Contributions
Abstract: P1853
Type: Poster
Abstract Category: Late breaking news
Background: Overweight is associated with an increased risk of multiple sclerosis (MS) in both adult and pediatric populations, yet underlying mechanism/s remain unknown. We hypothesized that altered adipose hormone (adipokine) levels may explain some of the association between adiposity and risk of developing MS.
Methods: Adipokine levels were screened by Luminex in sera of children with incident clinical episodes of acquired demyelinating syndromes (ADS), prospectively confirmed as having either MS or monophasic ADS (monoADS). Adipokine abnormalities implicated in univariable analysis that survived multivariable analysis were confirmed by ELISA. The impact of recombinant adiponectin (APN), and of APN-containing pediatric MS sera, was assessed on functional responses of normal human peripheral-blood CD14+ myeloid cells and T cells, as well as on human CNS-derived microglia by flow cytometry and PCR.
Results: Increased APN levels in children with MS compared to both monoADS and healthy control children were confirmed by ELISA, and were driven by higher levels of low and medium molecular weight APN isoforms. Recombinant APN as well as pediatric MS serum induced APN-dependent pro-inflammatory activation of CD14+ monocytes, and of activated CD4+ and CD8+ T cells (both directly, and indirectly through myeloid-cell activation). APN also induced human microglia activation while inhibiting their expression of quiescence molecules.
Conclusion: Abnormally elevated APN levels in children with MS may contribute to enhanced pro-inflammatory states of both innate and adaptive peripheral immune responses, as well as breach of CNS-resident microglia quiescence, providing a plausible and potentially targetable mechanism underlying the association between adiposity and multiple sclerosis.
Disclosure:
Giulia Fadda: nothing to disclose;
Mukanthu Nyirenda: nothing to disclose;
Ina Mexhitaj: nothing to disclose;
Luke Healy: nothing to disclose;
Laurence Poliquin-Lasnier: nothing to disclose;
Heather Hanwell: nothing to disclose;
Alex Saveriano: nothing to disclose;
Ayal Rozenberg: nothing to disclose;
Rui Li: nothing to disclose;
Craig S. Moore: nothing to disclose;
Chahrazed Belabani: nothing to disclose;
Trina Johnson: nothing to disclose;
Julia O'Mahony: nothing to disclose;
Ruth Ann Marrie: receives research funding from Canadian Institutes of Health Research, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, National Multiple Sclerosis Society, Rx & D Health Research Foundation, the Waugh Family Chair in Multiple Sclerosis, Crohn's and Colitis Canada, and has conducted clinical trials funded by Sanofi- Aventis.
Shannon Dunn: nothing to disclose;
Brenda Banwell: has served as an unpaid consultant to Biogen-Idec, Novartis, Teva Neuroscience, and Merck-Serono; as a remunerated central MRI reviewer for the present trial, and she is Chief Editor for MS and Related Disorders and funded by Canadian MS scientific research foundation (CMSRF), Canadian Multiple Sclerosis Society (CMSS), National Multiple Sclerosis Society (NMSS), and Canadian Institutes of Health Research (CIHR).
Amit Bar-Or: has participated as a speaker at meetings sponsored by, received consulting fees and/or received grant support from: Biogen Idec, Roche/Genentech, GlaxoSmithKline, Merck/EMD Serono, Medimmune, Novartis, Celgene/Receptos, Sanofi-Genzyme
Abstract: P1853
Type: Poster
Abstract Category: Late breaking news
Background: Overweight is associated with an increased risk of multiple sclerosis (MS) in both adult and pediatric populations, yet underlying mechanism/s remain unknown. We hypothesized that altered adipose hormone (adipokine) levels may explain some of the association between adiposity and risk of developing MS.
Methods: Adipokine levels were screened by Luminex in sera of children with incident clinical episodes of acquired demyelinating syndromes (ADS), prospectively confirmed as having either MS or monophasic ADS (monoADS). Adipokine abnormalities implicated in univariable analysis that survived multivariable analysis were confirmed by ELISA. The impact of recombinant adiponectin (APN), and of APN-containing pediatric MS sera, was assessed on functional responses of normal human peripheral-blood CD14+ myeloid cells and T cells, as well as on human CNS-derived microglia by flow cytometry and PCR.
Results: Increased APN levels in children with MS compared to both monoADS and healthy control children were confirmed by ELISA, and were driven by higher levels of low and medium molecular weight APN isoforms. Recombinant APN as well as pediatric MS serum induced APN-dependent pro-inflammatory activation of CD14+ monocytes, and of activated CD4+ and CD8+ T cells (both directly, and indirectly through myeloid-cell activation). APN also induced human microglia activation while inhibiting their expression of quiescence molecules.
Conclusion: Abnormally elevated APN levels in children with MS may contribute to enhanced pro-inflammatory states of both innate and adaptive peripheral immune responses, as well as breach of CNS-resident microglia quiescence, providing a plausible and potentially targetable mechanism underlying the association between adiposity and multiple sclerosis.
Disclosure:
Giulia Fadda: nothing to disclose;
Mukanthu Nyirenda: nothing to disclose;
Ina Mexhitaj: nothing to disclose;
Luke Healy: nothing to disclose;
Laurence Poliquin-Lasnier: nothing to disclose;
Heather Hanwell: nothing to disclose;
Alex Saveriano: nothing to disclose;
Ayal Rozenberg: nothing to disclose;
Rui Li: nothing to disclose;
Craig S. Moore: nothing to disclose;
Chahrazed Belabani: nothing to disclose;
Trina Johnson: nothing to disclose;
Julia O'Mahony: nothing to disclose;
Ruth Ann Marrie: receives research funding from Canadian Institutes of Health Research, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, National Multiple Sclerosis Society, Rx & D Health Research Foundation, the Waugh Family Chair in Multiple Sclerosis, Crohn's and Colitis Canada, and has conducted clinical trials funded by Sanofi- Aventis.
Shannon Dunn: nothing to disclose;
Brenda Banwell: has served as an unpaid consultant to Biogen-Idec, Novartis, Teva Neuroscience, and Merck-Serono; as a remunerated central MRI reviewer for the present trial, and she is Chief Editor for MS and Related Disorders and funded by Canadian MS scientific research foundation (CMSRF), Canadian Multiple Sclerosis Society (CMSS), National Multiple Sclerosis Society (NMSS), and Canadian Institutes of Health Research (CIHR).
Amit Bar-Or: has participated as a speaker at meetings sponsored by, received consulting fees and/or received grant support from: Biogen Idec, Roche/Genentech, GlaxoSmithKline, Merck/EMD Serono, Medimmune, Novartis, Celgene/Receptos, Sanofi-Genzyme