Distinct trajectories of humoral immune responses after SARS-CoV-2 mRNA vaccination in autoimmune inflammatory rheumatic diseases: A group-based trajectory analysis

Yamaguchi, Yuta; Amiya, Saori; Inokuchi, Shoichiro; Nagao, Sayaka; Kosaka, Kazuma; Nameki, Shinichiro; Murakami, Teruaki; Yoshimine, Yuko; Okita, Yasutaka; Kawasaki, Takahiro; Morita, Takayoshi; Tsujimoto, Kohei; Fujimoto, Jun; Nishide, Masayuki; Nishida, Sumiyuki; Narazaki, Masashi; Kato, Yasuhiro; Kumanogoh, Atsushi

doi:https://doi.org/10.1016/j.vaccine.2025.127771

Distinct trajectories of humoral immune responses after SARS-CoV-2 mRNA vaccination in autoimmune inflammatory rheumatic diseases: A group-based trajectory analysis

Yamaguchi, Yuta; Amiya, Saori; Inokuchi, Shoichiro et al.

Vaccine, 2025, 66, 127771

Number of Access:587（2026-06-10 19:36 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/103509

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Title	Distinct trajectories of humoral immune responses after SARS-CoV-2 mRNA vaccination in autoimmune inflammatory rheumatic diseases: A group-based trajectory analysis
Creator	ORCID 0000-0002-8314-9294 0000-0002-8314-9294 researchmap permalink yuta-yamaguchi yuta-yamaguchi Scopus Author ID 57221557193 57221557193 CreatorName Yamaguchi, Yuta
	CreatorName Amiya, Saori
	CreatorName Inokuchi, Shoichiro
	CreatorName Nagao, Sayaka
	CreatorName Kosaka, Kazuma
	CreatorName Nameki, Shinichiro
	CreatorName Murakami, Teruaki
	CreatorName Yoshimine, Yuko
	CreatorName Okita, Yasutaka
	NRID 1000070939587 1000070939587 ORCID 0000-0002-8625-7899 0000-0002-8625-7899 researchmap permalink t_kawasaki t_kawasaki Scopus Author ID 57220036727 57220036727 CreatorName Kawasaki, Takahiro
	NRID 1000090728685 1000090728685 ORCID 0000-0002-7111-9506 0000-0002-7111-9506 researchmap permalink M_taka M_taka Scopus Author ID 56591359800 56591359800 CreatorName Morita, Takayoshi
	NRID 1000000965824 1000000965824 ORCID 0000-0001-6958-2983 0000-0001-6958-2983 researchmap permalink Kohei_Tsujimoto Kohei_Tsujimoto Scopus Author ID 57196317291 57196317291 CreatorName Tsujimoto, Kohei
	CreatorName Fujimoto, Jun
	NRID 1000080812255 1000080812255 ORCID 0000-0001-6060-1228 0000-0001-6060-1228 researchmap permalink masayukinishide masayukinishide Scopus Author ID 37075377900 37075377900 CreatorName Nishide, Masayuki
	NRID 1000000403189 1000000403189 researchmap permalink sumi_nishi_12 sumi_nishi_12 Scopus Author ID 55190147500 55190147500 CreatorName Nishida, Sumiyuki
	NRID 1000000467573 1000000467573 ORCID 0000-0002-5613-4409 0000-0002-5613-4409 researchmap permalink mnarazaki mnarazaki Scopus Author ID 7004556201 7004556201 CreatorName Narazaki, Masashi
	NRID 1000030837050 1000030837050 ORCID 0000-0002-4050-2350 0000-0002-4050-2350 researchmap permalink katoY katoY Scopus Author ID 55473605900 55473605900 CreatorName Kato, Yasuhiro
	NRID 1000010294125 1000010294125 ORCID 0000-0003-4749-7117 0000-0003-4749-7117 researchmap permalink read0051725 read0051725 Scopus Author ID 6602726311 6602726311 CreatorName Kumanogoh, Atsushi
Subject	Coronavirus disease 2019
	Group-based trajectory modelling
	Multiple mRNA vaccination
	Severe acute respiratory syndrome coronavirus 2
Description	Yamaguchi Y., Amiya S., Inokuchi S., et al. Distinct trajectories of humoral immune responses after SARS-CoV-2 mRNA vaccination in autoimmune inflammatory rheumatic diseases: A group-based trajectory analysis. Vaccine 66, 127771 (2025); https://doi.org/10.1016/j.vaccine.2025.127771.
Abstract	Background: Patients with autoimmune inflammatory rheumatic diseases (AIRDs) are at a high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data on the effects of multiple (>3) vaccine doses and their influencing factors are limited. Understanding antibody dynamics after repeated vaccinations is essential for optimising vaccination strategies. Therefore, this study characterised the antibody response trajectories against SARS-CoV-2 and explored key clinical and immunological determinants. Methods: This single-centre retrospective cohort study included patients with AIRDs who received SARS-CoV-2 vaccinations between 1 February and 6 December 2021. Serum neutralising antibody titres from the first to fifth vaccinations were analysed using group-based trajectory modelling (GBTM). The clinical characteristics and serum cytokine levels were compared between the response groups. Results: The study included 293 patients with AIRDs. Three response trajectories were identified via GBTM: low responders (n = 13, 4·4%), middle responders (n = 122, 41·6%), and high responders (n = 158, 54·0%). Abatacept use was the strongest predictor of a low response (odds ratio 11·55, [95% confidence interval 2·27–58·82], p = 0·0032) but was also associated with a middle response (3·82, [1·18–12·29], p = 0·025). A middle response was also linked to older age (2·31 [1·38–3·85], p = 0·0014), mycophenolate mofetil use (3·03 [1·02–8·97], p = 0·045), anti-neutrophil cytoplasmic autoantibody-associated vasculitis (3·26 [1·29–8·19], p = 0·012), and rheumatoid arthritis (1·62 [1·02–8·97], p = 0·048), while systemic lupus erythematosus was inversely associated (0·49 [0·26–0·95], p = 0·035). Low responders exhibited elevated inflammatory mediators, including interleukin-6 and B-cell activating factor. Conclusion: We identified distinct antibody response trajectories in patients with AIRDs, including a subgroup with persistently low humoral immune responses despite repeated vaccinations. This study highlights the need for personalised vaccination strategies that consider individual clinical and immunological factors to optimise protection in this vulnerable populations.
Publisher	Elsevier Ltd
Source Title	Vaccine
Volume (Issue)	66
Page	127771
Date of Issued	2025-10-31
Language	English
Handle URL	https://hdl.handle.net/11094/103509
PISSN	0264410X
eISSN	18732518
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.vaccine.2025.127771
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Vaccine. 2025, 66, p. 127771
DC.title	Distinct trajectories of humoral immune responses after SARS-CoV-2 mRNA vaccination in autoimmune inflammatory rheumatic diseases: A group-based trajectory analysis
DC.creator	Yamaguchi, Yuta
	Amiya, Saori
	Inokuchi, Shoichiro
	Nagao, Sayaka
	Kosaka, Kazuma
	Nameki, Shinichiro
	Murakami, Teruaki
	Yoshimine, Yuko
	Okita, Yasutaka
	Kawasaki, Takahiro
	Morita, Takayoshi
	Tsujimoto, Kohei
	Fujimoto, Jun
	Nishide, Masayuki
	Nishida, Sumiyuki
	Narazaki, Masashi
	Kato, Yasuhiro
	Kumanogoh, Atsushi
DC.publisher	Elsevier Ltd
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-10-31
DC.identifier	https://doi.org/10.1016/j.vaccine.2025.127771
DC.subject	Coronavirus disease 2019
	Group-based trajectory modelling
	Multiple mRNA vaccination
	Severe acute respiratory syndrome coronavirus 2
DC.description	Yamaguchi Y., Amiya S., Inokuchi S., et al. Distinct trajectories of humoral immune responses after SARS-CoV-2 mRNA vaccination in autoimmune inflammatory rheumatic diseases: A group-based trajectory analysis. Vaccine 66, 127771 (2025); https://doi.org/10.1016/j.vaccine.2025.127771.
DCTERMS.abstract	Background: Patients with autoimmune inflammatory rheumatic diseases (AIRDs) are at a high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data on the effects of multiple (>3) vaccine doses and their influencing factors are limited. Understanding antibody dynamics after repeated vaccinations is essential for optimising vaccination strategies. Therefore, this study characterised the antibody response trajectories against SARS-CoV-2 and explored key clinical and immunological determinants. Methods: This single-centre retrospective cohort study included patients with AIRDs who received SARS-CoV-2 vaccinations between 1 February and 6 December 2021. Serum neutralising antibody titres from the first to fifth vaccinations were analysed using group-based trajectory modelling (GBTM). The clinical characteristics and serum cytokine levels were compared between the response groups. Results: The study included 293 patients with AIRDs. Three response trajectories were identified via GBTM: low responders (n = 13, 4·4%), middle responders (n = 122, 41·6%), and high responders (n = 158, 54·0%). Abatacept use was the strongest predictor of a low response (odds ratio 11·55, [95% confidence interval 2·27–58·82], p = 0·0032) but was also associated with a middle response (3·82, [1·18–12·29], p = 0·025). A middle response was also linked to older age (2·31 [1·38–3·85], p = 0·0014), mycophenolate mofetil use (3·03 [1·02–8·97], p = 0·045), anti-neutrophil cytoplasmic autoantibody-associated vasculitis (3·26 [1·29–8·19], p = 0·012), and rheumatoid arthritis (1·62 [1·02–8·97], p = 0·048), while systemic lupus erythematosus was inversely associated (0·49 [0·26–0·95], p = 0·035). Low responders exhibited elevated inflammatory mediators, including interleukin-6 and B-cell activating factor. Conclusion: We identified distinct antibody response trajectories in patients with AIRDs, including a subgroup with persistently low humoral immune responses despite repeated vaccinations. This study highlights the need for personalised vaccination strategies that consider individual clinical and immunological factors to optimise protection in this vulnerable populations.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	103509
citation_title	Distinct trajectories of humoral immune responses after SARS-CoV-2 mRNA vaccination in autoimmune inflammatory rheumatic diseases: A group-based trajectory analysis
citation_author	Yamaguchi, Yuta
	Amiya, Saori
	Inokuchi, Shoichiro
	Nagao, Sayaka
	Kosaka, Kazuma
	Nameki, Shinichiro
	Murakami, Teruaki
	Yoshimine, Yuko
	Okita, Yasutaka
	Kawasaki, Takahiro
	Morita, Takayoshi
	Tsujimoto, Kohei
	Fujimoto, Jun
	Nishide, Masayuki
	Nishida, Sumiyuki
	Narazaki, Masashi
	Kato, Yasuhiro
	Kumanogoh, Atsushi
citation_publisher	Elsevier Ltd
citation_language	English
citation_date	2025-10-31
citation_journal_title	Vaccine
citation_volume	66
citation_firstpage	127771
citation_doi	https://doi.org/10.1016/j.vaccine.2025.127771
citation_public_url	https://hdl.handle.net/11094/103509

Distinct trajectories of humoral immune responses after SARS-CoV-2 mRNA vaccination in autoimmune inflammatory rheumatic diseases: A group-based trajectory analysis

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