tetano
Editor, Senior Moderator
Life Sci Alliance
. 2024 Sep 17;7(12):e202402774.
doi: 10.26508/lsa.202402774. Print 2024 Dec. Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients
Shuhei Sakakibara[SUP] 1 [/SUP], Yu-Chen Liu[SUP] 2 [/SUP], Masakazu Ishikawa[SUP] 2 3 [/SUP], Ryuya Edahiro[SUP] 4 5 6 [/SUP], Yuya Shirai[SUP] 4 5 6 [/SUP], Soichiro Haruna[SUP] 7 [/SUP], Marwa Ali El Hussien[SUP] 7 [/SUP], Zichang Xu[SUP] 8 [/SUP], Songling Li[SUP] 8 [/SUP], Yuta Yamaguchi[SUP] 4 9 [/SUP], Teruaki Murakami[SUP] 4 9 [/SUP], Takayoshi Morita[SUP] 4 9 [/SUP], Yasuhiro Kato[SUP] 4 9 [/SUP], Haruhiko Hirata[SUP] 4 [/SUP], Yoshito Takeda[SUP] 4 [/SUP], Fuminori Sugihara[SUP] 10 [/SUP], Yoko Naito[SUP] 11 [/SUP], Daisuke Motooka[SUP] 2 11 12 [/SUP], Chao-Yuan Tsai[SUP] 7 [/SUP], Chikako Ono[SUP] 3 13 14 [/SUP], Yoshiharu Matsuura[SUP] 3 13 14 [/SUP], James B Wing[SUP] 3 15 14 [/SUP], Hisatake Matsumoto[SUP] 3 16 [/SUP], Hiroshi Ogura[SUP] 3 16 [/SUP], Masato Okada[SUP] 14 [/SUP], Atsushi Kumanogoh[SUP] 3 4 9 12 14 17 [/SUP], Yukinari Okada[SUP] 3 5 6 12 14 18 19 [/SUP], Daron M Standley[SUP] 3 8 14 [/SUP], Hitoshi Kikutani[SUP] 20 [/SUP], Daisuke Okuzaki[SUP] 2 3 11 12 17 [/SUP]
Affiliations
Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies. Half of the expanded CL-reactive clones exhibited strong binding to SARS-CoV-2 antigens. One such clone, CoV1804, was reactive to both CL and viral nucleocapsid (N), and further showed anti-nucleolar activity in human cells. Notably, antibodies sharing genetic features with CoV1804 were identified in COVID-19 patient-derived immunoglobulins, thereby constituting a novel public antibody. These public autoantibodies had numerous mutations that unambiguously enhanced anti-N reactivity, when causing fluctuations in anti-CL reactivity along with the acquisition of additional self-reactivities, such as anti-nucleolar activity, in the progeny. Thus, potentially CL-reactive precursors may have developed multiple self-reactivities through clonal selection, expansion, and somatic hypermutation driven by viral antigens. Our results revealed the nature of autoantibody production during COVID-19 and provided novel insights into the origin of virus-induced autoantibodies.
. 2024 Sep 17;7(12):e202402774.
doi: 10.26508/lsa.202402774. Print 2024 Dec. Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients
Shuhei Sakakibara[SUP] 1 [/SUP], Yu-Chen Liu[SUP] 2 [/SUP], Masakazu Ishikawa[SUP] 2 3 [/SUP], Ryuya Edahiro[SUP] 4 5 6 [/SUP], Yuya Shirai[SUP] 4 5 6 [/SUP], Soichiro Haruna[SUP] 7 [/SUP], Marwa Ali El Hussien[SUP] 7 [/SUP], Zichang Xu[SUP] 8 [/SUP], Songling Li[SUP] 8 [/SUP], Yuta Yamaguchi[SUP] 4 9 [/SUP], Teruaki Murakami[SUP] 4 9 [/SUP], Takayoshi Morita[SUP] 4 9 [/SUP], Yasuhiro Kato[SUP] 4 9 [/SUP], Haruhiko Hirata[SUP] 4 [/SUP], Yoshito Takeda[SUP] 4 [/SUP], Fuminori Sugihara[SUP] 10 [/SUP], Yoko Naito[SUP] 11 [/SUP], Daisuke Motooka[SUP] 2 11 12 [/SUP], Chao-Yuan Tsai[SUP] 7 [/SUP], Chikako Ono[SUP] 3 13 14 [/SUP], Yoshiharu Matsuura[SUP] 3 13 14 [/SUP], James B Wing[SUP] 3 15 14 [/SUP], Hisatake Matsumoto[SUP] 3 16 [/SUP], Hiroshi Ogura[SUP] 3 16 [/SUP], Masato Okada[SUP] 14 [/SUP], Atsushi Kumanogoh[SUP] 3 4 9 12 14 17 [/SUP], Yukinari Okada[SUP] 3 5 6 12 14 18 19 [/SUP], Daron M Standley[SUP] 3 8 14 [/SUP], Hitoshi Kikutani[SUP] 20 [/SUP], Daisuke Okuzaki[SUP] 2 3 11 12 17 [/SUP]
Affiliations
- PMID: 39288992
- DOI: 10.26508/lsa.202402774
Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies. Half of the expanded CL-reactive clones exhibited strong binding to SARS-CoV-2 antigens. One such clone, CoV1804, was reactive to both CL and viral nucleocapsid (N), and further showed anti-nucleolar activity in human cells. Notably, antibodies sharing genetic features with CoV1804 were identified in COVID-19 patient-derived immunoglobulins, thereby constituting a novel public antibody. These public autoantibodies had numerous mutations that unambiguously enhanced anti-N reactivity, when causing fluctuations in anti-CL reactivity along with the acquisition of additional self-reactivities, such as anti-nucleolar activity, in the progeny. Thus, potentially CL-reactive precursors may have developed multiple self-reactivities through clonal selection, expansion, and somatic hypermutation driven by viral antigens. Our results revealed the nature of autoantibody production during COVID-19 and provided novel insights into the origin of virus-induced autoantibodies.