HLA-DRB1 alleles associate with hypercalcemia in sarcoidosis. (October 2021)

• Record Type: Journal Article
• Authors: Werner, Joanna; Rivera, Natalia; Grunewald, Johan; Eklund, Anders; Iseda, Tomoko; Darlington, Pernilla; Kullberg, Susanna
• Is Part Of: Respiratory medicine. Volume 187(2021)
• Publication Date: 2021-10
• Subjects: Sarcoidosis -- Hypercalcemia -- HLA-DRB1 alleles; Chest -- Diseases -- Periodicals; Chest -- Diseases -- Great Britain -- Periodicals; Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases -- Periodicals; Appareil respiratoire -- Maladies -- Périodiques; Thorax -- Maladies -- Périodiques; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Electronic journals; 616.2
• DOI: 10.1016/j.rmed.2021.106537
• Languages: English
• ISSNs: 0954-6111

Abstract

Abstract: 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-Ca 2+ >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-Ca 2+ >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. Highlights: The HLA - DRB1 *04 allele is associated to hypercalcemia in sarcoidosis. Elevated ACE, EPM and renal insufficiency is more common in patients with SAHC. Sarcoidosis associated hypercalcemia is associated to a non-resolving disease.