Herttoniemi Hospital, Health Centre, City of Helsinki, PO Box 6300, 00099 Helsinki, Finland.
World J Gastroenterol. 2010 Jan 21;16(3):354-8. doi: 10.3748/wjg.v16.i3.354.
To explore whether predisposition to autoimmune gastritis (AIG) is found in human leukocyte antigen (HLA), cytokine or killer cell immunoglobulin-like receptor (KIR) gene variations.
Twelve Finnish patients with autoimmune-type severe atrophy of the gastric corpus were included. The patients' serum was analyzed for pepsinogen I and Helicobacter pylori (H. pylori) antibodies. DNA was separated and the patients were genotyped for HLA-A, B, Cw, DRB1 and DQB1 antigens, and studied for single nucleotide polymorphisms for the following cytokines: interleukin (IL)-1 gene cluster, IL-2, IL-4, IL-6, IL-10, IL-12, interferon gamma, transforming growth factor beta, and tumor necrosis factor alpha. Variation in KIR genes was also explored. The results were compared with prevalence of the polymorphisms in Finnish or European populations.
All patients had pepsinogen I levels below normal (mean: 11 microg/L, range: < 5 to 25 microg/L). Three patients had elevated H. pylori IgG antibodies, while H. pylori serology was negative in the rest of the patients. AIG patients carried significantly more often HLA-DRB104 (58%) and DQB103 (83%) than the general Finnish population did (28% and 51%, respectively; P = 0.045 and 0.034 by the Fisher's exact test). No patient was positive for HLA-B8-DRB1*03, a well-established autoimmune marker. Neither cytokine polymorphisms nor KIR gene variation showed association with AIG.
As explored with modern DNA-based methods, HLA-DRB104 and DQB103 alleles, but not HLA-B8-DRB1*03, may predispose to AIG.
探讨人类白细胞抗原(HLA)、细胞因子或杀伤细胞免疫球蛋白样受体(KIR)基因变异是否存在自身免疫性胃炎(AIG)易感性。
纳入 12 例芬兰自身免疫性胃体萎缩症患者。分析患者血清胃蛋白酶原 I 和幽门螺杆菌(H. pylori)抗体。分离 DNA,对 HLA-A、B、Cw、DRB1 和 DQB1 抗原进行基因分型,并对以下细胞因子的单核苷酸多态性进行研究:白细胞介素(IL)-1 基因簇、IL-2、IL-4、IL-6、IL-10、IL-12、干扰素γ、转化生长因子β和肿瘤坏死因子α。还探讨了 KIR 基因的变异。将结果与芬兰或欧洲人群的多态性发生率进行比较。
所有患者的胃蛋白酶原 I 水平均低于正常(平均:11μg/L,范围:<5 至 25μg/L)。3 例患者 H. pylori IgG 抗体升高,而其余患者 H. pylori 血清学检测为阴性。AIG 患者携带 HLA-DRB104(58%)和 DQB103(83%)的频率明显高于芬兰普通人群(分别为 28%和 51%;Fisher 确切检验 P=0.045 和 0.034)。没有患者 HLA-B8-DRB1*03 阳性,这是一种公认的自身免疫标志物。细胞因子多态性或 KIR 基因变异均与 AIG 无关。
采用现代基于 DNA 的方法发现,HLA-DRB104 和 DQB103 等位基因,但不是 HLA-B8-DRB1*03,可能使 AIG 易感性增加。