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142 Plasma SDF-1 Levels, SDF1-3A Genotype, and CXCR4 Expression on T Lymphocytes: Their Influence on Resistance to HIV-1 Infection and Its Progression
A. Soriano*1, C. Martinez1, E. Palou1, F. García1, M. Plana1, J. M. Aróstegui1, M. Lejeune1, J. del Romero2, C. Rodriguez2, A. Barrasa2, J. I. Lorenzo3 , J. M. Miró1, J. M. Gatell1, and T. Gallart1
1Hosp. Clin., Barcelona, Spain; 2Centro Médico Sandoval, Madrid, Spain; and 3Hosp. La Fe, Valencia, Spain
Background: The relationship between plasma SDF-1 levels, SDF1-3A genotype, and CXCR4 expression on T lymphocytes, and the impact of these integrated parameters on resistance to HIV infection and its progression to AIDS, remain undetermined.
Methods: PCR-RFLP, ELISA, flow cytometry. Subjects studied were: (1) 147 HIV+ patients: 82 long-term nonprogressors (LTNP), 40 typical progressors (TP), and 26 early asymptomatic individuals; (2) 60 exposed uninfected (EU) individuals: 30 with high-risk sexual exposure (EU-sex) and 30 hemophiliacs (EU-hem); and (3) 119 healthy controls. CCR5-delta32 homozygotes were absent.
Results: There were no significant differences in the frequency of homozygotes in HIV-1+ (4%), LTNP (2.4%), EU-hem (13.4%), EU-sex (0%), and HC (6.8%). The frequency of heterozygotes in HIV-1+ group (51.3%) and LTNP (59.8%) was higher than in EU (24.1 %) (p < 0.001) and HC (37.5%) (p = 0.05); the lowest frequency was found in EU-sex (16.7 vs. 30 % in EU-hem). As compared with HC, plasma SDF-1 was increased in EU-sex (p < 0.001) and in all HIV-1+ subgroups (p < 0.001) except in TP with opportunistic infections. The homozygous state was clearly associated with low plasma SDF-1 levels (p < 0.001 vs. heterozygotes and unmutated subjects). Plasma SDF-1 levels were negatively related to CXCR4 expression on CD4 and CD8 T lymphocytes.
Conclusions: The SDF1-3A homozygous state involves low plasma SDF-1 levels and it is not related to slow progression. Resistance to HIV-1 infection via high-risk sexual exposure was associated with high SDF-1 plasma levels, low frequency of heterozygous state and absence of homozygous state. HIV-1 infection is associated with an increased frequency of heterozygous state. In infected individuals, high SDF-1 levels can protect against progression to AIDS. This protective effect might be related in part to the SDF-1-mediated down-regulation of CXCR4 expression.
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