Contributions
Abstract: EP1307
Type: ePoster
Abstract Category: Clinical aspects of MS - 3 Paediatric MS
Background: Tryptophan (Trp) metabolites have been shown to modulate the immune response in EAE. We sought to determine if serum Trp levels are associated with the risk of MS or relapse rate in children with MS.
Methods: Paediatric-onset MS and clinically isolated syndrome (CIS) patients within 4 years of disease onset and controls < 22 years old were recruited at UCSF, a tertiary care center. Prospective relapse data after enrollment were used. Serum Trp was measured using liquid chromatography-mass spectrometry.
We extracted and amplified DNA from available stool samples (n=17) and performed 16S rRNA sequencing. We applied a validated algorithm to enable metagenomic predictions from this sequencing data, and drew inferences as to the potential functional capacity of the gut microbiota (PICRUSt; Phylogenetic Investigation of Communities by Reconstruction of Unobserved States).
Association between serum Trp level and disease risk was assessed by a logistic regression model, adjusted for age, sex and race/ethnicity. Negative binomial regression models adjusted for age, race/ethnicity, sex and disease-modifying therapies were used to assess the association between serum Trp levels and relapse rate. Association between relative abundance of microbial genes involved in Trp metabolism and time to relapse was assessed using Kaplan-Meier curves.
Results: Serum Trp was measured in 82 MS/CIS cases and 17 controls. The mean (standard deviation) of serum Trp level was 11.0 (2.3) mcg/ml in cases and 12.8 (2.7) mcg/ml in controls. Each 1 mg increase in serum Trp level decreased the odds of having MS by 24% (95% CI: 4% - 40%, p=0.024). There was no association between serum Trp levels and relapse rate in male patients, while each 1 mcg/ml increase in serum Trp in female patients was associated with a 26% decreased in the relapse incidence rate ratio (IRR: 0.74, 95% CI: 57% - 97%, p=0.026). Patients with a lower relative abundance of microbial genes involved in Trp catabolism had a shorter time to relapse during follow-up than those with higher abundance (log-rank test p=0.011, ≤ vs. > median relative abundance).
Conclusion: Higher serum Trp levels are associated with lower risk of developing MS in children and lower relapse rate in female patients with paediatric MS. Trp metabolism by gut microbiota may be involved in this process. Additional case and control samples are being tested.
Disclosure: Authors report no potential conflict of interest related to this work.
Abstract: EP1307
Type: ePoster
Abstract Category: Clinical aspects of MS - 3 Paediatric MS
Background: Tryptophan (Trp) metabolites have been shown to modulate the immune response in EAE. We sought to determine if serum Trp levels are associated with the risk of MS or relapse rate in children with MS.
Methods: Paediatric-onset MS and clinically isolated syndrome (CIS) patients within 4 years of disease onset and controls < 22 years old were recruited at UCSF, a tertiary care center. Prospective relapse data after enrollment were used. Serum Trp was measured using liquid chromatography-mass spectrometry.
We extracted and amplified DNA from available stool samples (n=17) and performed 16S rRNA sequencing. We applied a validated algorithm to enable metagenomic predictions from this sequencing data, and drew inferences as to the potential functional capacity of the gut microbiota (PICRUSt; Phylogenetic Investigation of Communities by Reconstruction of Unobserved States).
Association between serum Trp level and disease risk was assessed by a logistic regression model, adjusted for age, sex and race/ethnicity. Negative binomial regression models adjusted for age, race/ethnicity, sex and disease-modifying therapies were used to assess the association between serum Trp levels and relapse rate. Association between relative abundance of microbial genes involved in Trp metabolism and time to relapse was assessed using Kaplan-Meier curves.
Results: Serum Trp was measured in 82 MS/CIS cases and 17 controls. The mean (standard deviation) of serum Trp level was 11.0 (2.3) mcg/ml in cases and 12.8 (2.7) mcg/ml in controls. Each 1 mg increase in serum Trp level decreased the odds of having MS by 24% (95% CI: 4% - 40%, p=0.024). There was no association between serum Trp levels and relapse rate in male patients, while each 1 mcg/ml increase in serum Trp in female patients was associated with a 26% decreased in the relapse incidence rate ratio (IRR: 0.74, 95% CI: 57% - 97%, p=0.026). Patients with a lower relative abundance of microbial genes involved in Trp catabolism had a shorter time to relapse during follow-up than those with higher abundance (log-rank test p=0.011, ≤ vs. > median relative abundance).
Conclusion: Higher serum Trp levels are associated with lower risk of developing MS in children and lower relapse rate in female patients with paediatric MS. Trp metabolism by gut microbiota may be involved in this process. Additional case and control samples are being tested.
Disclosure: Authors report no potential conflict of interest related to this work.