Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978)

患有共济失调-毛细血管扩张症 (AT) 的患者患有进行性小脑共济失调、免疫缺陷、呼吸衰竭和癌症易感性。从临床角度来看，IgA缺乏的AT患者表现出更多的症状，可能预后更差。在这项研究中，我们分析了 2012 年至 2018 年间在法兰克福歌德大学就读的 659 名 AT 患者与 IgA 缺乏有关的死亡率和免疫数据，这些数据来自欧洲免疫缺陷协会 (ESID) 登记处和 66 名经典 AT 患者。我们研究了法兰克福队列的外周 B 细胞和 T 细胞亚群和 T 细胞库以及 ESID 登记中所有 AT 患者的存活率。AT 患者的淋巴细胞表型发生显着变化。所有亚群（CD3、CD4、CD8、CD19、CD4/CD45RA、和 CD8/CD45RA) 与标准值相比显着减少。IgA缺乏症患者（n  = 35) 的淋巴细胞计数明显低于无 IgA 缺乏的 AT 患者 ( n = 31) 由于幼稚 CD4 T 细胞、中央记忆 CD4 细胞和调节性 T 细胞的进一步减少。尽管与对照组相比，两个患者组的 TCR-ß 库都受到影响，但在有和没有 IgA 缺乏的患者之间没有检测到差异。IgA 缺乏症患者的总生存期显着降低。我们的数据首次显示，与没有 IgA 缺乏症的 AT 患者相比，IgA 缺乏症患者的淋巴细胞计数和亚群显着降低，这伴随着生存率降低。IgA 是一种简单的替代标志物，表明经典 AT 患者的预后最差。两项非介入性临床试验均在 2012 年（共济失调毛细血管扩张症感染易感性；NCT02345135）和 2017 年（感染易感性，共济失调毛细血管扩张症患者的肿瘤风险和肝脏疾病；NCT03357978)