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Session 66 Poster Abstracts
Pathogenesis: Determinants and Cellular Factors
Thursday, 1:30 - 3:30 pm
Hall D


334    
Mucosal Gene Expression Profiles and CD4+T-cell Percentages Are Characteristic of the Clinical Outcome in Long-term HIV-infected Non-progressors and Chronically HIV-infected patients
Sumathi Sankaran*1,4, M Guadalupe1,4, E Reay1,4, J Flamm2, T Prindiville3, and S Dandekar1,4
1MMI Genomics, Davis, CA, USA; 2Kaiser Permanente, Sacramento, CA, USA; 3Univ of California, Davis, USA; and 4Univ of California, Davis, USA

Background:  The mucosal immune system is impaired severely early in HIV infection. However, in long-term HIV-1-infected non-progressors (LTNP) mucosal CD4+ T cells are preserved. The main objective of this study was to determine the molecular processes in mucosal immune systems in relation to the disease outcome.

Methods:  Three human cohorts with diverse clinical status were investigated for the CD4+ T-cell numbers, viral loads, and gene-expression profiles in jejunal mucosal tissues and peripheral blood. The cohorts consisted of Group 1: LTNP (n = 3); Group 2: patients with high peripheral viral loads—HVL (n = 4); and Group 3: HIV-1 sero-negative healthy controls (n = 4). DNA microarray data analysis was performed using Microarraysuite, dCHIP, GENMAPP, and DAVID/EASE. HIV-1 viral RNA burden was measured by real time polymerase chain reaction (PCR) and T-cell subsets were quantified by flow cytometry and immunohistochemistry.

Results:  LTNP (Group 1) had undetectable viral loads in gut mucosa, while individuals in HVL (Group 2) had high viral burden in GALT. A signature gene expression profile characteristic of the clinical outcome was modulation of regulators of T-cell function, including inducible T-cell co-stimulator, T-cell immune regulator 1, and interleukin-12A (IN-12A). These genes were up-regulated in Group 1 LTNP while pro-inflammatory factors and the complement cascade were up-regulated in Group 2 HVL patients. Group 2 HVL patients showed an increased expression of lymphocyte mucosal trafficking molecules (a4b7 integrin) and apoptosis; also, digestive function-associated genes were down-modulated in this group. Dysregulation of expression of genes associated with protein, carbohydrate, and lipid metabolism was observed in Groups 1 and 2 patients.

Conclusions:  Genes regulating inflammation and cellular activation distinguished the patients with diverse clinical outcomes. Regulators of T-cell function dominated the expression profile in LTNP, while inflammation and tissue injury dominated that of HVL.

 

Keywords: GALT; Gene expression; LTNP