Longitudinal COVID-19 immune trajectories in patients with neurological autoimmunity on anti-CD20 therapy.
Longitudinal COVID-19 immune trajectories in patients with neurological autoimmunity on anti-CD20 therapy.
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DOI：
10.1016/j.msard.2022.104195
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发表时间：
2022-12
影响因子：
4
通讯作者：
Melamed, Esther
中科院分区：
文献类型：
--
作者：
Bazzi, Sam A.;Maguire, Cole;Holay, Nisha;Geltman, Janelle;Hurley, Kerin;DiPasquale, Chris;Abigania, Melissa;Olson, Eric;Ehrlich, Lauren I. R.;Triplett, Todd A.;Melamed, Esther
在 COVID-19 大流行期间，B 细胞耗竭疗法引起了神经免疫性疾病患者的临床关注，因为患者可能无法对 SARS-CoV-2 感染和疫苗接种产生足够的免疫反应。迄今为止的研究报告了关于 B 细胞耗尽患者中 SARS-CoV-2 感染后抗体产生程度和疫苗接种程度的相互矛盾的结果，主要集中在短期免疫分析上。我们的目标是跟踪患有神经免疫性疾病的 COVID-19 B 细胞耗尽患者在接种 COVID-19 和 SARS-CoV-2 疫苗后的纵向免疫反应。 2020 年至 2021 年间，德克萨斯大学奥斯汀分校戴尔医学院招募了 CD20 B 细胞耗尽的自身免疫患者和年龄/性别匹配的 SARS-CoV-2 阳性对照，前瞻性随访 12 个月，并在多个时间点评估尖峰 S1 受体结合域 (RBD) 抗体滴度、B 和 T 细胞组成以及 SARS-CoV-2 抗原特异性 T 细胞的频率。在一组 COVID-19 B 细胞耗尽的神经免疫患者 (n = 5)、COVID-19 非 B 细胞耗尽的自身免疫患者 (n = 15)、COVID-19 免疫功能正常的患者 (n = 117) 和健康对照 (n = 6) 的队列中评估了 SARS-CoV-2 感染和疫苗接种后的免疫反应，共 137 名参与者的 259 个样本。 4/5 B 细胞耗尽的患者产生了可检测到的抗刺突 RBD 抗体，其中 2 名患者通过疫苗接种增强了这种抗体。虽然刺突 RBD 抗体与 CD20+ B 细胞的存在相关，但只需要很少的 B 细胞。相比之下，在急性 COVID-19 疾病或疫苗接种期间 B 细胞室主要由 CD19+CD20-B 细胞组成的患者没有血清转化。有趣的是，B 细胞耗竭患者的循环 B 细胞 CD38 显着高，并同时表达 CD24 和 CD27，表明 B 细胞耗竭可能会影响 B 细胞激活模式。此外，无论血清转化如何，所有 B 细胞耗尽的患者都会对 SARS-CoV-2 抗原产生持续的 T 细胞反应。具体来说，所有患者都产生了幼稚的中枢记忆、效应记忆和效应记忆 RA+ T 细胞，这表明与对照组相比，B 细胞耗竭患者的 T 细胞记忆转换完整。我们在 B 细胞耗尽的患者中进行了迄今为止最长的 COVID-19 免疫分析，表明在 SARS-CoV-2 感染和疫苗接种后，体液和细胞免疫反应可以产生并持续长达 12 个月。值得注意的是，未能建立体液免疫并不会导致严重的疾病。我们还强调了可用作临床生物标志物的特定 T 和 B 细胞特征，以建议患者接种 SARS-CoV-2 疫苗的时间。
During the COVID-19 pandemic, B cell depleting therapies pose a clinical concern for patients with neuroimmune conditions, as patients may not mount a sufficient immune response to SARS-CoV-2 infection and vaccinations. Studies to-date have reported conflicting results on the degree of antibody production post-SARS-CoV-2 infection and vaccinations in B cell depleted patients, focusing primarily on short-term immune profiling. Our objective was to follow longitudinal immune responses in COVID-19 B cell depleted patients with neuroimmune disorders post-COVID-19 and SARS-CoV-2-vaccination. CD20 B cell depleted autoimmune patients and age/sex-matched controls positive for SARS-CoV-2 were recruited at Dell Medical School, UT Austin between 2020 and 2021, followed prospectively for 12 months and evaluated at multiple time points for spike S1 receptor binding domain (RBD) antibody titers, B and T cell composition, and frequency of T cells specific for SARS-CoV-2 antigens. Immune responses post-SARS-CoV-2 infection and vaccination were evaluated in a cohort of COVID-19 B cell depleted neuroimmune patients (n = 5), COVID-19 non-B cell depleted autoimmune patients (n = 15), COVID-19 immunocompetent patients (n = 117), and healthy controls (n = 6) for a total of 259 samples in 137 participants. 4/5 B cell-depleted patients developed detectable anti-spike RBD antibodies, which were boosted by vaccination in 2 patients. While spike RBD antibodies were associated with presence of CD20+ B cells, very few B cells were required. In contrast, patients whose B cell compartment primarily consisted of CD19+CD20– Bcells during acute COVID-19 disease or vaccination did not seroconvert. Interestingly, circulating Bcells in B cell depleted patients were significantly CD38high with co-expression of CD24 and CD27, indicating that B cell depletion may impact B cell activation patterns. Additionally, all B cell depleted patients mounted a sustained T cell response to SARS-CoV-2 antigens, regardless of seroconversion. Specifically, all patients developed naïve, central memory, effector memory, and effector memory RA+ T cells, suggesting intact T cell memory conversion in B cell depleted patients compared to controls. We present the longest COVID-19 immune profiling analysis to date in B cell depleted patients, demonstrating that both humoral and cellular immune responses can be generated and sustained up to 12 months post SARS-CoV-2 infection and vaccination. Notably, failure to establish humoral immunity did not result in severe disease. We also highlight specific T and B cell signatures that could be used as clinical biomarkers to advise patients on timing of SARS-CoV-2 vaccinations.
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影响因子：
27.4
作者：
Mrak, Daniel;Tobudic, Selma;Bonelli, Michael
通讯作者：
Bonelli, Michael
影响因子：
64.5
作者：
Sette A;Crotty S
通讯作者：
Crotty S
影响因子：
8
作者：
Sabatino JJ Jr;Mittl K;Rowles WM;McPolin K;Rajan JV;Laurie MT;Zamecnik CR;Dandekar R;Alvarenga BD;Loudermilk RP;Gerungan C;Spencer CM;Sagan SA;Augusto DG;Alexander JR;DeRisi JL;Hollenbach JA;Wilson MR;Zamvil SS;Bove R
通讯作者：
Bove R
DOI：
10.1038/s41573-020-00092-2
发表时间：
2021-03
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Lee DSW;Rojas OL;Gommerman JL
通讯作者：
Gommerman JL
影响因子：
4.7
作者：
Kos, Igor;Balensiefer, Benedikt;Kaddu-Mulindwa, Dominic
通讯作者：
Kaddu-Mulindwa, Dominic