Ida Erngren, Katarina Lundblad, Ivan Pavlovic, Asma Al-Grety, Anders Larsson, Kim Kultima, Joachim Burman
{"title":"自体造血干细胞移植后进行性多发性硬化症的生物标志物降低。","authors":"Ida Erngren, Katarina Lundblad, Ivan Pavlovic, Asma Al-Grety, Anders Larsson, Kim Kultima, Joachim Burman","doi":"10.1186/s12974-025-03511-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Autologous hematopoietic stem cell transplantation (AHSCT) has been increasingly used for treatment of relapsing-remitting multiple sclerosis (RRMS). Existing data suggest that AHSCT might alter the natural course of multiple sclerosis (MS) and postpone or even prevent the occurrence of progressive MS. This study aimed to investigate whether three cerebrospinal fluid biomarkers of progressive MS: Galectin-9, GDF-15, and YKL-40, were affected by treatment intervention with AHSCT for RRMS.</p><p><strong>Methods: </strong>RRMS patients treated with AHSCT at Uppsala University Hospital between 2011 and 2018 were considered for participation and included if CSF samples from baseline and at least one follow-up were available. CSF from healthy volunteers was included as controls. Galectin-9 and GDF-15 concentrations were determined with ELISA, and YKL-40 with electrochemiluminescence.</p><p><strong>Results: </strong>The final cohort comprised 45 RRMS patients and 32 controls. At baseline, MS patients had markedly higher CSF concentrations of Galectin-9 and YKL-40 and slightly higher GDF-15 than controls. Following AHSCT, biomarker concentrations decreased from baseline to the 1-year follow-up, with a median (IQR) of 454 (357-553) vs. 408 (328-495) pg/mL (P = 0.0002) for Galectin-9; 49 (38-79) vs. 45 (35 to 75) pg/mL (P = 0.012) for GDF-15, and 100 (54-164) vs. 58 (43-92) ng/mL (P < 0.0001) for YKL-40. Galectin-9 and YKL-40 concentrations decreased further and were even lower at the 2-year follow-up; median (IQR) 408 (328-495) vs. 376 (289-478) pg/mL (P = 0.0009) for Galectin-9; and 62 (37-96) vs. 56 (30-83) ng/mL (P < 0.0001) for YKL-40. Thereafter, the levels of all biomarkers were stable throughout the follow-up.</p><p><strong>Conclusion: </strong>Treatment with AHSCT was associated with sustained reductions in biomarkers linked to progressive MS, indicating its potential not only to achieve lasting remission but also to delay or prevent transition to SPMS. However, additional studies are necessary to confirm these findings and elucidate their long-term clinical significance.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"186"},"PeriodicalIF":10.1000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273295/pdf/","citationCount":"0","resultStr":"{\"title\":\"Biomarkers of progressive multiple sclerosis decrease following autologous hematopoietic stem cell transplantation.\",\"authors\":\"Ida Erngren, Katarina Lundblad, Ivan Pavlovic, Asma Al-Grety, Anders Larsson, Kim Kultima, Joachim Burman\",\"doi\":\"10.1186/s12974-025-03511-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Autologous hematopoietic stem cell transplantation (AHSCT) has been increasingly used for treatment of relapsing-remitting multiple sclerosis (RRMS). Existing data suggest that AHSCT might alter the natural course of multiple sclerosis (MS) and postpone or even prevent the occurrence of progressive MS. This study aimed to investigate whether three cerebrospinal fluid biomarkers of progressive MS: Galectin-9, GDF-15, and YKL-40, were affected by treatment intervention with AHSCT for RRMS.</p><p><strong>Methods: </strong>RRMS patients treated with AHSCT at Uppsala University Hospital between 2011 and 2018 were considered for participation and included if CSF samples from baseline and at least one follow-up were available. CSF from healthy volunteers was included as controls. Galectin-9 and GDF-15 concentrations were determined with ELISA, and YKL-40 with electrochemiluminescence.</p><p><strong>Results: </strong>The final cohort comprised 45 RRMS patients and 32 controls. At baseline, MS patients had markedly higher CSF concentrations of Galectin-9 and YKL-40 and slightly higher GDF-15 than controls. Following AHSCT, biomarker concentrations decreased from baseline to the 1-year follow-up, with a median (IQR) of 454 (357-553) vs. 408 (328-495) pg/mL (P = 0.0002) for Galectin-9; 49 (38-79) vs. 45 (35 to 75) pg/mL (P = 0.012) for GDF-15, and 100 (54-164) vs. 58 (43-92) ng/mL (P < 0.0001) for YKL-40. Galectin-9 and YKL-40 concentrations decreased further and were even lower at the 2-year follow-up; median (IQR) 408 (328-495) vs. 376 (289-478) pg/mL (P = 0.0009) for Galectin-9; and 62 (37-96) vs. 56 (30-83) ng/mL (P < 0.0001) for YKL-40. Thereafter, the levels of all biomarkers were stable throughout the follow-up.</p><p><strong>Conclusion: </strong>Treatment with AHSCT was associated with sustained reductions in biomarkers linked to progressive MS, indicating its potential not only to achieve lasting remission but also to delay or prevent transition to SPMS. However, additional studies are necessary to confirm these findings and elucidate their long-term clinical significance.</p>\",\"PeriodicalId\":16577,\"journal\":{\"name\":\"Journal of Neuroinflammation\",\"volume\":\"22 1\",\"pages\":\"186\"},\"PeriodicalIF\":10.1000,\"publicationDate\":\"2025-07-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273295/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neuroinflammation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12974-025-03511-6\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuroinflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12974-025-03511-6","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Biomarkers of progressive multiple sclerosis decrease following autologous hematopoietic stem cell transplantation.
Background: Autologous hematopoietic stem cell transplantation (AHSCT) has been increasingly used for treatment of relapsing-remitting multiple sclerosis (RRMS). Existing data suggest that AHSCT might alter the natural course of multiple sclerosis (MS) and postpone or even prevent the occurrence of progressive MS. This study aimed to investigate whether three cerebrospinal fluid biomarkers of progressive MS: Galectin-9, GDF-15, and YKL-40, were affected by treatment intervention with AHSCT for RRMS.
Methods: RRMS patients treated with AHSCT at Uppsala University Hospital between 2011 and 2018 were considered for participation and included if CSF samples from baseline and at least one follow-up were available. CSF from healthy volunteers was included as controls. Galectin-9 and GDF-15 concentrations were determined with ELISA, and YKL-40 with electrochemiluminescence.
Results: The final cohort comprised 45 RRMS patients and 32 controls. At baseline, MS patients had markedly higher CSF concentrations of Galectin-9 and YKL-40 and slightly higher GDF-15 than controls. Following AHSCT, biomarker concentrations decreased from baseline to the 1-year follow-up, with a median (IQR) of 454 (357-553) vs. 408 (328-495) pg/mL (P = 0.0002) for Galectin-9; 49 (38-79) vs. 45 (35 to 75) pg/mL (P = 0.012) for GDF-15, and 100 (54-164) vs. 58 (43-92) ng/mL (P < 0.0001) for YKL-40. Galectin-9 and YKL-40 concentrations decreased further and were even lower at the 2-year follow-up; median (IQR) 408 (328-495) vs. 376 (289-478) pg/mL (P = 0.0009) for Galectin-9; and 62 (37-96) vs. 56 (30-83) ng/mL (P < 0.0001) for YKL-40. Thereafter, the levels of all biomarkers were stable throughout the follow-up.
Conclusion: Treatment with AHSCT was associated with sustained reductions in biomarkers linked to progressive MS, indicating its potential not only to achieve lasting remission but also to delay or prevent transition to SPMS. However, additional studies are necessary to confirm these findings and elucidate their long-term clinical significance.
期刊介绍：
The Journal of Neuroinflammation is a peer-reviewed, open access publication that emphasizes the interaction between the immune system, particularly the innate immune system, and the nervous system. It covers various aspects, including the involvement of CNS immune mediators like microglia and astrocytes, the cytokines and chemokines they produce, and the influence of peripheral neuro-immune interactions, T cells, monocytes, complement proteins, acute phase proteins, oxidative injury, and related molecular processes.
Neuroinflammation is a rapidly expanding field that has significantly enhanced our knowledge of chronic neurological diseases. It attracts researchers from diverse disciplines such as pathology, biochemistry, molecular biology, genetics, clinical medicine, and epidemiology. Substantial contributions to this field have been made through studies involving populations, patients, postmortem tissues, animal models, and in vitro systems.
The Journal of Neuroinflammation consolidates research that centers around common pathogenic processes. It serves as a platform for integrative reviews and commentaries in this field.
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