Large Mitochondrial DNA Deletions in HIV Sensory Neuropathy.

Autor:	Roda RH; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA. rroda1@jhmi.edu., Bargiela D; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Chen W; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Perry K; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Ellis RJ; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Clifford DB; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Bharti A; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Kallianpur AR; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Oliveira MF; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Diaz MM; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Rubin LH; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Gavegnano C; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., McArthur JC; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Hoke A; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA., Polydefkis M; From the Department of Neurology (R.H.R., W.C., K.P., L.H.R., J.C.M., A.H., M.P.) and Department of Psychiatry (L.H.R.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (D.B.), Brigham and Women's Hospital, Boston, MA; Departments of Neurosciences and Psychiatry (R.J.E., M.M.D.) and Department of Medicine (A.B., M.F.O.), University of California, San Diego; Department of Neurology (D.B.C.), Washington University School of Medicine, St. Louis, MO; Departments of Genomic Medicine, Medicine, and Pediatrics (A.R.K.), Cleveland Clinic/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH; and Department of Pathology and Laboratory Medicine (C.G.), Joint Appointment in Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2021 Jul 13; Vol. 97 (2), pp. e156-e165. Date of Electronic Publication: 2021 May 04.
DOI:	10.1212/WNL.0000000000012142
Abstrakt:	Objective: The primary objective of this study was to evaluate the correlation of large mitochondrial DNA (mtDNA) deletions in skin samples of people with HIV (PWH) with measures of neuropathy and prior exposure to therapy. We hypothesized that deletions would be associated with neuropathy. As secondary objectives, we determined the correlation of deletion burden with demographic data and neuropathy measures. Methods: In this retrospective cohort study, we measured the accumulation of large mtDNA deletions in skin biopsies from PWH recruited as part of the AIDS Clinical Trials Group (ACTG). Our cohort includes individuals with and without sensory neuropathy, as well as individuals with normal or abnormal skin biopsies. Skin biopsies, sural and peroneal nerve conduction studies, total neuropathy score, and deletion burden scores were measured, along with baseline demographic data such as age, CD4+ cell count, viral counts, and prior nucleoside reverse transcriptase inhibitor exposures. Results: Sixty-seven PWH were enrolled in the study. The mean age of the cohort (n = 67) was 44 years (SD 6.8, range 32-65 years), and 9 participants were female. The mean CD4+ T-cell count was 168 cells/mm 3 (SD 97 cells/mm 3 , range 1-416 cells/mm 3 ) and mean viral load was 51,129 copies/mL (SD 114,586 copies/mL, range 147-657,775 copies/mL). We determined that there was a correlation between the total mtDNA deletion and intraepidermal nerve fiber density (IENFD) ( r = -0.344, p = 0.04) and sural nerve amplitude ( r = -0.359, p = 0.004). Conclusions: Both IENFD and sural nerve amplitude statistically correlate with mitochondrial mutation burden in PWH, specifically in those with HIV-associated sensory neuropathy as assessed by skin biopsy. (© 2021 American Academy of Neurology.)
Databáze:	MEDLINE
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