title: Persistent elevation of plasma osteopontin levels in HIV patients despite highly active antiretroviral therapy.
abstract: In human immunodeficiency virus (HIV) infection, not only HIV itself but also systemic immune activation plays a role in the disease progression to acquired immune deficiency syndrome (AIDS). The systemic immune activation may be present even during highly active antiretroviral therapy (HAART). An increased expression of osteopontin, a proinflammatory cytokine, during HAART was reported in lymph nodes of HIV infected individuals. Osteopontin is also known to be involved in the pathogenesis of various HAART-induced diseases. Here, we measured osteopontin and other inflammatory markers such as neopterin and galectin-9 using serially collected plasma from patients with HIV/AIDS to find novel markers for immune activation. Four AIDS patients complicated with various opportunistic infections and one acute HIV patient were studied. Osteopontin levels (normal levels: < 820 ng/ml) were elevated in all the patients (1,178-2,450 ng/ml). Likewise, galectin-9 levels (normal levels: < 46 pg/ml) were elevated in all patients (> 130 pg/ml), with the exceptionally high level in the acute HIV patient (4,196 pg/ml). Neopterin levels (normal ranges: 2-8 pmol/L) were elevated in four patients (21-99 pmol/L). After HAART, the levels of galectin-9 and neopterin apparently decreased, whereas the levels of osteopontin did not decrease. Thus, the high levels of osteopontin were sustained despite the clinical improvement. Fisher exact probability test showed that the mode of the changes was different between osteopontin and galectin-9, and between osteopontin and neopterin (p = 0.024). We therefore propose that the plasma osteopontin is a useful marker of immune activation during HAART and HAART-induced side effects.
authors.affiliation: Emerging Infectious Diseases, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Haorile
authors.initials: H
authors.lastname: Chagan-Yasutan
authors.forename: Hiroki
authors.initials: H
authors.lastname: Saitoh
authors.forename: Yugo
authors.initials: Y
authors.lastname: Ashino
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Arikawa
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
authors.forename: Shenwei
authors.initials: S
authors.lastname: Li
authors.forename: Motoki
authors.initials: M
authors.lastname: Usuzawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Oguma
authors.forename: Elizabeth Freda
authors.initials: EF
authors.lastname: O Telan
authors.forename: Chikwelu Larry
authors.initials: CL
authors.lastname: Obi
authors.forename: Toshio
authors.initials: T
authors.lastname: Hattori
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D037161:Galectins / Q000097:blood; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007107:Immune System; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D053495:Osteopontin / Q000097:blood*; D011336:Probability; D013997:Time Factors
chemical_list: D037161:Galectins; C105032:LGALS9 protein, human; D053495:Osteopontin; D019798:Neopterin