The Expression Of Vitamin D Pathway In Alopecia Areata And Clinical Meaning

Background Vitamin D is a steroid hormone,can be ingested orally or can be formed endogenously in cutaneous tissue following exposure to ultraviolent B light.Vitamin D₃ from both sources is metabolised in the liver to 25-hydroxyvitamin D（25（OH）D）,25（OH）D requires 25（OH）D₃-1-a-hydroxylase’s additional hydroxylation within the kidney to form 1,25-dihydroxyvitamin D（1,25（OH）2D₃）.25（OH）D₃ and 1,25（OH）2D₃ go into the cells by interacting with vitamin D blinding protein（DBP）.1,25（OH）2D₃ interacts with its vitamin D receptors（VDRs）and plays the role.Since 1983 s,it has shown that peripheral mononuclear leukocytes and active T cells express VDRS,which shown that vitamin D has an important role in immune system.Current data link vitamin D deficiency to many autoimmune diseases including SLE,psoriasis,multiple sclerosis.In vitro,vitamin D takes part in the regulation and differentiation of the cells of the immune system directly and indirectly: 1,25（OH）2D₃ inhibits the differentiation of monocytes into dendritic cells and maturation of dendritic cells,then inhibit the production of Th1 cells indirectly;inhibitthe production of Th1 and Th17 cells while promote the production of Th2 and Treg cells directly.Alopecia Areata,non-scar and inflammatory,which typical clinical manifestation is suddenly appear with well defined and circular mottled hair loss.The pathogenesis of it is not entirely clear yet,psychiatric factor,autoimmune and endocrine dyscrasia or genetic factor may play a role.Now Alopecia areata is considered as a cell—mediated,hair follicle—targeted autoimmune disease.Its main pathogenesis is loss of protection provided by hair follicle immuneprivilege,T cell mediated and the self-antigens involved.Some reports in home and foreign indicated that there were an abnormal expression of 25（OH）D in serum of patients with alopecia areata.A few researches showed that there were an abnormal expression of vitamin D receptor in serum and the lesion of hair-loss area.However,the correlation of severity,duration and course were controversial.Moreover,in vitro showed that T lymphocyte express vitamin D binding protein and vitamin D 1α-hydroxylase,their abnormal expression may effect the differentiation of T lymphocytes and production of relative cytokines.Alopecia areata is an autoimmune disease mediated by T lymphocytes,whether vitamin D blinding protein and vitamin D 1α-hydroxylase play a role has not been reported yet.Objective To investigate the expression of vitamin D metabolic pathway（25（OH）D₃,vitamin D blinding protein,1α-hydroxylase and vitamin D receptor）in peripheral blood of alopecia areata patients.To explore their possible role in the pathogenesis of alopecia areata.To provide a new target for clinical treatment and prognosis.Method To test the expression of 25（OH）D₃,vitamin D blinding protein,vitamin D 1α-hydroxylase and vitamin D receptor by enzyme-linked immunosorbent assay in 44 patients’ peripheral blood with alopecia areata.Compare the results to 44 healthy control people.To find out whether there are differences between two groups about the severity,duration,course.Result（1）The expression of 25（OH）D₃ in serum of patients with AA（27.41±11.18 ng/ml）was lower than the normal（33.57±6.51 ng/ml）,the difference was statistically significant（P<0.05）.The expression of CYP21b（4.66±1.40 ng/ml）、VDR（15.91±3.79 ng/ml）、DBP（27.86±5.06 ng/ml）in serum of patients with AA were all higher than the normal（1.95±0.44 ng/ml,8.72±1.66 ng/ml,12.32±3.26 ng/ml）,the difference was statistically significant（P<0.05）.（2）There were no significant differences in expression of 25（OH）D₃ between the patients less than 1 year（27.87±11.49 ng/ml）and longer than 1 year（26.16±10.63 ng/ml）,the patients with local AA（25.68±11.83 ng/ml）and extensive AA（28.60±10.78 ng/ml）,the patients in active AA（25.17±11.88 ng/ml）and non-active AA（29.36±9.17 ng/ml）,the patients in relapse（29.25±12.54 ng/ml）and non-relapse（23.83±6.96 ng/ml）.（P>0.05）.（3）The expression of CYP21 b in serum of patients in less than 1 year（5.26±1.29 ng/ml）was higher than longer than 1 year（4.17±1.32 ng/ml）,the difference was statistically significant（P<0.05）.There were no significant differences between the patients with local AA（4.17±1.32 ng/ml）and extensive AA（4.52±1.32 ng/ml）,the patients in active AA（4.67±1.15 ng/ml）and non-active AA（5.27±1.29 ng/ml）,the patients in relapse（4.43±1.36 ng/ml）and non-relapse（5.12±1.41 ng/ml）.（P>0.05）.（4）There were no significant differences in expression of VDR between the patients less than 1year（16.41±3.81 ng/ml）and longer than 1 year（15.50±3.80 ng/ml）,the patients with local AA（15.32±3.51 ng/ml）and extensive AA（16.32±3.40 ng/ml）,the patients in active AA（15.60±3.84 ng/ml）and non-active AA（18.05±3.93 ng/ml）,the patients in relapse（16.17±4.05 ng/ml）and non-relapse（15.42±3.30 ng/ml）.（P>0.05）.（5）The expression of DBP in serum of patients in active AA（4.67±1.15 ng/ml）higher than non-active AA（24.26±4.39 ng/ml）,the difference was statistically significant（P<0.05）.There were no significant differences between the patients less than 1 year（28.55±5.39 ng/ml）and longer than 1 year（27.29±4.82 ng/ml）,with local AA（26.79±5.69 ng/ml）and extensive AA（28.60±4.55 ng/ml）,the patients in relapse（27.38±4.96 ng/ml）and non-relapse（28.80±5.30 ng/ml）.（P>0.05）.Conclusion（1）The vitamin D pathway,25（OH）D₃、CYP21b、DBP、VDR may play a role in the pathogenesis of alopecia areata;（2）The expression of CYP21 b is associated with AA’s duration;（3）The expression of DBP is associated with AA’s activity.