简要报告：纤维化的循环标志物与HIV感染男性的免疫重建状态相关。
Brief report: Circulating markers of fibrosis are associated with immune reconstitution status in HIV-infected men.
作者信息
Tobolowsky F A, Wada N, Martinez-Maza O, Magpantay L, Koletar S L, Palella F J, Brown T T, Lake J E
机构信息
Department of Internal Medicine, Division of Infectious Diseases, University of Colorado, Denver, Colorado, United States of America.
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
出版信息
PLoS One. 2018 Jan 30;13(1):e0191606. doi: 10.1371/journal.pone.0191606. eCollection 2018.
INTRODUCTION
Lymphoid tissue fibrosis may contribute to incomplete immune reconstitution on antiretroviral therapy (ART) via local CD4+ T lymphocyte (CD4) depletion. Hyaluronic acid (HA) increases with fibrotic burden. CXCL4 concentrations increase in response to pro-fibrotic stimuli, but lower CXCL4 concentrations in HIV-infected individuals may reflect successful immune evasion by HIV. We investigated relationships between circulating HA and CXCL4 concentrations and immune reconstitution on ART in HIV-infected Multicenter AIDS Cohort Study participants.
METHODS
HIV-infected men on ART for >1 year with cryopreserved plasma samples and suppressed post-ART HIV-1 RNA were included. Men with post-ART CD4 <200 cells/mm3 were defined as immunologic non-responders (n = 25). Age-/race-matched men with post-ART CD4 >500 cells/mm3 served as controls (n = 49). HA and CXCL4 concentrations were measured via ELISA.
RESULTS
Median pre-ART CD4 was 297 cells/mm3 for non-responders vs 386 cells/mm3 for controls. Median post-ART CD4 was 141 cells/mm3 for non-responders and 815 cells/mm3 for controls. HIV infection duration was 23 years, with median time on ART 13 years for non-responders vs 11 years for controls. Pre-ART HA and CXCL4 concentrations did not vary by eventual immune reconstitution status. Post-ART HA concentrations tended to be higher (85 vs 36 ng/mL, p = 0.07) and CXCL4 concentrations were lower (563 vs 1459 ng/mL, p = 0.01) among non-responders. Among men with paired pre-/post-ART samples, non-responders had greater HA increases and CXCL4 decreases than controls (HA: 50 vs 12 ng/mL, p = 0.04; CXCL4: -1258 vs -405 ng/mL, p = 0.01).
CONCLUSIONS
Higher circulating concentrations of HA and lower concentrations of CXCL4 are associated with failure of immune reconstitution on ART.
引言
淋巴组织纤维化可能通过局部CD4 + T淋巴细胞（CD4）耗竭导致抗逆转录病毒治疗（ART）时免疫重建不完全。透明质酸（HA）随纤维化负担增加而升高。CXCL4浓度在促纤维化刺激下会升高，但HIV感染者中较低的CXCL4浓度可能反映了HIV成功的免疫逃逸。我们在感染HIV的多中心艾滋病队列研究参与者中调查了循环HA和CXCL4浓度与ART免疫重建之间的关系。
方法
纳入接受ART治疗超过1年且有冷冻保存血浆样本且ART后HIV-1 RNA被抑制的HIV感染男性。ART后CD4<200细胞/mm3的男性被定义为免疫无应答者（n = 25）。年龄和种族匹配的ART后CD4>500细胞/mm3的男性作为对照（n = 49）。通过ELISA测量HA和CXCL4浓度。
结果
无应答者ART前CD4中位数为297细胞/mm3，对照组为386细胞/mm3。无应答者ART后CD4中位数为141细胞/mm3，对照组为815细胞/mm3。HIV感染持续时间为23年，无应答者ART中位时间为13年，对照组为11年。ART前HA和CXCL4浓度不因最终免疫重建状态而异。无应答者ART后HA浓度倾向于更高（85对36 ng/mL，p = 0.07），CXCL4浓度更低（563对1459 ng/mL，p = 0.01）。在有配对ART前后样本的男性中，无应答者的HA升高和CXCL4降低幅度大于对照组（HA：50对12 ng/mL，p = 0.04；CXCL4：-1258对-405 ng/mL，p = 0.01）。
结论
较高的循环HA浓度和较低的CXCL4浓度与ART免疫重建失败有关。
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