Rossides Marios, Megadimou Vasiliki, Smed-Sörensen Anna, Eklund Anders, Kullberg Susanna, Darlington Pernilla
Department of Respiratory Medicine, Theme Inflammation and Ageing, Karolinska University Hospital, Stockholm, Sweden; Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Internal Medicine, Södersjukhuset, Stockholm, Sweden.
Respir Med Res. 2024 Nov;86:101142. doi: 10.1016/j.resmer.2024.101142. Epub 2024 Sep 26.
Genetics influence the clinical picture in sarcoidosis, a granulomatous heterogeneous disease often accompanied by elevated serum angiotensin converting enzyme (s-ACE). We aimed to investigate if certain HLA-DRB1 alleles correlate with the levels of s-ACE, known as a marker of the granuloma burden.
Medical journals of patients with sarcoidosis from a Swedish clinical registry were retrospectively examined to extract the highest recorded s-ACE value and analysed in relation to patient characteristics including phenotype [Löfgren syndrome (LS)/ non-LS], chest X-ray staging according to Scadding, treatment with immunosuppressants, presence of extrapulmonary manifestations (EPM), HLA-DRB1 alleles and prognosis (resolving vs. non-resolving disease within 2 years). Data were analysed with Fisher's exact test and Bonferroni correction was applied for HLA analyses.
Of 1204 patients included, 40% had s-ACE levels above reference value. In comparison with patients with normal s-ACE, those with elevated levels were more often classified into non-LS (78% vs 59%, p < 0.001), and Scadding stage II (50% vs 38%, p < 0.001) but less often Scadding stage I (33% vs 46%, p < 0.001) and had more often EPM (45% vs 23%, p < 0.001). The patients with HLA-DRB1×04 had more often elevated s-ACE (p < 0.01) while those with HLA-DRB1×03 commonly had normal levels (p < 0.001).
In this retrospective study, HLA alleles associated with s-ACE levels in sarcoidosis patients, which in turn correlated with occurrence of EPM. These findings shed some new light on possible mechanisms behind differences in s-ACE levels.
遗传学影响结节病的临床表现，结节病是一种肉芽肿性异质性疾病，常伴有血清血管紧张素转换酶（s-ACE）升高。我们旨在研究某些HLA-DRB1等位基因是否与s-ACE水平相关，s-ACE是肉芽肿负荷的一个标志物。
回顾性研究瑞典临床登记处结节病患者的医学记录，提取记录的最高s-ACE值，并分析其与患者特征的关系，包括表型[ Löfgren综合征（LS）/非LS]、根据Scadding标准的胸部X线分期、免疫抑制剂治疗、肺外表现（EPM）的存在、HLA-DRB1等位基因以及预后（2年内病情缓解与未缓解）。数据采用Fisher精确检验进行分析，HLA分析应用Bonferroni校正。
纳入的1204例患者中，40%的患者s-ACE水平高于参考值。与s-ACE正常的患者相比，s-ACE水平升高的患者更常被归类为非LS（78%对59%，p<0.001）和Scadding II期（50%对38%，p<0.001），但较少为Scadding I期（33%对46%，p<0.001），且更常伴有EPM（45%对23%，p<0.001）。携带HLA-DRB1×04的患者s-ACE水平升高更为常见（p<0.01），而携带HLA-DRB1×03的患者s-ACE水平通常正常（p<0.001）。
在这项回顾性研究中，HLA等位基因与结节病患者的s-ACE水平相关，而s-ACE水平又与EPM的发生相关。这些发现为s-ACE水平差异背后的可能机制提供了一些新的线索。
