title: Enhanced levels of CCL19 in patients with advanced acquired immune deficiency syndrome (AIDS).
abstract: Based on the ability to recruit lymphocytes and dendritic cells to lymphoid tissue and to promote inflammation, we hypothesized a role for dysregulated CCL19 and CCL21 levels in human immunodeficiency virus (HIV)-infected patients with advanced immunodeficiency, and in particular in those with accompanying Mycobacterium avium complex (MAC) infection. The hypothesis was explored by studies in HIV-infected patients with and without MAC infection, as well as in vitro, examining the ability of proteins from MAC to promote CCL19 and CCL21 responses in peripheral blood mononuclear cells (PBMC) during highly active anti-retroviral therapy (HAART). Our main findings were: (i) raised serum levels of CCL19 in HIV-infected patients with CD4(+)  T cell count <50 cells/µl compared with HIV-infected patients with CD4(+)  T cell count >500 cells/µl and healthy controls, with particularly high levels in those with MAC infection; (ii) elevated plasma levels of CCL19 predicted a higher mortality in acquired immune deficiency syndrome (AIDS)-patients, independent of ongoing MAC infection; and (iii) marked production of CCL19 in MAC-stimulated peripheral blood mononuclear cells (PBMC) and pronounced disturbances in MAC-induced CCL19 production in PBMC from HIV patients that was partly reversed during HAART. Our findings suggest the involvement of CCL19 in AIDS patients with advanced immunodeficiency, potentially mediating both adaptive and maladaptive responses.
authors.affiliation: Department of Infectious Diseases, St Olav's Hospital, Trondheim, Norway. jan.k.damas@ntnu.no
authors.forename: J K
authors.initials: JK
authors.lastname: Damås
authors.forename: O
authors.initials: O
authors.lastname: Øktedalen
authors.forename: T
authors.initials: T
authors.lastname: Ueland
authors.forename: L
authors.initials: L
authors.lastname: Landrø
authors.forename: J
authors.initials: J
authors.lastname: Barstad
authors.forename: F
authors.initials: F
authors.lastname: Müller
authors.forename: S S
authors.initials: SS
authors.lastname: Frøland
authors.forename: T H
authors.initials: TH
authors.lastname: Flo
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000097:blood / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001426:Bacterial Proteins / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D054415:Chemokine CCL19 / Q000097:blood*; D054421:Chemokine CCL21 / Q000097:blood; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D015269:Mycobacterium avium Complex / Q000276:immunology; D015270:Mycobacterium avium-intracellulare Infection / Q000097:blood / Q000276:immunology; D011379:Prognosis
chemical_list: D001426:Bacterial Proteins; D015415:Biomarkers; C515460:CCL19 protein, human; C515478:CCL21 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21