Lawless M W, White M, Mankan A K, O'Dwyer M J, Norris S
Hepatology Research Division and Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, St James Hospital, Dublin 8, Ireland.
Tissue Antigens. 2007 Oct;70(4):294-300. doi: 10.1111/j.1399-0039.2007.00895.x.
Monocyte chemoattractant protein-1 (MCP-1) is a major lymphocyte and inflammatory chemokine associated with persistent inflammatory states. Several abnormalities in the immune status of patients with hereditary hemochromatosis (HH) have been reported, suggesting an imbalance in their immune function. This may include persistent production of, or exposure to, inflammatory cytokines contributing to the pathogenesis of this disorder. The aim of this study was to assess MCP-1 levels in patients with HH and correlate these results with HFE status and iron indexes. One hundred and thirty-nine subjects diagnosed with HH (C282Y homozygotes = 87, C282Y/H63D = 26 heterozygotes, H63D homozygotes = 26), 27 healthy control subjects with no HFE mutation (N/N), and 18 normal subjects heterozygous for the H63D mutation served as age- and sex-matched controls. Ferritin and transferrin saturation and the presence of HFE mutation status were correlated with MCP-1 levels. Full white blood cell count analysis was also performed. We found a strongly significant decrease in MCP-1 protein levels in the C282Y homozygotes compared with the H63D homozygotes (P = 0.0009) and C282Y/H63D heterozygotes (P = 0.002). Similarly, MCP-1 protein levels in the C282Y homozygotes were decreased compared with the healthy controls (P = 0.00076). Furthermore, MCP-1 serum levels were elevated in H63D patients compared with the healthy controls (P = 0.0008). This study suggests for the first time that a differential expression of MCP-1 protein in patients with HH is associated with the specific HFE genetic component for iron overload. Therefore, these findings offer a possible explanation in the variable clinical spectrum of pathogenesis in patients with HH through abnormalities of an imbalance in the immune states of patients with HH.
单核细胞趋化蛋白-1（MCP-1）是一种与持续性炎症状态相关的主要淋巴细胞和炎症趋化因子。据报道，遗传性血色素沉着症（HH）患者的免疫状态存在多种异常，提示其免疫功能失衡。这可能包括炎症细胞因子的持续产生或暴露，从而导致该疾病的发病机制。本研究的目的是评估HH患者的MCP-1水平，并将这些结果与HFE状态和铁指标相关联。139名被诊断为HH的受试者（C282Y纯合子 = 87例，C282Y/H63D杂合子 = 26例，H63D纯合子 = 26例），27名无HFE突变的健康对照受试者（N/N），以及18名H63D突变杂合的正常受试者作为年龄和性别匹配的对照。铁蛋白、转铁蛋白饱和度以及HFE突变状态与MCP-1水平相关。还进行了全血细胞计数分析。我们发现，与H63D纯合子（P = 0.0009）和C282Y/H63D杂合子（P = 0.002）相比，C282Y纯合子的MCP-1蛋白水平显著降低。同样，与健康对照相比，C282Y纯合子的MCP-1蛋白水平也降低（P = 0.00076）。此外，与健康对照相比，H63D患者的MCP-1血清水平升高（P = 0.0008）。本研究首次表明，HH患者中MCP-1蛋白的差异表达与铁过载的特定HFE遗传成分相关。因此，这些发现通过HH患者免疫状态失衡的异常，为HH患者发病机制的可变临床谱提供了一种可能的解释。
