Deutsches Zentrum Immuntherapie, Friedrich-Alexander University Erlangen-Nuremberg, and University Hospital Erlangen, Erlangen, Germany.
Rheumatology Practice Bamberg, Bamberg, Germany.
Arthritis Rheumatol. 2022 Jan;74(1):33-37. doi: 10.1002/art.41914. Epub 2021 Nov 23.
B cell depletion is an established therapeutic principle in a wide range of autoimmune diseases. However, B cells are also critical for inducing protective immunity after infection and vaccination. We undertook this study to assess humoral and cellular immune responses after infection with or vaccination against SARS-CoV-2 in patients with B cell depletion and controls who are B cell-competent.
Antibody responses (tested using enzyme-linked immunosorbent assay) and T cell responses (tested using interferon-γ enzyme-linked immunospot assay) against the SARS-CoV-2 spike S1 and nucleocapsid proteins were assessed in a limited number of previously infected (n = 6) and vaccinated (n = 8) autoimmune disease patients with B cell depletion, as well as previously infected (n = 30) and vaccinated (n = 30) healthy controls.
As expected, B cell and T cell responses to the nucleocapsid protein were observed only after infection, while respective responses to SARS-CoV-2 spike S1 were found after both infection and vaccination. A SARS-CoV-2 antibody response was observed in all vaccinated controls (30 of 30 [100%]) but in none of the vaccinated patients with B cell depletion (0 of 8). In contrast, after SARS-CoV-2 infection, both the patients with B cell depletion (spike S1, 5 of 6 [83%]; nucleocapsid, 3 of 6 [50%]) and healthy controls (spike S1, 28 of 30 [93%]; nucleocapsid, 28 of 30 [93%]) developed antibodies. T cell responses against the spike S1 and nucleocapsid proteins were found in both infected and vaccinated patients with B cell depletion and in the controls.
These data show that B cell depletion completely blocks humoral but not T cell SARS-CoV-2 vaccination response. Furthermore, limited humoral immune responses are found after SARS-CoV-2 infection in patients with B cell depletion.
B 细胞耗竭是广泛的自身免疫性疾病的既定治疗原则。然而,B 细胞在感染和接种疫苗后诱导保护性免疫方面也至关重要。我们进行这项研究是为了评估 B 细胞耗竭的患者和 B 细胞功能正常的对照者在感染或接种 SARS-CoV-2 后的体液和细胞免疫反应。
我们检测了有限数量的先前感染(n=6)和接种疫苗(n=8)的自身免疫性疾病患者的 B 细胞耗竭以及先前感染(n=30)和接种疫苗(n=30)的健康对照者对 SARS-CoV-2 刺突 S1 和核衣壳蛋白的抗体和 T 细胞反应(通过干扰素-γ酶联免疫斑点试验进行检测)。
正如预期的那样,仅在感染后观察到对核衣壳蛋白的 B 细胞和 T 细胞反应,而对 SARS-CoV-2 刺突 S1 的相应反应则在感染和接种疫苗后均有发现。所有接种疫苗的对照者(30 例中有 30 例[100%])均出现 SARS-CoV-2 抗体反应,但在接种疫苗的 B 细胞耗竭患者中(8 例中有 0 例)则未观察到该反应。相比之下,在 SARS-CoV-2 感染后,B 细胞耗竭的患者(刺突 S1,6 例中有 5 例[83%];核衣壳,6 例中有 3 例[50%])和健康对照者(刺突 S1,30 例中有 28 例[93%];核衣壳,30 例中有 28 例[93%])均产生了抗体。在感染和接种疫苗的 B 细胞耗竭患者以及对照者中均发现了针对刺突 S1 和核衣壳蛋白的 T 细胞反应。
这些数据表明,B 细胞耗竭完全阻断了体液免疫,但不阻断 SARS-CoV-2 疫苗接种的 T 细胞反应。此外,在 B 细胞耗竭的患者中,在 SARS-CoV-2 感染后发现有限的体液免疫反应。