PMID- 34526035
OWN - NLM
STAT- MEDLINE
DCOM- 20220128
LR  - 20220128
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 22
IP  - 1
DP  - 2021 Sep 15
TI  - Association between circulating alpha-1 antitrypsin polymers and lung and liver 
      disease.
PG  - 244
LID - 10.1186/s12931-021-01842-5 [doi]
LID - 244
AB  - BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is considered one of the most 
      common genetic diseases and is characterised by the misfolding and polymerisation 
      of the alpha-1 antitrypsin (AAT) protein within hepatocytes. The relevance of 
      circulating polymers (CP) of AAT in the pathogenesis of lung and liver disease is 
      not completely understood. Therefore, the main objective of our study was to 
      determine whether there is an association between the levels of CP of AAT and the 
      severity of lung and liver disease. METHOD: This was a cross-sectional study in 
      patients with different phenotypes of AATD and controls. To quantify CP, a 
      sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT 
      polymers. Sociodemographic data, clinical characteristics, and liver and lung 
      parameters were collected. RESULTS: A cohort of 70 patients was recruited: 32 
      Pi*ZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP 
      were compared with a control group of 47 individuals (35 Pi*MM and 12 Pi*MS). ZZ 
      patients had the highest concentrations of CP (p < 0.001) followed by Z 
      heterozygous. The control group and patients with Pi*SS and Pi*SI had the lowest 
      CP concentrations. Pi*ZZ also had higher levels of liver stiffness measurements 
      (LSM) than the remaining AATD patients. Among patients with one or two Z alleles, 
      two patients with lung and liver impairment showed the highest concentrations of 
      CP (47.5 microg/mL), followed by those with only liver abnormality (n = 6, 
      CP = 34 microg/mL), only lung (n = 18, CP = 26.5 microg/mL) and no abnormalities (n = 23, 
      CP = 14.3 microg/mL). Differences were highly significant (p = 0.004). CONCLUSIONS: 
      Non-augmented Pi*ZZ and Z-patients with impaired lung function and increased 
      liver stiffness presented higher levels of CP than other clinical phenotypes. 
      Therefore, CP may help to identify patients more at risk of developing lung and 
      liver disease and may provide some insight into the mechanisms of disease.
CI  - (c) 2021. The Author(s).
FAU - Nunez, Alexa
AU  - Nunez A
AD  - Pneumology Department, Hospital Universitari Vall d Hebron, Vall d'Hebron 
      Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, P. Vall 
      d'Hebron 119-129, 08035, Barcelona, Spain.
AD  - Universitat Autonoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.
FAU - Belmonte, Irene
AU  - Belmonte I
AD  - Pneumology Department, Hospital Universitari Vall d Hebron, Vall d'Hebron 
      Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, P. Vall 
      d'Hebron 119-129, 08035, Barcelona, Spain.
FAU - Miranda, Elena
AU  - Miranda E
AD  - Department of Biology and Biotechnologies, 'Charles Darwin' and Pasteur Institute 
      - Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy.
FAU - Barrecheguren, Miriam
AU  - Barrecheguren M
AD  - Pneumology Department, Hospital Universitari Vall d Hebron, Vall d'Hebron 
      Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, P. Vall 
      d'Hebron 119-129, 08035, Barcelona, Spain.
FAU - Farago, Georgina
AU  - Farago G
AD  - Pneumology Department, Hospital Universitari Vall d Hebron, Vall d'Hebron 
      Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, P. Vall 
      d'Hebron 119-129, 08035, Barcelona, Spain.
FAU - Loeb, Eduardo
AU  - Loeb E
AD  - Pneumology Department, Teknon Medical Center, Barcelona, Spain.
FAU - Pons, Monica
AU  - Pons M
AD  - Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, 
      Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital 
      Campus, Barcelona, Spain.
FAU - Rodriguez-Frias, Francisco
AU  - Rodriguez-Frias F
AD  - Universitat Autonoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.
AD  - Department of Clinical Biochemistry, Hospital Universitari Vall d'Hebron, Vall 
      d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, 
      (CIBEREHD), Barcelona, Spain.
AD  - Clinical Biochemistry Research Group/Vall d'Hebron Institut de Recerca (VHIR), 
      Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
FAU - Gabriel-Medina, Pablo
AU  - Gabriel-Medina P
AD  - Department of Clinical Biochemistry, Hospital Universitari Vall d'Hebron, Vall 
      d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
FAU - Rodriguez, Esther
AU  - Rodriguez E
AD  - Pneumology Department, Hospital Universitari Vall d Hebron, Vall d'Hebron 
      Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, P. Vall 
      d'Hebron 119-129, 08035, Barcelona, Spain.
FAU - Genesca, Joan
AU  - Genesca J
AD  - Universitat Autonoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.
AD  - Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, 
      Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital 
      Campus, Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, 
      (CIBEREHD), Barcelona, Spain.
FAU - Miravitlles, Marc
AU  - Miravitlles M
AUID- ORCID: 0000-0002-9850-9520
AD  - Pneumology Department, Hospital Universitari Vall d Hebron, Vall d'Hebron 
      Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, P. Vall 
      d'Hebron 119-129, 08035, Barcelona, Spain. marcm@separ.es.
AD  - Universitat Autonoma de Barcelona, Bellaterra, 08193, Barcelona, Spain. 
      marcm@separ.es.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES), 
      Barcelona, Spain. marcm@separ.es.
FAU - Esquinas, Cristina
AU  - Esquinas C
AD  - Pneumology Department, Hospital Universitari Vall d Hebron, Vall d'Hebron 
      Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, P. Vall 
      d'Hebron 119-129, 08035, Barcelona, Spain.
AD  - Universitat Autonoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.
LA  - eng
PT  - Journal Article
DEP - 20210915
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (Biomarkers)
RN  - 0 (Polymers)
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
EIN - Respir Res. 2021 Nov 1;22(1):283. PMID: 34719403
MH  - Adult
MH  - Aged
MH  - Biomarkers/blood
MH  - Cross-Sectional Studies
MH  - Female
MH  - Humans
MH  - Liver Diseases/*blood/diagnosis/epidemiology
MH  - Lung Diseases/*blood/diagnosis/epidemiology
MH  - Male
MH  - Middle Aged
MH  - Polymers/*metabolism
MH  - alpha 1-Antitrypsin/*blood
MH  - alpha 1-Antitrypsin Deficiency/*blood/diagnosis/epidemiology
PMC - PMC8442448
OTO - NOTNLM
OT  - Alpha-1 antitrypsin deficiency
OT  - Circulating polymers
OT  - Emphysema
OT  - Liver disease
COIS- Cristina Esquinas has received speaker fees from CSL Behring. Marc Miravitlles 
      has received speaker or consulting fees from AstraZeneca, Bial, Boehringer 
      Ingelheim, Chiesi, Cipla, CSL Behring, Laboratorios Esteve, Gebro Pharma, Kamada, 
      GlaxoSmithKline, Grifols, Johson & Johnson, Menarini, Mereo Biopharma, Novartis, 
      pH Pharma, Palobiofarma SL, Rovi, TEVA, Spin Therapeutics, Verona Pharma and 
      Zambon, and research grants from Grifols. Miriam Barrecheguren has received 
      speaker fees from Grifols, Menarini, CSL Behring, GSK and consulting fees from 
      GSK, Novartis, Boehringer Ingelheim and Gebro Pharma. Esther Rodriguez has 
      received speaker fees from CSL Behring, TEVA and GlaxoSmithKline. The remaining 
      authors report no conflicts of interest.
EDAT- 2021/09/17 06:00
MHDA- 2022/01/29 06:00
PMCR- 2021/09/15
CRDT- 2021/09/16 05:45
PHST- 2021/07/02 00:00 [received]
PHST- 2021/09/08 00:00 [accepted]
PHST- 2021/09/16 05:45 [entrez]
PHST- 2021/09/17 06:00 [pubmed]
PHST- 2022/01/29 06:00 [medline]
PHST- 2021/09/15 00:00 [pmc-release]
AID - 10.1186/s12931-021-01842-5 [pii]
AID - 1842 [pii]
AID - 10.1186/s12931-021-01842-5 [doi]
PST - epublish
SO  - Respir Res. 2021 Sep 15;22(1):244. doi: 10.1186/s12931-021-01842-5.