Advertisement

Vitamin D Deficiency and Its Association with Inflammatory Markers, Lipid Profile and Regulatory T-cells in Pediatric Sickle Cell Disease Patients

  • Yesim Oztas
  • Selma Unal
  • Gulcin Eskandari
  • Lulufer Tamer
  • Nuriman Ozgunes
Original Article
  • 41 Downloads

Abstract

We investigated vitamin D deficiency in pediatric sickle cell disease patients and its association with selected bone, lipid and inflammatory parameters. The study included 64 patients (33 SS and 31 SB) and 21 carriers (AS). Blood was obtained to assess levels of vitamin D, WBC, CRP, Ca, P, ALP, PTH, triglyceride, total cholesterol, LDL, VLDL, HDL, IL-2, IL-12, TNF-α, IL-4, IL-6, IL-10 and regulatory T cells. The patients were grouped according to their genotype (SS, SB) and vitamin D status (low or normal). Carriers were also grouped as low or normal vitamin D. Laboratory findings were similar between low and normal Vit D groups in SS, SB and AS genotypes except a lower IL-12 in SB-low vitamin D compared SB-normal vitamin D group. Acute chest syndrome was more frequent in SS-low Vit D (63%) compared to SS-normal Vit D (25%), SB-low Vit D (21%) and SB-normal Vit D (33%) (P = 0.045). Both SS and SB with low vitamin D had higher VLDL (P = 0.006 and P = 0.022), TNF-α (P = 0.001) and regulatory T cells (P = 0.000) compared to AS-low vitamin D. Both SS and SB with normal vitamin D had higher levels of regulatory T cells (P = 0.000) compared to AS-normal vitamin D. Vit D was not a modifier of selected inflammation, bone and lipid parameters in sickle cell disease. Acute chest syndrome was comparably more frequent in SS-low vitamin D. Increase of regulatory T cells in the patients was a result of chronic inflammation in sickle cell disease.

Keywords

Sickle cell disease Genotype Vitamin D Cytokine TNF-α Regulatory T cell Lipid VLDL 

Notes

Funding

This study was funded by a grant from Turkish Scientific Research and Technical Council (112S243).

Compliance with Ethical Standards

Conflict of interest

Authors YO, SU, GE, LT and NO declare that they have no conflict of interest.

Research Involving Human Participants and/or Animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual children and their parents.

References

  1. 1.
    Vercellotti GM, Belcher JD (2014) Not simply misshapen red cells: multimolecular and cellular events in sickle vaso-occlusion. J Clin Invest 124(4):1462–1465CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Brittain JE, Parise LV (2007) Cytokines and plasma factors in sickle cell disease. Curr Opin Hematol 14(5):438–443CrossRefPubMedGoogle Scholar
  3. 3.
    Taylor SC, Shacks SJ, Qu Z et al (1997) Type 2 cytokine serum levels in healthy sickle cell disease patients. J Natl Med Assoc 89(11):753–757PubMedPubMedCentralGoogle Scholar
  4. 4.
    Emokpae MA, Uadia PO, Gadzama AA (2010) Correlation of oxidative stress and inflammatory markers with the severity of sickle cell nephropathy. Ann Afr Med 9(3):141–146CrossRefPubMedGoogle Scholar
  5. 5.
    Pathare A, Al Kindi S, Alnaqdy AA et al (2004) Cytokine profile of sickle cell disease in Oman. Am J Hematol 77:323–328CrossRefPubMedGoogle Scholar
  6. 6.
    Prietl B, Treiber G, Pieber TR et al (2013) Vitamin D and immune function. Nutrients 5(7):2502–2521PubMedGoogle Scholar
  7. 7.
    Taylor SC, Shacks SJ, Mitchell RA et al (1995) Serum interleukin-6 levels in the steady state of sickle cell disease. J Interferon Cytokine Res 15(12):1061–1064PubMedGoogle Scholar
  8. 8.
    Jackson TC, Krauss MJ, Debaun MR et al (2012) Vitamin D deficiency and comorbidities in children with sickle cell anemia. Pediatr Hematol Oncol 29(3):261–266CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Buison AM (2004) Low vitamin D status in children. J Pediatr 145:622–627CrossRefPubMedGoogle Scholar
  10. 10.
    Rovner AJ, Stallings VA, Kawchak DA et al (2008) High risk of vitamin D deficiency in children with sickle cell disease. J Am Diet Assoc 108(9):1512–1516CrossRefPubMedGoogle Scholar
  11. 11.
    Van Belle TL, Gysemans C, Mathieu C (2011) Vitamin D in autoimmune, infectious and allergic diseases: a vital player? Best Pract Res Clin Endocrinol Metab 25(4):617–632CrossRefPubMedGoogle Scholar
  12. 12.
    Chen S, Sims GP, Chen XX et al (2007) Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 179(3):1634–1647CrossRefPubMedGoogle Scholar
  13. 13.
    Adegoke SA, Smith OS, Adekile AD et al (2017) Relationship between serum 25-hydroxyvitamin D and inflammatory cytokines in paediatric sickle cell disease. Cytokine 96:87–93CrossRefPubMedGoogle Scholar
  14. 14.
    Oztas Y, Durukan I, Unal S et al (2011) Plasma protein oxidation is correlated positively with plasma iron levels and negatively with hemolysate zinc levels in sickle-cell anemia patients. Int J Lab Hematol 34(2):129–135CrossRefPubMedGoogle Scholar
  15. 15.
    Zorca S, Freeman L, Hildesheim M et al (2010) Lipid levels in sickle-cell disease associated with haemolytic severity, vascular dysfunction and pulmonary hypertension. Br J Haematol 149(3):436–445CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Rodriguez-Rodriguez E, Perea JM, Jimenez AI et al (2010) Fat intake and asthma in Spanish schoolchildren. Eur J Clin Nutr 64(10):1065–1071CrossRefPubMedGoogle Scholar
  17. 17.
    Binkley N, Ramamurthy R, Krueger D (2012) Low vitamin D status: definition, prevalence, consequences, and correction. Rheum Dis Clin N Am 38(1):45–59CrossRefGoogle Scholar
  18. 18.
    Jorde R, Grimnes G (2011) Vitamin D and metabolic health with special reference to the effect of vitamin D on serum lipids. Prog Lipid Res 50(4):303–312CrossRefPubMedGoogle Scholar
  19. 19.
    Muldoon MF, Marsland A, Flory JD et al (1997) Immune system differences in men with hypo- or hypercholesterolemia. Clin Immunol Immunopathol 84(2):145–149CrossRefPubMedGoogle Scholar
  20. 20.
    Rudensky AY (2011) Regulatory T cells and Foxp3. Immunol Rev 241(1):260–268CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Pathare A, Kindi SA, Daar S et al (2003) Cytokines in sickle cell disease. Hematology 8(5):329–337CrossRefPubMedGoogle Scholar
  22. 22.
    Rego MJ, da Silva RR, Pereira MC et al (2015) Evaluation of CD4(+)CD25(+)FoxP3(+) T cell populations, IL-10 production, and their correlation with clinical and biochemical parameters in sickle cell anemia patients with leg ulcers. Cytokine 75(2):310–315CrossRefPubMedGoogle Scholar
  23. 23.
    Lee MT, Licursi M, McMahon DJ (2015) Vitamin D deficiency and acute vaso-occlusive complications in children with sickle cell disease. Pediatr Blood Cancer 62(4):643–647CrossRefPubMedGoogle Scholar
  24. 24.
    Novelli EM, Gladwin MT (2016) Crises in sickle cell disease. Chest 149(4):1082–1093CrossRefPubMedGoogle Scholar
  25. 25.
    Tripette J, Connes P, Hedreville M et al (2010) Patterns of exercise-related inflammatory response in sickle cell trait carriers. Br J Sports Med 44(4):232–237CrossRefPubMedGoogle Scholar
  26. 26.
    Adam SS, Zaher G, Ibrahim M et al (2008) Markers of coagulation activation and inflammation in sickle cell disease and sickle cell trait. Blood 112(11):4813Google Scholar
  27. 27.
    Unal S, Oztas Y, Eskandari G, Gumus LT, Nuriman O (2014) Association between vitamin D and inflammation in sickle cell disease. Blood 124(21):4923Google Scholar

Copyright information

© Indian Society of Hematology and Blood Transfusion 2017

Authors and Affiliations

  1. 1.Department of Medical Biochemistry, Medical FacultyHacettepe UniversityAnkaraTurkey
  2. 2.Department of Pediatric Hematology, Medical FacultyMersin UniversityMersinTurkey
  3. 3.Department of Medical Biochemistry, Medical FacultyMersin UniversityMersinTurkey

Personalised recommendations