TY - JOUR
T1 - Plasma d -amino acids are associated with markers of immune activation and organ dysfunction in people with HIV
AU - Yap, Siew Hwei
AU - Lee, Cheng Siang
AU - Furusho, Aogu
AU - Ishii, Chiharu
AU - Shaharudin, Syahirah
AU - Zulhaimi, Nurul Syuhada
AU - Kamarulzaman, Adeeba
AU - Kamaruzzaman, Shahrul Bahyah
AU - Mita, Masashi
AU - Leong, Kok Hoong
AU - Hamase, Kenji
AU - Rajasuriar, Reena
N1 - Funding Information:
We would like to thank the patients who participated in this study. This research was conducted at the Immunotherapeutics Laboratory (ITL), University of Malaya. We would also like to thank all personnel in ITL for helping with the processing of clinical samples. This research was funded by Fundamental Research Grant Scheme (FRGS/1/2019/SKK08/UM/02/7) from Ministry of Higher Education, Government of Malaysia and supported by International Centre for Genetic Engineering and Biotechnology (CRP/MYS17-05). S.H.Y. was supported by an educational grant from Agilent Technologies, Inc (PV018-2017). S.H.Y. was also supported by JASSO program during her attachment in Kyushu University, Japan.
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Background:d-Amino acids (d-AAs) have been associated with age-associated conditions in the general population but their relevance in people with HIV (PWH), who experience accentuated/accelerated aging has not been studied. We compared d-AA levels in HIV-infected and uninfected controls and explored their association with markers of immune activation, gut permeability and organ dysfunction.Design:Case-control analysis.Method:Plasma samples from 60 antiretroviral therapy-treated HIV-infected individuals and 59 uninfected controls were analysed. A three-dimensional HPLC system was used to measure d-and l-asparagine, serine, alanine and proline and presented as %d-AA. Additionally, cell-associated and soluble markers of immune activation and senescence were characterized. Kidney and liver functions were expressed as estimated glomerular filtration rate and fibrosis-4 scores, respectively. Mann-Whitney and Spearman rank correlation coefficients were used for statistical analysis.Results:d-Asparagine, d-serine, d-alanine and d-proline were detectable in all plasma samples and correlated with age in HIV-infected and uninfected but not different between groups. Kynurenine/tryptophan ratio was positively correlated with all %d-AAs in PWH and with %d-serine and %d-proline in controls. %d-AAs were not consistently correlated with markers of gut permeability in both groups. All %d-AAs were also correlated with kidney function in both groups whereas age-associated accumulation of %d-asparagine, %d-serine and %d-proline were correlated with liver function and the VACS score in controls.Conclusion:Plasma d-AAs are associated with chronological age and correlated with markers of immune activation and organ decline, though variably, in PWH and controls. Their role in the biology of aging warrants further investigation.
AB - Background:d-Amino acids (d-AAs) have been associated with age-associated conditions in the general population but their relevance in people with HIV (PWH), who experience accentuated/accelerated aging has not been studied. We compared d-AA levels in HIV-infected and uninfected controls and explored their association with markers of immune activation, gut permeability and organ dysfunction.Design:Case-control analysis.Method:Plasma samples from 60 antiretroviral therapy-treated HIV-infected individuals and 59 uninfected controls were analysed. A three-dimensional HPLC system was used to measure d-and l-asparagine, serine, alanine and proline and presented as %d-AA. Additionally, cell-associated and soluble markers of immune activation and senescence were characterized. Kidney and liver functions were expressed as estimated glomerular filtration rate and fibrosis-4 scores, respectively. Mann-Whitney and Spearman rank correlation coefficients were used for statistical analysis.Results:d-Asparagine, d-serine, d-alanine and d-proline were detectable in all plasma samples and correlated with age in HIV-infected and uninfected but not different between groups. Kynurenine/tryptophan ratio was positively correlated with all %d-AAs in PWH and with %d-serine and %d-proline in controls. %d-AAs were not consistently correlated with markers of gut permeability in both groups. All %d-AAs were also correlated with kidney function in both groups whereas age-associated accumulation of %d-asparagine, %d-serine and %d-proline were correlated with liver function and the VACS score in controls.Conclusion:Plasma d-AAs are associated with chronological age and correlated with markers of immune activation and organ decline, though variably, in PWH and controls. Their role in the biology of aging warrants further investigation.
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U2 - 10.1097/QAD.0000000000003207
DO - 10.1097/QAD.0000000000003207
M3 - Article
C2 - 35212669
AN - SCOPUS:85131271029
VL - 36
SP - 911
EP - 921
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 7
ER -
