Adipokines Are Associated with Pediatric Multiple Sclerosis Risk and Course

Background: Obesity during adolescence confers an increased risk of multiple sclerosis (MS) in both adults and children. However, obesity-mediated inflammatory mechanisms require elucidation. In models of MS, leptin and fatty acid binding protein-4 (FABP-4) have been identified as proinflammatory adipokines, while adiponectin has anti-inflammatory effects.

Methods: Morning serum samples from 32 pediatric MS (POMS) patients (22 females;10 males) and 67 pediatric healthy controls (PHC) (47 females; 20 males) followed at Massachusetts General Hospital were studied. Levels of leptin, FABP-4 and adiponectin were compared between POMS and PHC groups, adjusting for sex, age and vitamin D3 levels. Associations between each marker and the time to next relapse was assessed using a Cox proportional hazards model. The association between each marker and EDSS was assessed using linear regression.

Results: Pediatric MS patients had significantly higher levels of leptin and FABP4 and significantly lower adiponectin than healthy controls. Higher levels of adiponectin were associated with a lower hazard of relapse. Similar differences were observed between POMS and PHC males for both leptin and adiponectin, and within females for FABP4. In females with MS, there was a trend for a positive association between higher leptin levels and higher disability scores. In males with MS, paradoxically, higher leptin levels were associated with longer time to next relapse. All these results remained significant after adjusting for Vitamin D.

Conclusions: FABP4 and leptin levels are higher, while adiponectin levels are lower in pediatric MS compared to controls in sex-specific patterns. These adipokines could serve as biomarkers and therapeutic targets of disease risk and course in early forms of MS.