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Aging and disease    2017, Vol. 8 Issue (3) : 250-256     DOI: 10.14336/AD.2016.0918
Short Communications |
Intercellular Adhesion Molecular-5 as Marker in HIV Associated Neurocognitive Disorder
Yuan Lin1, Wei Feili2, Zhang Xin1, Guo Xianghua2, Lu Xiaofan1, Su Bin1, Zhang Tong1, Wu Hao1,*, Chen Dexi2,3,*
1Center for Infectious Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
2Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
3The Affiliated Hospital of Qingdao University, Organ Transplantation Center, Qingdao, Shandong 266003, China
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Abstract  

Despite the use of antiretroviral drugs HIV associated neurocognitive disorders (HAND) are still common in HIV-seropositive patients. Identification of HIV patients with cognitive impairment in early-stage might benefit a great deal from disease progression monitoring and treatment adjustment. Intercellular adhesion molecule-5 (ICAM5), characteristically expressed on neuron, may suppress immune functions by inhibition of T cell activation in central nervous system. Previous studies have shown that ICAM5 could be detected in patients with brain injury. To investigate the relationship between cognitive impairment and ICAM5 in HIV patients, we compared soluble ICAM5 levels in paired CSF and plasma specimens from HIV-infected individuals with or without neurocognitive impairment. sICAM5 concentrations were measured by ICAM5 ELISA kit. A total of 41 Patients were classified into HIV infected with normal cognition (HIV-NC) and impaired cognition groups (HIV-CI) based on Memorial Sloan-Kettering Scale. CSF and plasma levels of sICAM5 in HIV-CI patients were significantly higher than HIV-NC group (p<0.0001, p=0.0054 respectively). sICAM5 concentrations in plasma strongly correlated with sICAM5 in CSF (r=0.7250, p<0.0001) and S100B in CSF (r=0.3812, p<0.0139). Among 6 follow-up patients we found that sICAM5 levels in CSF and plasma might change consistently with HAND progression. In summary, we have shown that the expressions of sICAM5 in CSF and plasma may correlate with neurocognitive impairment in HIV infected patients. The elevation of sICAM5 in plasma were correspond with that in CSF as a consequence of blood-brain barrier permeability changes. ICAM5 can serve as a potential and readily accessible biomarker to predict HIV associated neurocognitive disorder.

Keywords HIV      ICAM5      cognitive impairment      biomarker     
Corresponding Authors: Wu Hao,Chen Dexi   
About author:

These authors contributed equally to this work

Issue Date: 01 June 2017
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Yuan Lin
Wei Feili
Zhang Xin
Guo Xianghua
Lu Xiaofan
Su Bin
Zhang Tong
Wu Hao
Chen Dexi
Cite this article:   
Yuan Lin,Wei Feili,Zhang Xin, et al. Intercellular Adhesion Molecular-5 as Marker in HIV Associated Neurocognitive Disorder[J]. Aging and disease, 2017, 8(3): 250-256.
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http://www.aginganddisease.org/EN/10.14336/AD.2016.0918     OR     http://www.aginganddisease.org/EN/Y2017/V8/I3/250
CharacteristicsHIV-CIHIV-NCp-value
No. of Subjects1922
Age in years [median (IQR)]44 (40-47)40(24-45)
Gender [n (%)]
Male12 (63%)14 (64%)
Female7 (37%)8 (36%)
HIV RNA (log10 copies/ml) [median (IQR)]
CSF3.50 (2.05-5.50)a2.56 (1.08-3.60)bp=0.4460
Plasma5.24 (2.74-20.50)c4.10 (2.11-5.61)dp=0.7187
CD4+ cell count (cell/μl) [median (IQR)]80(32-184)90 (27-234)p=0.9646
CSF
cell count (cell/μl) [median (IQR)]36 (10-120)20 (10-25)p=0.0355
protein (mg/L) [median (IQR)]1300 (700-2360)400 (275-700)p=0.0005
No. of threated by HAART [n (%)]12 (63%)15 (68%)
Treatment duration (months) [median (range)]4 (2-6)6 (2-24)
Table 1  Demographic and disease characteristics of subjects
Figure 1.  Comparison of sICAM5 and S100B concentrations in paired CSF and plasma samples from 19 HIV-CI and 22 HIV-NC patients

The concentrations of sICAM5 whether in CSF or plasma samples from HIV-CI group were significantly higher than HIV-NC group. Additionally, the CSF levels of S100B were higher in HIV-CI patients (A). Plasma levels of sICAM5 were correlated with CSF levels of sICAM5 or S100B (B). Differences were analyzed by the Mann-Whitney U test. Spearman rank test was used for correlation analysis. p values of <0.05 were considered significant. Dots, sICAM5 or S100B concentrations in CSF or plasma for each study subject; horizontal lines, median values for each group.

Figure 2.  sICAM5 concentrations in CSF and plasma

The changes of sICAM5 in CSF and plasma samples from 6 follow-up HIV infected individuals are shown. In patients YN14, HN11 and YN09, the concentrations of sICAM5 in CSF and plasma elevated significantly along with the increase of MSK score, while in patients HN02, HN06 and YN03, whose MSK scores were relatively stable, the changes of sICAM5 concentration in CSF or plasma were not significant. CSF values are shown in circles and plasma values are shown in squares.

[1] Cysique LA, Maruff P, Brew BJ (2004). Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immune deficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J Neurovirol, 10: 350-57.
[2] Robertson KR, Smurzynski M, Parsons TD, et al. (2007). The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS, 21: 1915-21.
[3] Wright EJ, Nunn M, Joseph J, Robertson K, Lal L, Brew BJ (2008). NeuroAIDS in the Asia Pacific Region. J Neurovirol, 14: 465-73.
[4] Woods SP, Moore DJ, Weber E, Grant I (2009). Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev, 19: 152-68.
[5] Heaton RK, Clifford DB, Franklin DRJr, et al. (2010). HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology, 75: 2087-96.
[6] Simioni S, Cavassini M, Annoni JM,et al. (2010). Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS, 24: 1243-50.
[7] Thames AD, Kim MS, Becker BW, et al. (2011). Medication and finance management among HIV-infected adults: the impact of age and cognition. J Clin Exp Neuro- psychol, 33: 200-09.
[8] Mind Exchange Working Group (2013). Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the mind exchange program. Clin Infect Dis, 56: 1004-17.
[9] Bandaru VV, McArthur JC, Sacktor N et al. (2007). Associative and predictive biomarkers of dementia in HIV-1-infected patients. Neurology, 68: 1481-7.
[10] Bebell LM, Passmore JA, Williamson C et al. (2008). Relationship between levels of inflammatory cytokines in the genital tract and CD4+ cell counts in women with acute HIV-1 infection. J Infect Dis, 198: 710-4.
[11] Clifford DB, Fagan AM, Holtzman DM et al. (2009). CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease. Neurology, 73: 1982-7.
[12] Price RW, Epstein LG, Becker JT, Cinque P, Gisslen M, Pulliam L et al. (2007). Biomarkers of HIV-1 CNS infection and injury. Neurology, 69:1781-8.
[13] McGuire D (2009). CSF biomarkers in HIV dementia: through a glass darkly. Neurology, 73:1942-4.
[14] Nixon DE, Landay AL (2010). Biomarkers of immune dysfunction in HIV. Curr Opin HIV AIDS, 5(6): 498-503.
[15] Yuan L, Qiao L, Wei F, Yin J, Liu L, Ji Y, Smith D, Li N, Chen D (2013). Cytokines in CSF correlate with HIV-associated neurocognitive disorders in the post-HAART era in China. J Neurovirol, 19(2):144-9.
[16] Yuan L, Liu A, Qiao L, Sheng B, Xu M, Li W, Chen D (2015). The relationship of CSF and plasma cytokine levels in HIV infected patients with neurocognitive impairment. Biomed Res Int, 2015N:506872.
[17] Chavarria A, Cardenas G (2013). Neuronal influence behind the central nervous system regulation of the immune cells. Front Integr Neurosci, 7: 64.
[18] Tian L, Lappalainen J, Autero M, Hanninen S, Rauvala H, Gahmberg CG (2008). Shedded neuronal ICAM-5 suppresses T-cell activation. Blood, 111: 3615-25.
[19] Gahmberg CG, Tian L, Ning L, Nyman-Huttunen H (2008). ICAM-5--a novel two-facetted adhesion molecule in the mammalian brain. Immunol Lett, 117: 131-5.
[20] Tian L, Stefanidakis M, Ning L, Van Lint P, Nyman-Huttunen H, Libert C, Itohara S, Mishina M, Rauvala H, Gahmberg CG (2007). Activation of NMDA receptors promotes dendritic spine development through MMP- mediated ICAM-5 cleavage. J Cell Biol, 178: 687-700.
[21] Niedringhaus M, Chen X, Dzakpasu R, Conant K (2012). MMPs and soluble ICAM-5 increase neuronal excitability within in vitro networks of hippocampal neurons. PLoS One, 7: e42631.
[22] Ning L, Tian L, Smirnov S, Vihinen H, Llano O, Vick K, Davis RL, Rivera C, Gahmberg CG (2013). Interactions between ICAM-5 and beta1 integrins regulate neuronal synapse formation. J Cell Sci, 126: 77-89.
[23] Conant K, Lonskaya I, Szklarczyk A, Krall C, Steiner J, Maguire-Zeiss K, Lim ST (2011). Methamphetamine-associated cleavage of the synaptic adhesion molecule intercellular adhesion molecule-5. J Neurochem, 118: 521-32.
[24] Conant K, Wang Y, Szklarczyk A, Dudak A, Mattson MP, Lim ST (2010). Matrix metalloproteinase-dependent shedding of intercellular adhesion molecule-5 occurs with long-term potentiation. Neuroscience, 166: 508-21.
[25] Price RW, Brew B (1988). The AIDS dementia complex. J Infect Dis, 158:1079-83.
[26] Guo H, Tong N, Turner T, Epstein LG, McDermott MP, Kilgannon P, Gelbard HA (2000). Release of the neuronal glycoprotein ICAM-5 in serum after hypoxic-ischemic injury. Ann Neurol, 48: 590-602.
[27] Di Battista AP, Buonora JE, Rhind SG, Hutchison MG, Baker AJ, Rizoli SB, Diaz-Arrastia R, Mueller GP (2015). Blood biomarkers in moderate-to-severe traumatic brain injury:potential utility of a multi-marker approach in characterizing outcome. Front Neurol, 6: 110.
[28] Rieckmann P, Turner T, Kligannon P, Steinhoff BJ (1998). Telencephalin as an indicator for temporal-lobe dysfunction. Lancet, 352: 370-1.
[29] Annaert WG, Esselens C, Baert V,et al. (2001). Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins. Neuron, 32: 579-89.
[30] Hino H, Mori K, Yoshihara Y, Iseki E, Akiyama H, Nishimura T, Ikeda K, Kosaka K (1997). Reduction of telencephalin immunoreactivity in the brain of patients with Alzheimer's disease. Brain Res, 753: 353-7.
[31] Rieckmann P, Turner T, Kligannon P, Steinhoff BJ (1998). Telencephalin as an indicator for temporal-lobe dysfunction. Lancet, 352: 370-1.
[32] Lindsberg PJ, Launes J, Tian L, Valimaa H, Subramanian V, Siren J, Hokkanen L, Hyypia T, Carpen O, Gahmberg CG (2002). Release of soluble ICAM-5, a neuronal adhesion molecule, in acute encephalitis. Neurology, 58: 446-51.
[33] Tse MC, Lane C, Mott K, Onlamoon N, Hsiao HM, Perng GC (2009). ICAM-5 modulates cytokine/chemokine production in the CNS during the course of herpes simplex virus type 1 infection. J Neuroimmunol, 213: 12-9.
[34] Wu H, Brown EV, Acharya NK, Appelt DM, Marks A, Nagele RG, Venkataraman V (2016). Age-dependent increase of blood-brain barrier permeability and neuron- binding autoantibodies in S100B knockout mice. Brain Res, 1637: 154-67.
[35] Kazmierski R, Michalak S, Wencel-Warot A, Nowinski WL (2012). Serum tight-junction proteins predict hemorrhagic transformation in ischemic stroke patients. Neurology, 79: 1677-85.
[36] Blyth BJ, Farhavar A, Gee C, Hawthorn B, He H, Nayak A, Stocklein V, Bazarian JJ (2009). Validation of serum markers for blood-brain barrier disruption in traumatic brain injury. J Neurotrauma, 26: 1497-507.
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