Chandrakar Diksha, Patel Suprava, Wasnik Preetam N, Mohapatra Eli, Nanda Rachita, Shah Seema, Gupta Dablu L
Department of Biochemistry, All India Institute of Medical Sciences, Raipur, Chhattisgarh India.
Department of Medicine, All India Institute of Medical Sciences, Raipur, Chhattisgarh India.
Indian J Clin Biochem. 2024 Oct;39(4):557-564. doi: 10.1007/s12291-024-01204-0. Epub 2024 Mar 20.
Folic acid (FA) supplementation in sickle cell disease (SCD) patients lead to accumulation of unmetabolized folic acid (UMFA) which might influence the level of cytokines and NK cell activity and thus trigger the crisis event. The aim of the study was to investigate the effect of UMFA levels on immuno-inflammatory markers in SCD patients taking FA supplementation. The cross-sectional study was conducted on 60 HbSS confirmed SCD cases with 22 crisis and 38 cases at steady state of 15-40 years age group. Serum FA, 5-Methyl Tetrahydrofolate (5-MTHF), Dihydrofolate reductase, Interleukin-6 (IL-6), Highly sensitive C-Reactive Protein (HsCRP), and natural killer (NK) cell activity were estimated. More than 50% of the study population depicted presence of UMFA. The median UMFA level was significantly elevated in crisis group (131.8 ng/mL) as compared to the steady state group (36.31 ng/mL) ( = 0.041). The median value of HsCRP was significantly higher in the crisis group (18.41 mg/L) than the steady state group (2.04 mg/L) ( = 0.003). Similarly, IL-6 was higher in crisis group (13.29 pg/mL) than steady state group (5 pg/mL) ( = 0.060). The median NK cell activity was 39.28 nmol/L in crisis group and 35.31 nmol/L in steady state groups ( = 0.889). In bivariate correlation analysis, UMFA showed a significant negative correlation with NK cell activity (r = - 0.638; = < 0.001) and a positive correlation with IL-6 (r = 0.571; = 0.001) and HsCRP (r = 0.237; = 0.200). Accumulation of UMFA affect NK cell activity, thus influence the vulnerability for crisis state. Therefore, dosage modification for FA supplementation in SCD patients is suggested.
镰状细胞病（SCD）患者补充叶酸（FA）会导致未代谢叶酸（UMFA）蓄积，这可能会影响细胞因子水平和自然杀伤（NK）细胞活性，从而引发危机事件。本研究的目的是调查UMFA水平对补充FA的SCD患者免疫炎症标志物的影响。对60例确诊为HbSS的SCD病例进行了横断面研究，年龄在15至40岁之间，其中22例处于危机状态，38例处于稳定状态。检测了血清FA、5-甲基四氢叶酸（5-MTHF）、二氢叶酸还原酶、白细胞介素-6（IL-6）、高敏C反应蛋白（HsCRP）和NK细胞活性。超过50%的研究人群存在UMFA。与稳定状态组（36.31 ng/mL）相比，危机组的UMFA中位数水平显著升高（131.8 ng/mL）（P = 0.041）。危机组的HsCRP中位数（18.41 mg/L）显著高于稳定状态组（2.04 mg/L）（P = 0.003）。同样，危机组的IL-6（13.29 pg/mL）高于稳定状态组（5 pg/mL）（P = 0.060）。危机组的NK细胞活性中位数为39.28 nmol/L，稳定状态组为35.31 nmol/L（P = 0.889）。在双变量相关性分析中，UMFA与NK细胞活性呈显著负相关（r = -0.638；P < 0.001），与IL-6呈正相关（r = 0.571；P = 0.001），与HsCRP呈正相关（r = 0.237；P = 0.200）。UMFA的蓄积会影响NK细胞活性，从而影响危机状态的易感性。因此，建议对SCD患者补充FA的剂量进行调整。
