Machado Nicolle Rakanidis, do Nascimento Lais Alves, Fagundes Beatriz Oliveira, Borges João Vitor da Silva, Sgnotto Fabio da Ressureição, Bergamasco Isabella Siuffi, Fernandes Juliana Ruiz, Pinto Thalyta Nery Carvalho, Pietrobon Anna Julia, Benard Gil, Sato Maria Notomi, Victor Jefferson Russo
Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of São Paulo, São Paulo 05403-000, Brazil.
School of Medicine, Santo Amaro University (UNISA), São Paulo 04829-300, Brazil.
Vaccines (Basel). 2025 Jun 27;13(7):694. doi: 10.3390/vaccines13070694.
BACKGROUND/OBJECTIVES: COVID-19 has been associated with a wide range of immune responses, including the production of autoantibodies, particularly in severe cases. This study investigates the IgG autoantibody responses in patients with varying severities of COVID-19 infection and compares these responses with vaccinated individuals.
We utilized proteomic profiling to analyze autoantibody reactivity against a broad spectrum of proteins expressed in lymphoid and myeloid cell subsets in serum samples from severe and moderate COVID-19 patients, as well as vaccinated individuals who received the inactivated CoronaVac (Sinovac) vaccine.
Our findings indicate a marked increase in the diversity and number of IgG autoantibodies targeting intracellular and membrane-associated proteins in severe COVID-19 cases, compared to those with moderate cases of the disease. The autoantibody response in severe cases was found to primarily target proteins involved in immune cell activation, signaling, and differentiation, suggesting potential pathways of immune dysregulation and autoimmunity. In contrast, vaccinated individuals did not exhibit similar autoantibody reactivity, pointing to a more controlled immune response post-vaccination. Notably, no significant autoimmune responses were detected in the vaccinated cohort, suggesting that the inactivated vaccine does not induce autoreactive IgG. These findings align with the established safety profile of COVID-19 vaccines, especially in comparison to the heightened immune dysregulation observed in severe COVID-19 patients. The absence of a significant autoantibody response in vaccinated individuals supports the notion that vaccines, while inducing robust immune activation, do not typically trigger autoimmunity in healthy individuals.
Our study underscores the importance of distinguishing between the immune responses triggered by infection and vaccination and highlights the need for the continued monitoring of autoimmune responses in severe COVID-19 cases. Future research should focus on the long-term persistence and clinical relevance of these autoantibodies, particularly in individuals with pre-existing autoimmune conditions or genetic predispositions.
背景/目的：新冠病毒病（COVID-19）与多种免疫反应相关，包括自身抗体的产生，尤其是在重症病例中。本研究调查了不同严重程度的COVID-19感染患者的IgG自身抗体反应，并将这些反应与接种疫苗的个体进行比较。
我们利用蛋白质组学分析，检测了重症和中度COVID-19患者以及接种了灭活科兴新冠疫苗的个体血清样本中，针对淋巴和髓样细胞亚群中表达的多种蛋白质的自身抗体反应性。
我们的研究结果表明，与中度COVID-19病例相比，重症COVID-19病例中靶向细胞内和膜相关蛋白的IgG自身抗体的多样性和数量显著增加。重症病例中的自身抗体反应主要针对参与免疫细胞激活、信号传导和分化的蛋白质，提示免疫失调和自身免疫的潜在途径。相比之下，接种疫苗的个体未表现出类似的自身抗体反应性，表明接种疫苗后免疫反应更受控制。值得注意的是，在接种疫苗的队列中未检测到明显的自身免疫反应，这表明灭活疫苗不会诱导自身反应性IgG。这些发现与COVID-19疫苗已确立的安全性特征相符，特别是与重症COVID-19患者中观察到的免疫失调加剧相比。接种疫苗的个体中没有明显的自身抗体反应，这支持了疫苗虽然能诱导强大的免疫激活，但通常不会在健康个体中引发自身免疫的观点。
我们的研究强调了区分感染和疫苗接种引发的免疫反应的重要性，并强调了对重症COVID-19病例中自身免疫反应进行持续监测的必要性。未来的研究应关注这些自身抗体的长期持续性和临床相关性，特别是在已有自身免疫疾病或遗传易感性的个体中。
