Type I interferon-dependent gene MxA in perinatal HIV-infected patients under antiretroviral therapy as marker for therapy failure and blood plasmacytoid dendritic cells depletion.
BACKGROUND
To determine the role of interferon-alpha in controlling HIV infection we phenotypically and functionally analyzed circulating plasmacytoid dendritic cells (pDC), which are known to be the highest interferon-alpha producing cells, in 33 perinatally infected HIV+ patients undergoing standard antiretroviral therapy.


METHODS
Circulating pDC were identified by flow cytometry using anti-BDCA-2 monoclonal antibody and by measuring BDCA-2 mRNA by real-time PCR, while tissue-resident pDC were identified by immunohistochemistry. mRNA for interferon-alpha and MxA, a gene that is specifically induced by interferon-alpha, was quantified in peripheral blood cells by real-time PCR, while serum interferon-alpha protein was measured by ELISA.


RESULTS
While median values of pDC, both in terms of percentage and absolute number, were not statistically different from age-matched controls, interferon-alpha mRNA was increased in HIV-infected patients. However, in a group of patients with long disease duration, having a low number of both pDC and CD4+ lymphocytes and a significant increase of serum interferon-alpha, MxA mRNA was produced at high level and its expression directly correlated with HIV RNA copy numbers. Furthermore in patients displaying a low CD4+ blood cell count, a severe depletion of pDC in the tonsils could be documented.


CONCLUSIONS
HIV replication unresponsive to antiretroviral treatment in perinatal-infected patients with advanced disease and pDC depletion may lead to interferon-alpha expression and subsequent induction of MxA mRNA. Thus, the latter measurement may represent a valuable marker to monitor the clinical response to therapy in HIV patients.
Badolato
Raffaele
R
Istituto di Medicina Molecolare Angelo Nocivelli, Department of Pediatrics, University of Brescia, Brescia 25123, Italy. badolato@med.unibs.it
Ghidini
Claudia
C
Facchetti
Fabio
F
Serana
Federico
F
Sottini
Alessandra
A
Chiarini
Marco
M
Spinelli
Elena
E
Lonardi
Silvia
S
Plebani
Alessandro
A
Caimi
Luigi
L
Imberti
Luisa
L
D000293:Adolescent; D000328:Adult; D000375:Aging; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000473:pathology* / Q000821:virology; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D008221:Lymphoid Tissue / Q000473:pathology / Q000821:virology; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017211:Treatment Failure
D015415:Biomarkers; D007370:Interferon Type I; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D019204:GTP-Binding Proteins
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