Esteve-Solé Ana, Deyà-Martínez Àngela, Teixidó Irene, Ricart Elena, Gompertz Macarena, Torradeflot Maria, de Moner Noemí, Gonzalez Europa Azucena, Plaza-Martin Ana Maria, Yagüe Jordi, Juan Manel, Alsina Laia
Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Esplugues de Llobregat, Spain.
Functional Unit of Clinical Immunology, Sant Joan de Déu-Hospital Clinic, Barcelona, Spain.
Front Immunol. 2017 Sep 21;8:1123. doi: 10.3389/fimmu.2017.01123. eCollection 2017.
Although anti-TNF-α monoclonal antibodies are considered safe during pregnancy, there are no studies on the development of the exposed-infant immune system. The objective was to study for the first time the impact of throughout pregnancy exposure to anti-TNF-α has an impact in the development of the infant's immune system, especially B cells and the IL-12/IFN-γ pathway.
Prospective study of infants born to mothers with inflammatory bowel disease treated throughout pregnancy with anti-TNF-α (adalimumab/infliximab). Infants were monitored both clinically and immunologically at birth and at 3, 6, 12, and 18 months.
We included seven patients and eight healthy controls. Exposed infants had detectable levels of anti-TNF-α until 6 months of age; they presented a more immature B- and helper T-phenotype that normalized within 12 months, with normal immunoglobulin production and vaccine responses. A decreased Treg cell frequency at birth that inversely correlated with mother's peripartum anti-TNF-α levels was observed. Also, a decreased response after mycobacterial challenge was noted. Clinically, no serious infections occurred during follow-up. Four of seven had atopia.
This study reveals changes in the immune system of infants exposed during pregnancy to anti-TNF-α. We hypothesize that a Treg decrease might facilitate hypersensitivity and that defects in IL-12/IFN-γ pathway might place the infant at risk of intracellular infections. Pediatricians should be aware of these changes. Although new studies are needed to confirm these results, our findings are especially relevant in view of a likely increase in the use of these drugs during pregnancy in the coming years.
尽管抗TNF-α单克隆抗体在孕期被认为是安全的，但尚无关于暴露婴儿免疫系统发育的研究。目的是首次研究孕期全程暴露于抗TNF-α对婴儿免疫系统发育的影响，尤其是对B细胞和IL-12/IFN-γ通路的影响。
对患有炎症性肠病且在孕期全程接受抗TNF-α（阿达木单抗/英夫利昔单抗）治疗的母亲所生婴儿进行前瞻性研究。在婴儿出生时以及3、6、12和18个月时对其进行临床和免疫学监测。
我们纳入了7例患者和8名健康对照。暴露婴儿在6个月龄前可检测到抗TNF-α水平；他们表现出更不成熟的B细胞和辅助性T细胞表型，该表型在12个月内恢复正常，免疫球蛋白产生和疫苗反应正常。观察到出生时调节性T细胞频率降低，且与母亲围产期抗TNF-α水平呈负相关。此外，还注意到在受到分枝杆菌攻击后的反应降低。临床上，随访期间未发生严重感染。7例中有4例患有特应性。
本研究揭示了孕期暴露于抗TNF-α的婴儿免疫系统的变化。我们推测调节性T细胞减少可能促进超敏反应，而IL-12/IFN-γ通路缺陷可能使婴儿面临细胞内感染的风险。儿科医生应了解这些变化。尽管需要新的研究来证实这些结果，但鉴于未来几年孕期使用这些药物的可能性增加，我们的发现尤为重要。
