Inflammation in HIV-associated neurocognitive disorders

Item does not contain fulltextRU Radboud Universiteit, 6 juni 2016Promotores : Ven, A.J.A.M. van der, Mphahlele, J. Co-promotores : Stelma, F.F., Koopmans †, P.P

Has CXCL13 an added value in diagnosis of neurosyphilis?

Contains fulltext : 155396.pdf (publisher's version ) (Open Access)In patients with syphilis, central nervous system (CNS) involvement is often difficult to determine. In patients who also are infected with human immunodeficiency virus (HIV), this is even more challenging, as cerebrospinal fluid (CSF) pleocytosis can be attributed to HIV, syphilis, or both. Hence, this study investigated (i) CSF chemokine (C-X-C motif) ligand 13 (CXCL13) as a potential marker to diagnose neurosyphilis in HIV-infected individuals and (ii) the added value of CSF CXCL13 to conventional CSF biomarkers, such as the rapid plasma reagin test (RPR), in diagnosing neurosyphilis. We included 103 syphilis patients from two centers in The Netherlands: 47 non-HIV-infected patients and 56 HIV-infected patients. A positive CSF-RPR was regarded as the gold standard for neurosyphilis. CSF CXCL13 levels were significantly higher in neurosyphilis patients when neurosyphilis was diagnosed by CSF-RPR (P = 0.0002) than in the syphilis control group. The sensitivity and specificity of CSF CXCL13 (cutoff of 76.3 pg/ml) to diagnose neurosyphilis by using positive CSF-RPR as the gold standard were 50% and 90%, respectively. CSF CXCL13 had an added value to CSF-RPR positivity in 70% of HIV-positive patients and in 33% of HIV-negative patients. Our data show that CSF CXCL13 might be a potential additional marker in neurosyphilis when other markers are not conclusive. The added value of CSF CXCL13 measurement to the current neurosyphilis gold standard appears to benefit HIV-positive patients more than HIV-negative patients

Exercise and insulin signaling : a historical perspective

Neuropsychiatric symptoms in human immunodeficiency virus (HIV)-infected patients may be a late complication of efavirenz treatment. This study: 1) assessed the level of neuropsychiatric symptoms in HIV-infected patients on long-term efavirenz therapy; 2) explored the effect of a switch to non-efavirenz containing anti-retroviral treatment on neuropsychiatric symptoms. A consecutive series of 47 HIV-infected participants on long-term efavirenz treatment were included in an observational clinical trial. Participants completed three self-report questionnaires on neuropsychiatric symptoms. Patients switching to a non-efavirenz regimen were retested 2 weeks and 3 months after switching. Data were analyzed using repeated measures ANOVA to assess the effect of switching over time. A change in the percentage of patients scoring above norm scores after switching was analyzed using Chi square. Neuropsychiatric symptoms were common among HIV-infected patients on long-term efavirenz therapy, mainly depression, anxiety, stress, insufficiency in thinking and paranoia. After switching, these symptoms improved significantly to (near) normal levels. Our results show that neuropsychiatric symptoms are common among HIV-infected subjects and may be caused by long-term efavirenz use. Neuropsychiatric assessment, such as the Depression, Anxiety and Stress scale and Symptom Checklist 90, can identify those that may benefit from the discontinuation of efavirenz

The discriminative capacity of soluble Toll-like receptor (sTLR)2 and sTLR4 in inflammatory diseases

Contains fulltext : 138726.pdf (publisher's version ) (Open Access)BackgroundThe extracellular domains of cytokine receptors are released during inflammation, but little is known about the shedding of Toll-like receptors (TLR) and whether they can be used as diagnostic biomarkers.MethodsThe release of sTLR2 and sTLR4 was studied in in-vitro stimulations, as well as in-vivo during experimental human endotoxemia (n inverted question mark= inverted question mark11, 2 ng/kg LPS), and in plasma of 394 patients with infections (infectious mononucleosis, measles, respiratory tract infections, bacterial sepsis and candidemia) or non-infectious inflammation (Crohn inverted question marks disease, gout, rheumatoid arthritis, autoinflammatory syndromes and pancreatitis). Using C-statistics, the value of sTLR2 and sTLR4 levels for discrimination between infections and non-infectious inflammatory diseases, as well as between viral and bacterial infections was analyzed.ResultsIn-vitro, peripheral blood mononuclear cells released sTLR2 and sTLR4 by exposure to microbial ligands. During experimental human endotoxemia, plasma concentrations peaked after 2 hours (sTLR4) and 4 hours (sTLR2). sTLR4 did not correlate with cytokines, but sTLR2 correlated positively with TNF inverted question mark (rs inverted question mark= inverted question mark0.80, P inverted question mark< inverted question mark0.05), IL-6 (rs inverted question mark= inverted question mark0.65, P inverted question mark< inverted question mark0.05), and IL-1Ra (rs inverted question mark= inverted question mark0.57, P inverted question mark= inverted question mark0.06), and negatively with IL-10 (rs inverted question mark= inverted question mark-0.58, P inverted question mark= inverted question mark0.06), respectively. sTLR4 had a similar area under the ROC curve [AUC] for differentiating infectious and non-infectious inflammation compared to CRP: 0.72 (95% CI 0.66-0.79) versus 0.74 (95% CI 0.69-0.80) [P inverted question mark= inverted question mark0.80], while sTLR2 had a lower AUC: 0.60 (95% CI 0.54-0.66) [P inverted question mark= inverted question mark0.0004]. CRP differentiated bacterial infections better from viral infections than sTLR2 and sTLR4: AUC 0.94 (95% CI 0.90-0.96) versus 0.58 (95% CI 0.51-0.64) and 0.75 (95% CI 0.70-0.80), respectively [P inverted question mark< inverted question mark0.0001 for both].ConclusionssTLRs are released into the circulation, and suggest the possibility to use sTLRs as diagnostic tool in inflammatory conditions