Evaluating Soluble EMMPRIN as a Marker of Disease Activity in Multiple Sclerosis: Studies of Serum and Cerebrospinal Fluid

• Published in: PloS one 2016-10, Vol.11 (10), p.e0163802-e0163802
• Main Authors: Kaushik, Deepak K, Yong, Heather Y F, Hahn, Jennifer N, Silva, Claudia, Casha, Steven, Hurlbert, R John, Jacques, Francois H, Lisak, Robert, Khan, Omar, Ionete, Carolina, Larochelle, Catherine, Prat, Alex, Bar-Or, Amit, Yong, V Wee
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - blood; Amyotrophic Lateral Sclerosis - pathology; Antibodies - pharmacology; Basigin - blood; Basigin - cerebrospinal fluid; Biology; Biology and Life Sciences; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Case-Control Studies; CD147 antigen; CD28 Antigens - immunology; Cell activation; Cell adhesion & migration; Cell surface; Central nervous system; Central Nervous System Diseases - pathology; Cerebrospinal fluid; Computational fluid dynamics; Cuffs; Disease; Enzyme-Linked Immunosorbent Assay; Experimental allergic encephalomyelitis; Extracellular matrix; Female; Fluid; Fluids; Humans; Immunoglobulin G - cerebrospinal fluid; Inflammation; Leukocyte migration; Leukocytes; Leukocytes, Mononuclear - cytology; Lymphocyte Activation - drug effects; Lymphocytes T; Male; Matrix metalloproteinase; Matrix metalloproteinases; Medical research; Medicine and Health Sciences; Metalloproteinase; Middle Aged; Multiple sclerosis; Multiple Sclerosis - pathology; Pathology; Recurrence; Serum levels; Severity of Illness Index; T cells; T-Lymphocytes - cytology; T-Lymphocytes - metabolism; White blood cells; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0163802

Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is an inducer of matrix metalloproteinases and has roles in leukocyte activation and migration. We reported previously that in MS and its animal model, experimental autoimmune encephalomyelitis, cell surface-associated EMMPRIN was significantly elevated in leukocytes around inflammatory perivascular cuffs in the CNS. In this study we report that activated T-cells can secrete soluble form of EMMPRIN (sEMMPRIN) upon activation. As sEMMPRIN is also present in biological fluids, we determined whether sEMMPRIN is altered in the CSF and sera of MS subjects. Sera from individuals without neurological conditions served as controls, while CSFs collected from subjects undergoing discectomy, and without evidence of CNS pathology, were used as a comparator group. We found that serum levels of sEMMPRIN from clinically stable MS patients or other inflammatory conditions did not differ from control subjects. Paired serum and CSF samples demonstrated poor correlation of sEMMPRIN. Interestingly, sEMMPRIN levels were approximately 60% higher in CSFs compared to sera. sEMMPRIN CSF levels were significantly higher in secondary progressive compared to primary progressive subjects. Thus we conclude that measurement of sEMMPRIN in serum is not informative for disease activity in MS. The differential expression of sEMMPRIN in the CSF of primary and secondary progressive MS invites hypotheses of the still undefined roles of EMMPRIN in the CNS.