title: The neurologic significance of celiac disease biomarkers.
abstract: OBJECTIVE
  To report neurologic phenotypes and their etiologies determined among 68 patients with either (1) celiac disease (CD) or (2) no CD, but gliadin antibody positivity (2002-2012).
  
  
  METHODS
  Neurologic patients included both those with the CD-prerequisite major histocompatibility complex class II human leukocyte antigen (HLA)-DQ2/DQ8 haplotype, and those without. The 3 groups were as follows: group 1 (n = 44), CD or transglutaminase (Tg)-2/deamidated gliadin immunoglobulin (Ig)A/IgG detected; group 2 (n = 15), HLA-DQ2/DQ8 noncarriers, and gliadin IgA/IgG detected; and group 3 (n = 9), HLA-DQ2/DQ8 carriers, and gliadin IgA/IgG detected. Neurologic patients and 21 nonneurologic CD patients were evaluated for neural and Tg6 antibodies.
  
  
  RESULTS
  In group 1, 42 of 44 patients had CD. Neurologic phenotypes (cerebellar ataxia, 13; neuropathy, 11; dementia, 8; myeloneuropathy, 5; other, 7) and causes (autoimmune, 9; deficiencies of vitamin E, folate, or copper, 6; genetic, 6; toxic or metabolic, 4; unknown, 19) were diverse. In groups 2 and 3, 21 of 24 patients had cerebellar ataxia; none had CD. Causes of neurologic disorders in groups 2 and 3 were diverse (autoimmune, 4; degenerative, 4; toxic, 3; nutritional deficiency, 1; other, 2; unknown, 10). One or more neural-reactive autoantibodies were detected in 10 of 68 patients, all with autoimmune neurologic diagnoses (glutamic acid decarboxylase 65 IgG, 4; voltage-gated potassium channel complex IgG, 3; others, 5). Tg6-IgA/IgG was detected in 7 of 68 patients (cerebellar ataxia, 3; myelopathy, 2; ataxia and parkinsonism, 1; neuropathy, 1); the 2 patients with myelopathy had neurologic disorders explained by malabsorption of copper, vitamin E, and folate rather than by neurologic autoimmunity.
  
  
  CONCLUSIONS
  Our data support causes alternative to gluten exposure for neurologic dysfunction among most gliadin antibody-positive patients without CD. Nutritional deficiency and coexisting autoimmunity may cause neurologic dysfunction in CD.
authors.affiliation: From the Departments of Laboratory Medicine and Pathology (A.M., V.A.L., S.J.P., T.J.K.), Neurology (A.M., V.A.L., S.J.P.), Immunology (V.A.L., J.M.), and Gastroenterology (J.M.), College of Medicine, Mayo Clinic, Rochester, MN. mckeon.andrew@mayo.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: McKeon
authors.affiliation: From the Departments of Laboratory Medicine and Pathology (A.M., V.A.L., S.J.P., T.J.K.), Neurology (A.M., V.A.L., S.J.P.), Immunology (V.A.L., J.M.), and Gastroenterology (J.M.), College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
authors.affiliation: From the Departments of Laboratory Medicine and Pathology (A.M., V.A.L., S.J.P., T.J.K.), Neurology (A.M., V.A.L., S.J.P.), Immunology (V.A.L., J.M.), and Gastroenterology (J.M.), College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
authors.affiliation: From the Departments of Laboratory Medicine and Pathology (A.M., V.A.L., S.J.P., T.J.K.), Neurology (A.M., V.A.L., S.J.P.), Immunology (V.A.L., J.M.), and Gastroenterology (J.M.), College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kryzer
authors.affiliation: From the Departments of Laboratory Medicine and Pathology (A.M., V.A.L., S.J.P., T.J.K.), Neurology (A.M., V.A.L., S.J.P.), Immunology (V.A.L., J.M.), and Gastroenterology (J.M.), College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Joseph
authors.initials: J
authors.lastname: Murray
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood* / Q000134:cerebrospinal fluid*; D015220:Calcium Channels / Q000276:immunology; D002446:Celiac Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000276:immunology; D002524:Cerebellar Ataxia / Q000150:complications; D002648:Child; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology; D005903:Gliadin / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000150:complications; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011950:Receptors, Cholinergic / Q000276:immunology; D011503:Transglutaminases / Q000276:immunology; D055815:Young Adult
chemical_list: D000906:Antibodies; D015415:Biomarkers; D015220:Calcium Channels; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D024642:Potassium Channels, Voltage-Gated; D011950:Receptors, Cholinergic; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins