Serum citrate levels, haptoglobin haplotypes and transferrin receptor (CD71) in patients with HIV-1 infection.
BACKGROUND
The progression of HIV-1 infection towards its more advanced stages is accompanied by changes in iron metabolism and increased body iron stores.


METHODS
Given the ability of HIV to alter iron metabolism, we studied the principal (transferrin system) and alternative (citrate system) iron pathways in a group of 65 HIV-infected patients (symptomatic stage B1-B3) and in a group of 36 healthy seronegative individuals. We determined serum citrate levels, haptoglobin (Hp) haplotypes, expression of transferrin receptor (CD71) on cell lines infected with HIV-1 as well as iron markers including blood iron, transferrin and ferritin.


RESULTS
Our data showed decreased serum citrate levels in the HIV-infected patients compared to controls (92.9 +/- 22.4 microM/l vs 126.2 +/- 29.2 microM/L; p < 0.01). In particular, the serum citrate levels negatively correlated with HIV-1 RNA copy number (mean: 2.53 +/- 1.88 x 10(5)/ml, r(s) = 0.70, p < 0.01) and positively correlated with CD4+ T-lymphocyte count (mean: 241 +/- 168/ml, r(s) = 0.64, p > 0.05). Accordingly, blood iron, transferrin and red cell concentrations were lower in HIV-infected patients compared to the controls, whereas serum ferritin levels were higher in HIV-infected patients. Moreover, the Hp haplotype distribution showed significant differences only in the group of HIV-infected patients (p = 0.02; chi2 test).


CONCLUSIONS
Our results show that iron metabolism is altered in patients with HIV-1 infection. The alternative pathway (citrate system) is particularly affected, since when citrate levels are low, both aconitase activity and HIV-1 replication need iron.
Pugliese
A
A
Dept of Medical Surgery, University of Turin, Italy.
Gennero
L
L
Pescarmona
G P
GP
Beccattini
M
M
Morra
E
E
Orofino
G
G
Torre
D
D
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D002951:Citrates / Q000097:blood*; D005260:Female; D005293:Ferritins / Q000097:blood; D015658:HIV Infections / Q000503:physiopathology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006239:Haplotypes / Q000235:genetics*; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D012367:RNA, Viral / Q000097:blood; D011990:Receptors, Transferrin / Q000378:metabolism*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C068126:CD71 antigen; D002951:Citrates; D006242:Haptoglobins; D012367:RNA, Viral; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron