Journal of translational medicine · 2026
Molecular characterisation of telitacicept response phenotypes in systemic lupus erythematosus: an exploratory integrated transcriptome and B-cell receptor repertoire profiling study.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Chen Mengjie, Wang Wenlong, Cheng Yongjun, Tang Yuanjia
Аннотация
BACKGROUND: Telitacicept, a dual BAFF/APRIL inhibitor, has shown clinical efficacy in systemic lupus erythematosus (SLE), but the underlying molecular mechanisms remain incompletely understood.
METHODS: We performed an integrative longitudinal study in ten patients with SLE before and after telitacicept treatment, alongside ten healthy controls. Paired transcriptome RNA sequencing and dedicated B-cell receptor (BCR) sequencing and repertoire analysis were integrated with serial clinical phenotyping including SLEDAI-2 K, anti-dsDNA antibodies, and complement C3/C4 levels over 12 months of follow-up. Differential expression analysis, pathway enrichment, cell deconvolution, and BCR clonal tracking were conducted.
RESULTS: Telitacicept treatment was associated with reduced B-cell clonal diversity and decreased estimated plasma cell abundance, alongside partial reconstitution of naive B cells. Downregulation of PI3K-Akt and NF-κB pathway genes was observed. BCR repertoire analysis suggested loss of 58.7% of clones expressing IGHV4-34, IGHV3-30, and IGHV1-46, which correlated positively with baseline disease activity scores. An unexpected upregulation of interferon-stimulated genes (ISGs) was noted post-treatment, a signature not observed in independent cohorts receiving standard-of-care therapies. Exploratory subgrouping based on ISG dynamics suggested potential differences in clinical trajectory: the ISG-upregulated subgroup showed a more pronounced initial reduction in SLEDAI-2 K scores at three months, followed by a subsequent increase in disease activity scores during extended follow-up, whereas the non-upregulated subgroup maintained relatively stable scores.
CONCLUSIONS: These preliminary findings suggest that telitacicept may remodel the B-cell repertoire while concurrently modulating interferon pathways in SLE. The observed ISG upregulation generates hypotheses regarding post-treatment immune dynamics that warrant validation in larger, independent cohorts.
METHODS: We performed an integrative longitudinal study in ten patients with SLE before and after telitacicept treatment, alongside ten healthy controls. Paired transcriptome RNA sequencing and dedicated B-cell receptor (BCR) sequencing and repertoire analysis were integrated with serial clinical phenotyping including SLEDAI-2 K, anti-dsDNA antibodies, and complement C3/C4 levels over 12 months of follow-up. Differential expression analysis, pathway enrichment, cell deconvolution, and BCR clonal tracking were conducted.
RESULTS: Telitacicept treatment was associated with reduced B-cell clonal diversity and decreased estimated plasma cell abundance, alongside partial reconstitution of naive B cells. Downregulation of PI3K-Akt and NF-κB pathway genes was observed. BCR repertoire analysis suggested loss of 58.7% of clones expressing IGHV4-34, IGHV3-30, and IGHV1-46, which correlated positively with baseline disease activity scores. An unexpected upregulation of interferon-stimulated genes (ISGs) was noted post-treatment, a signature not observed in independent cohorts receiving standard-of-care therapies. Exploratory subgrouping based on ISG dynamics suggested potential differences in clinical trajectory: the ISG-upregulated subgroup showed a more pronounced initial reduction in SLEDAI-2 K scores at three months, followed by a subsequent increase in disease activity scores during extended follow-up, whereas the non-upregulated subgroup maintained relatively stable scores.
CONCLUSIONS: These preliminary findings suggest that telitacicept may remodel the B-cell repertoire while concurrently modulating interferon pathways in SLE. The observed ISG upregulation generates hypotheses regarding post-treatment immune dynamics that warrant validation in larger, independent cohorts.