eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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4/2023
vol. 48
 
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abstract:
Clinical immunology

Association of human leukocyte antigen class II alleles with epithelial cell apoptosis and extracellular matrix production in acute COVID-19

Ieva Vanaga
1, 2
,
Oksana Kolesova
1
,
Aleksandrs Kolesovs
1, 3
,
Gunta Sture
1, 2
,
Elvira Hagina
1
,
Jelena Storozenko
1
,
Liene Nikitina-Zake
1
,
Ludmila Viksna
1, 2

  1. Riga Stradins University, Riga, Latvia
  2. Riga East Clinical University Hospital, Riga, Latvia
  3. University of Latvia, Riga, Latvia
Cent Eur J Immunol 2023; 48 (4): 322-329
Online publish date: 2023/12/12
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Introduction:
Pathogenic mechanisms and long-term consequences of COVID-19 require attention in studies on SARS-CoV-2. The association of the severity of COVID-19 with genetic factors, such as human leukocyte antigen (HLA) genes, remains underexplored. Our study assessed the relationships between HLA class II alleles and COVID-19 severity and blood-based indicators of systemic inflammation and organ damage, serum markers of epithelial cell apoptosis such as caspase-cleaved CK18 fragment M30 (CK18-M30) and the extracellular matrix product hyaluronic acid (HA).

Material and methods:
The study included 101 hospitalized COVID-19 patients (mean age 60 ±14 years). Clinical tests were performed at admission to the hospital. The levels of CK18-M30 and HA were detected in serum by enzyme-linked immunosorbent assay (ELISA). HLA typing was performed in HLA-DRB1, -DQA1, and -DQB1 loci by the polymerase chain reaction with low-resolution sequence-specific primers.

Results:
Sixty-one patients had a non-severe and 40 had a severe or critical disease course (following the WHO definition). The severity was associated with older age, male gender, higher HA, CK18-M30, and some indicators of inflammation. Despite the lack of direct association between HLA alleles and the severity of COVID-19, the presence of HLA-DRB1*04 and 12 alleles in the genotype was associated with lowered or elevated HA, respectively. The HLA-DQB1*03:01 allele was associated with lowered CK18-M30, aspartate aminotransferase, and ferritin. In addition, HLA-DQB1*06:01 was associated with elevated alanine aminotransferase.

Conclusions:
Associations of HLA class II alleles with markers of epithelial cell apoptosis and extracellular matrix production indirectly support the influence of HLA genes on acute COVID-19 severity.

keywords:

liver, hyaluronic acid, cytokeratin 18, HLA class II, COVID-19, apoptosis

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