Anti-perilipin-1 autoantibodies in autoimmune Addison’s disease and related endocrine disorders

Immune-mediated lipodystrophy syndromes are rare autoimmune disorders characterized by complete or partial destruction of adipocytes in the body. Recently, autoantibodies against perilipin-1 (PLIN1-autoAbs) have been linked to lipodystrophy. Since various perilipins are expressed in the adrenal cortex and ovaries, we asked whether PLIN1-autoAbs were present in patients with adrenal dysfunction and other autoimmune endocrinopathies. Using a sensitive radiobinding immune assay we analyzed anti-PLIN1-autoAbs in 521 patients with endocrinopathies including Sjögren’s syndrome. We identified 22 (4.2%) PLIN1-autoAbs positive patients, of whom 15% had autoimmune polyendocrine syndrome type 1 (4/27), 4% autoimmune Addison’s disease and/or autoimmune polyendocrine syndrome type 2 (11/274), 8% type 1 diabetes patients (4/53), and 2% Sjögren’s syndrome patients (1/50). However, none of them had known lipodystrophy. In conclusion, PLIN1-autoAbs are found in subgroups of autoimmune endocrinopathies and indicate autoimmunity against adipose tissue, but their pathogenic role if any, remains to be defined. Investigating their role in disease progression and their potential as therapeutic targets could pave the way for novel interventions in autoimmune endocrine diseases.

免疫介导的脂肪营养不良综合征（Immune-mediated lipodystrophy syndromes）是一类罕见的自身免疫性疾病，以体内脂肪细胞完全或部分破坏为特征。近期研究发现，针对周脂素-1（perilipin-1）的自身抗体（PLIN1-autoAbs）与脂肪营养不良存在关联。由于多种周脂素在肾上腺皮质与卵巢中均有表达，本研究探讨了PLIN1-autoAbs是否存在于肾上腺功能不全患者及其他自身免疫性内分泌病患者体内。我们采用高灵敏度放射结合免疫分析法，对包括干燥综合征（Sjögren’s syndrome）在内的521名内分泌病患者体内的抗PLIN1自身抗体进行了检测分析。共检出22例PLIN1-autoAbs阳性患者，占比4.2%；其中15%的患者罹患1型自身免疫性多内分泌腺综合征（autoimmune polyendocrine syndrome type 1，4/27）、4%的患者罹患自身免疫性艾迪生病（autoimmune Addison’s disease）及/或2型自身免疫性多内分泌腺综合征（11/274）、8%为1型糖尿病患者（4/53），以及2%为干燥综合征患者（1/50）。但上述患者均未确诊脂肪营养不良。综上，PLIN1-autoAbs可在部分自身免疫性内分泌病亚组中检出，提示存在针对脂肪组织的自身免疫反应，但其致病作用（若存在）仍有待明确。探究此类自身抗体在疾病进展中的作用及作为治疗靶点的潜力，可为自身免疫性内分泌疾病的新型干预手段开辟新路径。