2235 Disability and pregnancy in multiple sclerosis: relationships with leukocyte telomere length

Background Ageing-related processes contribute to neurodegeneration and disability in multiple sclerosis (MS). Biomarkers of senescence such as leukocyte telomere length (LTL) could help personalise prognosis and treatment. A history of pregnancy has been shown to be protective against disability accumulation in women with MS¹: it is unclear if this could be partly mediated by LTL. We aimed to cross-sectionally characterise LTL in an MS cohort, and to correlate LTL with disability and pregnancy history.

Methods We extracted DNA from the whole blood of 301 patients attending an MS clinic (Alfred Health, Melbourne) Expanded Disability Status Scale (EDSS) score and pregnancy history (for 191 females) were obtained at sample collection. Additional data were extracted from the MSBase Registry.² LTL was determined in base pairs (bp) using real-time polymerase chain reaction.³

Results Disability was associated with shorter telomere length, a relationship that was robust to multivariable adjustment for demographic and clinical factors including chronological age (adjusted LTL reduction per 1.0 increase in EDSS = 92.8bp, 95% CI = 5.4–180.2bp). In females with pregnancy data, there were no significant relationships between adjusted LTL and history of pregnancy (LTL increase of 41.8bp, 95% CI = -457.7–541.3bp) or number of pregnancies (LTL increase of 10.5bp per pregnancy, 95% CI = -175.8–196.8bp).

Conclusion LTL was independently associated with cross-sectional disability, which likely reflects the relationship between neurological reserve and biological ageing in MS. Although adjusted LTL did not significantly differ by pregnancy history, longitudinal analyses to assess relationships with disability progression are needed.

References

1. Jokubaitis V, et al. Predictors of long-term disability accrual in relapse-onset multiple sclerosis. Ann Neurol 2016;80(1):89–100.

2. Butzkueven H, et al. MSBase: an international, online registry and platform for collaborative outcomes research in multiple sclerosis. Mult Scler 2016;12(6):769–74.

3. Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res 2002;30:e47–e47.