Increased CXCL12, a potential CSF biomarker for differential diagnosis of amyotrophic lateral sclerosis

被引:0
作者
Roca-Pereira, Sergio [1 ,2 ]
Dominguez, Raul [1 ,2 ,3 ]
Moreno Leon, Isabel [1 ,4 ]
Colomina, Maria J. [5 ]
Yelamos, Antonio Martinez [1 ,4 ,6 ]
Yelamos, Sergio Martinez [1 ,4 ,6 ]
Povedano, Monica [1 ,2 ,3 ]
Andres-Benito, Pol [1 ,2 ]
机构
[1] Bellvitge Biomed Res Inst IDIBELL, Grp Neurol Dis & Neurogenet, Barcelona 08907, Spain
[2] Inst Hlth Carlos III, Network Ctr Biomed Res Neurodegenerat Dis CIBERNED, Barcelona 08907, Spain
[3] Bellvitge Univ Hosp HUB, Serv Neurol, Funct Unit Amyotroph Lateral Sclerosis UFELA, Carrer Feixa Llarga S-N, Barcelona 08907, Spain
[4] Bellvitge Univ Hosp, Dept Neurol, Multiple Sclerosis Unit, Barcelona 08907, Spain
[5] Univ Barcelona UB, Bellvitge Univ Hosp, Anesthesia & Crit Care Dept, Barcelona 08907, Spain
[6] Univ Barcelona UB, Fac Med & Ciencies Salut, Dept Ciencies Clin, Barcelona 08907, Spain
关键词
ALS; diagnostic tool; CXCL12; CSF; CEREBROSPINAL-FLUID; NEUROFILAMENT LIGHT; SEVERITY; CRITERIA;
D O I
10.1093/braincomms/fcae271
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Amyotrophic lateral sclerosis is a debilitating and lethal neurodegenerative disorder marked by the gradual deterioration of motor neurons. Diagnosing amyotrophic lateral sclerosis is challenging due to the lack of reliable diagnostic tools, with clinical assessment being the primary criterion. Recently, increased levels of neurofilament light chain in CSF have been considered a useful biomarker in disease, correlating with disease progression but not specific for diagnosis. This study utilized enzyme-linked immunosorbent assay to measure CSF C-X-C motif chemokine ligand 12 levels in healthy controls, amyotrophic lateral sclerosis patients and patients with amyotrophic lateral sclerosis-mimic disorders, assessing its potential as a diagnostic biomarker and comparing it with neurofilament light chain levels. Our results confirmed previous findings, showing increased C-X-C motif chemokine ligand 12 levels in amyotrophic lateral sclerosis patients compared to healthy control (797.07 +/- 31.84 pg/mL versus 316.15 +/- 16.6 pg/mL; P = 0.000) and increased CSF neurofilament light chain levels in amyotrophic lateral sclerosis (4565.63 +/- 263.77 pg/mL) compared to healthy control (847.86 +/- 214.37 pg/mL; P = 0.000). Increased C-X-C motif chemokine ligand levels were specific to amyotrophic lateral sclerosis, not seen in amyotrophic lateral sclerosis-mimic conditions like myelopathies (252.20 +/- 23.16 pg/mL; P = 0.000), inflammatory polyneuropathies (270.24 +/- 32.23 pg/mL; P = 0.000) and other mimic diseases (228.91 +/- 29.20 pg/mL; P = 0.000). In contrast, CSF neurofilament light chain levels in amyotrophic lateral sclerosis overlapped with those in myelopathies (2900.11 +/- 872.20 pg/mL; P = 0.821) and other mimic diseases (3169.75 +/- 1096.65 pg/mL; P = 0.63), but not with inflammatory polyneuropathies (1156.4 +/- 356.6 pg/mL; P = 0.000). Receiver operating characteristic curve analysis indicated significant differences between the area under the curve values of C-X-C motif chemokine ligand and neurofilament light chain in their diagnostic capacities. C-X-C motif chemokine ligand could differentiate between amyotrophic lateral sclerosis and myelopathies (area under the curve 0.99 +/- 0.005), inflammatory polyneuropathies (area under the curve 0.962 +/- 0.027) and other mimic diseases (area under the curve 1.00 +/- 0.00), whereas neurofilament light chain was only effective in inflammatory polyneuropathies cases (area under the curve 0.92 +/- 0.048), not in myelopathies (area under the curve 0.71 +/- 0.09) or other mimic diseases (area under the curve 0.69 +/- 0.14). We also evaluated C-X-C motif chemokine ligand levels in plasma [amyotrophic lateral sclerosis (2022 +/- 81.8 pg/mL) versus healthy control (1739.43 +/- 77.3 pg/mL; P = 0.015)] but found CSF determination (area under the curve 0.97 +/- 0.012) to be more accurate than plasma determination (area under the curve 0.65 +/- 0.063). In plasma, single molecule array (SIMOA) neurofilament light chain determination [amyotrophic lateral sclerosis (86.00 +/- 12.23 pg/mL) versus healthy control (12.69 +/- 1.15 pg/mL); P = 0.000] was more accurate than plasma C-X-C motif chemokine ligand 12 (area under the curve 0.98 +/- 0.01405). These findings suggest that CSF C-X-C motif chemokine ligand 12 levels can enhance diagnostic specificity in distinguishing amyotrophic lateral sclerosis from amyotrophic lateral sclerosis-mimic disorders, compared to neurofilament light chain. Larger studies are needed to validate these results, but C-X-C motif chemokine ligand 12 determination shows promising diagnostic potential. Roca-Pereira et al. found C-X-C motif chemokine ligand 12 (CXCL12) more specific for amyotrophic lateral sclerosis compared to neurofilament light chain (NF-L), the current gold standard biomarker. While NF-L is altered in many pathologies, CXCL12's specificity underscores its relevance in amyotrophic lateral sclerosis pathophysiology and its potential utility in differential diagnosis of the disease. Graphical Abstract
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