Cruz Eugénia, Melo Graça, Lacerda Rosa, Almeida Susana, Porto Graça
Clinical Hematology, Santo António General Hospital, Porto, Portugal.
Blood Cells Mol Dis. 2006 Jul-Aug;37(1):33-9. doi: 10.1016/j.bcmd.2006.04.004. Epub 2006 Jun 9.
Hereditary hemochromatosis (HH) is a clinically heterogeneous disease. Among other factors, the individual immunological profile of CD8+ T-lymphocytes has been described to influence the severity of iron overload, with low numbers being negatively correlated with the total amount of body iron stored. With the objective of testing the modifier effect of the individual CD8+ T-lymphocyte profile on the levels of iron stores with age in HH, we reviewed the clinical and immunological data from a group of well-characterized C282Y homozygous HH subjects, regularly followed-up for a period of 20 years. A total of 70 subjects were analyzed. Sixty-four were adults (> or = 18 years): 42 males (mean age 47 +/- 14; range 22-75 years) and 22 females (mean age 46 +/- 14; range 19-65 years). Six were younger than 18 years, 5 males (mean age 9 +/- 4; range 5-14 years) and 1 female (15 years). The characterization of subjects included measurements, at diagnosis, of the iron parameters, transferrin saturation (TfSat) and serum ferritin, quantification of total body iron stores (TBIS) removed by phlebotomies, presence of associated clinical manifestations, and the T-cell immunophenotype (CD4+ and CD8+ T-lymphocytes) determined by flow cytometry. In general, statistically significant lower values of TfSat (67 +/- 17% vs. 89 +/- 14%, P = 0.0006) and ferritin levels (58 +/- 9 vs. 949 +/- 233 ng/ml, P = 0.02) were found in the young subjects in comparison to adults. After the age of 18, however, no further effect of age was significantly found on the biochemical iron parameters either in males or females. A modifier effect of the individual CD8+ T-lymphocyte profile on the association between iron stores and age was demonstrated by multiple regression analysis, where a significant correlation between TBIS and age was found only in males with low (< or = 0.41 x 10(6)/ml) CD8+ T-cell numbers (R2 = 0.43, P < 0.0001). In conclusion, in the present population of C282Y homozygous subjects, the CD8+ T-lymphocyte profile could be considered a modifier of the iron overload with increasing age in males, with low numbers predicting a severe outcome.
遗传性血色素沉着症（HH）是一种临床异质性疾病。在其他因素中，已有研究表明CD8 + T淋巴细胞的个体免疫特征会影响铁过载的严重程度，其数量较少与体内储存的总铁量呈负相关。为了测试个体CD8 + T淋巴细胞特征对HH患者铁储存水平随年龄变化的修饰作用，我们回顾了一组特征明确的C282Y纯合HH患者的临床和免疫数据，这些患者定期随访了20年。共分析了70名受试者。64名是成年人（≥18岁）：42名男性（平均年龄47±14岁；范围22 - 75岁）和22名女性（平均年龄46±14岁；范围19 - 65岁）。6名年龄小于18岁，5名男性（平均年龄9±4岁；范围5 - 14岁）和1名女性（15岁）。受试者的特征包括诊断时的铁参数、转铁蛋白饱和度（TfSat）和血清铁蛋白测量、通过放血去除的全身铁储存量（TBIS）定量、相关临床表现的存在以及通过流式细胞术测定的T细胞免疫表型（CD4 +和CD8 + T淋巴细胞）。总体而言，与成年人相比，年轻受试者的TfSat（67±17%对89±14%，P = 0.0006）和铁蛋白水平（58±9对949±233 ng/ml，P = 0.02）在统计学上显著较低。然而，18岁以后，无论男性还是女性，年龄对生化铁参数均未发现进一步的显著影响。多元回归分析证明了个体CD8 + T淋巴细胞特征对铁储存与年龄之间关联的修饰作用，其中仅在CD8 + T细胞数量低（≤0.41×10⁶/ml）的男性中发现TBIS与年龄之间存在显著相关性（R² = 0.43，P < 0.0001）。总之，在目前的C282Y纯合受试者群体中，CD8 + T淋巴细胞特征可被视为男性随着年龄增长铁过载的修饰因素，数量低预示着严重的结果。
