中华糖尿病杂志
中華糖尿病雜誌
중화당뇨병잡지
CHINES JOURNAL OF DLABETES MELLITUS
2014年
2期
81-85
,共5页
何予%李霞%黄干%杨琳%周智广
何予%李霞%黃榦%楊琳%週智廣
하여%리하%황간%양림%주지엄
糖尿病,1型%人白细胞抗原%分型%免疫学
糖尿病,1型%人白細胞抗原%分型%免疫學
당뇨병,1형%인백세포항원%분형%면역학
Diabetes mellitus,type 1%Human leukocyte antigen%Classification%Immunology
目的 通过对临床特征、锌转运体8自身抗体(ZnT8A)、分泌干扰素γ的谷氨酸脱羧酶65反应性T细胞(GAD65-IFN-γ-T细胞)检测情况的比较,探讨人白细胞抗原(HLA) DQ单体型对初诊特发性1型糖尿病免疫病因分型的价值.方法 将2000年3月至2011年12月收治的52例自发酮症或酮症酸中毒起病,谷氨酸脱羧酶抗体(GADA)、蛋白酪氨酸磷酸酶抗体(IA-2A)及胰岛素自身抗体(IAA)均阴性,且依赖胰岛素治疗的湖南省汉族新发1型糖尿病患者纳入本研究.放射配体法检测锌转运体8自身抗体(ZnT8A),酶联免疫斑点技术(ELISPOT)检测GAD65-IFN-γ-T细胞,聚合酶链反应(PCR)直接测序法测定HLA-DQ基因型.将研究对象分为HLA-DQ易感单体型携带组和HLA-DQ易感单体型不携带组,并以1年为间隔随访3年.比较两组起病初期的临床特征、ZnT8A及GAD65-IFN-γ-T细胞检测情况,随访时胰岛自身抗体的变化.两组间计数资料比较采用x2检验.结果 52例初诊特发性1型糖尿病患者中5例ZnT8A阳性,阳性率9.6％;16例ZnT8A阴性且接受GAD65-IFN-γ-T检测的患者中,2例GAD65-IFN-γ-T阳性,阳性率12.5％.与HLA-DQ易感单体型不携带组相比,携带组起病初期酮症程度更严重(Z=-2.84,P＜0.05),空腹C肽水平更低(x2 =0.38,P＜0.05).起病初期,携带组中1例患者GAD65-IFN-γ-T细胞检测呈阳性反应(1/5),而不携带组未检测到该细胞呈阳性患者.随访时,携带组中1例患者ZnT8A和IA-2A由阴转阳(1/18),不携带组中未有检测到抗体转阳患者.结论 部分特发性1型糖尿病患者体内存在ZnT8A和GAD65-IFN-γ-T细胞；携带HLA-DQ易感单体型的特发性1型糖尿病患者,较不携带者更加具有自身免疫倾向.胰岛自身免疫是部分初诊特发性1型糖尿病的病因,可能通过HLA-DQ单体型介导.
目的 通過對臨床特徵、鋅轉運體8自身抗體(ZnT8A)、分泌榦擾素γ的穀氨痠脫羧酶65反應性T細胞(GAD65-IFN-γ-T細胞)檢測情況的比較,探討人白細胞抗原(HLA) DQ單體型對初診特髮性1型糖尿病免疫病因分型的價值.方法 將2000年3月至2011年12月收治的52例自髮酮癥或酮癥痠中毒起病,穀氨痠脫羧酶抗體(GADA)、蛋白酪氨痠燐痠酶抗體(IA-2A)及胰島素自身抗體(IAA)均陰性,且依賴胰島素治療的湖南省漢族新髮1型糖尿病患者納入本研究.放射配體法檢測鋅轉運體8自身抗體(ZnT8A),酶聯免疫斑點技術(ELISPOT)檢測GAD65-IFN-γ-T細胞,聚閤酶鏈反應(PCR)直接測序法測定HLA-DQ基因型.將研究對象分為HLA-DQ易感單體型攜帶組和HLA-DQ易感單體型不攜帶組,併以1年為間隔隨訪3年.比較兩組起病初期的臨床特徵、ZnT8A及GAD65-IFN-γ-T細胞檢測情況,隨訪時胰島自身抗體的變化.兩組間計數資料比較採用x2檢驗.結果 52例初診特髮性1型糖尿病患者中5例ZnT8A暘性,暘性率9.6％;16例ZnT8A陰性且接受GAD65-IFN-γ-T檢測的患者中,2例GAD65-IFN-γ-T暘性,暘性率12.5％.與HLA-DQ易感單體型不攜帶組相比,攜帶組起病初期酮癥程度更嚴重(Z=-2.84,P＜0.05),空腹C肽水平更低(x2 =0.38,P＜0.05).起病初期,攜帶組中1例患者GAD65-IFN-γ-T細胞檢測呈暘性反應(1/5),而不攜帶組未檢測到該細胞呈暘性患者.隨訪時,攜帶組中1例患者ZnT8A和IA-2A由陰轉暘(1/18),不攜帶組中未有檢測到抗體轉暘患者.結論 部分特髮性1型糖尿病患者體內存在ZnT8A和GAD65-IFN-γ-T細胞；攜帶HLA-DQ易感單體型的特髮性1型糖尿病患者,較不攜帶者更加具有自身免疫傾嚮.胰島自身免疫是部分初診特髮性1型糖尿病的病因,可能通過HLA-DQ單體型介導.
목적 통과대림상특정、자전운체8자신항체(ZnT8A)、분비간우소γ적곡안산탈최매65반응성T세포(GAD65-IFN-γ-T세포)검측정황적비교,탐토인백세포항원(HLA) DQ단체형대초진특발성1형당뇨병면역병인분형적개치.방법 장2000년3월지2011년12월수치적52례자발동증혹동증산중독기병,곡안산탈최매항체(GADA)、단백락안산린산매항체(IA-2A)급이도소자신항체(IAA)균음성,차의뢰이도소치료적호남성한족신발1형당뇨병환자납입본연구.방사배체법검측자전운체8자신항체(ZnT8A),매련면역반점기술(ELISPOT)검측GAD65-IFN-γ-T세포,취합매련반응(PCR)직접측서법측정HLA-DQ기인형.장연구대상분위HLA-DQ역감단체형휴대조화HLA-DQ역감단체형불휴대조,병이1년위간격수방3년.비교량조기병초기적림상특정、ZnT8A급GAD65-IFN-γ-T세포검측정황,수방시이도자신항체적변화.량조간계수자료비교채용x2검험.결과 52례초진특발성1형당뇨병환자중5례ZnT8A양성,양성솔9.6％;16례ZnT8A음성차접수GAD65-IFN-γ-T검측적환자중,2례GAD65-IFN-γ-T양성,양성솔12.5％.여HLA-DQ역감단체형불휴대조상비,휴대조기병초기동증정도경엄중(Z=-2.84,P＜0.05),공복C태수평경저(x2 =0.38,P＜0.05).기병초기,휴대조중1례환자GAD65-IFN-γ-T세포검측정양성반응(1/5),이불휴대조미검측도해세포정양성환자.수방시,휴대조중1례환자ZnT8A화IA-2A유음전양(1/18),불휴대조중미유검측도항체전양환자.결론 부분특발성1형당뇨병환자체내존재ZnT8A화GAD65-IFN-γ-T세포；휴대HLA-DQ역감단체형적특발성1형당뇨병환자,교불휴대자경가구유자신면역경향.이도자신면역시부분초진특발성1형당뇨병적병인,가능통과HLA-DQ단체형개도.
Objective To investigate the role of human leukocyte antigen (HLA) DQ haplotype for immunoetiologic chassification of idiopathic type 1 diabetes by comparison of clinical features,zinc transporter 8 autoantibodies (ZnT8A),glutamic acid decarboxylase 65 (GAD65)-reactive interferon-γ-secreting T cells (GAD65-IFN-γ-T cells).Methods Fifty-two patients of Han People of Hunan Province origin with newly onset idiopathic type 1 diabetes were enrolled in this study from March 2000 to December 2011.The criteria for enrolment included: new-onset,unprovoked ketosis or ketoacidosis at onset; negative glutamic acid decarboxylase antibody(GADA),protein tyrosinephosphatase antibody (IA-2A) and insulin autoantibody(IAA); permanent insulin deficiency.ZnT8A were detected in all patients with radioligand assay.GAD65-IFN-γ-T cells were tested by enzyme linked immune spot (ELISPOT) in ZnT8A-negative patients.HLA-DQA1 and DQB1 alleles were identified with polymerase chain reaction (PCR) sequencebased genotyping (SBT).According to the situation of HLA-DQ susceptible haplotypes,patients with HLADQ genotyping were categorized into two groups,and were all visited annually for 3 consecutive years.Comparisons were made between the two groups in their clinical characteristics,ZnT8A and GAD65-IFN-γ-T cell status.Compare of qualitative data between two groups was progressed by using chi-square test.Results In this study group,ZnT8A was positive in 5 cases out of 52 (9.6％),and GAD65-IFN-γ-T cells were positive in 2 cases out of 16 patients with ZnT8A negative (12.5％).More severe diabetic ketoacidosis (DKA) (Z =-2.84,P ＜ 0.05) and lower fasting C protein (FCP) levels (x2 =0.38,P ＜ 0.05) at onset were observed in patients with HLA-DQ susceptible haplotypes.During the onset,GAD65-IFN-γ-T cells was positive in 1 patient carrying HLA-DQ susceptible haplotypes and there was none in patients with nonsusceptible HLA-DQ haplotypes.Islet autoantibodies (ZnT8A and IA-2A) turned positive in 1 patient with HLA-DQ susceptible haplotypes(1/18),while none was observed in patients with non-HLA-DQ susceptible haplotypes during the 3-year visit.Conclusions ZnT8A and GAD65-IFN-γ-T cells exist in some patients with idiopathic type 1 diabetes.The patients with idiopathic type 1 diabetes carry HLA-DQ susceptible haplotypes,compared with those without HLA-DQ haplotypes,present a autoimmune tendency.It implies that islet autoimmunity,to some extent,could be an etiology of idiopathic type 1 diabetes,which is probably mediated by HLA-DQ hapalotype.
