PMID- 25261501 OWN - NLM STAT- MEDLINE DCOM- 20150310 LR - 20211203 IS - 1526-632X (Electronic) IS - 0028-3878 (Print) IS - 0028-3878 (Linking) VI - 83 IP - 20 DP - 2014 Nov 11 TI - The neurologic significance of celiac disease biomarkers. PG - 1789-96 LID - 10.1212/WNL.0000000000000970 [doi] AB - 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. CI - (c) 2014 American Academy of Neurology. FAU - McKeon, Andrew AU - McKeon A AD - 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. FAU - Lennon, Vanda A AU - Lennon VA AD - 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. FAU - Pittock, Sean J AU - Pittock SJ AD - 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. FAU - Kryzer, Thomas J AU - Kryzer TJ AD - 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. FAU - Murray, Joseph AU - Murray J AD - 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. LA - eng GR - DK 057892/DK/NIDDK NIH HHS/United States GR - DK057892/DK/NIDDK NIH HHS/United States GR - NS065829/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140926 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 0 (Antibodies) RN - 0 (Biomarkers) RN - 0 (Calcium Channels) RN - 0 (HLA-DQ Antigens) RN - 0 (HLA-DQ2 antigen) RN - 0 (HLA-DQ8 antigen) RN - 0 (Potassium Channels, Voltage-Gated) RN - 0 (Receptors, Cholinergic) RN - 9007-90-3 (Gliadin) RN - EC 2.3.2.13 (Protein Glutamine gamma Glutamyltransferase 2) RN - EC 2.3.2.13 (Transglutaminases) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Animals MH - Antibodies/*blood MH - Biomarkers/*blood/*cerebrospinal fluid MH - Calcium Channels/immunology MH - Celiac Disease/blood/cerebrospinal fluid/*diagnosis/immunology MH - Cerebellar Ataxia/complications MH - Child MH - Female MH - GTP-Binding Proteins/immunology MH - Gliadin/*immunology MH - HLA-DQ Antigens/metabolism MH - Haplorhini MH - Humans MH - Male MH - Mice MH - Middle Aged MH - Peripheral Nervous System Diseases/complications MH - Potassium Channels, Voltage-Gated/immunology MH - Protein Glutamine gamma Glutamyltransferase 2 MH - Receptors, Cholinergic/immunology MH - Transglutaminases/immunology MH - Young Adult PMC - PMC4240435 EDAT- 2014/09/28 06:00 MHDA- 2015/03/11 06:00 PMCR- 2015/11/11 CRDT- 2014/09/28 06:00 PHST- 2014/09/28 06:00 [entrez] PHST- 2014/09/28 06:00 [pubmed] PHST- 2015/03/11 06:00 [medline] PHST- 2015/11/11 00:00 [pmc-release] AID - WNL.0000000000000970 [pii] AID - NEUROLOGY2014571471 [pii] AID - 10.1212/WNL.0000000000000970 [doi] PST - ppublish SO - Neurology. 2014 Nov 11;83(20):1789-96. doi: 10.1212/WNL.0000000000000970. Epub 2014 Sep 26.