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HIV感染中的抗心磷脂抗体与针对gp41膜近端外部区域的抗体、细胞相关HIV DNA及免疫激活独立相关。

Anticardiolipin antibodies in HIV infection are independently associated with antibodies to the membrane proximal external region of gp41 and with cell-associated HIV DNA and immune activation.

作者信息

Martinez Valérie, Diemert Marie-Claude, Braibant Martine, Potard Valérie, Charuel Jean-Luc, Barin Francis, Costagliola Dominique, Caumes Eric, Clauvel Jean-Pierre, Autran Brigitte, Musset Lucile

机构信息

Laboratory of Cellular Immunology, UMR INSERM 543, Paris, France.

出版信息

Clin Infect Dis. 2009 Jan 1;48(1):123-32. doi: 10.1086/595013.

DOI:10.1086/595013
PMID:19035778
Abstract

BACKGROUND

The demonstration of in vitro cardiolipin reactivity with 2 human immunodeficiency virus (HIV)-specific, broadly neutralizing antibodies (2F5 and 4E10) has prompted reevaluation of autoimmune manifestations in HIV infection.

METHODS

We evaluated autoantibodies, particularly anticardiolipin (aCL), in 67 untreated, asymptomatic, HIV-infected individuals with slow progression of HIV disease and their correlation with 2F5-, 4E10-, b12-, and 2G12-like antibodies directed against epitopes involved in broad neutralization, as well as their correlation with immune activation and virological and clinical indicators. Fifty individuals with chronic HIV infection and standard disease progression were control patients.

RESULTS

The majority of the study patients with slow progression of HIV disease were men (78%); their median age was 37 years, their median CD4+ cell count was 672 cells/mL, and their median plasma HIV load was 6200 copies/mL. The majority of the control patients were also men (76%), and most (62%) were receiving highly active antiretroviral therapy; their median age was 43 years, their median CD4+ cell count was 202 cells/mL, and their median plasma HIV load was 2265 copies/mL. aCL immunoglobulin G was detected at similar levels in 49% of patients with slow progression of HIV disease and in 58% of control patients. Viral load was positively associated with aCL in both groups (P < .001), independent of CD4+ cell counts. In patients with slow progression of HIV disease, aCL levels were also correlated with plasma HIV load and cell-associated DNA level (r = 0.486 and r = 0.516, respectively; P < .001), with the proportion of activated CD4+ cells, human leukocyte antigen-DR+ cells (r = 0.445; P = or < .001) but not activated CD8+ T cells, and with the level of B cell activation (quantified by soluble CD23; r = 0.354; P = .007). The level of aCL antibodies was associated with the level of antibodies to the membrane proximal region of gp41 (P = .003).

CONCLUSION

aCL is frequently detected in HIV-infected patients, regardless of disease stage, and is strongly linked with the level of viral replication, the level of CD4+ T and B cell activation, and the level of antibodies to the membrane proximal external region of gp41, independent of CD4+ cell deficiency.

摘要

背景

体外实验显示心磷脂与2种人类免疫缺陷病毒(HIV)特异性广泛中和抗体(2F5和4E10)发生反应,这促使人们重新评估HIV感染中的自身免疫表现。

方法

我们评估了67例未经治疗、无症状、HIV疾病进展缓慢的HIV感染者的自身抗体,尤其是抗心磷脂抗体(aCL),及其与针对广泛中和相关表位的2F5、4E10、b12和2G12样抗体的相关性,以及它们与免疫激活、病毒学和临床指标的相关性。50例慢性HIV感染且疾病进展正常的个体作为对照患者。

结果

大多数HIV疾病进展缓慢的研究患者为男性(78%);他们的年龄中位数为37岁,CD4 + 细胞计数中位数为672个/毫升,血浆HIV载量中位数为6200拷贝/毫升。大多数对照患者也是男性(76%),且大多数(62%)正在接受高效抗逆转录病毒治疗;他们的年龄中位数为43岁,CD4 + 细胞计数中位数为202个/毫升,血浆HIV载量中位数为2265拷贝/毫升。49%的HIV疾病进展缓慢患者和58%的对照患者中检测到的aCL免疫球蛋白G水平相似。两组中病毒载量均与aCL呈正相关(P < 0.001),与CD4 + 细胞计数无关。在HIV疾病进展缓慢的患者中,aCL水平还与血浆HIV载量和细胞相关DNA水平相关(分别为r = 0.486和r = 0.516;P < 0.001),与活化CD4 + 细胞、人类白细胞抗原-DR + 细胞的比例相关(r = 0.445;P = 或 < 0.001),但与活化CD8 + T细胞无关,且与B细胞活化水平相关(通过可溶性CD23定量;r = 0.354;P = 0.007)。aCL抗体水平与gp41膜近端区域抗体水平相关(P = 0.003)。

结论

无论疾病处于何阶段,HIV感染患者中均经常检测到aCL,且其与病毒复制水平、CD4 + T和B细胞活化水平以及gp41膜近端外部区域抗体水平密切相关,与CD4 + 细胞缺乏无关。

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