title: Oligoclonal bands in the cerebrospinal fluid of amyotrophic lateral sclerosis patients with disease-associated mutations.
abstract: In amyotrophic lateral sclerosis (ALS) cerebrospinal fluid (CSF) analysis is usually performed to exclude inflammatory processes of the central nervous system. Although in a small subset of patients an intrathecal synthesis of IgG is detectable, usually there is no clear explanation for this evidence. This study investigates the occurrence of oligoclonal bands (OCBs) in the CSF of a large series of ALS patients, attempting a correlation with genotype data. CSF was collected from 259 ALS patients. CSF parameters were measured according to standard procedures, and detection of OCBs performed by isoelectric focusing. The patients were screened for mutations in SOD1, FUS, TARDBP, ANG, OPTN, and C9ORF72. We observed the presence of OCBs in the CSF of 9/259 ALS patients (3.5 %), and of disease-associated mutations in 12 cases. OCBs were significantly more frequent in mutation carriers compared to the remaining cohort (3/12 vs 6/247; p < 0.01). Among patients with OCBs, two patients had the TARDBP p.A382T mutation (one of which in homozygous state), and one the ANG p.P-4S variant. Both patients carrying the p.A382T mutation had an atypical phenotype, one of them manifesting signs suggestive of a cerebellar involvement, and the other presenting neuroradiological findings suggestive of an inflammatory disorder of the central nervous system. Our results suggest that ALS patients with OCBs may harbor mutations in disease-causing genes. We speculate that mutations in both TARDBP and ANG genes may disrupt the blood-brain barrier (BBB), promoting local immune responses and neuroinflammation. The role of mutant TARDBP and ANG genes on BBB integrity of ALS patients warrants further investigation.
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy.
authors: Nicola
authors: N
authors: Ticozzi
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy; Doctoral School in Molecular Medicine, Università degli Studi di Milano, 20122 Milan, Italy.
authors: Cinzia
authors: C
authors: Tiloca
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy; Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, 'Dino Ferrari' Center, Università degli Studi di Milano, 20122 Milan, Italy.
authors: Niccolò E
authors: NE
authors: Mencacci
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy.
authors: Claudia
authors: C
authors: Morelli
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy; Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, 'Dino Ferrari' Center, Università degli Studi di Milano, 20122 Milan, Italy.
authors: Alberto
authors: A
authors: Doretti
authors: Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, 20095 Cusano Milanino, Milan, Italy.
authors: Daniela
authors: D
authors: Rusconi
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy.
authors: Claudia
authors: C
authors: Colombrita
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy.
authors: Davide
authors: D
authors: Sangalli
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy.
authors: Federico
authors: F
authors: Verde
authors: Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, 20095 Cusano Milanino, Milan, Italy; Department of Biology and Genetics for Medical Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
authors: Palma
authors: P
authors: Finelli
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy.
authors: Stefano
authors: S
authors: Messina
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy; Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, 'Dino Ferrari' Center, Università degli Studi di Milano, 20122 Milan, Italy.
authors: Antonia
authors: A
authors: Ratti
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, 20149 Milan, Italy; Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, 'Dino Ferrari' Center, Università degli Studi di Milano, 20122 Milan, Italy.
authors: Vincenzo
authors: V
authors: Silani
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000235:genetics* / Q000473:pathology; D001772:Blood Cell Count; D001799:Blood Sedimentation; D001921:Brain / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D000073885:C9orf72 Protein; D018797:Cell Cycle Proteins; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid*; D011506:Proteins / Q000235:genetics; D012259:Ribonuclease, Pancreatic / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D035582:Transcription Factor TFIIIA / Q000235:genetics
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D043025:Oligoclonal Bands; D011506:Proteins; C000606290:SOD1 protein, human; D035582:Transcription Factor TFIIIA; D002097:C-Reactive Protein; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C046366:angiogenin; D012259:Ribonuclease, Pancreatic