Perturbation of monocyte subsets in iron-deficient children – a shift to a pro-inflammatory state?

Main Article Content

Nimisha Dhankar
Richa Gupta
Shyam Lata Jain
Shramana Mandal
Beauty Sarkar

Keywords

Iron Deficiency Anemia, Children, Monocyte subsets, Flow cytometry

Abstract

Background Iron deficiency anemia (IDA) is the most prevalent micronutrient deficiency in preschool children in developing countries including India. IDA is associated with immune perturbation, which is reflected in greater frequency of infections in these children. Recent research has shown three distinct monocyte subsets with distinct functions linked to infectious, inflammatory, and autoimmune diseases. These subsets have not been studied in children with IDA.


Objective The aim of the study was to assess the percentage of monocyte population and the three subset populations in children with IDA and to compare the data with age-matched healthy controls.


Methods Venous blood samples (5 mL) from 40 IDA children and 20 controls were collected after taking informed consent. Monocyte subpopulations were compared across the two groups. The outcome variables were calculated using Students Independent t-test or Mann–Whitney U test. P-value of <0.05 was taken as significant.


Results No significant difference was found in the absolute numbers as well as percentages of total monocytes between the control and case (study) group. Children in the IDA group showed a significant (p = 0.03) decrease in the nonclassical subset population when compared to the control group.


Conclusion This is the first study done on monocyte subsets in iron-deficient children. Decrease in nonclassical monocytes observed may be associated with a pro-inflammatory state and increased risk of inflammatory and auto immune diseases. Follow-up studies are needed to confirm these findings.

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References

1. World Health Organization. The global prevalence of anaemia in 2011. Geneva: World Health Organization; 2015.

2. Oski FA, Honig AS, Helu B, Howanitz P. Effect of iron therapy on behavior performance in nonanemic, iron-deficient infants. Pediatrics. 1983;60:877–880.

3. Akman M, Cebeci D, Okur V, Angin H, Abali O, Akman AC. The effects of iron deficiency on infants’ developmental test performance. Acta Paediatr Oslo Nor. 2004;93(10):1391–1396. 10.1111/j.1651-2227.2004.tb02941.x

4. Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr. 2001;131:568S–580S. 10.1093/jn/131.2.568S

5. Walter T, Arredondo S, Arevalo M, Stekel A. Effect of iron therapy on phagocytosis and bactericidal activity in neutrophils of iron-deficient infants. Am J Gin Nutr. 1986;44:877–882. 10.1093/ajcn/44.6.877

6. Yetgin S, Altay C, Ciliv G, et al. Myeloperoxidase activity and bactericidal function of PMN in iron deficiency. Acta Haematol. 1979;61:10–14. 10.1159/000207620

7. Kulapongs P, Suskind R, Vithayasi V, et al. Cell mediated immunity and phagocytosis and killing function in children with severe iron deficiency anemia. Lancet. 1974;21:680–691. 10.1016/S0140-6736(74)93264-4

8. Ziegler-Heitbrock L, Hofer TPJ. Toward a refined definition of monocyte subsets. Front Immunol. 2013;4:23. 10.3389/fimmu.2013.00023

9. Ziegler-Heitbrock L. Monocyte subsets in man and other species. Cell Immunol. 2014;289:135–139. 10.1016/j.cellimm.2014.03.019

10. Woollard KJ, Geissmann F. Monocytes in atherosclerosis: subsets and functions. Nature Rev Cardiol. 2010;7:77–86. 10.1038/nrcardio.2009.228

11. Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis. Annu Rev Immunol. 2009;27:165–197. 10.1146/annurev.immunol.021908.132620

12. Sadeghian MH, Keramati MR, Ayatollahi H, Manavifar L, Enaiati H, Mahmoudi M. Serum immunoglobulins in patients with iron deficiency anemia. Indian J Hematol Blood Transfus. 2010;26:45–48. 10.1007/s12288-010-0025-3

13. Ahluwalia N, Sun J, Krause D, Mastro A, Handte G. Immune function is impaired in iron-deficient, homebound, older women. Am J Clin Nutr. 2004;79(3):516–521. 10.1093/ajcn/79.3.516

14. Berrak SG, Angaji M, Turkkan E, Canpolat C, Timur C, Demiralp-Eksioglu EZ. The effects of iron deficiency on neutrophil/monocyte oxidative burst response in children. Blood. 2006;108(11):3722. 10.1182/blood.V108.11.3722.3722

15. Ekiz C, Agaoglu L, Karakas Z, Gurel N, Yalcin I. The effect of iron deficiency anemia on the function of the immune system. Hematol J. 2005;5(7):579–583. 10.1038/sj.thj.6200574

16. Mukherjee R, Kanti Barman P, Kumar Thatoi P, Tripathy R, Kumar Das B, Ravindran B. Non-classical monocytes display inflammatory features: validation in sepsis and systemic lupus erythematous. Sci Rep. 2015;5(1):13886. 10.1038/srep13886

17. Wong KL, Tai JJ-Y, Wong WC, Han H, Sem X, Yeap WH, et al. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood. 2011;118:16–31. 10.1182/blood-2010-12-326355

18. Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, et al. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol. 2007;8:639–646. 10.1038/ni1467

19. Eljaszewicz A, Kleina K, Grubczak K, Radzikowska U, Zembko P, Kaczmarczyk P, et al. Elevated numbers of circulating very small embryonic-like stem cells (VSELs) and intermediate CD14++CD16+ monocytes in IgA nephropathy. Stem Cell Rev Rep. 2018;14(5):686–693. 10.1007/s12015-018-9840-y

20. Ren X, Mou W, Su C, Chen X, Zhang H, Cao B, et al. Increase in peripheral blood intermediate monocytes is associated with the development of recent-onset type 1 diabetes mellitus in children. Int J Biol Sci. 2017;13(2):209–218. 10.7150/ijbs.15659

21. Oppenheimer SJ. Iron and its relation to immunity and infectious disease. J Nutr. 2001;131(2):616S–635S. 10.1093/jn/131.2.616S