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联合免疫抑制会损害炎症性肠病患者对破伤风和百日咳疫苗接种的免疫原性。

Combined Immunosuppression Impairs Immunogenicity to Tetanus and Pertussis Vaccination Among Patients with Inflammatory Bowel Disease.

作者信息

Dezfoli Seper, Horton Henry A, Thepyasuwan Nattapaun, Berel Dror, Targan Stephan R, Vasiliauskas Eric A, Dubinsky Marla, Shih David Q, Kaur Manreet, McGovern Dermot P B, Ippoliti Andrew, Feldman Edward J, Melmed Gil Y

机构信息

Division of Gastroenterology, Department of Medicine, F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.

出版信息

Inflamm Bowel Dis. 2015 Aug;21(8):1754-60. doi: 10.1097/MIB.0000000000000448.

Abstract

BACKGROUND

Pertussis epidemics have recently emerged across the United States, prompting broad public health recommendations for adult Tdap vaccination (tetanus, diphtheria, acellular pertussis). The impact of immunosuppressive regimens for inflammatory bowel disease (IBD) on vaccine responses to the Tdap vaccine is not known.

METHODS

We performed a prospective controlled trial between April 2011 and March 2012. Adults with IBD were consecutively stratified based on therapeutic regimen into one of 5 groups: A: no IBD therapy or 5-aminosalicylates alone; B: maintenance biologic monotherapy; C: maintenance immunomodulator monotherapy; D: combined biologic and immunomodulator therapy; and E: healthy age-matched controls. Subjects received Tdap, and serum antibody levels against tetanus toxoid, pertussis toxoid, and filamentous hemagglutinin (FHA) were drawn just before and approximately 4 weeks after vaccination. The primary outcome was the booster response rate to each antigen. Secondary outcomes included the differences in pregeometric and postgeometric mean titers.

RESULTS

A total of 98 subjects enrolled, and 84 completed the study. Tetanus response rates were 55%, 56%, 40%, 27%, and 63% across groups A to E, respectively. Group D rates were lower than those of group B (P = 0.02). Postvaccination pertussis toxoid responses were 59%, 72%, 47%, 45%, and 75%, while FHA responses were 86%, 72%, 80%, 64%, and 75% across groups A to E, respectively. Prevaccination and postvaccination geometric mean titer differences for FHA were lower in group D than those in group A (P = 0.05).

CONCLUSIONS

Antibody responses to tetanus and pertussis vaccination may be affected by therapeutic drug regimen. Patients with IBD should optimally receive Tdap before starting immunomodulators, particularly when used in combination with anti-tumor necrosis factor alpha agents.

摘要

背景

近期美国各地出现百日咳疫情,促使针对成人接种破伤风、白喉、无细胞百日咳(Tdap)疫苗出台了广泛的公共卫生建议。炎症性肠病(IBD)的免疫抑制方案对Tdap疫苗免疫反应的影响尚不清楚。

方法

我们在2011年4月至2012年3月期间进行了一项前瞻性对照试验。患有IBD的成人根据治疗方案连续分层为5组之一:A组:未接受IBD治疗或仅使用5-氨基水杨酸酯;B组:维持性生物单药治疗;C组:维持性免疫调节剂单药治疗;D组:生物制剂与免疫调节剂联合治疗;E组:年龄匹配的健康对照。受试者接种Tdap疫苗,在接种前及接种后约4周采集血清,检测破伤风类毒素、百日咳毒素和丝状血凝素(FHA)的抗体水平。主要结局是对每种抗原的加强免疫反应率。次要结局包括接种前和接种后几何平均滴度的差异。

结果

共纳入98名受试者,84名完成研究。A至E组的破伤风反应率分别为55%、56%、40%、27%和63%。D组的反应率低于B组(P = 0.02)。接种后百日咳毒素反应率在A至E组分别为59%、72%、47%、45%和75%,而FHA反应率分别为86%、72%、80%、64%和75%。D组接种前和接种后FHA的几何平均滴度差异低于A组(P = 0.05)。

结论

破伤风和百日咳疫苗接种的抗体反应可能受治疗药物方案影响。IBD患者在开始使用免疫调节剂之前,尤其是与抗肿瘤坏死因子α药物联合使用时,应优先接种Tdap疫苗。

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