Tiniakou Eleni, Casciola-Rosen Livia, Thomas Mekha A, Manabe Yuka, Antar Annukka Ar, Damarla Mahendra, Hassoun Paul M, Gao Li, Wang Zitong, Zeger Scott, Rosen Antony
Division of Rheumatology, Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USA.
Division of Infectious Diseases, Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USA.
Clin Transl Immunology. 2024 Dec 26;13(12):e70019. doi: 10.1002/cti2.70019. eCollection 2024.
CD209L and its homologous protein CD209 act as alternative entry receptors for the SARS-CoV-2 virus and are highly expressed in the virally targeted tissues. We tested for the presence and clinical features of autoantibodies targeting these receptors and compared these with autoantibodies known to be associated with COVID-19.
Using banked samples ( = 118) from Johns Hopkins patients hospitalised with COVID-19, we defined autoantibodies against CD209 and CD209L by enzyme-linked immunosorbent assay (ELISA). Clinical associations of these antibodies were compared with those of patients with anti-interferon (IFN) and anti-angiotensin-converting enzyme-2 (ACE2) autoantibodies.
Amongst patients hospitalised with COVID-19, 19.5% (23/118) had IgM autoantibodies against CD209L and were more likely to have coronary artery disease (44% vs 19%, = 0.03). Antibodies against CD209 were present in 5.9% (7/118); interestingly, all 7 were male ( = 0.02). In our study, the presence of either antibody was positively associated with disease severity [OR 95% confidence interval (95% CI): 1.80 (0.69-5.03)], but the association did not reach statistical significance. In contrast, 10/118 (8.5%) had IgG autoantibodies against IFNα, and 21 (17.8%) had IgM antibodies against ACE2. These patients had significantly worse prognosis (intubation or death) and prolonged hospital stays. However, when adjusting for patient characteristics on admission, only the presence of anti-ACE2 IgM remained significant [pooled common OR (95% CI), 4.14 (1.37, 12.54)].
We describe IgM autoantibodies against CD209 and CD209L amongst patients hospitalised with COVID-19. These were not associated with disease severity. Conversely, patients with either anti-ACE2 IgM or anti-IFNα IgG antibodies had worse outcomes. Due to the small size of the study cohort, conclusions drawn should be considered cautiously.
CD209L及其同源蛋白CD209作为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒的替代进入受体，在病毒靶向组织中高表达。我们检测了靶向这些受体的自身抗体的存在情况和临床特征，并将其与已知与2019冠状病毒病（COVID-19）相关的自身抗体进行比较。
我们使用约翰·霍普金斯医院收治的COVID-19住院患者的储存样本（n = 118），通过酶联免疫吸附测定（ELISA）确定针对CD209和CD209L的自身抗体。将这些抗体的临床关联与抗干扰素（IFN）和抗血管紧张素转换酶2（ACE2）自身抗体患者的临床关联进行比较。
在COVID-19住院患者中，19.5%（23/118）有抗CD209L的IgM自身抗体，且更有可能患有冠状动脉疾病（44%对19%，P = 0.03）。抗CD209的抗体存在于5.9%（7/118）的患者中；有趣的是，所有7例均为男性（P = 0.02）。在我们的研究中，任一抗体的存在与疾病严重程度呈正相关[比值比95%置信区间（95%CI）：1.80（0.69 - 5.03）]，但该关联未达到统计学意义。相比之下，118例中有10例（8.5%）有抗IFNα的IgG自身抗体，21例（17.8%）有抗ACE2的IgM抗体。这些患者的预后明显更差（插管或死亡）且住院时间延长。然而，在对入院时的患者特征进行调整后，只有抗ACE2 IgM的存在仍然具有统计学意义[合并共同比值比（95%CI），4.14（1.37，12.54）]。
我们描述了COVID-19住院患者中抗CD209和CD209L的IgM自身抗体。这些抗体与疾病严重程度无关。相反，抗ACE2 IgM或抗IFNα IgG抗体的患者预后更差。由于研究队列规模较小，得出的结论应谨慎考虑。
