PMID- 32850873 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2296-858X (Print) IS - 2296-858X (Electronic) IS - 2296-858X (Linking) VI - 7 DP - 2020 TI - High APRIL Levels Are Associated With Slow Disease Progression and Low Immune Activation in Chronic HIV-1-Infected Patients. PG - 299 LID - 10.3389/fmed.2020.00299 [doi] LID - 299 AB - Objective: B-cell-activating factor (BAFF) has been determined to be involved in HIV-1 infection and is correlated with disease progression, while its homologous molecule, a proliferation-inducing ligand (APRIL), is less frequently reported, and its role remains unclear. We aimed to characterize the APRIL levels in subjects with different HIV-1 infection statuses and determine the relationships with disease progression and immune activation. Methods: The plasma levels of APRIL were compared among 17 long-term non-progressors (LTNPs), 17 typical progressors (TPs), 10 ART-treated patients, and 10 healthy donors (HDs). Seventeen LTNPs and a subset of TPs (n = 6) who initiated ART were assessed longitudinally. The correlations between the APRIL levels and markers of disease progression, B-cell count and specific antibody response, and markers of immune activation and functional cells were analyzed. Results: The circulating APRIL levels were significantly elevated in the LTNPs relative to the TPs, ART-treated patients, and HDs. The longitudinal investigation revealed that the APRIL levels were decreased during follow-up in the LTNPs. ART did not significantly influence the APRIL levels. The levels of plasma APRIL were negatively correlated with the plasma HIV-1 viral load and cellular HIV-1 DNA levels and positively correlated with the CD4(+) T-cell count and CD4/CD8 ratio. An inverse correlation was observed between the APRIL and BAFF levels. Furthermore, the APRIL levels were negatively correlated with the frequency of activated CD8(+) T cells and levels of interferon gamma-induced protein 10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1). Finally, positive correlations were observed among the APRIL levels, the frequency of CD8(+)CD28(+) T cells, and natural killer (NK) cell count. Conclusion: The APRIL levels were elevated in the LTNPs and negatively correlated with disease progression and immune activation, suggesting likely protective activity in HIV-1 infection. CI - Copyright (c) 2020 Liu, Li, Han, Qiu, Song, Li, Zhang, Wang, Feng, Liu, Wang, Sun and Li. FAU - Liu, Yubin AU - Liu Y AD - Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. FAU - Li, Xiuxia AU - Li X AD - Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. FAU - Han, Yang AU - Han Y AD - Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. FAU - Qiu, Zhifeng AU - Qiu Z AD - Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. FAU - Song, Xiaojing AU - Song X AD - Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. FAU - Li, Bingxiang AU - Li B AD - Institute of Medical Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Kunming, China. AD - Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Kunming, China. FAU - Zhang, Han AU - Zhang H AD - Institute of Medical Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Kunming, China. AD - Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Kunming, China. FAU - Wang, Hongye AU - Wang H AD - Institute of Medical Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Kunming, China. AD - Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Kunming, China. FAU - Feng, Kai AU - Feng K AD - Institute of Medical Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Kunming, China. AD - Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Kunming, China. FAU - Liu, Longding AU - Liu L AD - Institute of Medical Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Kunming, China. AD - Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Kunming, China. FAU - Wang, Jingjing AU - Wang J AD - Institute of Medical Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Kunming, China. AD - Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Kunming, China. FAU - Sun, Ming AU - Sun M AD - Institute of Medical Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Kunming, China. AD - Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Kunming, China. FAU - Li, Taisheng AU - Li T AD - Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. AD - Clinical Immunology Center, Chinese Academy of Medical Sciences, Beijing, China. AD - School of Medicine, Tsinghua University, Beijing, China. LA - eng PT - Journal Article DEP - 20200717 PL - Switzerland TA - Front Med (Lausanne) JT - Frontiers in medicine JID - 101648047 PMC - PMC7396611 OTO - NOTNLM OT - APRIL OT - BAFF OT - HIV-1 disease progression OT - antibody response OT - functional cells OT - immune activation EDAT- 2020/08/28 06:00 MHDA- 2020/08/28 06:01 PMCR- 2020/07/17 CRDT- 2020/08/28 06:00 PHST- 2019/12/02 00:00 [received] PHST- 2020/05/26 00:00 [accepted] PHST- 2020/08/28 06:00 [entrez] PHST- 2020/08/28 06:00 [pubmed] PHST- 2020/08/28 06:01 [medline] PHST- 2020/07/17 00:00 [pmc-release] AID - 10.3389/fmed.2020.00299 [doi] PST - epublish SO - Front Med (Lausanne). 2020 Jul 17;7:299. doi: 10.3389/fmed.2020.00299. eCollection 2020.