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Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection
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نویسنده
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suh j. ,sinclair e. ,peterson j. ,lee e. ,kyriakides t.c. ,li f. ,hagberg l. ,fuchs d. ,price r.w. ,gisslen m. ,spudich s.
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منبع
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journal of neuroinflammation - 2014 - دوره : 11 - شماره : 0
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چکیده
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Background: central nervous system (cns) inflammation is a mediator of brain injury in hiv infection. to study the natural course of cns inflammation in the early phase of infection,we analyzed longitudinal levels of soluble and cellular markers of inflammation in cerebrospinal fluid (csf) and blood,beginning with primary hiv-1 infection (phi). methods: antiretroviral-naïve subjects identified as having phi (less than one year since hiv transmission) participated in phlebotomy and lumbar puncture at baseline and at variable intervals thereafter. mixed-effects models were used to analyze longitudinal levels of csf neopterin and percentages of activated cluster of differentiation (cd)4+ and cd8+ t-cells (co-expressing cd38 and human leukocyte antigen-d-related (hla-dr)) in blood and csf. results: a total of 81 subjects were enrolled at an average of 100 days after hiv transmission and had an average follow-up period of 321 days,with the number of visits ranging from one to 13. at baseline,the majority of subjects had csf neopterin concentrations above the upper limit of normal. the baseline concentration was associated with the longitudinal trajectory of csf neopterin. in subjects with baseline levels of less than 21 nmol/l,a cutoff value obtained from a mixed-effects model,csf neopterin increased by 2.9% per 10 weeks (n=33; p <0.001),whereas it decreased by 6.7% in subjects with baseline levels of more than 21 nmol/l (n=11; p=0.001). in a subset with available flow cytometry data (n=42),the percentages of activated cd4+ and cd8+ t-cells in csf increased by 0.8 (p <0.001) and 0.73 (p=0.02) per 10 weeks,respectively. conclusions: neopterin levels and the percentages of activated cd4+ and cd8+ t-cells in csf progressively increase in most subjects without treatment during early hiv-1 infection,suggesting an accrual of intrathecal inflammation,a major contributor to neuropathology in hiv infection. © suh et al.; licensee biomed central ltd.
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کلیدواژه
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Activated T-cells; Central Nervous System Viral Infections; HIV; Immune Activation; Inflammation; Neopterin
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آدرس
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yale school of medicine,367 cedar street,new haven,ct 06510, United States, ucsf school of medicine,department of medicine,1001 potrero avenue,sfgh 100,san francisco,ca 94143, United States, ucsf school of medicine,department of neurology,1001 potrero avenue,sfgh 1,san francisco,ca 94110, United States, ucsf school of medicine,department of neurology,1001 potrero avenue,sfgh 1,san francisco,ca 94110, United States, yale center for analytical sciences,yale university,300 george street,suite 555,new haven,ct 06520, United States, yale center for analytical sciences,yale university,300 george street,suite 555,new haven,ct 06520, United States, university of gothenburg,department of infectious diseases,journalvägen 10,gothenburg,416 85, Sweden, innsbruck medical university,division of biological chemistry,innrain 80,innsbruck,6020, Austria, ucsf school of medicine,department of neurology,1001 potrero avenue,sfgh 1,san francisco,ca 94110, United States, university of gothenburg,department of infectious diseases,journalvägen 10,gothenburg,416 85, Sweden, yale school of medicine,department of neurology,300 george street,new haven,ct 06510, United States
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Authors
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