Cerebrospinal Fluid Haptoglobin (Hp) Levels are elevated in MS patients with progressive disease (P5.213)

OBJECTIVE: To investigate the role of haptoglobin (Hp) in MS. BACKGROUND: Hp is an acute phase protein, with known antioxidant and anti-inflammatory activity. Hp is also involved in regulation of the immune system. CSF Hp is elevated in neuromyelitis optica (NMO). In addition, certain haptoglobin phenotypes are specifically associated with different diseases. Here, we investigated CSF levels of Hp and determined Hp phenotypic expression in plasma obtained from clinically definite MS patients with relapsing-remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS) disease. DESIGN/METHODS: CSF Hp levels were determined by ELISA in RRMS (N=28), SPMS (N=101), and PPMS (N=26) patients. In 58 MS patients, paired CSF and serum Hp levels as well as corresponding albumin values were measured to determine CNS specificity. Hp phenotypes (Hp1-1, Hp2-1, Hp2-2) in plasma were detected by Western blot. To further validate the CNS specific Hp response, we investigated Hp immunostaining in MS brain tissue. RESULTS: We found significantly elevated CSF Hp levels in progressive MS compared to RRMS with no such differences observed in the CSF albumin indexes. No correlation was seen with plasma levels suggesting that this is a CNS specific response. Levels of CSF Hp were similar in SPMS and PPMS. In human brain MS lesions, macrophage and reactive astrocytes are positive for Hp and these findings are not seen in normal appearing white matter again suggesting a CNS based pathogenesis for the elevated CSF Hp levels. The plasma Hp2-2 phenotype was over represented in PPMS patients as compared to SPMS or RRMS patients. CONCLUSIONS: CSF Hp concentration was increased in progressive type MS patients when compared with RRMS patients. The elevated haptoglobin in CSF appears to correlate with CNS specific events. Hp2-2 phenotype in PPMS patients may suggest a vulnerability to oxidative stress. Study Supported by: Shubert Foundation Disclosure: Dr. Ulloa has nothing to disclose. Dr. Alahiri has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Sadiq has nothing to disclose.