PMID- 24078718 OWN - NLM STAT- MEDLINE DCOM- 20140403 LR - 20220309 IS - 1468-330X (Electronic) IS - 0022-3050 (Linking) VI - 85 IP - 3 DP - 2014 Mar TI - Immune reactivity to neurofilament proteins in the clinical staging of amyotrophic lateral sclerosis. PG - 274-8 LID - 10.1136/jnnp-2013-305494 [doi] AB - BACKGROUND: Neurofilament (NF) proteins detection in biological fluids as a by-product of axonal loss is technically challenging and to date relies mostly on cerebrospinal fluid (CSF) measurements. Plasma antibodies against NF proteins and particularly to their soluble light chain (NF-L) could be a more practical surrogate marker for disease staging in amyotrophic lateral sclerosis (ALS), an invariably fatal and clinically heterogeneous neuromuscular disorder. METHODOLOGY: We have used a recombinant neurofilament light chain (NF-L) protein for the ELISA detection of antibodies against NF proteins in plasma samples from a well-characterised cohort of ALS individuals (n:73). The use of an established functional rating scale and of a recently proposed staging of disease progression allowed stratification of the ALS cohort based on disease stage, site of onset, survival and speed of disease progression. RESULTS: Antibody levels to NF proteins in plasma were significantly higher in ALS individuals compared to healthy controls (p<0.001). Higher NF plasma immunoreactivity was seen in advanced ALS cases (stage IVA-B) compared to earlier phases of the disease (p<0.05). There was no difference in anti-NF plasma antibodies between ALS individuals treated with riluzole and untreated patients; although riluzole-treated ALS cases with an earlier age of onset and with a shorter diagnostic delay displayed higher anti-NFL antibody levels compared to untreated ALS patients with similar features. CONCLUSIONS: Immunoreactivity to plasma NF-L and homologous NF proteins is informative of the stage of disease progression in ALS. The determination of NF antibody levels in plasma could be added to the growing panel of disease-monitoring biomarkers in ALS targeting cytoskeletal antigens. FAU - Puentes, Fabiola AU - Puentes F AD - Neuroimmunology Unit, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, , London, UK. FAU - Topping, Joanne AU - Topping J FAU - Kuhle, Jens AU - Kuhle J FAU - van der Star, Baukje J AU - van der Star BJ FAU - Douiri, Abdel AU - Douiri A FAU - Giovannoni, Gavin AU - Giovannoni G FAU - Baker, David AU - Baker D FAU - Amor, Sandra AU - Amor S FAU - Malaspina, Andrea AU - Malaspina A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130927 PL - England TA - J Neurol Neurosurg Psychiatry JT - Journal of neurology, neurosurgery, and psychiatry JID - 2985191R RN - 0 (Antibodies) RN - 0 (Biomarkers) RN - 0 (Neurofilament Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Recombinant Proteins) RN - 0 (neurofilament protein L) RN - 7LJ087RS6F (Riluzole) SB - IM MH - Aged MH - Amyotrophic Lateral Sclerosis/*diagnosis/drug therapy/immunology MH - Antibodies/blood/immunology MH - Biomarkers/blood MH - Case-Control Studies MH - Disease Progression MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Humans MH - Male MH - Middle Aged MH - Neurofilament Proteins/blood/*immunology MH - Neuroprotective Agents/therapeutic use MH - Recombinant Proteins MH - Riluzole/therapeutic use OTO - NOTNLM OT - ALS EDAT- 2013/10/01 06:00 MHDA- 2014/04/04 06:00 CRDT- 2013/10/01 06:00 PHST- 2013/10/01 06:00 [entrez] PHST- 2013/10/01 06:00 [pubmed] PHST- 2014/04/04 06:00 [medline] AID - jnnp-2013-305494 [pii] AID - 10.1136/jnnp-2013-305494 [doi] PST - ppublish SO - J Neurol Neurosurg Psychiatry. 2014 Mar;85(3):274-8. doi: 10.1136/jnnp-2013-305494. Epub 2013 Sep 27.