Philip Rémi, Elhani Inès, Gallou Sophie, Boysson Hubert De, Martin Silva Nicolas, Georgin-Lavialle Sophie, Deshayes Samuel, Aouba Achille
Department of Clinical Immunology and Internal Medicine, CHU of Caen Normandie, 14000 Caen, France; Normandie Univ, UNICAEN, CHU de Caen Normandie, 14000 Caen, France.
AP-HP, Tenon Hospital, Department of Internal Medicine, Paris, France; Sorbonne Université, Centre de Recherche Saint-Antoine (CRSA) INSERM UMRS-938, USA; National French Reference Centre for Auto-inflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA), France.
Autoimmun Rev. 2025 Jan 31;24(2):103722. doi: 10.1016/j.autrev.2024.103722. Epub 2024 Dec 11.
Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathophysiology remains incompletely understood, involving genetic and epigenetic factors. However, an increasing small subset of patients present with monogenic lupus, providing insight into the pathogenesis of the disease. This systematic review focuses on SLE associated with A20 haploinsufficiency (HA20), a monogenic disorder associated with tumor necrosis factor alpha-induced protein 3 gene (TNFAIP3) variants. Besides the mainly auto-inflammatory phenotypic expression of HA20 mimicking Behçet's disease spectrum, some of its clinical and biological manifestations are part of the spectrum of autoimmune diseases, including glomerulonephritis as well as the frequent presence of antinuclear antibodies, sometimes with anti-DNA specificity. Among all the 191 HA20 patients reported in the literature, we identified 16 patients (8.4 %) with a compatible diagnosis of SLE. When estimable, the SLICC 2012 and EULAR/ACR 2019 classification criteria were positive for 92.9 % of them. A majority had multi-system involvement, mainly cutaneous (81.3 %), musculoskeletal (56.3 %), and/or renal (56.3 %) manifestations. They also seemed to exhibit differences compared to other SLE patients: higher prevalence of fever, chronic cutaneous lupus erythematosus, oral and genital ulcers, neuropsychiatric manifestations, autoimmune cytopenia, and elevated biologic inflammatory markers. This review highlights the necessity of considering TNFAIP3 variants in SLE patients with early-onset disease, familial history, and/or specific clinical manifestations suggestive of autoinflammatory diseases. Recognizing HA20-SLE patients may improve our understanding of SLE pathogenesis and lead to better therapeutic strategies for these patients.
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其病理生理学仍未完全明确，涉及遗传和表观遗传因素。然而，越来越多的一小部分患者表现为单基因狼疮，这为了解该疾病的发病机制提供了线索。本系统综述聚焦于与A20单倍体不足（HA20）相关的SLE，HA20是一种与肿瘤坏死因子α诱导蛋白3基因（TNFAIP3）变异相关的单基因疾病。除了HA20主要的模仿白塞病谱系的自身炎症表型表达外，其一些临床和生物学表现也是自身免疫性疾病谱系的一部分，包括肾小球肾炎以及抗核抗体的频繁出现，有时具有抗DNA特异性。在文献报道的所有191例HA20患者中，我们确定了16例（8.4%）符合SLE诊断。在可评估时，SLICC 2012和EULAR/ACR 2019分类标准对其中92.9%的患者呈阳性。大多数患者有多系统受累，主要表现为皮肤（81.3%）、肌肉骨骼（56.3%）和/或肾脏（56.3%）表现。与其他SLE患者相比，他们似乎也存在差异：发热、慢性皮肤型红斑狼疮、口腔和生殖器溃疡、神经精神表现、自身免疫性血细胞减少症以及生物炎症标志物升高的患病率更高。本综述强调了在患有早发性疾病、家族史和/或提示自身炎症性疾病的特定临床表现的SLE患者中考虑TNFAIP3变异的必要性。识别HA20-SLE患者可能会增进我们对SLE发病机制的理解，并为这些患者带来更好的治疗策略。
