高炎症细胞因子 IL-6 和 IFN-γ 与肾移植受者抗 SARS-CoV-2 刺突蛋白特异性血清转化相关。
Higher pro-inflammatory cytokines IL-6 and IFN-γ are associated with anti-SARS-CoV-2 spike protein-specific seroconversion in renal allograft recipients.
机构信息
Department of Nephrology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
出版信息
Transpl Infect Dis. 2023 Oct;25(5):e14133. doi: 10.1111/tid.14133. Epub 2023 Aug 21.
BACKGROUND
Maintenance immunosuppressive regimens are speculated to hamper immunogenic response against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in renal transplant recipients (RTRs) compared to the healthy population. Healthy people with SARS-CoV-2 infection often develop neutralizing antibodies and secret copious quantities of cytokines, leading to virus clearance and sometimes more severe immune-related complications.
METHODS
RTRs, either acquired SARS-CoV-2 infection (infection group, n = 132) or were vaccinated with two vaccine doses (vaccination group, n = 78) against SARS-CoV-2, were recruited in the study. Thirty-five unvaccinated RTRs, without anti-SARS-CoV-2 spike protein-specific antibodies, were also included as control. Cytokines interleukine-6 (IL-6), interferon-γ (IFN-γ), TGF-β, and IL-10 were measured using ELISA. The SARS-CoV-2 spike protein-specific IgG-titer was measured by chemiluminescent microparticle immunoassay methods.
RESULTS
The seroconversion rate in the infection group was 115/132 (87.12%), with a median antibody titer 706.40 au/mL (IQR, 215.45-1844.42), and in the vaccination group was 63/78 (80.76%) with antibody titer 1454.20 au/mL (IQR, 80.52-3838.75). The IL-6, IFN-γ, TGF-β, and IL-10 levels were significantly higher in both the infection and vaccination group compared to healthy control. In the infection group, pro-inflammatory cytokines IL-6 (55.41 ± 24.30 vs. 31.64 ± 16.98 pg/mL, p < .001) and IFN-γ (91.21 ± 33.09 vs. 61.69 ± 33.28 pg/mL, p = .001) were significantly higher in the seroconverter group as compared to non-seroconverter. Similarly, in the vaccination group, pro-inflammatory cytokines IL-6 (50.31 ± 25.67 vs. 30.00 ± 11.19 pg/mL; p = .002) and IFN-γ (65.70 ± 39.78 vs. 32.14 ± 17.48 pg/mL; p = .001) were significantly higher in the seroconverter group compared to non-seroconverter. In contrast, TGF-β (820.96 ± 415.78 vs. 1045.57 ± 204.66; p = .046) was higher in non-seroconverter.
CONCLUSIONS
Pro-inflammatory cytokines IL-6 and IFN-γ were significantly associated with seroconversion after SARS-CoV-2 infection and vaccination in RTRs.
背景
与健康人群相比，维持性免疫抑制方案可能会阻碍肾移植受者（RTR）对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的免疫应答。患有 SARS-CoV-2 感染的健康人通常会产生中和抗体并大量分泌细胞因子，从而导致病毒清除，有时还会出现更严重的免疫相关并发症。
方法
本研究招募了感染 SARS-CoV-2（感染组，n=132）或接种两剂 SARS-CoV-2 疫苗（接种组，n=78）的 RTR。还纳入了 35 名未接种疫苗且无抗 SARS-CoV-2 刺突蛋白特异性抗体的 RTR 作为对照。使用 ELISA 法测定白细胞介素 6（IL-6）、干扰素-γ（IFN-γ）、TGF-β和 IL-10 细胞因子。使用化学发光微粒子免疫测定法测定 SARS-CoV-2 刺突蛋白特异性 IgG 滴度。
结果
感染组的血清转化率为 115/132（87.12%），中位数抗体滴度为 706.40 au/mL（IQR，215.45-1844.42），接种组为 63/78（80.76%），抗体滴度为 1454.20 au/mL（IQR，80.52-3838.75）。与健康对照组相比，感染组和接种组的 IL-6、IFN-γ、TGF-β和 IL-10 水平均显著升高。在感染组中，与非血清转化者相比，促炎细胞因子 IL-6（55.41±24.30 与 31.64±16.98 pg/mL，p<0.001）和 IFN-γ（91.21±33.09 与 61.69±33.28 pg/mL，p=0.001）水平显著更高。同样，在接种组中，与非血清转化者相比，促炎细胞因子 IL-6（50.31±25.67 与 30.00±11.19 pg/mL；p=0.002）和 IFN-γ（65.70±39.78 与 32.14±17.48 pg/mL；p=0.001）水平显著更高。相比之下，TGF-β（820.96±415.78 与 1045.57±204.66；p=0.046）在非血清转化者中更高。
结论
在 RTR 中，SARS-CoV-2 感染和接种疫苗后，促炎细胞因子 IL-6 和 IFN-γ 与血清转化率显著相关。
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