Correlation Between GAD Antibody Levels and Severity of Gastrointestinal Motility Dysfunction as Determined by Wireless Motility Capsule Testing

Abstract

Introduction: There is an increasing body of evidence identifying an immune mediated role in the pathogenesis of both paraneoplastic and non-paraneoplastic gastrointestinal dysmotility. One such mechanism is an antibody mediated pathway involving Glutamic Acid Decarboxylase (GAD). Our objective in this study is to determine if the level of circulating GAD antibody correlates with the severity of gastrointestinal dysmotility, or the number of bowel segments impacted as determined by wireless motility capsule(WMC) testing. Methods: The study was conducted as a retrospective cohort analysis. We included all patients seen at The Cleveland Clinic who had a WMC study ordered between 2009 to 2017, and who also had positive Glutamic Acid Decarboxyase (GAD) antibodies. Patients were identified by CPT codes for WMC in the electronic medical record. Patients were excluded from the study if they failed the WMC due to technical failure. A total 304 completed WMT and also had GAD antibody measured. Of these patients, 35 had positive GAD antibodies (>5 IU/mL). Gastric emptying time (GET), Small Bowel Transit time (SBTT), and Large Bowel Transit time (LBTT) were measured using WMC data. The data from the WMC was compared to corresponding GAD antibody levels using pairwise correlation analysis after eliminating outliers. Additionally, the results were transformed to categorical data (abnormal or not) for evaluation of portions of the gastrointestinal tract involved. Abnormal measurements included a GET >4h, SBTT > 6h, or an LBTT >59h. Results: Results were calculated based on GET, SBTT and LBTT independently, as well as SLBTT and WGTT relative to the GAD antibodies. GAD antibody concentrations do not appear to correlate with the degree of gastrointestinal dysmotility as measured by WMC (Table 1). Conclusion: Based on this review of data, it seems that GAD antibody levels cannot be used as a predictor of disease severity, or to predict the location of gastrointestinal dysmotility. However, more research is needed. Empiric treatment with IVIg should not be used in patients with high GAD antibody levels in the absence of additional supportive data. A larger sample size is needed to confirm the findings of this study, and to identify further correlations.441 Figure 1. Correlation of emptying times and GAD levels