Fitzsimons Edward J, Houston Tracey, Munro Robin, Sturrock Roger D, Speekenbrink Anthony B J, Brock Jeremy H
University of Glasgow, Western Infirmary, Glasgow, UK.
Arthritis Rheum. 2002 Apr 15;47(2):166-71. doi: 10.1002/art.10247.
We have investigated in vitro erythroblast iron metabolism in the anemia of rheumatoid arthritis (RA). We also have examined the results in relation to bone marrow iron status in an attempt to explain the reported difference between serum soluble transferrin receptor (sTfR) values in anemia of chronic disease (ACD) and iron deficiency anemia (IDA) in patients with RA.
Bone marrow was examined in 29 anemic patients with RA, 9 healthy volunteers, and 6 patients with simple IDA. High purity erythroblast fractions were prepared from these bone marrow samples. Erythroblast surface TfR expression and iron uptake was assessed in vitro using (125)I-transferrin (Tf) and (59)Fe-Tf, respectively. The efficiency of erythroblast surface TfR function for Tf-iron uptake was determined by relating total iron uptake at 4 hours to surface TfR number. Serum sTfR values were measured for the RA anemia group, which was subdivided as RA-ACD (marrow iron present) or RA-IDA (marrow iron absent) on the basis of visible reticuloendothelial (RE) marrow iron stores.
High purity (87 +/- 5%) erythroblast fractions were obtained from 35 of the 44 marrow samples. Erythroblasts obtained from patients with simple IDA showed a significant increase in surface TfR expression (P = 0.0003) and Tf-iron uptake (P = 0.001). RA anemia also led to a significant increase in erythroblast Tf-iron uptake (P = 0.016). This increase was not associated with an increase in surface TfR expression (P = 0.5), but was seen to occur as a result of a significant increase in the efficiency of surface TfR for Tf-iron uptake (P = 0.027). Within the RA anemia group, the increase in erythroblast Tf- iron uptake at 4 hours was more evident for RA-IDA (3.96 +/- 1.73 versus 1.66 +/- 0.66; P = 0.03) than for RA-ACD (2.69 +/- 1.18 versus 1.66 +/- 0.66; P = 0.057). This additional erythroblast response to absent RE iron stores led to a highly significant difference in serum sTfR values between RA-IDA and RA-ACD (40.2 +/- 14.0 versus 23.9 +/- 5.3 nmoles/liter; P = 0.001)
An increase in erythroblast surface TfR efficiency for Tf-iron uptake compensates for the low plasma iron levels associated with anemia in RA and helps to maintain RA erythroblast iron uptake. With adequate RE iron stores, this increased efficiency limits intracellular iron deprivation and consequently reduces the need to increase surface TfR expression. As a result, serum sTfR levels in RA-ACD remain within the normal range. RA erythroblasts, however, are still able to respond to any additional worsening of the iron supply caused by absent RE iron stores. This additional response causes the highly significant increase in serum sTfR values seen between RA-IDA and RA-ACD.
我们研究了类风湿关节炎（RA）贫血患者体外成红细胞的铁代谢情况。我们还检查了与骨髓铁状态相关的结果，以试图解释报告中RA患者慢性病贫血（ACD）和缺铁性贫血（IDA）血清可溶性转铁蛋白受体（sTfR）值之间的差异。
对29例贫血RA患者、9名健康志愿者和6例单纯IDA患者进行了骨髓检查。从这些骨髓样本中制备了高纯度的成红细胞组分。分别使用（125）I -转铁蛋白（Tf）和（59）Fe - Tf在体外评估成红细胞表面TfR表达和铁摄取。通过将4小时时的总铁摄取量与表面TfR数量相关联，确定成红细胞表面TfR对Tf -铁摄取的功能效率。对RA贫血组测定血清sTfR值，并根据可见的网状内皮（RE）骨髓铁储存情况将其细分为RA - ACD（存在骨髓铁）或RA - IDA（不存在骨髓铁）。
44份骨髓样本中的35份获得了高纯度（87±5%）的成红细胞组分。从单纯IDA患者获得的成红细胞表面TfR表达（P = 0.0003）和Tf -铁摄取（P = 0.001）显著增加。RA贫血也导致成红细胞Tf -铁摄取显著增加（P = 0.016）。这种增加与表面TfR表达的增加无关（P = 0.5），而是由于表面TfR对Tf -铁摄取的效率显著增加所致（P = 0.027）。在RA贫血组中，RA - IDA在4小时时成红细胞Tf -铁摄取的增加（3.96±1.73对1.66±0.66；P = 0.03）比RA - ACD（2.69±1.18对1.66±0.66；P = 0.057）更明显。这种成红细胞对RE铁储存缺失的额外反应导致RA - IDA和RA - ACD之间血清sTfR值存在高度显著差异（40.2±14.0对23.9±5.3纳摩尔/升；P = 0.001）
成红细胞表面TfR对Tf -铁摄取效率的增加补偿了与RA贫血相关的低血浆铁水平，并有助于维持RA成红细胞的铁摄取。有足够的RE铁储存时，这种增加的效率限制了细胞内铁缺乏，因此减少了增加表面TfR表达的需求。结果，RA - ACD中的血清sTfR水平保持在正常范围内。然而，RA成红细胞仍然能够对RE铁储存缺失导致的铁供应的任何进一步恶化做出反应。这种额外反应导致RA - IDA和RA - ACD之间血清sTfR值显著增加。
