Abstract
BackgroundThe 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 objectivesTo identify any HLA-association with SAHC, and to phenotypically characterize this patient group. Methods66 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. ResultsHLA-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. ConclusionsSAHC 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 mechanisms behind and which patients are at risk of developing sarcoidosis associated hy percalcemia (SAHC) have not been addressed
We found that the proportion of patients with HLADRB1*04 increased the more pronounced hypercalcemia
The frequency of human leukocyte antigen (HLA)-DRB1*04 in our control group was comparable to the frequency previously reported in Swedish sarcoidosis patients with non-Lofgren’s syn drome (LS) [3]
Summary
The mechanisms behind and which patients are at risk of developing sarcoidosis associated hy percalcemia (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. 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. Patients with SAHC more often disclosed renal insufficiency, elevated ACE, EPM, and a non-resolving disease than controls. Conclusions: SAHC is associated with a more severe disease phenotype, patients carrying the HLADRB1*04 allele are at higher risk for SAHC. Genetic factors influence the risk of sarcoidosis, and different HLA-DRB1 alleles are associated with the disease and target-organ phenotypes [3]. HLA-DRB1*04 is associated with extrapulmonary manifestations (EPM), ocular sarcoidosis [4,5,6], HLA-DRB1*03 with Lofgren’s syndrome and resolving disease, and HLA-DRB1*14 and HLA-DRB1*15 are associated with a non-resolving disease course [7,8]
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