The Association Between Vitamin D and Inflammation in Sickle Cell Disease
Authors: Unal Selma , Oztas Yesim , Eskandari Gulcin , Gumus Lulufer Tamer , Nuriman Ozgunes 
Published: October 2019

Abstract
Sickle Cell Disease (SCD) is characterized by periodic vaso-occlusive crises, chronic hemolysis and frequent infections that are accompanied by pain and organ damage. Inflammation has substantial role in SCD pathogenesis. Patients exhibit elevated leukocyte counts, abnormal activation of granulocytes, monocytes, and endothelial cells, and increased levels of multiple inflammatory mediators. Vitamin D, a secosteroid hormone synthesized in the skin or derived from nutritional sources, serves a variety of functions that include immunomodulation, bone homoeostasis and wound healing. Deficiency of vitamin D has been linked to autoimmune diseases, carcinogenesis, and importantly, different inflammatory diseases. Vitamin D deficiency is seen frequently in patients with SCD. However, relationship between inflammation and vitamin D deficiency in SCD pathogenesis has not been investigated, yet.
In this study, we aimed to investigate the relation between vitamin D levels and inflammation in children with SCD. For this purpose, 64 patients with SCD, 21 SCD trait, and 21 healthy controls were included in this study. The local ethics committee approved the study and informed consent was obtained from the children and parents. Vitamin D status was expressed as low, if plasma vitamin D levels were lower than 20 ng/ml. The SCD patients were grouped as Group 0 which includes steady state patients with low vitamin D levels (n=21), Group 1 which includes vaso-occlusive crisis patients with low vitamin D levels (n=18), Group 2 which includes steady state patients with normal vitamin D levels (n=16), Group 3 which includes vaso-occlusive crisis patients with normal vitamin D levels (n=9). The SCD trait patients were grouped in Group 4 and healthy children were grouped in Group 5. Levels of vitamin D and inflammatory parameters were determined in all groups; bone parameters were studied in SCD patients and SCD traits. WBC count and levels of CRP, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α and IFN-γ were determined as inflammatory markers. Vitamin D levels lower than 20 ng/ml were found in 61% of SCD patients, in 33% of SCD traits and in 84% of healthy children. We could not find any relation between vitamin D levels and WBC, CRP and bone markers in SCD patients. Vitamin D is correlated to TNF-α in Group 0 (R=0.589 and P=0.005), to IL-10 in Group 1 (R=0.612 and P=0.046), to IL-12 in Group 2 (R=-0.549 and P=0.028) and to IL-4 (R=0.695 and P=0.038) and IL-6 (R=0.865 and P=0.003) in Group 3. TNF-α levels were higher in the groups who had vaso-occlusive crises (Group 1 and 3) than the groups who were at steady state (Group 0 and 2).
Vaso-occlusive crisis are the result of interactions between sickle erythrocytes, inflammatory cytokines and endothelium. Deficiency of vitamin D that has effects on endothelial dysfunction and cytokines, has possibly contributed to the pathogenesis of SCD. However, we could not show a concrete association between vitamin D and inflammation, possibly there are other molecules or markers modulating this association. Additionally our patient number may not be high enough to show this association. Our study is valuable for it's the first study on investigating the possible association between vitamin D and inflammation in SCD. Research on this topic should be continued with larger groups and novel biomarkers.

Disclosures
No relevant conflicts of interest to declare.