title: Increased osteopontin plasma levels in multiple sclerosis patients correlate with bone-specific markers.
abstract: The pro-inflammatory cytokine osteopontin has been found to be highly expressed in multiple sclerosis lesions and plasma levels are increased during relapses in relapse-onset multiple sclerosis patients. The objective was to determine the relationship between osteopontin plasma and cerebrospinal fluid levels in relation to the immunoglobulin G index. In addition, osteopontin plasma levels were compared with osteopontin mRNA levels in peripheral blood mononuclear cells and bone-specific markers to analyse whether osteopontin may be peripherally produced. Osteopontin and bone-specific markers were determined in paired plasma-cerebrospinal fluid samples and serum samples of relapse-onset multiple sclerosis patients (n = 36), respectively. Osteopontin mRNA levels were determined by quantitative polymerase chain reaction analysis. Compared to healthy controls (n = 20), plasma osteopontin levels were significantly increased in relapsing-remitting multiple sclerosis patients and correlated (r = 0.43, p = 0.013) with the immunoglobulin G index. In contrast, cerebrospinal fluid osteopontin levels correlated neither with plasma osteopontin in paired samples nor with the immunoglobulin G index. Since osteopontin mRNA levels in peripheral blood mononuclear cells of relapsing-remitting multiple sclerosis patients did not correlate with osteopontin plasma levels, peripheral blood mononuclear cells might not be the major source for the increased osteopontin plasma levels. Osteopontin plasma levels correlated (r = 0.42, p = 0.035) with the bone-specific degradation product C-telopeptide of type-1 collagen. In addition, another immunomodulatory molecule involved in bone metabolism, 25-OH vitamin D, correlated negatively (r = -0.359, p = 0.048) with the immunoglobulin G index. This study suggests that bone-related molecules like osteopontin and vitamin D with important immunomodulatory functions are related to the immunoglobulin G index in relapsing-remitting multiple sclerosis patients.
authors.affiliation: Department of Clinical Chemistry and Hematology, Orbis Medical Center, Sittard-Geleen, The Netherlands. m.vogt@orbisconcern.nl
authors.forename: Mario H J
authors.initials: MH
authors.lastname: Vogt
authors.forename: Joop
authors.initials: J
authors.lastname: ten Kate
authors.forename: Roosmarie J M
authors.initials: RJ
authors.lastname: Drent
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D024042:Collagen Type I / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000134:cerebrospinal fluid / Q000235:genetics; D009426:Netherlands; D015675:Osteocalcin / Q000097:blood; D053495:Osteopontin / Q000097:blood* / Q000134:cerebrospinal fluid / Q000235:genetics; D010455:Peptides / Q000097:blood; D012333:RNA, Messenger / Q000097:blood; D015854:Up-Regulation; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D007074:Immunoglobulin G; D010455:Peptides; D012333:RNA, Messenger; C506895:SPP1 protein, human; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D053495:Osteopontin; D014807:Vitamin D; C104450:25-hydroxyvitamin D