The blood-brain barrier, TWEAK, and neuropsychiatric involvement in human systemic lupus erythematosus and primary Sjögren's syndrome.

OBJECTIVE: A prevailing hypothesis for neuropsychiatric involvement in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome is that brain reactive autoantibodies enter the brain through a disrupted blood-brain barrier. Our aim was to investigate whether TNF-like weak inducer of apoptosis (TWEAK) plays a role in cerebral involvement in human SLE and primary Sjögren's syndrome, and whether an impaired blood-brain barrier is a prerequisite for neuropsychiatric manifestations. METHODS: TWEAK was measured in the cerebrospinal fluid and serum and compared with markers of blood-brain barrier permeability (Q-albumin and MRI contrast-enhanced lesions) and S100B, an astrocyte activation marker in 50 SLE and 52 primary Sjögren's syndrome patients. Furthermore, we estimated the general intrathecal B-cell activation (IgG index), measured anti-NR2 antibodies in cerebrospinal fluid, and explored whether these variables were associated with neuropsychiatric manifestations. RESULTS: No associations were found between TWEAK in the cerebrospinal fluid or serum and neuropsychiatric manifestations in SLE nor in primary Sjögren's syndrome patients. Furthermore, no associations were found between neuropsychiatric manifestations and indicators of blood-brain barrier integrity or astroglial activity. Anti-NR2 antibodies were associated with impaired visuospatial processing (odds ratio 4.9, P = 0.03) and motor functioning (odds ratio 6.0, P = 0.006). CONCLUSION: No clinical neuropsychiatric manifestations could be attributed to impaired integrity of the blood-brain barrier, or to TWEAK levels in cerebrospinal fluid or serum in either patient group. The TWEAK concentration was considerably higher in the cerebrospinal fluid than in blood, which indicates intrathecal production. We hypothesize that increased TWEAK and S100B result from immunological stress caused by brain-reactive antibodies produced by brain residing immune cells.

Fatigue in psoriasis: a controlled study.

BACKGROUND: Fatigue is associated with various chronic inflammatory diseases, but few studies have focused on its occurrence in psoriasis. OBJECTIVES: To describe fatigue prevalence and degree among patients with chronic plaque psoriasis vs. age- and sex-matched healthy subjects, and to examine how fatigue is influenced by essential clinical and demographic factors. METHODS: In 84 patients and 84 healthy subjects, fatigue severity was assessed using three different generic fatigue instruments: the fatigue Visual Analogue Scale (fVAS), the Fatigue Severity Scale (FSS) and the Short Form 36 (SF-36) Vitality scale. Cut-off scores for clinically important fatigue were defined as ≥ 4 for FSS, ≥ 50 for fVAS and ≤ 35 for the SF-36 Vitality scale. Disease activity was evaluated using the Psoriasis Area and Severity Index (PASI), and the impact on quality of life with the Dermatology Life Quality Index (DLQI). RESULTS: Patients and healthy control subjects, respectively, showed median fVAS scores of 51 [interquartile range (IQR) 21-67] and 11 (IQR 3-20); FSS scores of 4 (IQR 2·5-5·3) and 1·6 (IQR 1·1-2·2); and SF-36 Vitality scores of 43 (IQR 25-85) and 73 (IQR 65-85). The rates of clinically important fatigue among patients vs. healthy controls, respectively, were 51% vs. 4% (fVAS); 52% vs. 4% (FSS); and 42% vs. 2% (SF-36 Vitality) (P < 0·001 for all differences). Fatigue was associated with DLQI scores, but not PASI scores, in univariate analysis but not in multivariate analysis. CONCLUSIONS: Nearly 50% of patients with psoriasis suffered from substantial fatigue. Fatigue severity was associated with smoking, pain and depression, but not with psoriasis severity.

Migraine in patients with systemic lupus erythematosus is associated with reduced cerebral grey matter volume but not with measures of glial activation or anti-NR2 or anti-P antibodies.

BACKGROUND AND PURPOSE: Migraine is frequent in patients with systemic lupus erythematosus (SLE), but the pathogenesis and pathophysiology are poorly understood. Migraine is assumed to be a consequence of abnormal neuronal excitability. Based on the hypothesis that the threshold for migraine is lower in SLE patients due to cerebral disturbances, whether structural abnormalities of the brain or relevant biomarkers are associated with headaches in SLE was investigated. METHODS: Sixty-seven SLE patients and age- and gender-matched healthy subjects participated. Volumes of grey matter (GM) and white matter (WM) were estimated from cerebral magnetic resonance images with SPM8 software. Anti-NR2 and anti-P antibodies and protein S100B were measured in cerebrospinal fluid. RESULTS: In regression analyses, larger GM volumes in SLE patients reduced the odds for headache in general [odds ratio (OR) 0.98, P = 0.048] and for migraine in particular (OR 0.95, P = 0.004). No localized loss of GM was observed. Larger WM volumes in patients increased the odds for migraine (OR 1.04, P = 0.007). These findings could not be confirmed in healthy subjects. Neither anti-NR2 and anti-P antibodies nor S100B were associated with headaches in SLE patients. CONCLUSIONS: Systemic lupus erythematosus patients with migraine have a diffuse reduction in GM compared to patients without migraine. This finding was not observed in healthy subjects with migraine, and selected biomarkers did not indicate specific pathophysiological processes in the brain. These findings indicate that unknown pathogenic processes are responsible for the increased frequency of migraine in SLE patients.