Gris J C, Toulon P, Brun S, Maugard C, Sarlat C, Schved J F, Berlan J
Consultation et Laboratoire d'Hématologie, CHU, Nimes, France.
Thromb Haemost. 1996 Jul;76(1):38-45.
The high prevalence of free protein S deficiency in human immunodeficiency virus (HIV)-infected patients is poorly understood. We studied 38 HIV seropositive patients. Free protein S antigen values assayed using the polyethylene-glycol precipitation technique (PEG-fS) were statistically lower in patients than in controls. These values using a specific monoclonal antibody-based ELISA (MoAb-fS) and the values of protein S activity (S-act) were not statistically different between patients and controls. C4b-binding protein values were not different from control values. In patients, PEG-fS values were lower than MoAb-fS values. Ten patients had a PEG-fS deficiency, 4 patients had a MoAb-fS deficiency and 8 had a S-act deficiency. Protein S activity and MoAb-fS were lower in clinical groups with poor prognosis and in patients with AIDS but PEG-fS was not. A trend for reduced S-act/MoAb-fS ratios was observed in patients. PEG-fS was negatively correlated with anticardiolipin antibody titers whereas MoAb-fS was not. The plasma of PEG-fS deficient HIV-patients contained high amounts of flow cytometry detectable microparticles which were depleted from plasma by PEG precipitation. The microparticles were partly CD42b and CD4 positive but CD8 negative. These micro-particles were labelled by an anti free protein S monoclonal antibody. The observed differences between MoAb-fS and PEG-fS values were correlated with the amount of detectable plasma microparticles, just like the differences between MoAb-fS and S-act. Plasma microparticles correlated with anticardiolipin antibody titers. In summary, free protein S antigen in HIV infected patients is underestimated when the PEG precipitation technique is used due to the presence of elevated levels of microparticles that bind protein S. The activity of free protein S is also impaired by high levels of microparticles. The prevalence of free protein S deficiency in HIV positive patients is lower than previously published (4/38, approximately 10%) and is correlated with poor prognosis. By implication, use of a PEG precipitation technique might give artefactually low free protein S antigen values in other patient groups if high numbers of microparticles are present. In HIV patients, high titers of anticardiolipin antibodies are associated with high concentrations of cell-derived plasma microparticles.
人类免疫缺陷病毒（HIV）感染患者中游离蛋白S缺乏的高患病率目前了解甚少。我们研究了38例HIV血清阳性患者。采用聚乙二醇沉淀技术（PEG-fS）检测的游离蛋白S抗原值在患者中统计学上低于对照组。使用基于特异性单克隆抗体的ELISA（MoAb-fS）检测的这些值以及蛋白S活性（S-act）值在患者和对照组之间无统计学差异。C4b结合蛋白值与对照值无差异。在患者中，PEG-fS值低于MoAb-fS值。10例患者存在PEG-fS缺乏，4例患者存在MoAb-fS缺乏，8例患者存在S-act缺乏。在预后不良的临床组和艾滋病患者中，蛋白S活性和MoAb-fS较低，但PEG-fS并非如此。在患者中观察到S-act/MoAb-fS比值降低的趋势。PEG-fS与抗心磷脂抗体滴度呈负相关，而MoAb-fS则不然。PEG-fS缺乏的HIV患者血浆中含有大量可通过流式细胞术检测到的微粒，这些微粒通过PEG沉淀从血浆中去除。这些微粒部分为CD42b和CD4阳性，但CD8阴性。这些微粒被抗游离蛋白S单克隆抗体标记。观察到的MoAb-fS和PEG-fS值之间的差异与可检测到的血浆微粒数量相关，MoAb-fS和S-act之间的差异也是如此。血浆微粒与抗心磷脂抗体滴度相关。总之，由于存在与蛋白S结合的微粒水平升高，当使用PEG沉淀技术时，HIV感染患者中的游离蛋白S抗原被低估。游离蛋白S的活性也受到高水平微粒的损害。HIV阳性患者中游离蛋白S缺乏的患病率低于先前报道（4/38，约10%），且与预后不良相关。这意味着，如果存在大量微粒，在其他患者组中使用PEG沉淀技术可能会人为地给出低游离蛋白S抗原值。在HIV患者中，高滴度的抗心磷脂抗体与高浓度的细胞源性血浆微粒相关。
