Safety and efficacy of monthly high-dose vitamin D3 supplementation in children and adolescents with sickle cell disease.

Little is known about the impact of vitamin D supplementation on hand grip strength (HGS) and health-related quality of life (HRQoL) in children and adolescents with sickle cell disease (SCD). We aimed to evaluate the safety and efficacy of monthly high-dose vitamin D3 supplementation and its implications on bone mineral density (BMD), HGS, and HRQoL in patients with SCD and healthy controls. The study included 42 children with SCD and 42 healthy matched controls. The study participants were supplemented with high-dose monthly oral vitamin D3. Changes in the serum level of 25(OH) vitamin D3, maximum HGS, and BMD from baseline to 6 months were assessed, and the HRQoL questionnaire and Childhood Health Assessment Questionnaire (CHAQ) were used to evaluate the functional capacity. At baseline, SCD subjects had poorer growth status indicated by negative Z scores. Suboptimal BMD was detected by significantly lower Z score, and lower HGS and worse HRQL parameters were found compared to the controls (P < 0.001). Median 25(OH) vitamin D3 was significantly lower in SCD patients compared to controls (16.5 vs. 28 ng/mL, respectively (P < 0.001)). After 6 months of vitamin D supplementation, there was significant improvement in the DEXA Z-score (P < 0.001), limitation of physical health (P = 0.02), pain scores (P < 0.001), and CHAQ grades (P = 0.01) in SCD patients. A significant improvement in HGS (P < 0.001 and P = 0.005) as well as the CHAQ score (P < 0.001 and P = 0.003) was detected in the SCD group and controls, respectively. There were no reported clinical adverse events (AEs) or new concomitant medications (CMs) during the study duration, and safe levels of Ca and 25 (OH) D3 were observed at 3 and 6 months for both groups. There was a significant positive correlation between HGS and total physical score (r = 0.831, P < 0.001) and a negative correlation with CHAQ score (r = - 0.685, P < 0.001). We also detected a significant positive correlation between vitamin D levels at 6 months and HGS (r = 0.584, P < 0.001), pain score (r = 0.446, P < 0.001), and a negative correlation with CHAQ score (r = - 0.399, P < 0.001).   Conclusion: Monthly oral high-dose vitamin D supplementation was safe and effective in improving vitamin D levels, HGS, and HRQoL in SCD children and healthy subjects, and BMD scores in SCD patients. Further randomized controlled trials are warranted to assess an optimal dosing strategy and to investigate the impact on clinically significant outcomes in children and adolescents with SCD and their healthy counterparts.   Trial registration: ClinicalTrials.gov , identifier NCT06274203, date of registration: 23/02/2024, retrospectively registered. What is known: • Several studies have reported a high prevalence of vitamin D deficiency and suboptimal bone mineral density (BMD) in sickle cell disease (SCD) patients. • Musculoskeletal dysfunction is reported in SCD patients with a negative impact on physical activity and health-related quality of life (HRQL). • Little is known regarding the impact of vitamin D3 supplementation in children and adolescents with SCD. What is new: • We found that monthly oral high-dose vitamin D3 supplementation was safe, tolerated, and effective in improving serum vitamin D levels, HGS, BMD scores, and HRQL in SCD patients.

Immunohistochemical expression of regulatory T cells (CD4 + CD25 + bright FOXP3 + ) in pemphigus patients.

BACKGROUND: Pemphigus is a series of autoimmune skin disorders caused by IgG. Regulatory T cells (Tregs) are a subset of CD4+ T cells that mostly block pathogenic immune responses mediated by self-reactive cells; therefore, a lack of Tregs or a malfunction in their activity could lead to a loss of tolerance and the development of autoimmunity. AIMS: To evaluate the expression of lesional and perilesional Treg markers (CD4 + CD25 + bright FOXP3 + ) in pemphigus patients. PATIENTS AND METHODS: Twenty-three pemphigus patients and 20 healthy controls were included in this study. The expression of CD4 , CD25, and Foxp3 was evaluated by immunohistochemistry. RESULTS: There was statistically significant increase in CD4+ T lymphocytes in lesional skin of pemphigus compared to perilesional skin and control group (p-value: 0.001). There was statistically significant decrease in CD25+ and Foxp3+ cells in lesional skin compared to perilesional and control group (p-value: <0.001, 0.025, respectively). CONCLUSION: The reduction of lesional skin Tregs may play an important role in the pemphigus pathogenesis.

Association of TNFAIP3 gene polymorphism (rs5029939) with susceptibility and clinical phenotype of systemic lupus erythematosus.

Objectives: This study aims to investigate the association of the tumor necrosis factor-alpha inducible protein 3 (TNFAIP3) (rs5029939) gene single nucleotide polymorphism (SNP) with the risk of systemic lupus erythematosus (SLE) and its clinical manifestations in a cohort of SLE patients. Patients and methods: This study included a total of 180 participants (18 males, 72 females; mean age: 30.9±10.1 years; range 17 to 59 years) including 90 SLE patients and 90 healthy controls between March 2017 and February 2020. The TNFAIP3 rs5029939 gene polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all participants. Results: There was a significant difference in genotype distribution of the TNFAIP3 rs5029939 SNP between SLE patients and healthy controls, where CG genotype was more common in SLE patients (53.3%) than controls (11.1%) (p=0.001). We found a significant difference in G allele frequency of TNFAIP3 (rs5029939) (37.8% with SLE vs. 5.6% with controls, p=0.001). Genotype CG was significantly associated with lupus nephritis and neuropsychiatric manifestations (p<0.05). Although the response to treatment was numerically higher with the genotype CC, it did not reach statistical significance (p=0.4). Conclusion: Our study suggests that TNFAIP3 rs5029939 gene polymorphism is associated with SLE susceptibility and may have an impact on its clinical phenotype. As such association differs among populations of diverse ethnic backgrounds, larger genome-wide association studies are warranted to further elucidate genetic associations.