in therapy after TDM, patients with penetrating CD disease had low IFX levels and higher C-reactive protein levels at 12 months before TDM.ConclusionsPatients with IBD with therapeutic IFX levels tend to have increased endoscopic/radiological remission rates. However, an appropriate change in management based on TDM was absent in the majority of patients, potentially reflecting the need to have a dashboard to support and guide clinicians in decision-making.     

Optimization of a rapid test for antibodies to the Chlamydia trachomatis antigen Pgp3

Serological surveillance for trachoma could allow monitoring of transmission levels in areas that have achieved elimination targets. Platforms that allow testing in basic laboratories or testing of easy-to-manage samples such as dried blood spots would contribute to the feasibility of serologic testing. Blood from 506 1–12-year-olds in 2 villages in Kongwa district, Tanzania, was tested for antibodies against the antigen Pgp3. Whole blood, plasma, and dried blood spots (DBS) were tested in lab and field settings using a cassette-enclosed Pgp3 lateral flow assay (LFA-cassette) and a pared-back “dipstick” assay (LFA-dipstick). DBS were also tested with a bead-based multiplex assay (MBA). There was no significant difference in antibody positivity between the MBA and either LFA format (ranging from 42.5% to 48.4%). Interrater agreement between an expert rater and 3 different raters in field and lab settings was uniformly good, with Cohen's kappa >0.81 in all cases.     

Prevalence of anti-endothelial cell antibodies in patients with autoimmune diseases

Summary The prevalence of anti-endothelial cell antibodies (AECA) of IgA, IgG and IgM classes was studied by means of enzyme-linked immunosorbent assays (ELISA) in 466 patients with autoimmune/inflammatory disorders. The reference limits in the ELISAs for the AECA were determined from a random population sample of 249 subjects. The frequency of AECA was highest in patients with SLE (n=42), 14.6% mainly of IgG class, and the presence of AECA correlated with disease activity in these patients. In the RA patient group (n=200), 9.5% had AECA, mostly of IgA type. We found no association between the presence of AECA and extra-articular manifestations of RA or survival rate. In patients with undefined connective tissue disease (n=57), ankylosing spondylitis (n=109), and psoriatic arthritis (n=58), the frequency of AECA corresponded to that of the random population sample. In a cohort of samples sent to the laboratory for determination of anti-nuclear antibodies (ANA) there was a correlation between the presence of ANA and AECA. Our findings indicate that RA patients are characterized by IgA class AECA, whereas SLE patients have IgG class AECA also correlating to disease activity.     

肾综合征出血热自然感染和人工免疫后的抗体形成

目的 调查肾综合征出血热(hemorrhagic fever with renal syndrome,HFRS)病毒自然感染,分析免疫接种后抗体变化规律,为调整出血热预防控制策略提供依据.方法 采取分层整群抽样方法,在出血热高发病区、低发病区和非疫区共抽取600人,进行发病调查和血清IgG抗体酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测.结果 既往出血热发病人群IgG水平＞高发区接种人群＞低发区接种人群＞高发区非发病非接种人群＞低发区非发病非接种人群;既往出血热病例的IgG水平每10年衰降25％,30年后仍是接种人群的2倍以上;高发病区汉坦病毒隐性感染率33％,低发病区隐性感染率为23％;完成基础免疫接种即可获得较高抗体水平,末次接种5 ～ 10年后抗体水平下降40％,10～20年下降60％.结论 出血热显性感染可获得持久免疫力,在出血热历史疫区隐性感染率较高,出血热疫苗末次接种7～8年需再加强一针.     

阿达木单抗治疗强直性脊柱炎致播散性结核病一例并文献复习

目的 探讨应用阿达木单克隆抗体(简称“单抗”)治疗强直性脊柱炎致播散性结核病的临床特点、诊治要点和治疗转归。 方法 回顾性分析福建省福州肺科医院2019年6月10日收治的1例应用阿达木单抗治疗强直性脊柱炎致播散性结核病的临床资料、诊治经过及随访情况,并进行文献复习。以“adalimumab”和“disseminated tuberculosis”为检索词对PubMed数据库进行检索,以“阿达木单抗”和“播散性结核病”为检索词通过万方数据库和中国知网对中文文献进行检索,检索时间截止到2019年9月,经过筛选剔除,共获取相关文献34篇,其中中文文献0篇,英文文献34篇。删去重复的文献并剔除可能为阿达木单抗以外的肿瘤坏死因子α(TNF-α)致播散性结核病及TNF-α致其他播散性疾病的报道,共筛选出具备详细病例资料的文献8篇,共获得8例患者,结合本研究收集的患者,对其临床特征、诊断和治疗情况进行分析。 结果 本例患者为男性,28岁。因“强直性脊柱炎”接受阿达木单抗治疗,治疗2个月后出现咳嗽、气促、腹胀、发热,入院后经胸部CT、胸膜活检及支气管镜等检查,诊断为“播散性结核病(双肺、右侧支气管、胸腔、腹腔、心包、纵隔淋巴结、锁骨上淋巴结、腹腔淋巴结、盆腔淋巴结、脾)”。给予“3H-R-Z-E/9H-R-E”方案治疗,辅以异烟肼支气管局部雾化吸入,行抗结核药物治疗后症状改善。治疗第5个月,CT复查提示“肺部病变减少,纵隔内部分淋巴结肿大较前缩小,增厚的支气管管壁较前变薄,管腔较前通畅,胸、腹腔积液明显吸收。截止到2019年12月,患者仍处于规则的抗结核药物治疗中。文献检索后获得8例患者,加上本例,共9例患者。其中,男3例,女6例;年龄9~75岁,平均年龄(50.44±25.19)岁。9例患者中,5例开始使用阿达木单抗治疗之前的结核病筛查试验结果为阴性,1例既往有抗结核治疗史,1例曾进行过预防性抗结核治疗,3例有与结核病患者的密切接触史。诊断明确行抗结核药物治疗后,5例患者转归良好。3例转归差,其中1例病情持续进展,并发消化道出血;1例颅内病灶持续进展;1例出现急性呼吸窘迫综合征,最终死亡。1例转归不明。 结论 阿达木单抗可致播散性结核病,准备接受阿达木单抗治疗的患者均应在用药前进行结核病筛查,治疗过程中应该警惕潜伏性结核感染转为活动性结核病及新发结核感染,停用阿达木单抗和及时行抗结核药物治疗是预后良好的关键。     

Evaluation of immune responses to an oral typhoid vaccine,Ty21a,in children from 2 to 5 years of age in Bangladesh

Young children are very susceptible to typhoid fever, emphasizing the need for vaccination in under five age groups. The parenteral Vi polysaccharide vaccine is not immunogenic in children under 2 years and the oral Ty21a vaccine (Vivotif) available in capsular formulation is only recommended for those over 5 years.     

Stratégies d’exploration de l’allo-immunisation plaquettaire pour la prévention et la prise en charge des inefficacités transfusionnelles plaquettaires

Platelet refractoriness is a serious complication for patients receiving recurrent platelet transfusions, which can be explained by non-immune and immune causes. Human Leukocyte Antigens (HLA) allo-immunization, especially against HLA class I, is the major cause for immune platelet refractoriness. To a lesser extent, allo-antibodies against specific Human Platelet Antigen (HPA) are also involved. Pregnancy, transplantation and previous transfusions can lead to allo-immune reaction against platelet antigens. After transfusion, platelet count is decreased by accelerated platelet destruction related to antibodies fixation on incompatible platelet antigens. New laboratory tests for allo-antibodies identification were developed to improve sensibility and specificity, especially with the LUMINEX^® technology. The good use and interpretation of these antibodies assays can improve strategies for platelet refractoriness prevention and management with a patient adapted response. Compatible platelets units can be selected according to their identity with recipient typing or immune compatibility regarding HLA or HPA antibodies or HLA epitope compatibility. Prospective studies are needed to further confirm the clinical benefit of new allo-antibodies identification methods and consensus strategies for immune platelet refractoriness management.     

应用斑点ELISA快速研究鸡卵黄抗体IgY的理化性质

目的应用斑点ELISA研究卵黄抗体的理化性质,使多克隆抗体的性质得以确定,为今后更好地研究和利用该抗体奠定基础。方法将制备的卵黄抗体用不同的方法(加热、酸、碱、酶等)处理后,再用斑点ELISA检测卵黄抗体的剩余活性。结果IgY有很好的耐热性,巴氏消毒不会使IgY失活。卵黄抗体在pH>5和<9的环境下,37℃3h后仍保持部分活性。卵黄抗体在室温存放4个月后仍保持部分活性。在pH<5时,胃蛋白酶能发挥作用,使卵黄抗体失去活性。结论IgY的高度稳定性,使得这一多克隆抗体的保存和运输较方便,有利于IgY的推广和使用。     

白细胞介素17A在银屑病发病及治疗中的研究进展

【摘要】 近十余年来的基础和临床研究发现并确立了Th17/白细胞介素17A（IL-17A）在银屑病发病中的核心地位。IL-17A不仅能影响角质形成细胞的增殖活性和细胞功能,对银屑病免疫病理环境中的免疫细胞和相关细胞因子也有很重要的调控作用。近年来针对IL-17A通路的单抗如司库奇尤单抗、ixekizumab、brodalumab等在国内外陆续上市,在临床应用中展现出了显著的疗效。本文介绍IL-17A在银屑病发病机制中的作用以及靶向IL-17A及其受体IL-17RA生物治疗的最新进展。     

Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: a real-world experience

BackgroundMigraine frequency increases after the cessation of successful preventive treatment with CGRP(-receptor) monoclonal antibodies (mAbs). In this study, we aimed to evaluate the course of migraine after treatment resumption.MethodsPatients with migraine, who started treatment with the same CGRP(-R) mAb after a three-month drug holiday were included in this analysis. We collected headache data at four prospective visits: 1) during the four weeks before the initial mAb treatment (baseline); 2) during the four weeks before the last mAb injection; 3) in weeks 13–16 of the drug holiday; 4) in weeks 9–12 after treatment restart. Outcomes were the changes in monthly migraine days (MMD), monthly headache days (MHD), monthly days with acute medication use (AMD) and Headache Impact Test-6 (HIT-6) scores across the observation period.ResultsThis study included 39 patients (erenumab n = 16; galcanezumab/ fremanezumab n = 23). MMD decreased from 12.3 ± 6.3 at the end of the drug holiday to 7.8 ± 5.5 three months after treatment restart (p = 0.001). The improvement after treatment resumption was similar to the response in the initial treatment period (baseline: 12.3 ± 6.3 MMD vs. 7.5 ± 5.2 MMD before treatment interruption). MHD and AMD showed a significant improvement after treatment restart. HIT-6 scores decreased, indicating a diminished impact of headache on everyday life.ConclusionsReinitiation of treatment with CGRP(-R) mAbs after a drug holiday leads to a significant reduction of migraine frequency and medication use as well as improvement in quality of life.