Persistent Elevation of Plasma Osteopontin Levels in HIV Patients Despite Highly Active Antiretroviral Therapy

Persistent Elevation of Plasma Osteopontin Levels in HIV Patients Despite Highly Active Antiretroviral Therapy

HAORILE CHAGAN-YASUTAN,¹ HIROKI SAITOH,¹ YUGO ASHINO,¹ TOMOHIRO ARIKAWA,² MITSUOMI HIRASHIMA,² SHENWEI LI,^1,3 MOTOKI USUZAWA,^1,3 SHIGERU OGUMA,⁴ ELIZABETH FREDA O. TELAN,⁵ CHIKWELU LARRY OBI⁶ and TOSHIO HATTORI¹

¹Emerging Infectious Diseases, Graduate School of Medicine, Tohoku University, Sendai, Japan
²Department of Immunology and Immunopathology, Kagawa University, Takamatsu, Japan
³Japan Foundation for AIDS Prevention
⁴Medical Informatics Division, Takeda General Hospital, Kyoto, Japan
⁵NRL-STD-AIDS Cooperative Central Laboratory, Manila, Philippines
⁶Academic and research directorate, Walter Sisulu University, Nelson Mandela Drive, Mathatha, Eastern Cape, South Africa

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 neopteirn (p = 0.024). We therefore propose that the plasma osteopontin is a useful marker of immune activation during HAART and HAART-induced side effects.

Keywords —— HIV/AIDS; HAART; Immune Activation; Osteopontin; Galectin-9.

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Tohoku J. Exp. Med., 2009, 218, 285-292

Correspondence: Toshio Hattori, MD., Emerging Infectious Diseases, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8574, Japan.

e-mail: hatori286@yahoo.co.jp