Familial autoimmunity in neurological patients with GAD65 antibodies: an interview-based study
| Autor: | Vincent Navarro, Nicole Fabien, Renata Ursu, David Goncalves, Lucie Hopes, Benjamin Thomas, Hélène-Marie Lanoiselée, Bastien Joubert, Cécile Julier, Marie Benaiteau, Olivier Casez, Alberto Vogrig, Clémentine Montagnac, François Ducray, Hugo Chaumont, Sergio Muñiz-Castrillo, Jérôme Honnorat |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Neurology Glutamic-acid decarboxylase Autoimmunity Stiff-Person Syndrome medicine.disease_cause Antibodies Autoimmune Diseases 03 medical and health sciences 0302 clinical medicine medicine Genetic predisposition Genetics Inheritance Patterns Humans 030212 general & internal medicine Family history Cerebellar ataxia Autoantibodies Limbic encephalitis Stiff-person syndrome business.industry Glutamate Decarboxylase Family aggregation medicine.disease 3. Good health Immunology Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Journal of neurology. 268(7) |
| ISSN: | 1432-1459 |
| Popis: | The common co-occurrence of autoimmune systemic diseases in patients with neurological disorders and antibodies against glutamic acid decarboxylase 65 (GAD65) suggests a shared genetic predisposition to these disorders. However, the nature and frequency of familial aggregation of autoimmune diseases, which might also support this hypothesis, have been poorly investigated. Herein, an exploratory, interview-based study was conducted with the aim of describing the autoimmune diseases displayed by the relatives of GAD65 neurological patients, their frequency, kinship, and potential patterns of inheritance. Patients were enrolled only if they had GAD65 antibodies in the cerebrospinal fluid and typical clinical phenotypes associated with such antibodies (stiff-person syndrome, cerebellar ataxia, limbic encephalitis, or temporal lobe epilepsy). A total of 65 patients were included in the study, and 44/65 (67.7%) reported family history of autoimmunity, including first-degree relatives in 36/65 (55.4%); the sibling recurrence risk (λS) was 5.5, reinforcing the hypothesis of an underlying strong genetic predisposition. Most pedigrees with familial autoimmunity (38/44, 86.4%) showed multiple autoimmune diseases, all but 2 of them with diabetes mellitus or autoimmune thyroid disease, therefore resembling autoimmune polyendocrine syndromes. Inheritance patterns were diverse, possibly autosomal dominant in 17/44 (38.6%) pedigrees or autosomal recessive in 5/44 (11.4%), and un-defined or complex in 24/44 (54.5%). However, a total of 21/65 (32.3%) patients had no identified family history of autoimmunity. In conclusion, these results suggest a variable and heterogeneous genetic predisposition to GAD65 neurological disorders, possibly involving multiple loci and modes of inheritance with different contribution in each family. |
| Databáze: | OpenAIRE |
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