METHODS: In an exploratory cohort, CSF cytokines were evaluated by means of Multiplex technology (Bio-Plex Pro-Human Cytokine, GF and Diabetes 27-Plex Panel, Bio-Plex Pro-Human Chemokines 40-Plex Panel, Bio-Plex Pro-Human Inflammation Assays 37-Plex Panel) in a cohort of Other Not Inflammatory Neurological Disorders (ONIND) and in cohort of patients with MS, stratified according to BBB damage into QALB+ and QALB- MS patients. In the validation cohort, we evaluated the relevant molecules in a cohort of MS patients, stratified again into QALB+ and QALB-, including also Neurofilament Light (NfL) and Chitinase 3-like 1 (CHI3L1) CSF concentration.
RESULTS: While MIP-1α, CXCL-13, and CCL-22 CSF concentrations were higher in both MS groups compared to ONIND, in QALB+ MS CSF concentrations of CXCL-9 (17.85 ± 4.69 pg/mL), CXCL-10 (476.5 ± 324.3 pg/mL), and IL-16 (96.08 ± 86.17 pg/mL) were higher than in QALB- MS (8.98 ± 5368 pg/mL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.05, and 47.35 ± 36.87 pg/mL, p < 0.005, respectively) and ONIND (8.98 ± 5368 pg/mlL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.005, and 47.35 ± 36.87 pg/mL, p < 0.001, respectively). A strong correlation was observed between CXCL-9 and CXCL-10 in all MS groups (all r>0.75, all p < 0.001). In the validation cohort again CXCL-10 CSF concentration were higher in QALB+ MS than in QALB- MS (94.25 ± 64.75 vs 153.8 ± 99.52, p < 0.05), while no difference was observed in serum. CSF NfL (1642 ± 1963 vs 3231 ± 3492 pg/mL, p < 0.05) and CHI3L1 (183.9 ± 86.62 vs 262 ± 137.5 ng/mL, p < 0.05) were increased in QALB+ MS.
CONCLUSIONS: BBB damage in MS is linked to a specific CSF cytokines pattern (CXCL-9, CXCL-10, IL-16), that are also involved in astrocyte-microglia interaction. To what extent their continuous production in the CNS may mark a more severe disease course merits to be investigated.
方法:在探索性队列中,CSF细胞因子通过多重技术(Bio-PlexPro-Human细胞因子,GF和糖尿病27-Plex小组,Bio-PlexPro-Human趋化因子40-Plex面板,Bio-PlexPro-人类炎症分析37-Plex小组)在其他非炎症性神经疾病(ONIND)和MS患者队列中,根据BBB损害分层为QALB+和QALB-MS患者。在验证队列中,我们评估了一组MS患者的相关分子,再次分层为QALB+和QALB-,还包括神经丝光(NfL)和几丁质酶3样1(CHI3L1)CSF浓度。
结果:而MIP-1α,与ONIND相比,两个MS组的CXCL-13和CCL-22CSF浓度均较高,在QALB+MSCSF中CXCL-9的浓度(17.85±4.69pg/mL),CXCL-10(476.5±324.3pg/mL),和IL-16(96.08±86.17pg/mL)高于QALB-MS(8.98±5368pg/mL,p<0.005,281.0±180.9pg/mL,p<0.05,和47.35±36.87pg/mL,分别为p<0.005)和ONIND(8.98±5368pg/mlL,p<0.005,281.0±180.9pg/mL,p<0.005,和47.35±36.87pg/mL,p分别<0.001)。在所有MS组中观察到CXCL-9和CXCL-10之间的强相关性(所有r>0.75,所有p<0.001)。在验证队列中,QALB+MS的CXCL-10CSF浓度高于QALB-MS(94.25±64.75vs153.8±99.52,p<0.05),而血清没有观察到差异。CSFNfL(1642±1963vs3231±3492pg/mL,p<0.05)和CHI3L1(183.9±86.62vs262±137.5ng/mL,p<0.05)在QALB+MS中增加。
结论:MS中的BBB损伤与特定的CSF细胞因子模式(CXCL-9,CXCL-10,IL-16)有关,也参与星形胶质细胞-小胶质细胞的相互作用。在多大程度上,它们在CNS中的连续产生可能标志着更严重的疾病进程值得研究。