Soluble CD163 as a marker of macrophage activity in newly diagnosed patients with multiple sclerosis

TY - JOUR

T1 - Soluble CD163 as a marker of macrophage activity in newly diagnosed patients with multiple sclerosis

AU - Stilund, Morten

AU - Reuschlein, Ann-Kathrin

AU - Christensen, Tove

AU - Møller, Holger Jon

AU - Rasmussen, Peter Vestergaard

AU - Petersen, Thor

PY - 2014/6/2

Y1 - 2014/6/2

N2 - BACKGROUND: Soluble CD163 (sCD163) is a macrophage specific protein known to be up-regulated in serum from patients with multiple sclerosis (MS).OBJECTIVE: To investigate sCD163 in serum and CSF (cerebrospinal fluid) from patients undergoing MS diagnostic work-up and analyse its potential as a diagnostic biomarker.METHODS: After a full MS diagnostic work-up, including collection of paired samples of CSF and serum, 183 patients were evaluated for inclusion in this study. Patients were divided into groups based on their diagnosis. Patients with normal clinical and paraclinical findings were grouped as symptomatic controls. Serum and CSF levels of sCD163 were determined by enzyme-linked immunosorbent assay (ELISA).RESULTS: sCD163 could be measured in all serum and CSF samples. A high sCD163 CSF/serum ratio in relation to molecular weight was found, strongly indicating local production in the CNS. Median levels of sCD163 were significantly decreased in serum and significantly elevated in CSF in patients with relapsing-remitting, and primary-progressive MS. There were, however, some overlaps of the measures between groups. In a receiver operating characteristic (ROC) analysis sCD163 CSF/serum ratio had an area under the curve of 0.72.CONCLUSION: The sCD163 CSF/serum ratio was significantly increased in patients with MS and may reflect macrophage activation in MS lesions. These results suggest that primary progressive MS also is driven by inflammation in which the innate immune system plays a pivotal role.

AB - BACKGROUND: Soluble CD163 (sCD163) is a macrophage specific protein known to be up-regulated in serum from patients with multiple sclerosis (MS).OBJECTIVE: To investigate sCD163 in serum and CSF (cerebrospinal fluid) from patients undergoing MS diagnostic work-up and analyse its potential as a diagnostic biomarker.METHODS: After a full MS diagnostic work-up, including collection of paired samples of CSF and serum, 183 patients were evaluated for inclusion in this study. Patients were divided into groups based on their diagnosis. Patients with normal clinical and paraclinical findings were grouped as symptomatic controls. Serum and CSF levels of sCD163 were determined by enzyme-linked immunosorbent assay (ELISA).RESULTS: sCD163 could be measured in all serum and CSF samples. A high sCD163 CSF/serum ratio in relation to molecular weight was found, strongly indicating local production in the CNS. Median levels of sCD163 were significantly decreased in serum and significantly elevated in CSF in patients with relapsing-remitting, and primary-progressive MS. There were, however, some overlaps of the measures between groups. In a receiver operating characteristic (ROC) analysis sCD163 CSF/serum ratio had an area under the curve of 0.72.CONCLUSION: The sCD163 CSF/serum ratio was significantly increased in patients with MS and may reflect macrophage activation in MS lesions. These results suggest that primary progressive MS also is driven by inflammation in which the innate immune system plays a pivotal role.

KW - Antigens, CD

KW - Antigens, Differentiation, Myelomonocytic

KW - Enzyme-Linked Immunosorbent Assay

KW - Humans

KW - Macrophages

KW - Multiple Sclerosis

KW - Receptors, Cell Surface

U2 - 10.1371/journal.pone.0098588

DO - 10.1371/journal.pone.0098588

M3 - Journal article

C2 - 24886843

SN - 1932-6203

VL - 9

SP - e98588

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 6

ER -