Duell Frida, Högelin Klara Asplund, Vlad Benjamin, Neidhart Stephan, Khademi Mohsen, Jelcic Ilijas, Hansson Magnus, Al Nimer Faiez
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Eur J Neurol. 2025 Jul;32(7):e70291. doi: 10.1111/ene.70291.
To investigate the relation between intrathecal antibody production, as reflected by kappa free light chain (KFLC) metrics, and multiple sclerosis (MS) prognosis-related markers and study its modulation following MS treatment.
This study comprised matched plasma and cerebrospinal fluid (CSF) samples from a total of 130 persons with MS (pwMS), 99 of whom were untreated at baseline. Paired samples from 73 pwMS (18 on dimethyl fumarate (DMF), 10 on fingolimod, 6 on natalizumab, 25 on rituximab (RTX) and 14 after autologous hematopoietic stem cell transplantation (HSCT)) were used to analyze treatment effects on KFLC metrics. KFLC was measured by nephelometry while clinical and paraclinical data were collected from the patient charts. HLA typing was performed with SNP genotyping.
The KFLC local concentration (KFLC loc) and index was higher in HLA-DRB1*15:01 carriers and correlated with the number of CSF mononuclear cells, IgG index, and CSF levels of CXCL13 and neurofilament light chain, the latter particularly during remission (r = 0.27, p = 0.045). With regard to treatment effects, we found that treatment with DMF, RTX, and HSCT resulted in a decrease of CSF-KFLC levels and/or KFLC loc and index. Interestingly, the rate of decrease in KFLC index correlated with time since first treatment (r = -0.41, p = 0.045).
These findings support an involvement of intrathecal antibodies in non-relapsing MS pathology and inform on the effect of current treatments. The slow rate of decrease in KFLC index following B cell depletion stresses the need for early treatment start.
通过κ游离轻链（KFLC）指标反映鞘内抗体产生情况，并研究其与多发性硬化症（MS）预后相关标志物之间的关系，以及在MS治疗后的变化情况。
本研究纳入了130例MS患者（pwMS）配对的血浆和脑脊液（CSF）样本，其中99例在基线时未接受治疗。使用73例pwMS的配对样本（18例接受富马酸二甲酯（DMF）治疗、10例接受芬戈莫德治疗、6例接受那他珠单抗治疗、25例接受利妥昔单抗（RTX）治疗以及14例接受自体造血干细胞移植（HSCT）后）分析治疗对KFLC指标的影响。通过比浊法测量KFLC，同时从患者病历中收集临床和副临床数据。采用单核苷酸多态性基因分型进行HLA分型。
HLA - DRB1*15:01携带者的KFLC局部浓度（KFLC loc）和指数较高，且与CSF单核细胞数量、IgG指数以及CXCL13和神经丝轻链的CSF水平相关，后者在缓解期尤为明显（r = 0.27，p = 0.045）。关于治疗效果，我们发现DMF、RTX和HSCT治疗导致CSF-KFLC水平和/或KFLC loc及指数降低。有趣的是，KFLC指数的降低速率与首次治疗后的时间相关（r = -0.41，p = 0.045）。
这些发现支持鞘内抗体参与非复发型MS病理过程，并为当前治疗效果提供了信息。B细胞耗竭后KFLC指数下降缓慢，强调了早期开始治疗的必要性。
