Background

The mechanisms behind and which patients are at risk of developing sarcoidosis associated hypercalcemia (SAHC) have not been addressed. Different human leukocyte antigen (HLA) alleles associate with disease phenotypes in sarcoidosis. Insights into associations between HLA alleles, clinical phenotype and calcium levels may provide clues to mechanisms behind SAHC and help monitoring patients at risk for SAHC.

Aims and objectives

To identify any HLA-association with SAHC, and to phenotypically characterize this patient group.

Methods

66 patients with SAHC (s-Ca²⁺>1.33 mmol/L) and 150 normocalcemic patients as controls were identified in a cohort of sarcoidosis patients. Data on HLA-DRB1 alleles, sex, angiotensin-converting enzyme (ACE), creatinine, extrapulmonary manifestations (EPM), age at sarcoidosis diagnosis, and how long after diagnosis SAHC emerged, were retrieved.

Results

HLA-DRB1*04 was more common in patients with SAHC and the proportion of patients with HLA-DRB1*04 increased the more pronounced hypercalcemia. In patients with s-Ca²⁺>1.4 mmol/L, 20 out of 30 carried the HLA-DRB1*04 allele (67%, p < 0.01). Patients with SAHC more often disclosed renal insufficiency, elevated ACE, EPM, and a non-resolving disease than controls. The mean duration between sarcoidosis diagnosis and detection of SAHC was 1.39 years.

Conclusions

SAHC is associated with a more severe disease phenotype, particularly patients carrying the HLA-DRB1*04 allele are at higher risk for SAHC. HLA-assessment in the clinic can be a way to identify these patients. The results provide a basis for future studies on the connection between HLA-DRB1*04 and SAHC mechanisms.

中文翻译：

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HLA-DRB1 等位基因与结节病中的高钙血症相关

背景

尚未解决背后的机制以及哪些患者有发生结节病相关高钙血症 (SAHC) 的风险。不同的人类白细胞抗原 (HLA) 等位基因与结节病的疾病表型相关。深入了解 HLA 等位基因、临床表型和钙水平之间的关联可能为 SAHC 背后的机制提供线索，并有助于监测有 SAHC 风险的患者。

目的和目标

确定与 SAHC 的任何 HLA 关联，并确定该患者组的表型特征。

方法

在结节病患者队列中确定了66 名 SAHC (s-Ca ²⁺ >1.33 mmol/L) 患者和 150 名正常血钙患者作为对照。检索了有关HLA-DRB1等位基因、性别、血管紧张素转换酶 (ACE)、肌酐、肺外表现 (EPM)、结节病诊断时的年龄以及诊断后多久出现 SAHC 的数据。

结果

HLA-DRB1*04在SAHC患者中更常见，HLA-DRB1*04患者比例增加的高钙血症更明显。^{在 s-Ca 2+} >1.4 mmol/L的患者中，30 人中有 20 人携带HLA-DRB1*04等位基因（67%，p < 0.01）。与对照组相比，SAHC 患者更常表现出肾功能不全、ACE、EPM 升高和无法解决的疾病。从结节病诊断到 SAHC 检测的平均时间为 1.39 年。

结论

SAHC 与更严重的疾病表型相关，特别是携带HLA-DRB1*04等位基因的患者发生 SAHC 的风险更高。临床中的 HLA 评估可以成为识别这些患者的一种方式。该结果为未来研究HLA-DRB1*04与SAHC机制之间的联系提供了基础。