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Peer-reviewedCC BY 4.0Frontiers in Neurology

Clinical characteristics associated with GAD65 antibodies: a comparative study between high and low GAD65-ab cohorts

  • Paula Lombardo-Del Toro1,2
  • Sònia Jaraba1,3
  • Guillermo Hernández-Pérez1
  • Velina Nedkova4
  • Carlos Casasnovas4
  • Serge Jauma-Classen5
  • Laura Gonzalez-Mera3,4
  • Roser Gómez-Llopico5
  • Lydia García-Serrano6
  • Jacint Sala-Padró1
  • Francisco Morandeira6
  • Mercè Falip1
6 affiliations
  1. 1Epilepsy Unit, Neurology Service, Hospital Universitario de Bellvitge
  2. 2Neurology Service, Hospital Sant Joan Despí Moisès Broggi, Consorci Sanitari Integral
  3. 3Neurology Service, Hospital de Viladecans
  4. 4Neuromuscular Unit, Neurology Service, Hospital Universitario de Bellvitge
  5. 5Movement Disorders Unit, Neurology Service, Hospital Universitario de Bellvitge
  6. 6Central Laboratory Service, Immunology Department, Hospital Universitario de Bellvitge
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Abstract

Introduction: The frequency of neurological manifestations associated with serum GAD65 antibodies (NeuGAD) varies across studies, and the risk of neurological involvement in patients with high GAD65-ab titers remains unclear. This study aimed to determine the prevalence and clinical characteristics of neurological manifestations in patients with high (≥2,000 IU/mL) versus low (<2,000 IU/mL) serum GAD65-ab titers.

Methods: We compared two cohorts: one cohort of 194 patients with diabetes mellitus (DM) diagnosed between 2000 and 2005 with positive low GAD65-ab titers, and a cohort of 150 patients with high GAD65-ab titers collected between 2013 and 2024. Groups were compared using the Mann–Whitney U test, chi-square/Fisher’s exact test, and multivariable logistic regression.

Results: Among patients with high GAD65-ab titers, 32/150 (21.3%) had NeuGAD, most frequently presenting as epilepsy (13/32, 40.6%). Of the 128 patients with DM, 17 (13.3%) had NeuGAD. DM was present in 112/118 (94.1%) patients without NeuGAD, with frequencies varying by neurological syndrome without reaching significance. Age at NeuGAD onset was significantly lower in patients with DM than without DM (43.8 ± 13.5 vs. 55.4 ± 14.1 years, p = 0.03). None of the 194 low-titer patients developed NeuGAD (0%; 95% CI 0.0–1.9%).

Conclusion: NeuGAD developed in 13.3% of DM patients with high GAD65-ab titers, while none of the low-titer patients developed NeuGAD, and it appeared at a younger age in patients with DM. We recommend serial GAD65-ab testing in patients with DM and high GAD65-ab titers, and prompt neurology referral when neurological symptoms arise, to allow earlier NeuGAD diagnosis.

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Cite

BibTeXRIS
BibTeX
@article{toro2026clinical,
  title = {{Clinical characteristics associated with GAD65 antibodies: a comparative study between high and low GAD65-ab cohorts}},
  author = {Paula Lombardo-Del Toro and Sònia Jaraba and Guillermo Hernández-Pérez and Velina Nedkova and Carlos Casasnovas and Serge Jauma-Classen and Laura Gonzalez-Mera and Roser Gómez-Llopico and Lydia García-Serrano and Jacint Sala-Padró and Francisco Morandeira and Mercè Falip},
  journal = {Frontiers in Neurology},
  year = {2026},
  month = oct,
  doi = {10.3389/fneur.2026.1976777},
  url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1976777/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Clinical characteristics associated with GAD65 antibodies: a comparative study between high and low GAD65-ab cohorts
AU  - Paula Lombardo-Del Toro
AU  - Sònia Jaraba
AU  - Guillermo Hernández-Pérez
AU  - Velina Nedkova
AU  - Carlos Casasnovas
AU  - Serge Jauma-Classen
AU  - Laura Gonzalez-Mera
AU  - Roser Gómez-Llopico
AU  - Lydia García-Serrano
AU  - Jacint Sala-Padró
AU  - Francisco Morandeira
AU  - Mercè Falip
PY  - 2026
DA  - 2026/10/19
JO  - Frontiers in Neurology
DO  - 10.3389/fneur.2026.1976777
UR  - https://www.frontiersin.org/articles/10.3389/fneur.2026.1976777/full
AB  - Introduction: The frequency of neurological manifestations associated with serum GAD65 antibodies (NeuGAD) varies across studies, and the risk of neurological involvement in patients with high GAD65-ab titers remains unclear. This study aimed to determine the prevalence and clinical characteristics of neurological manifestations in patients with high (≥2,000 IU/mL) versus low (<2,000 IU/mL) serum GAD65-ab titers.  Methods: We compared two cohorts: one cohort of 194 patients with diabetes mellitus (DM) diagnosed between 2000 and 2005 with positive low GAD65-ab titers, and a cohort of 150 patients with high GAD65-ab titers collected between 2013 and 2024. Groups were compared using the Mann–Whitney U test, chi-square/Fisher’s exact test, and multivariable logistic regression.  Results: Among patients with high GAD65-ab titers, 32/150 (21.3%) had NeuGAD, most frequently presenting as epilepsy (13/32, 40.6%). Of the 128 patients with DM, 17 (13.3%) had NeuGAD. DM was present in 112/118 (94.1%) patients without NeuGAD, with frequencies varying by neurological syndrome without reaching significance. Age at NeuGAD onset was significantly lower in patients with DM than without DM (43.8 ± 13.5 vs. 55.4 ± 14.1 years, p = 0.03). None of the 194 low-titer patients developed NeuGAD (0%; 95% CI 0.0–1.9%).  Conclusion: NeuGAD developed in 13.3% of DM patients with high GAD65-ab titers, while none of the low-titer patients developed NeuGAD, and it appeared at a younger age in patients with DM. We recommend serial GAD65-ab testing in patients with DM and high GAD65-ab titers, and prompt neurology referral when neurological symptoms arise, to allow earlier NeuGAD diagnosis.
SN  - 1664-2295
ER  -