Casado J L, Abad-Fernández M, Moreno S, Pérez-Elías M J, Moreno A, Bernardino J I, Vallejo A
Department of Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain.
HIV Med. 2015 Apr;16(4):240-8. doi: 10.1111/hiv.12206. Epub 2015 Jan 21.
Different immune alterations have been described in HIV-infected patients with visceral leishmaniasis (VL). We aimed to identify the immunological factors involved in the lack of immunological recovery and VL relapses in HIV-infected patients with VL, by comparison with other HIV-infected patients.
We carried out a cross-sectional study of 55 patients receiving suppressive combination antiretroviral therapy (cART) for at least 1 year: nine with previous relapsing VL, 20 with an immunodiscordant response (IDR) to cART (CD4 count < 200 cells/μL) and no previous VL, and 26 with a concordant response (CR) to cART (CD4 count > 350 cells/μL) without VL. Immunosenescence was investigated by analysing CD57(+) CD28(-) levels, immune activation by analysing CD38(+) HLA-DR(+) levels, inflammation by analysing interleukin (IL)-6 levels, and microbial translocation by analysing lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels.
In VL patients, the median time since VL diagnosis was 42 months, and all patients had had at least one relapse despite suppressive cART for a median time of 43 months. Patients with previously diagnosed VL had a higher CD8 T-cell activation level (P < 0.001) than those with IDR. Also, levels of IL-6, LPS and especially sCD14, associated with bacterial translocation and additional monocyte activation, were significantly increased in patients with previous VL compared with patients with IDR (P = 0.048, P = 0.049 and P < 0.001, respectively). In addition, patients with previous VL had higher levels of CD8 T-cell senescence. Notably, the levels of immune activation and inflammation in patients with previous VL were not related to the time of VL diagnosis, the number of VL relapses, or hepatitis C virus (HCV) coinfection.
Our data demonstrate that VL patients had an even worse immunological status than patients with IDR, which was probably associated with increased microbial translocation and additional monocyte/macrophage activation. These data explain the observed lack of immunological recovery and the occurrence of VL relapses in HIV-infected patients with previous VL.
已在感染人类免疫缺陷病毒（HIV）且患有内脏利什曼病（VL）的患者中描述了不同的免疫改变。我们旨在通过与其他感染HIV的患者进行比较，确定导致感染HIV且患有VL的患者免疫恢复不足和VL复发的免疫因素。
我们对55名接受至少1年抑制性联合抗逆转录病毒疗法（cART）的患者进行了一项横断面研究：9名曾有VL复发史，20名对cART有免疫不协调反应（IDR，CD4细胞计数<200个/μL）且既往无VL，26名对cART有协调反应（CR，CD4细胞计数>350个/μL）且无VL。通过分析CD57(+)CD28(-)水平研究免疫衰老，通过分析CD38(+)HLA-DR(+)水平研究免疫激活，通过分析白细胞介素（IL）-6水平研究炎症，通过分析脂多糖（LPS）和可溶性CD14（sCD14）水平研究微生物易位。
在VL患者中，自VL诊断以来的中位时间为42个月，尽管接受了中位时间为43个月的抑制性cART，但所有患者至少有一次复发。既往诊断为VL的患者的CD8 T细胞激活水平高于IDR患者（P<0.001）。此外，与细菌易位和额外单核细胞激活相关的IL-6、LPS尤其是sCD14水平，既往有VL的患者显著高于IDR患者（分别为P=0.048、P=0.049和P<0.001）。此外，既往有VL的患者的CD8 T细胞衰老水平更高。值得注意的是，既往有VL的患者的免疫激活和炎症水平与VL诊断时间、VL复发次数或丙型肝炎病毒（HCV）合并感染无关。
我们的数据表明，VL患者的免疫状态比IDR患者更差，这可能与微生物易位增加和额外的单核细胞/巨噬细胞激活有关。这些数据解释了在既往有VL的感染HIV的患者中观察到的免疫恢复不足和VL复发的发生情况。
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