Hasan Ali Omar, Bomze David, Risch Lorenz, Brugger Silvio D, Paprotny Matthias, Weber Myriam, Thiel Sarah, Kern Lukas, Albrich Werner C, Kohler Philipp, Kahlert Christian R, Vernazza Pietro, Bühler Philipp K, Schüpbach Reto A, Gómez-Mejia Alejandro, Popa Alexandra M, Bergthaler Andreas, Penninger Josef M, Flatz Lukas
Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Clin Infect Dis. 2021 Nov 2;73(9):e2869-e2874. doi: 10.1093/cid/ciaa1496.
Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there are little data on possible immunoglobulin (Ig) A-mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and whether IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome, our approach focused on antiphospholipid antibodies (aPL).
In this retrospective cohort study, clinical data and aPL from 64 patients with COVID-19 were compared from 3 independent tertiary hospitals (1 in Liechtenstein, 2 in Switzerland). Samples were collected from 9 April to 1 May 2020.
Clinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID; 41%), a discovery cohort with severe illness (sdCOVID; 22%) and a confirmation cohort with severe illness (scCOVID; 38%). Total IgA, IgG, and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P = .01; scCOVID, P < .001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anticardiolipin IgA (sdCOVID and scCOVID, P < .001), anticardiolipin IgM (sdCOVID, P = .003; scCOVID, P< .001), and anti-beta 2 glycoprotein-1 IgA (sdCOVID and scCOVID, P< .001). Systemic lupus erythematosus was excluded from all patients as a potential confounder.
Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity.
2019年冠状病毒病（COVID-19）重症患者常出现与自身免疫性疾病相似的并发症。迄今为止，关于免疫球蛋白（Ig）A介导的自身免疫反应的数据很少。在此，我们旨在确定COVID-19是否与强烈的总IgA反应相关，以及IgA抗体是否与重症并发症相关。由于血栓形成事件在重症COVID-19中很常见，且类似于抗磷脂综合征的高凝状态，我们的研究重点是抗磷脂抗体（aPL）。
在这项回顾性队列研究中，比较了来自3家独立三级医院（列支敦士登1家，瑞士2家）的64例COVID-19患者的临床数据和aPL。样本采集于2020年4月9日至5月1日。
对64例COVID-19患者的临床记录进行了回顾，并分为轻症队列（mCOVID；41%）、重症发现队列（sdCOVID；22%）和重症确认队列（scCOVID；38%）。使用临床诊断试剂盒检测总IgA、IgG和aPL。重症与总IgA升高显著相关（sdCOVID，P = 0.01；scCOVID，P < 0.001），但与总IgG无关。在aPL中，两个重症队列均与抗心磷脂IgA升高显著相关（sdCOVID和scCOVID，P < 0.001）、抗心磷脂IgM升高（sdCOVID，P = 0.003；scCOVID，P < 0.001）以及抗β2糖蛋白-1 IgA升高（sdCOVID和scCOVID，P < 0.001）。所有患者均排除系统性红斑狼疮作为潜在混杂因素。
较高的总IgA和IgA-aPL与重症始终相关。这些新数据强烈表明，可能在支气管黏膜中触发的强烈抗病毒IgA反应会诱发全身自身免疫。
