Abstract
The soluble transferrin receptor (sTfR) distinguishes iron deficiency anemia from other types of anemia. Refractory iron deficiency anemia is often the onset symptom in malabsorption-induced celiac disease. We evaluated whether sTfR levels distinguish celiac disease-associated iron deficiency anemia from iron deficiency anemia of other origin. To this aim we measured sTfR and ferritin levels and their ratio (the sTfR/ferritin index) and other hematological parameters in 42 anemic children (20 with and 22 without celiac disease) vs. 22 non-anemic children with celiac disease and 31 healthy controls (age range 4–12years). Hemoglobin parameters, mean cell volume, and serum iron and ferritin levels were decreased to a similar extent in the anemic patients (celiac and non-celiac). The sTfR level in non-anemic celiac patients was similar to that of normal controls (1.7±0.35mg/L), whereas it was significantly increased in non-celiac and celiac anemic patients (2.2±0.5mg/L, p<0.05 and 2.7±1.2mg/L, p<0.001, respectively). The sTfR/ferritin index was also increased more in the anemic celiac patients (mean 4.4, range 1.5–12.0) than in anemic non-celiac children (mean 2.6, range 1.4–4.0) compared with non-anemic children (mean 1.2, range 0.7–2.0). Differences were more pronounced when ferritin was <5ng/mL. Thus, the sTfR/ferritin index may be a predictive measure in discriminating anemic patients with celiac disease from those without celiac disease.
References
1 Aisen P, Litsowski I. Iron transport and storage proteins [review]. Annu Rev Biochem 1980; 49: 357–93. 10.1146/annurev.bi.49.070180.002041Search in Google Scholar
2 Bomford AB, Munro HN. Transferrin and its receptor: their role in cell function. Hepatology 1985; 5: 870–5. 10.1002/hep.1840050528Search in Google Scholar
3 Huebers HA, Finch CA. The physiology of transferrin and transferrin receptors [review]. Physiol Rev 1987; 67: 520–82. 10.1152/physrev.1987.67.2.520Search in Google Scholar
4 Thorstensen K, Romslo I. The role of transferrin in the mechanism of cellular uptake. Biochem J 1990; 271: 1–10. 10.1042/bj2710001Search in Google Scholar
5 Cook JD, Dassenko S, Skikne BS. Serum transferrin receptor as an index of iron absorption. Br J Haematol 1990; 75: 603–9. 10.1111/j.1365-2141.1990.tb07806.xSearch in Google Scholar
6 Cook JD, Baynes RD, Skikne BS. The physiological significance of circulating transferrin receptors. Adv Exp Med Biol 1994; 352: 119–26. 10.1007/978-1-4899-2575-6_9Search in Google Scholar
7 Ferguson BJ, Skikne BS, Simpson KM, Baynes RD, Cook JD. Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia. J Lab Clin Med 1992; 119: 385–90. Search in Google Scholar
8 Punnonen K, Irjala K, Rajamaki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood 1997; 89: 1052–7. 10.1182/blood.V89.3.1052Search in Google Scholar
9 R'zik S, Loo M, Beguin Y. Reticulocyte transferrin receptor (TfR) expression and contribution to soluble TfR levels. Haematologica 2001; 86: 244–51. Search in Google Scholar
10 Punnonen K, Irjala K, Rajamaki A. Iron deficiency anemia is associated with high serum levels of transferrin receptor. Clin Chem 1994; 40: 774–80. 10.1093/clinchem/40.5.774Search in Google Scholar
11 Suominen P, Punnonen K, Rajamaki A, Irjala K. Evaluation of a new immunoenzymometric assay for measuring soluble transferrin receptor to detect iron deficiency in anemic patients. Clin Chem 1997; 43: 1641–6. 10.1093/clinchem/43.9.1641Search in Google Scholar
12 Baynes RD. Assessment of iron status [review]. Clin Biochem 1996; 29: 209–15. 10.1016/0009-9120(96)00010-KSearch in Google Scholar
13 Carroccio A, Iannitto E, Catavaio F, Montalto G, Tumminello M, Campagna P, et al. Sideropenic anemia and celiac disease. Dig Dis Sci 1998; 43: 673–8. 10.1023/A:1018896015530Search in Google Scholar
14 Corazza GR, Valentini RA, Andreani ML, D'Anchino M, Leva MT, Ginaldi L, et al. Subclinical celiac disease is a frequent cause of iron-deficiency anemia. Scand J Gastroenterol 1995; 30: 153–6. 10.3109/00365529509093254Search in Google Scholar
15 Unsworth DJ, Lock RJ, Harvey RF. Improving the diagnosis of coeliac disease anaemic woman. Br J Haematol 2000; 111: 898–901. Search in Google Scholar
16 Tursi A, Giorgetti G, Brandimarte G, Rubino E, Lombardi D, Gasberrini G. Prevalence and clinical presentation of subclinical/silent coeliac disease in adults: an analysis on a 12-year observation. Hepatogastroenterology 2001; 48: 462–4. Search in Google Scholar
17 Garrido C. Prevalence of monosymptomatic coeliac disease in patients with iron deficiency anaemia. Gastroenterol Hepatol 1997; 20: 172–4. Search in Google Scholar
18 Barton R. Iron deficiency anaemia patients must be screened for coeliac disease. Br Med J 1997; 314: 1759–60. Search in Google Scholar
19 Bottaro G, Castaldo F, Rotolo N, Spina M, Corazza GR. The clinical pattern of subclinical celiac disease: an analysis on 1026 consecutive cases. Am J Gastroeneterol 1999; 94: 691–6. 10.1016/S0002-9270(98)00819-3Search in Google Scholar
20 Anand BS, Callender ST, Warmer GT. Absorption of inorganic and haemoglobin iron in coeliac disease. Br J Haematol 1977; 37: 409:14. 10.1111/j.1365-2141.1977.tb01012.xSearch in Google Scholar
21 Working group of the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN). Revised criteria for diagnosis of coeliac disease. Arch Dis Child 1990;65:909–11. 10.1136/adc.65.8.909Search in Google Scholar
22 Raya G, Henny J, Steinmetz J, Herbeth B, Siest G. Soluble transferrin receptor (sTfR): biological variations and reference limits. Clin Chem Lab Med 2001; 39: 1162–8. 10.1515/CCLM.2001.183Search in Google Scholar
23 Mast AE, Blinder MA, Gronowski A, Chumley C, Scott MG. The clinical utility of the serum transferrin receptor in the evaluation of iron deficiency anemia. Clin Chem 1998; 44: 45–51. 10.1093/clinchem/44.1.45Search in Google Scholar
24 Souroujon M, Ashkenazi A, Lupo M, Levin S, Hegesh E. Serum ferritin levels in celiac disease. Am J Clin Pathol 1982; 77: 82–6. 10.1093/ajcp/77.1.82Search in Google Scholar
25 Stahlberg MR, Savilahti E, Siimes MA. Iron deficiency in celiac disease is mild and it is detected and corrected by gluten-free diet. Acta Paediatr Scand 1991; 80: 190–3. 10.1111/j.1651-2227.1991.tb11832.xSearch in Google Scholar
26 Barisani D, Parafioriti A, Conte D, Koch RO, Weiss G, Bardella M. Divalent metal transporter and transferrin receptor expression in duodenal biopsies from celiac patients [abstract]. Dig Dis Week 2001; 20–23 May. 10.1016/S0016-5085(08)83389-6Search in Google Scholar
27 Skikne BS, Flowers CH, Cook JD. Serum transferrin receptor: a quantitative measure of tissue iron deficiency. Blood 1990; 75: 1870–6. 10.1182/blood.V75.9.1870.1870Search in Google Scholar
28 Feelders RA, Kuiper-Kramer EP, Van Heijk HG. Structure, function and clinical significance of transferrin receptors. Clin Chem Lab Med 1999; 37: 1–10. 10.1515/CCLM.1999.001Search in Google Scholar
29 Maiuri L, Troncone R, Fais S, Coletta S, Picarelli A, Pollone F. Crypt epithelial cells express the 4F2 antigen in untreated coeliac mucosa. Adv Exp Med Biol 1995; 371B: 1363–5. Search in Google Scholar
30 Maiuri L, Ciacci C, Auricchio S, Brown V, Quarantino S, Londei M. Interleukin 15 mediates epithelial changes in celiac disease. Gastroenterology 2000; 119: 996–1006. 10.1053/gast.2000.18149Search in Google Scholar
31 Romaldini CC, Barbieri D, Okay TS, Raiz R Jr, Cancado EL. Serum soluble interleukin-2 receptor, interleukon-6, and tumor necrosis factor-alpha levels in children with celiac disease: response to treatment. J Pediatr Gastroenterol Nutr 2002; 35: 513–7. 10.1097/00005176-200210000-00010Search in Google Scholar
32 Klausner RD, Rouault TA, Harford JB. Regulating the fate of mRNA: the control of cellular iron metabolism. Cell 1993; 72: 19–28. 10.1016/0092-8674(93)90046-SSearch in Google Scholar
©2005 by Walter de Gruyter Berlin New York
