Intrathecal cytokine and chemokine profiling in neuropsychiatric lupus or lupus complicated with central nervous system infection

Abstract

The aims of this study are to investigate the cytokine, chemokine and adhesion molecule profiles in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus and systemic lupus erythematosus with central nervous system infection. Experimental sets were established which included 108 patients and 132 cerebrospinal fluid samples. The patients were grouped as neuropsychiatric systemic lupus erythematosus (n = 54), systemic lupus erythematosus with central nervous system infection (n = 16), systemic lupus erythematosus controls (n=20), and non-inflammatory neurological disease (n=18). The dynamic changes of 21 patients in the neuropsychiatric systemic lupus erythematosus group before and after induction therapy were further analyzed. IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNFalpha, IFN gamma, IP-10, MCP-1, RANTES, VCAM-1, and P-selectin were measured in cerebrospinal fluid samples by using a fluorescent bead-based assay. Cerebrospinal fluid levels of IL-8, MCP-1, P-selectin and VCAM-1 were significantly increased in neuropsychiatric systemic lupus erythematosus compared with systemic lupus erythematosus controls. IL-6, IL-17, IL-8 and VCAM-1 were higher in systemic lupus erythematosus with central nervous system infection than in systemic lupus erythematosus controls. Among systemic lupus erythematosus with central nervous system infection, the IL-6, IL-17, IL-8 and IP-10 levels were higher than those in neuropsychiatric systemic lupus erythematosus. After sufficient induction therapy, IL-8, MCP-1, P-selectin, VCAM-1 and IL-6 in patients with neuropsychiatric systemic lupus erythematosus decreased significantly. Levels of all molecules tested in non-inflammatory central nervous system disease were not different from those of systemic lupus erythematosus controls. From our data, the intrathecal cytokine/chemokine profile is different among patients with neuropsychiatric systemic lupus erythematosus, systemic lupus erythematosus complicated with central nervous system infection and systemic lupus erythematosus controls. IL-8, MCP-1, VCAM-1, P-selectin and IL-6 in cerebrospinal fluid are effective parameters to monitor neuropsychiatric systemic lupus erythematosus disease activity and response to treatment. Significantly elevated IL-17, IL-6, and to a lesser extent, IL-8, favors central nervous system infection in systemic lupus erythematosus.

Serum and urine interleukin‐17A levels as biomarkers of disease activity in systemic lupus erythematosus

“…This phenomenon can be explained by the small sample size in each category of organ or system manifestation and therefore are not powered enough to detect any significant difference in serum or urine IL‐17A. In addition to that, the total serum IL‐17A levels may not accurately reflect the overall disease activity as the expression may be localized to the affected tissues only such as in the cerebrospinal fluid (CSF) and skin . We also did not find any correlations between serum or urine IL‐17A levels with cumulative organ damage measured with SLICC damage index and this was consistent with other studies …”

Neuropsychiatric disease in murine lupus is dependent on the TWEAK/Fn14 pathway

“…Lupus patients with CNS manifestations have higher CSF levels of TNF, IL-6, and IL-10 as compared to patients with multiple sclerosis or controls with non-inflammatory neurologic disease [34], while intrathecal levels of IL-6, IL-8, and RANTES, all of which are TWEAK-inducible, were significantly increased in NPLSE patients [35]. Indeed, there is interest in using CSF cytokine profiling for the diagnosis of acute confusional state in lupus patients [36], or to distinguish between NPSLE and non-NPSLE complicated with CNS infection [37]. …”

Neuropsychiatric lupus: a mosaic of clinical presentations

“…In some cases, such as vasculitis, aseptic meningitis, and transverse myelitis, it may have a high yield in diagnosis. Several reports demonstrated immunological markers such as anti-DNA antibodies, oligoclonal banding, immune complexes, IL-6, and markers of B-cell activation in the CSF of NPSLE patients [73-75]. …”