Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
Scand J Immunol. 2022 May;95(5):e13151. doi: 10.1111/sji.13151. Epub 2022 Mar 2.
Rheumatoid arthritis (RA) patients present higher risk of SARS-CoV-2 infection (COVID-19), and proper management of the disease in this population requires a better understanding of how the immune system controls the virus. We analyzed the T cell and B cell phenotypes, and their repertoire in a pair of monozygotic twins with RA mismatched for COVID-19 infection. Twin- was not infected, while Twin+ was infected and effectively controlled the infection. We found no significant changes on the αβ T cell composition, while γδ T cells and B cells presented considerable expansion of memory population in Twin+ and robust T/B cell responses to several SARS-CoV-2 peptides. T cell receptor β/γ-chain and immunoglobulin heavy chain next-generation sequencing depicted a remarkable higher diversity in Twin+ compared with Twin-, despite no significant changes being found in variable/joining family usage. Repertoire overlap analyses showed that, although being identical twins, very few clones were shared between them, indicating that COVID-19 may lead to deep changes on the immune cell repertoire in RA patients. Altogether, our results indicate that RA patients may develop robust and persistent COVID-19-specific T/B cell responses; γδ T cells and B cells may play a key role in the management of COVID-19 in RA, and the infection may lead to a profound reshaping of immune cell receptor specificities.
类风湿关节炎 (RA) 患者感染 SARS-CoV-2(COVID-19)的风险较高,因此需要更好地了解免疫系统如何控制病毒,从而对该人群进行疾病的适当管理。我们分析了一对 COVID-19 感染情况不一致的同卵双胞胎 RA 患者的 T 细胞和 B 细胞表型及其受体库。双胞胎中的 Twin- 未感染,而 Twin+ 感染且有效地控制了感染。我们发现 αβ T 细胞组成没有明显变化,而 γδ T 细胞和 B 细胞在 Twin+ 中呈现出记忆细胞群体的显著扩张,并且对多种 SARS-CoV-2 肽产生了强大的 T/B 细胞反应。T 细胞受体 β/γ 链和免疫球蛋白重链的下一代测序显示,Twin+ 的多样性明显高于 Twin-,尽管在可变/连接家族的使用中没有发现显著变化。受体库重叠分析表明,尽管是同卵双胞胎,但它们之间共享的克隆很少,这表明 COVID-19 可能导致 RA 患者的免疫细胞受体库发生深刻变化。总之,我们的研究结果表明,RA 患者可能会产生强大而持久的 COVID-19 特异性 T/B 细胞反应;γδ T 细胞和 B 细胞可能在 RA 患者 COVID-19 的管理中发挥关键作用,并且感染可能导致免疫细胞受体特异性的深刻重塑。