PMID- 34325227
OWN - NLM
STAT- MEDLINE
DCOM- 20220208
LR  - 20220208
IS  - 1532-3064 (Electronic)
IS  - 0954-6111 (Linking)
VI  - 187
DP  - 2021 Oct
TI  - HLA-DRB1 alleles associate with hypercalcemia in sarcoidosis.
PG  - 106537
LID - S0954-6111(21)00243-2 [pii]
LID - 10.1016/j.rmed.2021.106537 [doi]
AB  - 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.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Werner, Joanna
AU  - Werner J
AD  - Department of Respiratory Medicine, Theme Inflammation and Infection, Karolinska 
      University Hospital, 171 76, Stockholm, Sweden; Department of Medicine Solna, 
      Respiratory Medicine Division, Karolinska Institutet, 171 77, Stockholm, Sweden. 
      Electronic address: joanna.werner@ki.se.
FAU - Rivera, Natalia
AU  - Rivera N
AD  - Department of Medicine Solna, Respiratory Medicine Division, Karolinska 
      Institutet, 171 77, Stockholm, Sweden. Electronic address: natalia.rivera@ki.se.
FAU - Grunewald, Johan
AU  - Grunewald J
AD  - Department of Respiratory Medicine, Theme Inflammation and Infection, Karolinska 
      University Hospital, 171 76, Stockholm, Sweden; Department of Medicine Solna, 
      Respiratory Medicine Division, Karolinska Institutet, 171 77, Stockholm, Sweden. 
      Electronic address: johan.grunewald@ki.se.
FAU - Eklund, Anders
AU  - Eklund A
AD  - Department of Medicine Solna, Respiratory Medicine Division, Karolinska 
      Institutet, 171 77, Stockholm, Sweden. Electronic address: anders.eklund@sll.se.
FAU - Iseda, Tomoko
AU  - Iseda T
AD  - Department of Medicine Solna, Respiratory Medicine Division, Karolinska 
      Institutet, 171 77, Stockholm, Sweden. Electronic address: tomoko.iseda@capio.se.
FAU - Darlington, Pernilla
AU  - Darlington P
AD  - Department of Internal Medicine, Sjukhusbacken 10, Sodersjukhuset, 118 83, 
      Stockholm, Sweden; Department of Clinical Science and Education, Sodersjukhuset 
      and Karolinska Institutet, 171 77, Stockholm, Sweden. Electronic address: 
      pernilla.darlington@sll.se.
FAU - Kullberg, Susanna
AU  - Kullberg S
AD  - Department of Respiratory Medicine, Theme Inflammation and Infection, Karolinska 
      University Hospital, 171 76, Stockholm, Sweden; Department of Medicine Solna, 
      Respiratory Medicine Division, Karolinska Institutet, 171 77, Stockholm, Sweden. 
      Electronic address: susanna.kullberg@sll.se.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210722
PL  - England
TA  - Respir Med
JT  - Respiratory medicine
JID - 8908438
RN  - 0 (HLA-DRB1 Chains)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - *Alleles
MH  - Calcium/blood
MH  - Cohort Studies
MH  - Female
MH  - *Genetic Association Studies
MH  - *Genetic Predisposition to Disease
MH  - HLA-DRB1 Chains/*genetics
MH  - Humans
MH  - Hypercalcemia/etiology/*genetics
MH  - Male
MH  - Patient Acuity
MH  - Phenotype
MH  - Risk
MH  - Sarcoidosis/etiology/*genetics
MH  - Time Factors
OTO - NOTNLM
OT  - HLA-DRB1 alleles
OT  - Hypercalcemia
OT  - Sarcoidosis
EDAT- 2021/07/30 06:00
MHDA- 2022/02/09 06:00
CRDT- 2021/07/29 20:21
PHST- 2021/01/25 00:00 [received]
PHST- 2021/06/19 00:00 [revised]
PHST- 2021/07/03 00:00 [accepted]
PHST- 2021/07/30 06:00 [pubmed]
PHST- 2022/02/09 06:00 [medline]
PHST- 2021/07/29 20:21 [entrez]
AID - S0954-6111(21)00243-2 [pii]
AID - 10.1016/j.rmed.2021.106537 [doi]
PST - ppublish
SO  - Respir Med. 2021 Oct;187:106537. doi: 10.1016/j.rmed.2021.106537. Epub 2021 Jul 
      22.