Spectrum of neurological manifestations, existence of diabetes mellitus, and 5-year mortality and cancer association outcomes in a cohort of Omani patients with positive anti- GAD autoimmunity.

Publisher: Taylor & Francis Country of Publication: England NLM ID: 101271248 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-8409 (Electronic) Linking ISSN: 1744666X NLM ISO Abbreviation: Expert Rev Clin Immunol Subsets: MEDLINE

Publication: 2015- : Abingdon, Oxford : Taylor & Francis
Original Publication: London, UK : Future Drugs Ltd., 2005-

Glutamate Decarboxylase*/immunology ; Neoplasms*/immunology ; Neoplasms*/mortality ; Autoantibodies*/blood ; Autoantibodies*/immunology ; Autoimmunity*; Humans ; Oman/epidemiology ; Male ; Female ; Adolescent ; Child ; Adult ; Retrospective Studies ; Child, Preschool ; Young Adult ; Diabetes Mellitus/immunology ; Diabetes Mellitus/mortality ; Middle Aged ; Follow-Up Studies ; Nervous System Diseases/immunology ; Nervous System Diseases/mortality ; Cohort Studies

Objectives: There is scarce data in the literature concerning the anti-GAD65 antibodies (GAD-Abs) autoimmunity in the Omani population.
Methods: Retrospective cohort study included GAD-Abs positive patients ( n  = 444) presented to a tertiary referral center in Oman from January 2005 until January 2018, with a five-year follow-up to study the cancer association and mortality outcomes.
Results: Out of 444 patients, 27 patients (6.1%) showed GAD-Abs related neurological disorders. Adult age group was significantly associated with more GAD-Abs related neurological manifestations compared to pediatric and adolescents age group ( p  = 0.045). There was no association between the presence or absence of neurological manifestations with diabetes mellitus nor the titer level of GAD-Abs. Refractory status epilepticus and stiff person syndrome were the main causes of death in patients with neurological manifestations over five years and none of them found to have associated cancer.
Conclusion: The GAD-Abs autoimmunity represents a spectrum of neurological manifestations with variable severity and outcome among Omanis with positive GAD-Abs testing. The results of this study will serve as a platform for future studies to address the impact of GAD-Abs autoimmunity on the morbidity, mortality and treatment efficacy in the Omani population.

Keywords: Anti-GAD; Oman; antibodies; autoimmunity; cancer; diabetes; mortality
Local Abstract: [plain-language-summary] Autoimmunity in humans can affect almost all organs in the body and results from abnormal activation of the immune system. GAD autoimmunity is an autoimmune disorder that can affect the pancreas as well as the nervous system by targeting specific sites in the microstructures of these organs called Glutamic Acid Decarboxylase (GAD). This can lead to the development of diabetes mellitus and/or nervous system malfunctioning manifested as epilepsy, cognitive impairment, gait abnormalities, etc. Unfortunately, the mechanism of developing this autoimmune disorder and its effects on the pancreas and nervous system are not well understood, and this hinders proper diagnosis and management. The available laboratory tests can diagnose the presence of markers for this autoimmune disorder but cannot predict the development of its various manifestations. In this study, we focused on the association between having a positive laboratory test result and the presence or absence of diabetes mellitus and nervous system manifestations in order to gain a better insight into the possible outcome after 5 years. The results of this study will help physicians to optimize diagnostics and treatment strategies. Further studies are required to enhance our understanding of this peculiar autoimmune disorder in humans.

EC 4.1.1.15 (Glutamate Decarboxylase)
0 (Autoantibodies)
EC 4.1.1.15 (glutamate decarboxylase 2)
0 (anti-GAD65 autoantibody)

Date Created: 20240821 Date Completed: 20241119 Latest Revision: 20241119

20241120

10.1080/1744666X.2024.2395853

39167450