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. 2017 Dec 5;5(1):e416.
doi: 10.1212/NXI.0000000000000416. eCollection 2018 Jan.

Multiplex family with GAD65-Abs neurologic syndromes

Aude Belbezier  1 , Bastien Joubert  1 , Gonzalo Montero-Martin  1 , Marcelo Fernandez-Vina  1 , Nicole Fabien  1 , Véronique Rogemond  1 , Emmanuel Mignot  1 , Jérôme Honnorat  1
Affiliations

Multiplex family with GAD65-Abs neurologic syndromes

Aude Belbezier et al. Neurol Neuroimmunol Neuroinflamm. .

Abstract

Objective: Neurologic autoimmune syndromes associated with anti-glutamate acid decarboxylase 65 antibodies (GAD65-Abs) are rare and mostly sporadic.

Methods: We describe a niece and her aunt with GAD65-Abs neurologic syndromes. High-resolution HLA typing of Class I and Class II alleles was performed using next-generation sequencing.

Results: The proband had cerebellar ataxia and probable limbic encephalitis features, whereas her niece had stiff-person syndrome. Both had a high titer of GAD65-Abs in serum and CSF and showed signs of inflammation in CSF. Both affected members carried the same rare recombinant DRB1*15:01:01∼DQA1*01:02:01∼DQB1*05:02:01 haplotype, which may or may not be involved in disease susceptibility. Of interest, other unaffected members of the family either had the same HLA haplotype but normal serum GAD65-Abs or had different HLA types but a high titer of serum GAD65-Abs without neurologic symptoms, suggesting cumulative effects.

Conclusions: This unique association strengthens the concept that hereditary factors, possibly including specific HLA haplotypes, play a role in neurologic syndromes associated with GAD65-Abs.

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Figures

Figure
Figure. Family tree with the HLA haplotyping of 6 members of the family
The colors indicate the bioclinical characteristics of the patients. Black circle: patients with GAD65-Abs without neurologic syndromes (III3 and III4). Red circle: patient with GAD65-Abs and cerebellar ataxia (II3). Blue circle: patient with GAD65-Abs and stiff-person syndrome (III5). Green circle: patients with TPO-Abs (II3, III3, and III5).
See this image and copyright information in PMC

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