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分析 COVID-19 第三次疫苗接种后自身免疫性肝炎患者的体液和细胞免疫反应。

Analysis of the humoral and cellular response after the third COVID-19 vaccination in patients with autoimmune hepatitis.

机构信息

I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.

出版信息

Liver Int. 2023 Feb;43(2):393-400. doi: 10.1111/liv.15368. Epub 2022 Aug 8.

Abstract

BACKGROUND & AIMS: To explore the humoral and T-cell response to the third COVID-19 vaccination in autoimmune hepatitis (AIH).

METHODS

Anti-SARS-CoV-2 antibody titers were prospectively determined in 81 AIH patients and 53 healthy age- and sex-matched controls >7 days (median 35) after the first COVID-19 booster vaccination. The spike-specific T-cell response was assessed using an activation-induced marker assay (AIM) in a subset of patients.

RESULTS

Median antibody levels were significantly lower in AIH compared to controls (10 908 vs. 25 000 AU/ml, p < .001), especially in AIH patients treated with MMF (N = 14, 4542 AU/ml, p = .004) or steroids (N = 27, 7326 AU/ml, p = .020). Also, 48% of AIH patients had antibody titers below the 10% percentile of the healthy controls (9194 AU/ml, p < .001). AIH patients had a high risk of failing to develop a spike-specific T-cell response (15/34 (44%) vs. 2/16 (12%), p = .05) and showed overall lower frequencies of spike-specific CD4 + T cells (median: 0.074% vs 0.283; p = .01) after the booster vaccination compared to healthy individuals. In 34/81 patients, antibody titers before and after booster vaccination were available. In this subgroup, all patients but especially those without detectable/low antibodies titers (<100 AU/ml) after the second vaccination (N = 11/34) showed a strong, 148-fold increase.

CONCLUSION

A third COVID-19 vaccination efficiently boosts antibody levels and T-cell responses in AIH patients and even seroconversion in patients with the absent immune response after two vaccinations, but to a lower level compared to controls. Therefore, we suggest routinely assessing antibody levels in AIH patients and offering additional booster vaccinations to those with suboptimal responses.

摘要

背景与目的

探讨第三次 COVID-19 疫苗接种对自身免疫性肝炎(AIH)患者体液和 T 细胞反应的影响。

方法

前瞻性检测了 81 例 AIH 患者和 53 名年龄和性别匹配的健康对照者在首次 COVID-19 加强针接种后 >7 天(中位数为 35 天)的抗 SARS-CoV-2 抗体滴度。在患者亚组中使用激活诱导标志物测定法(AIM)评估棘突特异性 T 细胞反应。

结果

与对照组相比,AIH 患者的抗体水平显著降低(中位数 10908 比 25000 AU/ml,p<0.001),尤其是接受吗替麦考酚酯(N=14,4542 AU/ml,p=0.004)或皮质类固醇(N=27,7326 AU/ml,p=0.020)治疗的 AIH 患者。此外,48%的 AIH 患者的抗体滴度低于健康对照组的第 10 百分位数(9194 AU/ml,p<0.001)。AIH 患者未能产生棘突特异性 T 细胞反应的风险较高(15/34 [44%]比 2/16 [12%],p=0.05),与健康个体相比,加强针接种后棘突特异性 CD4+T 细胞的总体频率较低(中位数:0.074%比 0.283%;p=0.01)。在 81 例患者中,有 34 例患者可获得加强针接种前后的抗体滴度。在该亚组中,所有患者但尤其是那些在第二次接种后抗体滴度检测不到/低(<100 AU/ml,N=11/34)的患者,抗体滴度均呈强烈的 148 倍增加。

结论

第三次 COVID-19 疫苗接种可有效提高 AIH 患者的抗体水平和 T 细胞反应,甚至在两次接种后无免疫反应的患者中也可产生血清转化,但与对照组相比,其水平较低。因此,我们建议常规评估 AIH 患者的抗体水平,并对抗体反应欠佳的患者提供额外的加强针接种。

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