Gonzalez-Mancera Miguel S, Johnson Britt, Mirsaeidi Mehdi
University of Miami, Miller School of Medicine, Pulmonary and Critical Care Division, USA.
Metabolic Genetics and Immunology, Invitae Corporation, San Francisco, CA, USA.
Respir Med Case Rep. 2020 Jun 12;30:101125. doi: 10.1016/j.rmcr.2020.101125. eCollection 2020.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in cellular proliferation, apoptosis, and differentiation. Mutations in the STAT3 gene have been associated with dysregulation of the immune system giving rise to primary immunodeficiency syndromes (PID). Clinically, patients may present with very broad manifestations, and its diagnosis is usually very challenging. Proper treatment remains unclear, and limited options are available.
We report an adult male patient with long-standing history of immunodeficiency, who was found to have infection. Two-hundred and seven immunogenes were sequenced using next-generation sequencing technology (NGS).
A STAT3 heterozygous missense pathologic variant was identified in the patient located in the transactivation domain (TA) of STAT3, associated with a gain of functionality, leading to recurrent bronchopulmonary infections, and involvement of multiple organ systems.
Severe cases of autoimmunity should prompt for evaluation of PIDs in the setting of genetic mutations. Anti-IL-6 therapy may benefit patients with STAT3 GOF mutations. These patients should also be screened for lymphoproliferative disorders.
信号转导与转录激活因子3（STAT3）是一种参与细胞增殖、凋亡和分化的转录因子。STAT3基因的突变与免疫系统失调有关，可导致原发性免疫缺陷综合征（PID）。临床上，患者可能表现出非常广泛的症状，其诊断通常极具挑战性。合适的治疗方法仍不明确，可用的选择有限。
我们报告了一名有长期免疫缺陷病史的成年男性患者，发现其有感染。使用下一代测序技术（NGS）对207个免疫基因进行了测序。
在患者中鉴定出一个STAT3杂合错义病理变异，位于STAT3的反式激活结构域（TA），与功能获得相关，导致反复的支气管肺部感染和多器官系统受累。
严重的自身免疫病例应促使在基因突变背景下评估PID。抗IL-6治疗可能使STAT3功能获得性突变患者受益。这些患者还应筛查淋巴增殖性疾病。
