tetano
Editor, Senior Moderator
Clin Biochem
. 2024 Dec 15:110865.
doi: 10.1016/j.clinbiochem.2024.110865. Online ahead of print. Immune complexome analysis reveals an autoimmune signature predictive of COVID-19 severity
Marino Moriishi[SUP] 1 [/SUP], Takahiro Takazono[SUP] 2 [/SUP], Junya Hashizume[SUP] 3 [/SUP], Nozomi Aibara[SUP] 1 [/SUP], Yuki Jimbayashi Kutsuna[SUP] 4 [/SUP], Masaki Okamoto[SUP] 5 [/SUP], Toyomitsu Sawai[SUP] 6 [/SUP], Teppei Hoshino[SUP] 7 [/SUP], Yusuke Mori[SUP] 7 [/SUP], Yuichi Fukuda[SUP] 8 [/SUP], Yukikazu Awaya[SUP] 9 [/SUP], Hirotomo Yamanashi[SUP] 10 [/SUP], Yuichiro Furusato[SUP] 11 [/SUP], Toyoshi Yanagihara[SUP] 12 [/SUP], Hirotaka Miyamoto[SUP] 13 [/SUP], Kayoko Sato[SUP] 3 [/SUP], Yukinobu Kodama[SUP] 3 [/SUP], Shusaku Mizukami[SUP] 14 [/SUP], Noriho Sakamoto[SUP] 15 [/SUP], Kazuko Yamamoto[SUP] 16 [/SUP], Kei Sakamoto[SUP] 17 [/SUP], Katsunori Yanagihara[SUP] 18 [/SUP], Koichi Izumikawa[SUP] 19 [/SUP], Takahiro Maeda[SUP] 1 [/SUP], Mikiro Nakashima[SUP] 1 [/SUP], Kiyoyasu Fukushima[SUP] 20 [/SUP], Hiroshi Mukae[SUP] 15 [/SUP], Kaname Ohyama[SUP] 21 [/SUP]
Affiliations
Background: The factors contributing to the development of severe coronavirus disease 2019 (COVID-19) following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. Although the presence of immune complexes (ICs), formed between antibodies and their antigens, has been linked to COVID-19 severity, their role requires further investigation, and the antigens within these ICs are yet to be characterized.
Method: Here, a C1q enzyme-liked immunosorbent assay and immune complexome analysis were used to determine IC concentrations and characterize IC antigens, respectively, in the sera of 64 unvaccinated COVID-19 patients with PCR-confirmed SARS-CoV-2 infection, enrolled at seven participating centers in 2020. For the analysis, the patients were split into the severe (n = 35) and non-severe (n = 28) groups on the basis of their COVID-19 symptoms.
Results: We found that neither serum IC concentration nor IC antigen number was associated with COVID-19 severity. However, we identified six IC antigens, which were significantly enriched in the severe versus non-severe group. These IC antigens were all derived from human proteins, namely haptoglobin, the serum amyloid A-2 protein, the serum amyloid A-1 protein, clusterin, and lipopolysaccharide-binding protein, and complement-factor-H-related protein 3. Meanwhile, we found no association between COVID-19 severity and IC antigens derived from SARS-CoV-2 proteins. Collectively, the six IC antigens predicted COVID-19 severity with a moderate degree of accuracy (area under the receiver operating characteristic curve = 0.90, sensitivity = 94 %, specificity = 79 %).
Conclusions: The IC antigen signature identified in this study may have important implications for the diagnosis and treatment of severe COVID-19.
Keywords: COVID-19; Immune complex; Immune complexome analysis; SARS-CoV-2.
. 2024 Dec 15:110865.
doi: 10.1016/j.clinbiochem.2024.110865. Online ahead of print. Immune complexome analysis reveals an autoimmune signature predictive of COVID-19 severity
Marino Moriishi[SUP] 1 [/SUP], Takahiro Takazono[SUP] 2 [/SUP], Junya Hashizume[SUP] 3 [/SUP], Nozomi Aibara[SUP] 1 [/SUP], Yuki Jimbayashi Kutsuna[SUP] 4 [/SUP], Masaki Okamoto[SUP] 5 [/SUP], Toyomitsu Sawai[SUP] 6 [/SUP], Teppei Hoshino[SUP] 7 [/SUP], Yusuke Mori[SUP] 7 [/SUP], Yuichi Fukuda[SUP] 8 [/SUP], Yukikazu Awaya[SUP] 9 [/SUP], Hirotomo Yamanashi[SUP] 10 [/SUP], Yuichiro Furusato[SUP] 11 [/SUP], Toyoshi Yanagihara[SUP] 12 [/SUP], Hirotaka Miyamoto[SUP] 13 [/SUP], Kayoko Sato[SUP] 3 [/SUP], Yukinobu Kodama[SUP] 3 [/SUP], Shusaku Mizukami[SUP] 14 [/SUP], Noriho Sakamoto[SUP] 15 [/SUP], Kazuko Yamamoto[SUP] 16 [/SUP], Kei Sakamoto[SUP] 17 [/SUP], Katsunori Yanagihara[SUP] 18 [/SUP], Koichi Izumikawa[SUP] 19 [/SUP], Takahiro Maeda[SUP] 1 [/SUP], Mikiro Nakashima[SUP] 1 [/SUP], Kiyoyasu Fukushima[SUP] 20 [/SUP], Hiroshi Mukae[SUP] 15 [/SUP], Kaname Ohyama[SUP] 21 [/SUP]
Affiliations
- PMID: 39689808
- DOI: 10.1016/j.clinbiochem.2024.110865
Background: The factors contributing to the development of severe coronavirus disease 2019 (COVID-19) following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. Although the presence of immune complexes (ICs), formed between antibodies and their antigens, has been linked to COVID-19 severity, their role requires further investigation, and the antigens within these ICs are yet to be characterized.
Method: Here, a C1q enzyme-liked immunosorbent assay and immune complexome analysis were used to determine IC concentrations and characterize IC antigens, respectively, in the sera of 64 unvaccinated COVID-19 patients with PCR-confirmed SARS-CoV-2 infection, enrolled at seven participating centers in 2020. For the analysis, the patients were split into the severe (n = 35) and non-severe (n = 28) groups on the basis of their COVID-19 symptoms.
Results: We found that neither serum IC concentration nor IC antigen number was associated with COVID-19 severity. However, we identified six IC antigens, which were significantly enriched in the severe versus non-severe group. These IC antigens were all derived from human proteins, namely haptoglobin, the serum amyloid A-2 protein, the serum amyloid A-1 protein, clusterin, and lipopolysaccharide-binding protein, and complement-factor-H-related protein 3. Meanwhile, we found no association between COVID-19 severity and IC antigens derived from SARS-CoV-2 proteins. Collectively, the six IC antigens predicted COVID-19 severity with a moderate degree of accuracy (area under the receiver operating characteristic curve = 0.90, sensitivity = 94 %, specificity = 79 %).
Conclusions: The IC antigen signature identified in this study may have important implications for the diagnosis and treatment of severe COVID-19.
Keywords: COVID-19; Immune complex; Immune complexome analysis; SARS-CoV-2.