Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.
Front Immunol. 2023 Dec 20;14:1268207. doi: 10.3389/fimmu.2023.1268207. eCollection 2023.
Liver manifestations and in particular portal hypertension (PH) contribute significantly to morbidity and mortality of patients with common variable immunodeficiency disorders (CVID). Screening strategies and early detection are limited due to the lack of specific diagnostic tools.
We evaluated clinical, immunological, histological, and imaging parameters in CVID patients with clinical manifestation of portal hypertension (CVID+PH).
Portal hypertension was present in 5.6% of CVID patients and was associated with high clinical burden and increased mortality (18%). Longitudinal data on clinical and immunological parameters in patients before and during clinically manifest portal hypertension revealed a growing splenomegaly and increasing gamma-glutamyl transferase (GGT) and soluble interleukin 2 receptor (SIL-2R) levels with decreasing platelets over time. While ultrasound of the liver failed to detect signs of portal hypertension in most affected patients, transient elastography was elevated in all patients. All CVID+PH patients had reduced naïve CD45RA+CD4+ T-cells (mean of 6,2%). The frequency of severe B-lymphocytopenia (Euroclass B-) was higher in CVID+PH patients. The main histological findings included lymphocytic infiltration, nodular regenerative hyperplasia-like changes (NRH-LC), and porto(-septal) fibrosis.
CVID patients with lower naïve CD45RA+CD4+ T-cells or severely reduced B-cells might be at higher risk for portal hypertension. The combination of biochemical (increasing sIL-2R, GGT, and decreasing platelets) and imaging parameters (increasing splenomegaly) should raise suspicion of the beginning of portal hypertension.
肝脏表现，尤其是门静脉高压（PH），显著增加了普通变异性免疫缺陷病（CVID）患者的发病率和死亡率。由于缺乏特定的诊断工具，因此筛查策略和早期检测受到限制。
我们评估了有门静脉高压临床表现的 CVID 患者（CVID+PH）的临床、免疫、组织学和影像学参数。
门静脉高压存在于 5.6%的 CVID 患者中，与高临床负担和增加的死亡率（18%）相关。在临床明显的门静脉高压之前和期间，对患者的临床和免疫参数的纵向数据显示，随着时间的推移，脾肿大逐渐增加，γ-谷氨酰转移酶（GGT）和可溶性白细胞介素 2 受体（SIL-2R）水平升高，血小板计数降低。虽然大多数受影响的患者的肝脏超声未能检测到门静脉高压的迹象，但所有患者的瞬时弹性成像均升高。所有 CVID+PH 患者均存在幼稚 CD45RA+CD4+T 细胞减少（平均值为 6.2%）。CVID+PH 患者严重 B 淋巴细胞减少症（Euroclass B-）的频率更高。主要组织学发现包括淋巴细胞浸润、结节性再生性增生样改变（NRH-LC）和门脉（隔）纤维化。
幼稚 CD45RA+CD4+T 细胞较低或严重减少 B 细胞的 CVID 患者可能有更高的门静脉高压风险。生化（sIL-2R、GGT 升高和血小板减少）和影像学参数（脾肿大增加）的组合应引起对门静脉高压开始的怀疑。
