Soluble CSF interleukin 2 receptor as indicator of neurosarcoidosis

Abstract

Neurosarcoidosis (NS) represents an important differential diagnosis of multiple sclerosis (MS). However, thus far no reliable laboratory marker of neurosarcoidosis exists. The objective of this study was to evaluate whether cerebrospinal fluid (CSF) levels of soluble interleukin 2 receptor (sIL2-R) distinguish NS and other inflammatory disorders of the central nervous system. For this purpose, 139 paired CSF and serum samples from 11 patients with NS, 21 with MS, 10 with CNS vasculitis, 22 with bacterial meningitis, 17 with viral meningitis/encephalitis, seven with neurotuberculosis, and 18 healthy donors were assessed for sIL2-R using an enzyme-linked immunosorbent assay. We found that sIL2-R CSF levels above 150 pg/ml identified untreated NS patients with an overall accuracy of 93% against a group of non-infectious CNS-diseases. Furthermore, an increase in sIL2-R in the CSF was associated with and preceded the outbreak of new neurological symptoms. In conclusion, these findings suggest that sIL2-R measurement in the CSF may be a valuable tool in the diagnosis and follow-up of patients with suspected and proven neurosarcoidosis.

Challenges in the diagnosis and treatment of neurosarcoidosis

“…A genetically predisposed condition of selective involvement of the nervous system can also be suggested by the evidence of a significant and specific elevation of some biomarkers in neurosarcoidosis in comparison to controls, revealing that neurosarcoidosis could be sustained partly by specific genetic profiles as found for sarcoidosis in general (29)(30)(31).…”

“…Increased sIL2 receptor activity in the CSF might actually help to discriminate neurosarcoidosis from other chronic inflammatory CNS diseases (31). Cells in the CSF (number and type of cells) as well as antibody indices (IgM, IgA, IgG) are often pathologic and may reflect disease activity (72).…”

Neurosarcoidosis Flare Following Urinary Tract Infection with Extended Spectrum Beta Lactamase Producing Escherichia coli

“…CSF analysis shows elevated protein in about 54% cases [8]. An increased concentration of interleukin-2 receptors in CSF (over 150 pg/mL) can point towards neurosarcoidosis, although the presence of concomitant infection makes this test less sensitive [9]. Studies have shown that serum ACE level does not correlate well with disease activity due to low sensitivity and genetic polymorphism [10][11].…”

Neurosarcoidosis

“…31 Increased CSF lactate and other markers of inflammation may also be seen. In one recent study, elevated CSF-soluble interleukin-2 receptor levels over 150 pg/mL detected untreated neurosarcoidosis patients with a 61% sensitivity and 93% specificity in comparison with healthy control subjects 33 Levels were found to change accordingly with disease activity and treatment status in serial measurements of patients with neurosarcoidosis. Although serum angiotensin-converting enzyme (ACE) is still widely used in evaluating systemic disease, CSF ACE is less helpful in the diagnosis of neurosarcoidosis given its low sensitivity (13%-25%) and has been absent even in the setting of a positive brain biopsy.…”

“…Although serum angiotensin-converting enzyme (ACE) is still widely used in evaluating systemic disease, CSF ACE is less helpful in the diagnosis of neurosarcoidosis given its low sensitivity (13%-25%) and has been absent even in the setting of a positive brain biopsy. 33,34 Cytology, flow cytometry, and cultures (fungal, bacterial, and viral) should be obtained in all patients with suspected neurosarcoidosis because malignancy and infectious meningitis may demonstrate very similar MRI and CSF findings, including hypoglycorrhachia. In known sarcoidosis patients who are chronically immunosuppressed, progressive multifocal leukoencephalopathy should be excluded with polymerase chain reaction studies for JC virus DNA.…”