Rasel Ahmed, Shoma Hayat, Asaduzzaman Asad, Israt Jahan, Moriam Akter Munni, Ruma Begum, Sarah Khurshid, Morium Akter Mukta, Zhahirul Islam
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Serum levels of TGF-<i>β</i>1 and anti-GM1 autoantibodies were assessed using enzyme-linked immunosorbent assays. The tetra-primer amplification refractory mutation system-PCR was used to detect the targeted <i>TGF-β1</i> gene SNPs. In this study, 79% of patients were reported with antecedent events, primarily diarrhea (44%). Overall, 89% of patients were affected with severe GBS; among them, 17% required mechanical ventilation and 21% remained functionally disabled after 6 months. TGF-<i>β</i>1 serum levels were significantly higher in GBS patients compared to HCs (<i>p</i> < 0.0001), demonstrating a cut-off of > 414.02 ng/mL for GBS. In addition, serum levels were correlated to higher GBS-disability scores (<i>r</i><sub>s</sub> = 0.338, <i>p</i> < 0.0001) and were associated with severe GBS (<i>p</i> = 0.04). Elevated TGF-<i>β</i>1 concentration was associated with poor clinical outcomes in patients at 6 months of disease onset (<i>p</i> = 0.006). The TGF-<i>β</i>1-509 T/T genotype was more frequent in <i>Campylobacter jejuni</i>-seropositive patients compared to seronegative patients (OR = 2.87, <i>p</i><sub><i>c</i></sub> = 0.04), especially in those with the axonal GBS variant (OR = 3.8, <i>p</i><sub><i>c</i></sub> = 0.07). However, no significant associations were found between <i>TGF-β1</i> SNPs and overall the disease susceptibility or serum TGF-<i>β</i>1 concentration. The study concluded that elevated serum TGF-<i>β</i>1 concentration is associated with both GBS susceptibility and clinical severity and is linked to worse functional outcomes. While the –509 T/T genotype may be linked to <i>C. jejuni</i>–driven axonal GBS, there was no overall polymorphism association with GBS risk or cytokine levels. These findings might be crucial in understanding and predicting disease susceptibility and severity of GBS.</p>","PeriodicalId":6939,"journal":{"name":"Acta Neurologica Scandinavica","volume":"2025 1","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ane/2063433","citationCount":"0","resultStr":"{\"title\":\"Elevated Serum TGF-β1 Is Linked to Guillain–Barré Syndrome Severity in Bangladeshi Patients: No Association With TGF-β1 −509C/T and +869C/T Polymorphisms\",\"authors\":\"Rasel Ahmed, Shoma Hayat, Asaduzzaman Asad, Israt Jahan, Moriam Akter Munni, Ruma Begum, Sarah Khurshid, Morium Akter Mukta, Zhahirul Islam\",\"doi\":\"10.1155/ane/2063433\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Guillain–Barré syndrome (GBS) is an autoimmune peripheral nerve disorder characterized by progressive muscle weakness. Transforming growth factor-beta 1 (TGF-<i>β</i>1) is a major immune-regulating cytokine; therefore, serum concentration of TGF-<i>β</i>1 and its genotypes may contribute to developing GBS. This study is aimed at evaluating the changes in TGF-<i>β</i>1 serum level in GBS and investigating the association of <i>TGF-β1</i> gene +869C/T and −509C/T) single-nucleotide polymorphisms (SNPs) with GBS susceptibility and TGF-<i>β</i>1 cytokine level. A case–control study was conducted with 200 GBS patients and 200 age-, sex-, and ethnicity-matched healthy controls (HCs). Serum levels of TGF-<i>β</i>1 and anti-GM1 autoantibodies were assessed using enzyme-linked immunosorbent assays. The tetra-primer amplification refractory mutation system-PCR was used to detect the targeted <i>TGF-β1</i> gene SNPs. In this study, 79% of patients were reported with antecedent events, primarily diarrhea (44%). Overall, 89% of patients were affected with severe GBS; among them, 17% required mechanical ventilation and 21% remained functionally disabled after 6 months. TGF-<i>β</i>1 serum levels were significantly higher in GBS patients compared to HCs (<i>p</i> < 0.0001), demonstrating a cut-off of > 414.02 ng/mL for GBS. In addition, serum levels were correlated to higher GBS-disability scores (<i>r</i><sub>s</sub> = 0.338, <i>p</i> < 0.0001) and were associated with severe GBS (<i>p</i> = 0.04). Elevated TGF-<i>β</i>1 concentration was associated with poor clinical outcomes in patients at 6 months of disease onset (<i>p</i> = 0.006). The TGF-<i>β</i>1-509 T/T genotype was more frequent in <i>Campylobacter jejuni</i>-seropositive patients compared to seronegative patients (OR = 2.87, <i>p</i><sub><i>c</i></sub> = 0.04), especially in those with the axonal GBS variant (OR = 3.8, <i>p</i><sub><i>c</i></sub> = 0.07). However, no significant associations were found between <i>TGF-β1</i> SNPs and overall the disease susceptibility or serum TGF-<i>β</i>1 concentration. The study concluded that elevated serum TGF-<i>β</i>1 concentration is associated with both GBS susceptibility and clinical severity and is linked to worse functional outcomes. While the –509 T/T genotype may be linked to <i>C. jejuni</i>–driven axonal GBS, there was no overall polymorphism association with GBS risk or cytokine levels. 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引用次数: 0
摘要
格林-巴罗综合征(GBS)是一种以进行性肌肉无力为特征的自身免疫性周围神经疾病。转化生长因子-β1 (TGF-β1)是一种主要的免疫调节细胞因子;因此,血清TGF-β1浓度及其基因型可能与GBS的发生有关。本研究旨在评价TGF-β1血清水平在GBS中的变化,探讨TGF-β1基因+869C/T和- 509C/T单核苷酸多态性(snp)与GBS易感性和TGF-β1细胞因子水平的关系。对200名GBS患者和200名年龄、性别和种族匹配的健康对照(hc)进行了病例对照研究。采用酶联免疫吸附法检测血清TGF-β1和抗gm1自身抗体水平。采用四引物扩增难解突变系统- pcr检测TGF-β1基因snp。在这项研究中,79%的患者报告有既往事件,主要是腹泻(44%)。总体而言,89%的患者患有严重的GBS;其中17%需要机械通气,21%在6个月后仍然功能残疾。与hcc患者相比,GBS患者血清中TGF-β1水平显著升高(p < 0.0001), GBS的临界值为414.02 ng/mL。此外,血清水平与较高的GBS-残疾评分相关(rs = 0.338, p < 0.0001),与严重的GBS相关(p = 0.04)。TGF-β1浓度升高与患者发病6个月时的不良临床结果相关(p = 0.006)。TGF-β1-509 T/T基因型在空肠弯曲杆菌血清阳性患者中较血清阴性患者更为常见(OR = 2.87, pc = 0.04),尤其是轴突GBS变异患者(OR = 3.8, pc = 0.07)。然而,TGF-β1 snp与总体疾病易感性或血清TGF-β1浓度之间未发现显著相关性。该研究得出结论,血清TGF-β1浓度升高与GBS易感性和临床严重程度相关,并与较差的功能预后相关。虽然-509 T/T基因型可能与肠弧菌驱动的轴突GBS有关,但与GBS风险或细胞因子水平没有总体多态性关联。这些发现可能对了解和预测GBS的疾病易感性和严重程度至关重要。
Elevated Serum TGF-β1 Is Linked to Guillain–Barré Syndrome Severity in Bangladeshi Patients: No Association With TGF-β1 −509C/T and +869C/T Polymorphisms
Guillain–Barré syndrome (GBS) is an autoimmune peripheral nerve disorder characterized by progressive muscle weakness. Transforming growth factor-beta 1 (TGF-β1) is a major immune-regulating cytokine; therefore, serum concentration of TGF-β1 and its genotypes may contribute to developing GBS. This study is aimed at evaluating the changes in TGF-β1 serum level in GBS and investigating the association of TGF-β1 gene +869C/T and −509C/T) single-nucleotide polymorphisms (SNPs) with GBS susceptibility and TGF-β1 cytokine level. A case–control study was conducted with 200 GBS patients and 200 age-, sex-, and ethnicity-matched healthy controls (HCs). Serum levels of TGF-β1 and anti-GM1 autoantibodies were assessed using enzyme-linked immunosorbent assays. The tetra-primer amplification refractory mutation system-PCR was used to detect the targeted TGF-β1 gene SNPs. In this study, 79% of patients were reported with antecedent events, primarily diarrhea (44%). Overall, 89% of patients were affected with severe GBS; among them, 17% required mechanical ventilation and 21% remained functionally disabled after 6 months. TGF-β1 serum levels were significantly higher in GBS patients compared to HCs (p < 0.0001), demonstrating a cut-off of > 414.02 ng/mL for GBS. In addition, serum levels were correlated to higher GBS-disability scores (rs = 0.338, p < 0.0001) and were associated with severe GBS (p = 0.04). Elevated TGF-β1 concentration was associated with poor clinical outcomes in patients at 6 months of disease onset (p = 0.006). The TGF-β1-509 T/T genotype was more frequent in Campylobacter jejuni-seropositive patients compared to seronegative patients (OR = 2.87, pc = 0.04), especially in those with the axonal GBS variant (OR = 3.8, pc = 0.07). However, no significant associations were found between TGF-β1 SNPs and overall the disease susceptibility or serum TGF-β1 concentration. The study concluded that elevated serum TGF-β1 concentration is associated with both GBS susceptibility and clinical severity and is linked to worse functional outcomes. While the –509 T/T genotype may be linked to C. jejuni–driven axonal GBS, there was no overall polymorphism association with GBS risk or cytokine levels. These findings might be crucial in understanding and predicting disease susceptibility and severity of GBS.
期刊介绍:
Acta Neurologica Scandinavica aims to publish manuscripts of a high scientific quality representing original clinical, diagnostic or experimental work in neuroscience. The journal''s scope is to act as an international forum for the dissemination of information advancing the science or practice of this subject area. Papers in English will be welcomed, especially those which bring new knowledge and observations from the application of therapies or techniques in the combating of a broad spectrum of neurological disease and neurodegenerative disorders. Relevant articles on the basic neurosciences will be published where they extend present understanding of such disorders. Priority will be given to review of topical subjects. Papers requiring rapid publication because of their significance and timeliness will be included as ''Clinical commentaries'' not exceeding two printed pages, as will ''Clinical commentaries'' of sufficient general interest. Debate within the speciality is encouraged in the form of ''Letters to the editor''. All submitted manuscripts falling within the overall scope of the journal will be assessed by suitably qualified referees.