Association of Hepcidin and Erythroferrone Levels with Anemia in Systemic Lupus Erythematosus Patients

Main Article Content

Sirichan Chunhakan

Abstract

Objectives: To study the association of hepcidin and erythroferrone (ERFE) levels with hemoglobin levels in systemic lupus erythematosus (SLE) patients.


Methods: Forty-two serum samples collected from SLE patients were categorized into anemia and without anemia using hemoglobin levels. Forty blood donors were included as control group, all serum was collected from leftover specimen. Hepcidin and ERFE were measured in patients and control group using enzyme-linked immunosorbent (ELISA) kit.


Results: Hepcidin and ERFE showed the highest levels in anemic SLE patients and were statistically significantly higher than in non-anemic SLE patients and control group, while hepcidin and ERFE were statistically significantly higher in non-anemic SLE patients than control group. In SLE patients, hepcidin and erythroferrone were statistically negatively correlated with hemoglobin. There was no statistically significant correlation between hepcidin and erythroferrone levels.


Conclusion: Elevated serum hepcidin and erythroferrone levels were associated with anemia in SLE patients. Whereas hepcidin and erythroferrone were independent of each other in causing anemia and both values were not appropriate to be used as markers of anemia status in SLE patients.

Article Details

How to Cite
Chunhakan, S. (2021). Association of Hepcidin and Erythroferrone Levels with Anemia in Systemic Lupus Erythematosus Patients. Vajira Medical Journal : Journal of Urban Medicine, 65(Supplement November), S91–100. https://doi.org/10.14456/vmj.2021.55
Section
Original Articles

References

Justiz Vaillant AA, Goyal A, Bansal P, Varacallo M. Systemic Lupus Erythematosus. [Updated 2020 Nov 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. [cited 2021 Feb 15] Available from: https://www.ncbi.nlm.nih.gov/books/NBK535405/

Shaikh MA, Memon I, Ghori RA. Frequency of anaemia in patients with systemic lupus erythaematosus at tertiary care hospitals. J Pak Med Assoc 2010;60(10):822-5.

Sasidharan PK, Bindya M, Sajeeth Kumar KG. Haematological manifestations of SLE at initial presentation: is it underestimated? ISRN Haematol 2012;2012:961872. doi: 10.5402/2012/961872.

Mittal S, Agarwal P, Wakhlu A, Kumar A, Mehrotra R, Mittal S. Anaemia in systemic lupus erythematosus based on iron studies and soluble transferrin receptor levels. J Clin Diagn Res 2016;10(6):EC08-11. doi: 10.7860/JCDR/2016/17930.7961.

Beyan E, Beyan C, Turan M. Haematological presentation in systemic lupus erythaematosus and its relationship with disease activity. Haematology 2007;12(3):257-61.

Fraenkel PG. Anemia of inflammation: A review. Med Clin North Am 2017; 101(2): 285-96.

Ganz T. Anemia of Inflammation. N Engl J Med 2019; 381(12):1148-57.

Girelli D, Nemeth E, Swinkels DW. Hepcidin in the diagnosis of iron disorders. Blood 2016;127(23):2809-13.

Wrighting DM, Andrews NC. Interleukin-6 induces hepcidin expression through STAT3. Blood 2006;108:3204-9.

Dagli M, Yilmaz S, Sivrikaya A, Cehk G, Vatansev H. The role of prohepcidin and hepcidin in anemia associated with systemic lupus erythemayosus. World Appl Sci J 2011;13(9):2032-6.

Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM, et al. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol 2007;27(5):461-6.

Hu S, Xiao W, Kong F, Ke D, Qin R, Su M. Regulatory T cells and their molecular markers in peripheral blood of the patients with systemic lupus erythematosus. J Huazhong Univ Sci Technolog Med Sci 2008;28(5):549-52.

Wu Y, Cai B, Zhang J, Shen B, Huang Z, Tan C, et al. IL-1β and IL-6 are highly expressed in RF+ IgE+ systemic lupus erythematous subtype. J Immunol Res 2017;2017:5096741. doi:10.1155/2017/5096741.

Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 2014;46(7):678-84.

Pasricha SR, McHugh K, Drakesmith H. Regulation of Hepcidin by Erythropoiesis: The Story So Far. Annu Rev Nutr 2016;36:417-34.

El-Gamal RAE, Abdel-Messih IY, Habashy DM, Zaiema SEG, Pessar SA. Erythroferrone, the new iron regulator: evaluation of its levels in Egyptian patients with β thalassemia. Ann Hematol 2020;99:31-9.

Mangaonkar AA, Thawer F, Son J, Ajebo G, Xu H, Barrett NJ, et al. Regulation of iron homeostasis through the erythroferrone-hepcidin axis in sickle cell disease. Br J Haematol 2020;189(6):1204-9.

Hanudel MR, Rappaport M, Chua K, Gabayan V, Qiao B, Jung G, et al. Levels of the erythropoietinresponsive hormone erythroferrone in mice and humans with chronic kidney disease. Haematologica 2018;103(4):e141-2. doi: 10.3324/haematol.2017.181743.

Srole DN, Ganz T. Erythroferrone structure, function, and physiology: Iron homeostasis and beyond. J Cell Physiol 2021;236(7):4888-901.

Hulley SB, Cummings SR, Browner WS, Grady DG, Newman TB. Designing clinical research: an epidemiologic approach. 4thed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013. Appendix 6C, p. 79.

El-Shafey AM, Kamel LM, Fikry AA, Nasr MM, Abdel Galil SM. Serum hepcidin and interleukin-6 in systemic lupus erythematosus patients: crucial factors for correction of anemia. Egyptian Rheumatology and Rehabilitation 2020;47:14. doi: 10.1186/s43166-020-00006-5

Ali ET, Jabbar AS, Mohammed AN. A Comparative Study of interleukin 6, inflammatory markers, ferritin, and hematological profile in rheumatoid arthritis patients with anemia of chronic disease and iron deficiency anemia. Anemia 2019;2019:3457347. doi: 10.1155/2019/3457347

Chen Y, Xu W, Yang H, Shao M, Xu S, Deng J, et al. Serum levels of hepcidin in rheumatoid arthritis and its correlation with disease activity and anemia: A meta-analysis. Immunol Invest 2021;50(2-3):243-58.

Demirag MD, Haznedaroglu S, Sancak B, Konca C, Gulbahar O, Ozturk MA, et al. Circulating hepcidin in the crossroads of anemia and inflammation associated with rheumatoid arthritis. Intern Med 2009;48(6):421-6.

Youssef SR, Hassan EH, Morad CS, Elazab Elged AA, El-Gamal RA. Erythroferrone Expression in Anemic Rheumatoid Arthritis Patients: Is It Disordered Iron Trafficking or Disease Activity? J Inflamm Res 2021;14:4445-55.

Voulgarelis M, Kokori SI, Ioannidis JP, Tzioufas AG, Kyriaki D, Moutsopoulos HM. Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin. Ann Rheum Dis 2000;59(3):217-22.

Luo XY, Yang MH, Peng P, Wu LJ, Liu QS, Chen L, et al. Anti-erythropoietin receptor antibodies in systemic lupus erythematosus patients with anemia. Lupus 2013;22:121–7.

Seldin MM, Peterson JM, Byerly MS, Wei Z, Wong GW. Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J Biol Chem 2012;287(15):11968-80.

de Oliveira Dos Santos AR, de Oliveira Zanuso B, Miola VFB, Barbalho SM, Santos Bueno PC, Flato UAP, et al. Adipokines, myokines, and hepatokines: crosstalk and metabolic repercussions. Int J Mol Sci 2021;22(5):2639. doi: 10.3390/ijms22052639.

Ray P, Le Manach Y, Riou B, Houle TT. Statistical Evaluation of a Biomarker. Anesthesiology 2010;112(4):1023-40.