title: Metabotropic glutamate receptor type 1 autoimmunity: Clinical features and treatment outcomes.
abstract: OBJECTIVE
  To describe retrospectively the clinical associations of immunoglobulin G (IgG) targeting metabotropic glutamate receptor 1 (mGluR1-IgG).
  
  
  METHODS
  Specimens of 9 patients evaluated on a service basis in the Mayo Clinic Neuroimmunology Laboratory by tissue-based immunofluorescence assay (IFA) yielded a robust, synaptic immunostaining pattern consistent with mGluR1-IgG (serum, 9; CSF, 2 available). Transfected HEK293 cell-based assay (CBA) confirmed mGluR1 specificity in all 11 specimens. A further 2 patients were detected in Germany primarily by CBA.
  
  
  RESULTS
  The median symptom onset age for the 11 patients was 58 years (range 33-81 years); 6 were male. All 9 Mayo Clinic patients had subacute onset of cerebellar ataxia, 4 had dysgeusia, 1 had psychiatric symptoms, and 1 had cognitive impairment. All were evaluated for malignancy, but only 1 was affected (cutaneous T-cell lymphoma). One developed ataxia post-herpes zoster infection. Head MRIs were generally atrophic or normal-appearing, and CSF was inflammatory in just 1 of 5 tested, though mGluR1-IgG was detected in both specimens submitted. Five patients improved (attributable to immunotherapy in 4, spontaneously in 1), 3 stabilized (attributable to immunotherapy in 2, cancer therapy in 1), and 1 progressively declined (untreated). The 2 German patients had ataxia, but fulfilled multiple sclerosis diagnostic criteria (1 relapsing-remitting, 1 progressive). However, both had histories of hematologic malignancy (acute lymphocytic leukemia and mantle cell lymphoma), and had mGluR1-IgG detected in serum by CBA (weakly positive on tissue-based IFA).
  
  
  CONCLUSIONS
  mGluR1 autoimmunity represents a treatable form of cerebellar ataxia. Dysgeusia may be a diagnostic clue. Paraneoplastic, parainfectious, or idiopathic causes may occur.
authors.affiliation: From the Department of Neurology (A.S.L.-C.), Mayo Clinic, Jacksonville, FL; Institute of Experimental Immunology (L.K., C.P.), Euroimmun AG, Lubeck; Department of Neuroimmunology (T.K.), Ludwig Maximilian University, Munich, Germany; and Departments of Laboratory Medicine and Pathology (S.R.H., S.J.P., A.M.) and Neurology (S.J.P., A.M.), Mayo Clinic, Rochester, MN.
authors.forename: A Sebastian
authors.initials: AS
authors.lastname: Lopez-Chiriboga
authors.affiliation: From the Department of Neurology (A.S.L.-C.), Mayo Clinic, Jacksonville, FL; Institute of Experimental Immunology (L.K., C.P.), Euroimmun AG, Lubeck; Department of Neuroimmunology (T.K.), Ludwig Maximilian University, Munich, Germany; and Departments of Laboratory Medicine and Pathology (S.R.H., S.J.P., A.M.) and Neurology (S.J.P., A.M.), Mayo Clinic, Rochester, MN.
authors.forename: Lars
authors.initials: L
authors.lastname: Komorowski
authors.affiliation: From the Department of Neurology (A.S.L.-C.), Mayo Clinic, Jacksonville, FL; Institute of Experimental Immunology (L.K., C.P.), Euroimmun AG, Lubeck; Department of Neuroimmunology (T.K.), Ludwig Maximilian University, Munich, Germany; and Departments of Laboratory Medicine and Pathology (S.R.H., S.J.P., A.M.) and Neurology (S.J.P., A.M.), Mayo Clinic, Rochester, MN.
authors.forename: Tania
authors.initials: T
authors.lastname: Kümpfel
authors.affiliation: From the Department of Neurology (A.S.L.-C.), Mayo Clinic, Jacksonville, FL; Institute of Experimental Immunology (L.K., C.P.), Euroimmun AG, Lubeck; Department of Neuroimmunology (T.K.), Ludwig Maximilian University, Munich, Germany; and Departments of Laboratory Medicine and Pathology (S.R.H., S.J.P., A.M.) and Neurology (S.J.P., A.M.), Mayo Clinic, Rochester, MN.
authors.forename: Christian
authors.initials: C
authors.lastname: Probst
authors.affiliation: From the Department of Neurology (A.S.L.-C.), Mayo Clinic, Jacksonville, FL; Institute of Experimental Immunology (L.K., C.P.), Euroimmun AG, Lubeck; Department of Neuroimmunology (T.K.), Ludwig Maximilian University, Munich, Germany; and Departments of Laboratory Medicine and Pathology (S.R.H., S.J.P., A.M.) and Neurology (S.J.P., A.M.), Mayo Clinic, Rochester, MN.
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Hinson
authors.affiliation: From the Department of Neurology (A.S.L.-C.), Mayo Clinic, Jacksonville, FL; Institute of Experimental Immunology (L.K., C.P.), Euroimmun AG, Lubeck; Department of Neuroimmunology (T.K.), Ludwig Maximilian University, Munich, Germany; and Departments of Laboratory Medicine and Pathology (S.R.H., S.J.P., A.M.) and Neurology (S.J.P., A.M.), Mayo Clinic, Rochester, MN.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
authors.affiliation: From the Department of Neurology (A.S.L.-C.), Mayo Clinic, Jacksonville, FL; Institute of Experimental Immunology (L.K., C.P.), Euroimmun AG, Lubeck; Department of Neuroimmunology (T.K.), Ludwig Maximilian University, Munich, Germany; and Departments of Laboratory Medicine and Pathology (S.R.H., S.J.P., A.M.) and Neurology (S.J.P., A.M.), Mayo Clinic, Rochester, MN. mckeon.andrew@mayo.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: McKeon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015551:Autoimmunity / Q000276:immunology*; D002524:Cerebellar Ataxia / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018094:Receptors, Metabotropic Glutamate / Q000097:blood / Q000276:immunology*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D007074:Immunoglobulin G; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1