title: Changes in PINCH levels in the CSF of HIV+ individuals correlate with hpTau and CD4 count.
abstract: Several studies report associations between the particularly interesting new cysteine histidine-rich (PINCH) protein and HIV-associated CNS disease. PINCH is detected in the CSF of HIV patients, and changes in levels during disease may be indicative of changes in disease status over time. PINCH binds hyperphosphorylated Tau (hpTau) in the brain and CSF, but little is known about the relevance of these interactions to HIV CNS disease. In this study, PINCH and hpTau levels were assessed in three separate CSF samples collected longitudinally from 20 HIV+ participants before and after initiating antiretroviral therapy or before and after a change in the treatment regimen. The intervals were approximately 1 (T2) and 3-7 (T3) months from the initial visit (baseline, T1). Correlational analyses were conducted for CSF levels of PINCH and hpTau and other variables including blood CD4 T-cell count, plasma and CSF viral burden, CSF neopterin, white blood cell (WBC) count, and antiretroviral CNS penetration effectiveness (CPE). Values for PINCH and hpTau were determined for each patient by calculating the fold changes between the second (T2) and third measurements (T3) from the baseline measurement (T1). Statistical analyses showed that the fold changes in CSF PINCH protein from T1 to T2 were significantly higher in participants with CD4 counts >200 cells/mm(3) at T2 compared to those with CD4 counts <200 cells/mm(3) at T2. This trend persisted irrespective of plasma or CSF viral burden or antiretroviral therapy CPE scores. The fold changes in PINCH levels between T1 and T2, and T1 and T3 were highly correlated to the fold changes in hpTau at T2/T1 and T3/T1 (correlation coefficient = 0.69, p < 0.001; correlation coefficient = 0.83, p < 0.0001, respectively). In conclusion, in these HIV participants, changes in CSF levels of PINCH appear to correlate with changes in blood CD4 count and with changes in CSF hpTau levels, but not with plasma or CSF viral burden, neopterin, WBC, or antiretroviral regimen CPE.
authors.affiliation: School of Medicine, Department of Neuroscience, Temple University, 3500 N. Broad Street, MERB 750, Philadelphia, PA, 19140, USA.
authors.forename: Radhika
authors.initials: R
authors.lastname: Adiga
authors.forename: Ahmet Y
authors.initials: AY
authors.lastname: Ozdemir
authors.forename: Alexandra
authors.initials: A
authors.lastname: Carides
authors.forename: Melissa
authors.initials: M
authors.lastname: Wasilewski
authors.forename: William
authors.initials: W
authors.lastname: Yen
authors.forename: Pallavi
authors.initials: P
authors.lastname: Chitturi
authors.forename: Ronald
authors.initials: R
authors.lastname: Ellis
authors.forename: Dianne
authors.initials: D
authors.lastname: Langford
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000134:cerebrospinal fluid*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015153:Blotting, Western; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D060588:LIM Domain Proteins / Q000134:cerebrospinal fluid*; D008297:Male; D008565:Membrane Proteins / Q000134:cerebrospinal fluid; D008875:Middle Aged; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D044966:Anti-Retroviral Agents; D060588:LIM Domain Proteins; C088088:LIMS1 protein, human; D008565:Membrane Proteins; D016875:tau Proteins