SOX13抗体对酮症倾向糖尿病患者胰岛功能的影响

Effect of SOX13 antibody on islet β cell function in ketosis-prone diabetes

目的 探讨SOX13抗体(sry related HMG box 13-antibody,SOX13-Ab)对酮症倾向糖尿病(KPD)患者胰岛功能的影响,进一步确定SOX13-Ab在KPD患者中的自身免疫反应特征.方法 2005年1月至2009年11月对南京鼓楼医院内分泌科就诊的245例KPD患者[男138例,女107例,年龄33(1～80)岁]均检测SOX13-Ab、谷氨酸脱羧酶抗体(GAD-Ab)和蛋白酪氨酸磷酸酶抗体(IA-2A),以SOX13-Ab单一阳性患者为病例组,以GAD-Ab、IA-2A单一阳性及抗体均阴性组患者为对照组,比较4组患者的胰岛功能.各组平均C肽水平采用中位数(四分位数间距)表示,经自然对数转化后进一步采用方差分析比较组间差异.结果 (1)女性患者中SOX13-Ab单一阳性、GAD-Ab单一阳性组空腹C肽(FCP)和餐后2 h C肽(PCP)水平分别为166.0(300.0)和166.5(159.3)、285.0(527.0)和231.0(502.5)pmol/L,均显著低于抗体阴性组[FCP为287.5(302.7)pmol/L、PCP为528.0(774.0)pmol/L;均P＜0.05];(2)发病年龄≤40岁或病程≤5年的KPD患者中,其FCP水平SOX13-Ab组[166.0(56.0)vs 228.0(250.0)pmol/L]、GAD-Ab单一阳性组[191.0(137.5)vs 324.0(340.0)pmol/L]均显著低于抗体阴性组[167.1(223.1)vs 324.0(340.0)pmol/L];而在病程＞5年的KPD患者中,GAD-Ab单一阳性组FCP水平为130.0(458.8)pmol/L、SOX13-Ab单一阳性组为189.5(357.7)pmol/L,两组比较差异有统计学意义(P＜0.05);(3)协方差分析显示SOX13-Ab单一阳性与抗体阴性组之间FCP、PCP比较差异无统计学意义(P＞0.05);而GAD-Ab/SOX13-Ab双阳性组FCP与抗体阴性组比较差异有统计学意义(P＜0.05);(4)GAD-Ab、IA-2A单一阳性组内FCP与病程均呈显著负相关(r值分别为-0.500、-0.821,P值分别为0.007、0.023),而SOX13-Ab单一阳性组内FCP与病程之间无显著负相关性(r=-0.104,P=0.606).结论 SOX13-Ab对KPD患者胰岛功能的影响弱于GAD-Ab.

Objective To explore the effect of SOX13 antibody(sry related HMG box 13-antibody,SOX13-Ab)on islet β cell function and to further determine the characteristics of autoimmune response of SOX13-Ab in ketosis-prone diabetes(KPD). Methods During the period from January 2005 to November 2009, the 245 KPD patients (male:138, female:107; age:33(1.0 to 80.0)years) who visited a doctor in Department of Endocrinology at Nanjing Drum Tower Hospital were recruited and screened for SOX13-Ab,GDA-Ab and IA-2A. Then according to SOX13-Ab, GAD-Ab and IA-2A starus, the diabetes were divided into SOX13-Ab, GAD-Ab, IA-2A positive groups and antibody-negative group. The effect of SOX13-Ab on islet β cell function was evaluated by comparison of C-peptide levels among the four subgroups. The mean levels of C-peptide in different subgroups were expressed as median(IQR), then analysed with ANOVA after being In-transformed. Results The fasting C-peptide(FCP) and/or postprandial C-peptide(PCP) levels in SOX13-Ab or GAD-Ab positive groups were significantly lower than that in antibody-negative group among female KPD ( FCP: 166.0 (300.0) vs 287.5 ( 302.7 ) pmol/L, 166.5 ( 159.3 ) vs 287.5 ( 302.7 ) pmol/L;PCP: 285.0 ( 527.0) vs 528.0 ( 774.0 ) pmol/L, 231.0 ( 502.5 ) vs 528.0 ( 774.0 ) pmol/L, all P ＜ 0.05 ) or KPD patients with age-onset ≤40 years ( FCP: 166.0 ( 56.0) vs 228.0 ( 250.0 ) pmol/L, 166.0 ( 241.8 ) vs 228.0 (250.0) pmol/L, all P ＜ 0.05 ) or duration ≤ 5 years ( FCP: 191.0 ( 137.5 ) vs 324.0 ( 340.0 )pmol/L, 167.1(223.1) vs 324.0 (340.0) pmol/L,all P＜0.05). While among patients with duration ＞5 years,the levels of FCP in GAD-Ab positive group were significantly lower than that in SOX13-Ab positive group ( 130.0(458.8 ) vs 189.5 ( 357.7 ) pmol/L, P ＜ 0.05 ). The comparison of β cell function among groups with different islet antibody status was made using an ANOVA model, which showed that no significant difference in FCP and PCP levels between SOX13-Ab positive and antibody-negative group, while the difference in FCP levels was significant between GAD-Ab/SOX13-Ab positive and antibody-negative group. There was significantly adverse relationship between duration and β cell function in KPD patients positive for GAD-Ab or IA-2A( GAD-Ab:r = -0.500 ,P =0.007;IA-2A:r = - 0.821 ,P =0.023 ), while in KPD patients positive for SOX13-Ab, there was no significantly adverse relationship between duration and β cell function( r= -0.104,P =0.606). Conclusions The effect of SOX13-Ab is less marked than that of GAD-Ab on β cell function in KPD patients.