应用HLA-DQ基因型对自身抗体阴性1型糖尿病的再分型

Subclassificatin of seronegative type 1 diabetic subjects with HLA-DQ genotypes

目的 探讨自身抗体阴性 1型糖尿病患者疾病表型与HLA DQ基因型之间的关系 ,以及HLA DQ基因型可否对自身抗体阴性的 1型糖尿病再分型。方法 61例自发酮症起病的糖尿病患者纳入本研究 ,检测其谷氨酸脱羧酶抗体、酪氨酸磷酸酶抗体及甲状腺自身抗体 ,并进行HLA DQ基因分型。根据 1型糖尿病HLA DQ易感基因型的有无 ,将抗体阴性组进一步分为有HLA DQ易感基因型组 (A组 )和无HLA DQ易感基因型组 (B组 )。比较抗体阳性组与抗体阴性组、A组与B组在起病状况、临床特征等方面的差异。结果 61例患者中 ,3 2例 (52 5% )存在一种或多种血清自身抗体。 2 9例自身抗体阴性的患者中 ,18例携带 1～ 4个 1型糖尿病HLA DQ易感基因型 (即为A组 ) ,另 11例不携带 1型糖尿病HLA DQ易感基因型 (即为B组 )。与抗体阴性组相比 ,抗体阳性组存在发病年龄较年轻、体重指数 (BMI)较低、发病时酮症酸中毒程度较严重、C肽水平较低等特点。与B组相比 ,A组患者具有在发病时酮症酸中毒程度较严重、C肽水平较低、BMI较低等特征。结论 自身抗体阴性的 1型糖尿病患者中 ,携带HLA DQ易感基因型者显示出更接近 1A型糖尿病的临床特征 ,需进一步研究此类患者中可能存在的某种未能检测出的自身免疫反应。HLA DQ基因型可对自身抗体阴性的 1型?

ObjectiveTo reveal the relationship between disease phenotype and HLA-DQ genotype in autoantibody-negative type 1 diabetics and to explore whether HLA-DQ genotypes can reclassify seronegative type 1 diabetic patients. MethodsSixty-one diabetics with unprovoked ketosis or ketoacidosis at presentation were tested for glutamic acid decarboxylase antibody (GAD-Ab)?tyrosine phosphata se antibody (IA2-Ab)?thyroglobulin antibody(TGA)?thyroid peroxidase antibody (TPO-Ab) and HLA-DQ genotype. GAD-Ab and IA2-Ab were measured with radioligand assay. TGA and TPO-Ab were evaluated using RIA. Sequence-based genotyping (SBT) was used to determine the alleles of HLA-DQA1 and DQB1. Autoantibody negative patients were subdivided into group A (with type 1 diabetes susceptible alleles) and group B (without type 1 diabetes susceptible alleles).Clinical characteristics, including age, sex, mode of presentation, body mass index (BMI), islet beta-cell function and current treatment were compared between the autoantibody-positive and autoantibody-negative patients and between group A and B. ResultsAmong the 61 patients, 29 (47.5%) were negative for all the antibodies tested, while 31 (50.8%) were positive for one or more antibodies tested. 5 (8.2%) were positive for all those 4 antibodies. As for genetic analysis, 18 of the 29 seronegative patients carried 1-4 HLA-DQ risk alleles, while the other 11 did not carry any type 1 diabetes susceptible alleles tested. As compared with the autoantibody-negative patients, younger age at onset, less obesity, severer degree of diabetic ketoacidosis (DKA) and lower C peptide were found in the autoantibody-positive ones . As compared with group B, less obesity [BMI:(22.4±4.4) kg/m 2 vs (25.8±3.7) kg/m 2, P=0.03], severer degree of DKA[CO 2CP: (16.3±7.1) [LM]mmol/L vs (19.2±2.0) mmol/L, P=0.01; pH: 7.26±0.20 vs 7.34±0.06, P=0.03], and lower C peptide , and lower C peptide [fasting C peptide: (254.6±189.4) pmol/L vs (458.7±274.1) pmol/L, P=0.06] were observed in group A. During follow-up, 73%(8/11) patients in group B discontinued insulin therapy and maintained acceptable glycemic control by either diet or oral hypoglycemic agents (OHA), while only 28% (5/18) of the patients in group A discontinued and maintained control with OHA (28% vs 73%, P<0.01). Among those who kept on using insulin, group A patients required higher insulin dosage than those of group B [(0.43±0.16) U·kg -1 ·d -1 vs (0.24±0.18) U·kg -1 ·d -1 , P=0.07]. ConclusionsAutoantibody-negative diabetics, if with susceptible HLA-DQ genotypes, presented more type 1A-like features, implying possible existence of as yet unidentified immunologic abnormalities in these patients. HLA-DQ risk genotypes may reclassify seronegative type 1 diabetics. Those who are autoantibody negative but carry susceptible HLA-DQ genotypes, should not be diagnosed as type 1B diabetes.