The incidence of anaemia and the use of the ELISA method for measuring hepcidin levels in children with inflammatory bowel disease
Authors:
J. Houda 1; P. Džubák 1,2; E. Karásková 1; D. Holub 2; D. Vydra 1; D. Mlčůchová 2; M. Hajdúch 2; O. †pozler 3; D. Pospíšilová 1
Authors‘ workplace:
Dětská klinika při LF UP a FN, Olomoucpřednosta prof. MUDr. V. Mihál, CSc.
1; Laboratoř experimentální medicíny, Ústav molekulární a translační medicíny, Lékařská fakulta UP, Olomoucředitel doc. MUDr. M. Hajdúch, Ph. D.
2; Dětská klinika LF a FN, Hradec Královépřednosta prof. MUDr. M. Bayer, CSc.
3
Published in:
Čes-slov Pediat 2014; 69 (3): 137-147.
Category:
Original Papers
Overview
The aim of the study was to identify the incidence of anemia in children with inflammatory bowel disease (IBD) (n=133), to define characteristics of anemia and to assess the results of hepcidin measurement by ELISA test in selected group of IBD patients (n=56). Anemia was found in 47.7% of patients. The ferritin level was decreased and the soluble transferrin level was increased in 43% of anemic patients. These findings correspond with a combination of iron deficient anemia (IDA) and anemia of chronic diseases (ACD). A typical laboratory feature of ACD with increased ferritin level was present in only 7.7% of anemic patients. Mean value of hepcidin level in patients with IBD was 42.0 ng/ml (SD 34.1), which is in normal range delivered by ELISA kit manufacturer (13.3–54.4 ng/ml). The hepcidin levels were increased in 55% of the female IBD patients and in 18% of the male patients. The statistically significant positive correlation between hepcidin and CRP levels was found (R=0.30 and p<0.041). The hepcidin levels were significantly higher in young adults over 18 years old than in children aged <18 years.
Our findings suggest that ACD is the most common type of anemia in IBD children and it is accompanied with true iron deficiency. These results differ from currently published data in adult IBD patients. Measuring hepcidin levels is a helpful tool in iron deficiency diagnosis and may represent an important indicator when selecting the most appropriate treatment option. It may also help clarify the hierarchy of regulatory mechanisms in iron metabolism.
Key words:
anaemia of chronic diseases, iron deficiency anaemia, inflammatory bowel diseases, hepcidin, ferroportin, ELISA
Sources
1. IBD Working Group of the European Society for Paediatric Gastroenterology. Hepatology and Nutrition. Inflammatory bowel disease in children and adolescents: recommendations for diagnosis--the Porto criteria. J Pediatr Gastroenterol Nutr 2005; 41 (1): 1–7.
2. Lukáš M. Farmakoterapie idiopatických střevních zánětů. Prakt Lékáren 2009; 5 (4):164–167.
3. Wyllie R, Hyams JS, Kay M. Pediatric Gastrointestinal and Liver Disease. 4th ed. Philadelphia: Elsevier Saunders, 2011: 472–504.
4. Bergamaschi G, Di Sabatino A, Albertini R, et al. Prevalence and pathogenesis of anemia in inflammatory bowel disease. Influence of anti-tumor necrosis factor-alpha treatment. Haematologica 2010; 95 (2): 199–205.
5. Wells CW, Lewis S, Barton JR, et al. Effects of changes in hemoglobin level on quality of life and cognitive function in inflammatory bowel disease patients. Inflamm Bowel Dis 2006; 12 (2): 123–130.
6. Goodhand JR, Kamperidis N, Rao A, et al. Prevalence and management of anemia in children, adolescents, and adults with inflammatory bowel disease. Inflamm Bowel Dis 2012; 18 (3): 513–519.
7. Gerasimidis K, McGrogan P, Edwards CA. The aetiology and impact of malnutrition in paediatric inflammatory bowel disease. J Hum Nutr Diet 2011; 24 (4): 313–326.
8. Ganz T. Hepcidin and its role in regulating systemic iron metabolism. Hematology Am Soc Hematol Educ Program 2006; 507: 29–35.
9. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004; 17: 306.
10. Hyams JS, Ferry GD, Mandel FS, et al. Development and validation of a pediatric Crohn‘s disease activity index. J Pediatr Gastroenterol Nutr 1991; 12 (4): 439–447.
11. Otley A, Loonen H, Parekh N, et al. Assessing activity of pediatric Crohn‘s disease: which index to use? Gastroenterology 1999; 116 (3): 527–531.
12. Turner D, Hyams J, Markowitz J, et al. Appraisal of the pediatric ulcerative colitis activity index (PUCAI). Inflamm Bowel Dis 2009; 15 (8): 1218–1223.
13. Wiskin AE, Fleming BJ, Wootton SA, et al. Anaemia and iron deficiency in children with inflammatory bowel disease. J Crohns Colitis 2012; 6 (6): 686–691.
14. Wilson A, Reyes E, Ofman J. Prevalence and outcomes of anemia in inflammatory bowel disease: a systematic review of the literature. Am J Med 2004; 116 (Suppl 7A): S44–S49.
15. Theurl I, Finkenstedt A, Schroll A, et al. Growth differentiation factor 15 in anaemia of chronic disease, iron deficiency anaemia and mixed type anaemia. Br J Haematol 2010; 148 (3): 449–455.
16. Oustamanolakis P, Koutroubakis IE, Messaritakis I, et al. Serum hepcidin and prohepcidin concentrations in inflammatory bowel disease. Eur J Gastroenterol Hepatol 2011; 23 (3): 262–268.
17. Arnold J, Sangwaiya A, Bhatkal B, et al. Hepcidin and inflammatory bowel disease: dual role in host defence and iron homoeostasis. Eur J Gastroenterol Hepatol 2009; 21 (4): 425–429.
18. Galesloot TE, Vermeulen SH, Geurts-Moespot AJ, et al. Serum hepcidin: reference ranges and biochemical correlates in the general population. Blood 2011; 117 (25): e218–225.
19. Ganz T, Olbina G, Girelli D, et al. Immunoassay for human serum hepcidin. Blood 2008 Nov 15; 112 (10): 4292–4292.
20. Kroot JJ, Kemna EH, Bansal SS, et al. Results of the first international round robin for the quantification of urinary and plasma hepcidin assays: need for standardization. Haematologica 2009; 94 (12): 1748–1752.
21. Wrighting DM, Andrews NC. Interleukin-6 induces hepcidin expression through STAT3. Blood 2006; 108 (9):3204–3209.
22. Huang H, Constante M, Layoun A, et al. Contribution of STAT3 and SMAD4 pathways to the regulation of hepcidin by opposing stimuli. Blood 2009; 113 (15): 3593–3599.
23. Nicolas G, Chauvet C, Viatte L, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 2002; 110 (7): 1037–1044.
24. Kautz L, Meynard D, Monnier A, et al. Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver. Blood 2008 Aug 15; 112 (4): 1503–1509.
25. Andriopoulos B Jr, Corradini E, Xia Y, et al. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet 2009; 41 (4): 482–487.
26. Meynard D, Kautz L, Darnaud V, et al. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet 2009; 41 (4): 478–481.
27. Peyssonnaux C, Zinkernagel AS, Schuepbach RA, et al. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest 2007; 117 (7): 1926–1932.
28. Pinto JP, Ribeiro S, Pontes H, et al. Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPalpha. Blood 2008 Jun 15; 111 (12): 5727–5733.
29. Šuláková A, Pozler O, Nováčková L, et al. Prevalence a typ anemie v době stanovení diagnózy nespecifického střevního zánětu u dětí. Čes-slov Pediat 2012; 67 (1): 3–10.
30. Pospíšilová D, Houda J, Holub D, et al. Význam stanovení hladiny hepcidinu v diagnostice vybraných typů anemií v dětském věku. Transfuze Hematol dnes 2012; 18 (2): 58–65.
Labels
Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
2014 Issue 3
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