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Clinical manifestations of the anti-IgLON5 disease
Carles Gaig1, Francesc Graus2, Yarko Compta1
1From the Neuroimmunology Program (C. Gaig, F.G., A.I., L.S., J.S., J.D.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Department of Neurology (C. Gaig, F.G., Y.C., M.J.M., A.I., J.S.), Multidisciplinary Sleep Disorders Unit (C. Gaig, A.I., J.S.), Parkinson's Disease & Movement Disorders Unit (Y.C., M.J.M.), and Department of Immunology (G.E.), Hospital Clinic, Barcelona, Spain; Department of Neurology (B.H.), Medical University of Innsbruck, Austria; Department of Neurology (L.B.), Hospital Universitari i Politècnic La Fe; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) (L.B., L.S., J.D.), Valencia, Spain; Department of Neurology and Institute of Neurogenetics (N.P., K.-P.W.), University of Lübeck, Germany; Department of Movement Disorders and Neurology (C. Giordana), Centre Hospitalier Universitaire Nice, France; Department of Neurology (A.H.), Division of Sleep Medicine and Neuromuscular Disorders, University Hospital Muenster, Germany; Clinical Neurosciences (K.K.), St Vincent's Hospital, Melbourne, Australia; Department of Neurology (J.L.), Ulm University, Germany; Department of Neurology (S.M.), Medical University of Vienna, Austria; Department of Neurology (T.M.), Centre Hospitalier de Luxembourg; Department of Neurology (J.P.-P.), Hospital de la Santa Creu i Sant Pau, Barcelona; Department of Neurology (I.P.), Hospital La Paz, Madrid, Spain; Department of Neurology (C.S.), University Medical Center of the Johannes Gutenberg University Mainz, Germany; Neurology Division (M.S.), Hospital das Clínicas, São Paulo University, Brazil; Department of Neurology (N.T.), Hospital Clínico Universitario, Valladolid, Spain; Institute of Clinical Chemistry (K.-P.W.), University Hospital Schleswig-Holstein, Lübeck, Germany; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.
Objective:
To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies.
Methods:
This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques.
Results:
Patients' median age was 64 years (range 46-83). Symptoms that led to initial consultation included sleep problems (8 patients; 36%), gait abnormalities (8; 36%), bulbar dysfunction (3; 14%), chorea (2; 9%), and cognitive decline (1; 5%). By the time of diagnosis of the disorder, 4 syndromes were identified: (1) a sleep disorder with parasomnia and sleep breathing difficulty in 8 (36%) patients; (2) a bulbar syndrome including dysphagia, sialorrhea, stridor, or acute respiratory insufficiency in 6 (27%); (3) a syndrome resembling progressive supranuclear palsy (PSP-like) in 5 (23%); and (4) cognitive decline with or without chorea in 3 (14%). All patients eventually developed parasomnia, sleep apnea, insomnia, or excessive daytime sleepiness. HLA-DRB1*10:01 and HLA-DQB1*05:01 were positive in 13/15 (87%) patients; the DRB1*10:01 allele was 36 times more prevalent than in the general population. Among 16 patients with paired serum and CSF samples, 14 had IgLON5 antibodies in both, and 2 only in serum (both had a PSP-like syndrome). Twenty of 21 patients had IgG1 and IgG4 antibodies; the latter predominated in 16.
Conclusions:
Patients with IgLON5 antibodies develop a characteristic sleep disorder preceded or accompanied by bulbar symptoms, gait abnormalities, oculomotor problems, and, less frequently, cognitive decline. IgG4 subclass antibodies predominate over IgG1; we confirm a strong association with the HLA-DRB1*10:01 allele.