PMID- 35835469 OWN - NLM STAT- MEDLINE DCOM- 20220816 LR - 20221002 IS - 1468-330X (Electronic) IS - 0022-3050 (Linking) VI - 93 IP - 9 DP - 2022 Sep TI - Clinical value of cell-based assays in the characterisation of seronegative myasthenia gravis. PG - 995-1000 LID - 10.1136/jnnp-2022-329284 [doi] AB - OBJECTIVE: Patients with myasthenia gravis without acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) antibodies detected by radioimmunoprecipitation assays (RIAs) are classified as seronegative myasthenia gravis (SNMG). Live cell-based assays (l-CBAs) can detect additional antibodies to clustered AChR, MuSK and low-density lipoprotein receptor-related protein 4 (LRP4), but positivity rates are variable and both clinical relevance and utility of CBA platforms remain unclear. METHODS: Sera from 82 patients with SNMG were tested by l-CBAs. Human embryonic kidney cells were transfected to individually express clustered AChR, MuSK or LRP4; or transfected to jointly express both clustered adult AChR and MuSK. Sera from 30 and 20 patients positive by RIA for AChR or MuSK antibodies were used as comparators. RESULTS: 53 of 82 (72%) patients with SNMG had generalised and 29 (28%) had ocular disease. The clustered AChR CBA detected antibodies in 16 of 82 patients (19.5%; including 4 patients with solely fetal AChR antibodies), while 7 of 82 (8.5%) patients had MuSK antibodies. A novel exploratory combined adult AChR-MuSK l-CBA efficiently detected all these antibodies in a subset of the SNMG cohort. No LRP4 antibodies were identified. Overall, patients with SNMG with clustered AChR antibodies, CBA-positive MuSK-MG or triple seronegative were younger, had less severe disease than patients with RIA-positive MG and had a better clinical outcome when immunotherapy was started soon after disease onset, although the time interval from onset to immunotherapy was not different when compared with patients with RIA-positive MG. CONCLUSION: Around one-third of patients with SNMG had AChR or MuSK antibodies by l-CBAs, which were efficiently detected with a combined l-CBA. The results in this large and unselected cohort of patients with MG demonstrate the diagnostic usefulness of performing CBAs and the importance of making these tests more widely available. CI - (c) Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Damato, Valentina AU - Damato V AUID- ORCID: 0000-0003-1740-4522 AD - Neuroscience Department, Catholic University of the Sacred Heart, Rome, Italy valentina.damato@unicatt.it. AD - Department of Neurosciences, Drugs and Child Health, University of Florence, Florence, Italy. AD - Oxford Autoimmune Neurology Group, University of Oxford, Oxford, UK. FAU - Spagni, Gregorio AU - Spagni G AD - Neuroscience Department, Catholic University of the Sacred Heart, Rome, Italy. AD - Neurology Institute, Fondazione Policlinico Gemelli IRCSS, Rome, Italy. FAU - Monte, Gabriele AU - Monte G AUID- ORCID: 0000-0002-4763-7784 AD - Neuroscience Department, Catholic University of the Sacred Heart, Rome, Italy. AD - Neuroscience Department, Bambino Gesu Children's Hospital IRCCS, Rome, Italy. FAU - Woodhall, Mark AU - Woodhall M AD - Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. FAU - Jacobson, Leslie AU - Jacobson L AD - Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. FAU - Falso, Silvia AU - Falso S AD - Neuroscience Department, Catholic University of the Sacred Heart, Rome, Italy. FAU - Smith, Thomas AU - Smith T AD - Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. FAU - Iorio, Raffaele AU - Iorio R AUID- ORCID: 0000-0002-6270-0956 AD - Neurology Institute, Fondazione Policlinico Gemelli IRCSS, Rome, Italy. FAU - Waters, Patrick AU - Waters P AUID- ORCID: 0000-0003-4142-2667 AD - Oxford Autoimmune Neurology Group, University of Oxford, Oxford, UK. AD - Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. FAU - Irani, Sarosh R AU - Irani SR AUID- ORCID: 0000-0002-7667-9748 AD - Oxford Autoimmune Neurology Group, University of Oxford, Oxford, UK. AD - Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. FAU - Vincent, Angela AU - Vincent A AD - Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. FAU - Evoli, Amelia AU - Evoli A AD - Neuroscience Department, Catholic University of the Sacred Heart, Rome, Italy. AD - Neurology Institute, Fondazione Policlinico Gemelli IRCSS, Rome, Italy. LA - eng GR - MR/V007173/1/MRC_/Medical Research Council/United Kingdom GR - U54 NS115054/NS/NINDS NIH HHS/United States GR - 104079/Z/14/Z/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220714 PL - England TA - J Neurol Neurosurg Psychiatry JT - Journal of neurology, neurosurgery, and psychiatry JID - 2985191R RN - 0 (Autoantibodies) RN - 0 (Receptors, Cholinergic) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Adult MH - Autoantibodies MH - Cohort Studies MH - Humans MH - *Myasthenia Gravis/diagnosis MH - *Receptor Protein-Tyrosine Kinases MH - Receptors, Cholinergic OTO - NOTNLM OT - MYASTHENIA OT - NEUROIMMUNOLOGY OT - NEUROMUSCULAR COIS- Competing interests: AV and the University of Oxford held a patent for detection of MuSK antibody assays (expired 2020), licensed to Athena Diagnostics; AV received a proportion of royalties. SRI and PW are co-applicants and receive royalties on patent application WO/2010/046716 entitled 'Neurological Autoimmune Disorders' (the patent has been licensed for the development of assays for LGI1 and other VGKC-complex antibodies) and have filed two other patents regarding autoantibody diagnostic algorithms. EDAT- 2022/07/15 06:00 MHDA- 2022/08/17 06:00 CRDT- 2022/07/14 20:43 PHST- 2022/03/22 00:00 [received] PHST- 2022/06/28 00:00 [accepted] PHST- 2022/07/15 06:00 [pubmed] PHST- 2022/08/17 06:00 [medline] PHST- 2022/07/14 20:43 [entrez] AID - jnnp-2022-329284 [pii] AID - 10.1136/jnnp-2022-329284 [doi] PST - ppublish SO - J Neurol Neurosurg Psychiatry. 2022 Sep;93(9):995-1000. doi: 10.1136/jnnp-2022-329284. Epub 2022 Jul 14.