目的:高IgG水平被认为是自身免疫性肝炎(AIH)的标志。尽管有临床疾病活动的证据,但AIH患者亚组的IgG在正常范围内。尚未探索该生物标志物的临床意义。
方法:在一项欧洲多中心研究中,我们比较了生化,从诊断时AIH和IgG值正常的患者到年龄和性别匹配的典型AIH表现IgG升高的对照组的临床和组织学特征.诊断时评估数据,治疗12个月后和最后一次随访。
结果:在1,318例AIH患者中,130(10%)在呈递时具有正常的IgG。诊断时的组织学和生化参数,以及治疗反应,组间无差异。与典型AIH组相比,正常IgG组的稳定缓解治疗更常见(24vs.8%;p=0.0012)。对照组患者不仅IgG水平较高(29.5±5.8vs.12.5±3.2g/L;p<0.0001),但也有更高的IgG/IgA比率(9.3±6.9与5.4±2.4;p<0.0001)在诊断时。IgG/IgA比率仅在典型AIH患者中下降,并且在12个月后组间不再有差异(6.3±4.3vs.5.5±2.2;p=0.1),表明典型AIH中IgG的选择性增加及其通过免疫抑制的抑制。自身抗体滴度在典型的AIH组中较高,但不控制IgG水平。
结论:与具有典型生化特征的AIH相比,诊断时IgG水平正常的患者(i)表现出相似的生化指标,血清学和组织学特征以及可比的治疗反应,(ii)似乎缺乏在典型的活动性AIH疾病中观察到的血清IgG水平的选择性升高,(iii)可能代表成功停药的机会较高的亚组。
背景:自身免疫性肝炎(AIH)的特征是免疫球蛋白G(IgG)升高,因此,这被用作主要的诊断标准,以及监测治疗反应。然而,正常IgG并不排除AIH的诊断。因此,我们在此评估了一项大型多中心研究中AIH和IgG正常患者的特征.这项研究表明,所有AIH患者中约有10%的IgG正常;这些患者与其他AIH患者在生化标志物方面没有区别,肝脏组织学,疾病严重程度和治疗反应,但可能代表停药后缓解机会较高的亚组。
OBJECTIVE: High IgG levels are considered a hallmark of autoimmune hepatitis (AIH). A subgroup of patients with AIH has IgG within the normal range despite evidence of clinical disease activity. The clinical significance of this biomarker has not been explored.
METHODS: In a European multicentre study we compared biochemical, clinical and histological features from patients with AIH and normal IgG-values at diagnosis to an age- and sex-matched control group of patients with typical AIH presenting with elevated IgG. Data were assessed at diagnosis, after 12 months of therapy and at last follow-up.
RESULTS: Out of 1,318 patients with AIH, 130 (10%) had normal IgG at presentation. Histological and biochemical parameters at diagnosis, as well as treatment response, showed no difference between groups. Stable remission off treatment was achieved more commonly in the normal IgG group than in the typical AIH group (24 vs. 8%; p = 0.0012). Patients of the control group not only had higher IgG levels (29.5 ± 5.8 vs. 12.5 ± 3.2 g/L; p <0.0001), but also a higher IgG/IgA ratio (9.3 ± 6.9 vs. 5.4 ± 2.4; p <0.0001) at diagnosis. The IgG/IgA ratio only declined in patients with typical AIH and was no longer different between groups after 12 months (6.3 ± 4.3 vs. 5.5 ± 2.2; p = 0.1), indicating a selective increase of IgG in typical AIH and its suppression by immunosuppression. Autoantibody titres were higher in the typical AIH group, but not when controlled for IgG levels.
CONCLUSIONS: Compared to AIH with typical biochemical features, patients with normal IgG levels at diagnosis (i) show similar biochemical, serological and histological features and comparable treatment response, (ii) appear to lack the selective elevation of serum IgG levels observed in typical active AIH disease, (iii) may represent a subgroup with a higher chance of successful drug withdrawal.
BACKGROUND: A characteristic feature of autoimmune hepatitis (AIH) is an elevation of immunoglobulin G (IgG), which is therefore used as a major diagnostic criterion, as well as to monitor treatment response. Nevertheless, normal IgG does not preclude the diagnosis of AIH. Therefore, we herein assessed the features of patients with AIH and normal IgG in a large multicentre study. This study demonstrates that about 10% of all patients with AIH have normal IgG; these patients are indistinguishable from other patients with AIH with respect to biochemical markers, liver histology, disease severity and treatment response, but might represent a subgroup with a higher chance of remission after drug withdrawal.