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甲氨蝶呤会削弱免疫介导的炎症性疾病患者对BNT162b2 mRNA新冠疫苗的免疫原性。

Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease.

作者信息

Haberman Rebecca H, Herati Ramin, Simon David, Samanovic Marie, Blank Rebecca B, Tuen Michael, Koralov Sergei B, Atreya Raja, Tascilar Koray, Allen Joseph R, Castillo Rochelle, Cornelius Amber R, Rackoff Paula, Solomon Gary, Adhikari Samrachana, Azar Natalie, Rosenthal Pamela, Izmirly Peter, Samuels Jonathan, Golden Brian, Reddy Soumya M, Neurath Markus F, Abramson Steven B, Schett Georg, Mulligan Mark J, Scher Jose U

机构信息

Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA.

NYU Langone Psoriatic Arthritis Center, New York University School of Medicine, New York, New York, USA.

出版信息

Ann Rheum Dis. 2021 Oct;80(10):1339-1344. doi: 10.1136/annrheumdis-2021-220597. Epub 2021 May 25.

DOI:10.1136/annrheumdis-2021-220597
PMID:34035003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8219484/
Abstract

OBJECTIVE

To investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.

METHODS

Established patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response.

RESULTS

Although healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination.

CONCLUSIONS

In two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

摘要

目的

研究接受免疫调节治疗的免疫介导性炎症疾病(IMID)患者对新型冠状病毒 mRNA(mRNA COVID-19)疫苗的体液免疫和细胞免疫反应。

方法

纽约大学朗格尼健康中心确诊的 IMID 患者(n = 51)接受 BNT162b2 mRNA 疫苗接种,在基线和第二次免疫后进行评估。健康受试者作为对照(n = 26)。分析针对刺突蛋白的 IgG 抗体反应以评估体液免疫反应。使用高参数光谱流式细胞术进一步分析对严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的细胞免疫反应。还对来自德国埃尔朗根的第二个独立验证队列的对照(n = 182)和 IMID 患者(n = 31)进行了体液免疫反应分析。

结果

尽管健康受试者(n = 208)和接受生物治疗的 IMID 患者(大多使用肿瘤坏死因子阻滞剂,n = 37)表现出强烈的抗体反应(超过 90%),但那些接受甲氨蝶呤治疗的 IMID 患者(n = 45)仅有 62.2% 的病例获得了充分反应。同样,接受甲氨蝶呤治疗的 IMID 患者在接种疫苗后未表现出 CD8 + T 细胞活化增加。

结论

在两个独立的 IMID 患者队列中,甲氨蝶呤作为一种广泛用于治疗多种 IMID 的免疫调节剂,对 COVID-19 mRNA 疫苗的体液免疫和细胞免疫反应产生了不利影响。尽管与疫苗效力相关的免疫原性精确阈值尚未确定,但我们的研究结果表明,对于正在服用甲氨蝶呤的 IMID 患者,可能需要探索不同的策略来提高针对 SARS-CoV-2 的免疫效力,就像在增强对其他病毒疫苗的免疫原性方面所证明的那样。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f3/8458073/d1dba6736692/annrheumdis-2021-220597f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f3/8458073/b8bd9d595459/annrheumdis-2021-220597f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f3/8458073/d1dba6736692/annrheumdis-2021-220597f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f3/8458073/b8bd9d595459/annrheumdis-2021-220597f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f3/8458073/d1dba6736692/annrheumdis-2021-220597f02.jpg

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