Changes in PINCH levels in the CSF of HIV+ individuals correlate with hpTau and CD4 count.

TitleChanges in PINCH levels in the CSF of HIV+ individuals correlate with hpTau and CD4 count.
Publication TypeJournal Article
Year of Publication2014
AuthorsAdiga, R, Ozdemir, AY, Carides, A, Wasilewski, M, Yen, W, Chitturi, P, Ellis, R, Langford, D
JournalJ Neurovirol
Date Published2014 Aug
KeywordsAdaptor Proteins, Signal Transducing, Adult, Anti-Retroviral Agents, Blotting, Western, CD4 Lymphocyte Count, Drug Therapy, Combination, Enzyme-Linked Immunosorbent Assay, External, Female, HIV Infections, Humans, LIM Domain Proteins, Male, Membrane Proteins, Middle Aged, Phosphorylation, tau Proteins

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.

Alternate JournalJ Neurovirol
PubMed ID24817145
PubMed Central IDPMC4104596
Grant ListR01 MH107340 / MH / NIMH NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
R01 MH085602 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
P30 MH092177 / MH / NIMH NIH HHS / United States
MH085602 / MH / NIMH NIH HHS / United States
R01MH58076 / MH / NIMH NIH HHS / United States