Glutamic Acid Decarboxylase 65 Antibody Titer Levels Help Differentiate Stiff Person Syndrome Spectrum Disorders from Other Conditions
Aisha Elfasi1, Brendan Lindgren1, Mario Caturegli2, Herbert Chen 1, Ashley Miles1, Scott Newsome1
1Neurology, 2Immunology, Johns Hopkins Hospital
Objective:
To characterize glutamic acid decarboxylase 65 (GAD65)-antibody (Ab) testing patterns along with associated clinical findings and differentiating properties of titer levels with a stiff person syndrome spectrum disorder (SPSD) diagnosis.
Background:
Anti GAD65-Ab seropositivity is commonly encountered in clinical practice. These autoantibodies can be associated with several systemic disorders as well as neurologic disorders such as SPSD. The lack of specificity of GAD65-Ab makes it a challenging biomarker for differentiating between disorders and can lead to misdiagnoses.
Design/Methods:
We conducted a retrospective chart review of GAD65-Ab labs completed though the Johns Hopkins laboratories (n=2894); Enzyme Linked Immunoassay method was utilized. We assessed data from all neurology clinics determining reason(s) for GAD65-Ab testing and documenting final/working diagnosis determined by treating clinician. Abnormal values were separated into quartiles to assess potential thresholds for diagnoses.
Results:
Neurology providers ordered 29.0% of GAD65-Ab labs (840/2894). GAD65-Ab was abnormal (titer >5.0 IU/mL) in 30.3% of all samples (877/2894) and in 44.4% of neurology ordered labs (373/840). Most common reasons for ordering GAD65-Ab were stiffness and spasms. Abnormal GAD65-Ab titers ranged from 5.1 to 6,690,000 IU/mL. Mean age (range) of patients with abnormal GAD65-Ab was 55 years (18 – 88) and 72.7% were female. All patients with abnormal GAD65-Ab in 3rd and 4th quartile values (mean titer; range) (176,059; 52,850 – 379,735.4 IU/mL and 1,065,179; 382,541 – 6,690,000 IU/mL, respectively) and 90% in 2nd quartile (14,958; 338.6 – 51,517 IU/mL) were diagnosed with SPSD. In contrast, 44% in the first quartile (115.9; 5.1 – 333 IU/mL) were determined to have a diagnosis other than SPSD. Future analyses will include data from non-neurology clinics.
Conclusions:
GAD65-Ab testing is often requested by neurology and non-neurology providers for various reasons. GAD65-Ab titers vary widely depending on the associated condition. However, high titers appear specific for an SPSD diagnosis in the appropriate clinical setting.