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

Vanaga I, Kolesova O, Kolesovs A, et al. Association of human leukocyte antigen class II alleles with epithelial cell apoptosis and extracellular matrix production in acute COVID-19. Central European Journal of Immunology. 2023;48(4):322-329. doi:10.5114/ceji.2023.133684.

APA

Vanaga, I., Kolesova, O., Kolesovs, A., Sture, G., Hagina, E.,  & Storozenko, J. et al. (2023). Association of human leukocyte antigen class II alleles with epithelial cell apoptosis and extracellular matrix production in acute COVID-19. Central European Journal of Immunology, 48(4), 322-329. https://doi.org/10.5114/ceji.2023.133684

Chicago

Vanaga, Ieva, Oksana Kolesova, Aleksandrs Kolesovs, Gunta Sture, Elvira Hagina, Jelena Storozenko,  and Liene Nikitina-Zake et al. 2023. "Association of human leukocyte antigen class II alleles with epithelial cell apoptosis and extracellular matrix production in acute COVID-19". Central European Journal of Immunology 48 (4): 322-329. doi:10.5114/ceji.2023.133684.

Harvard

Vanaga, I., Kolesova, O., Kolesovs, A., Sture, G., Hagina, E., Storozenko, J., Nikitina-Zake, L.,  and Viksna, L. (2023). Association of human leukocyte antigen class II alleles with epithelial cell apoptosis and extracellular matrix production in acute COVID-19. Central European Journal of Immunology, 48(4), pp.322-329. https://doi.org/10.5114/ceji.2023.133684

MLA

Vanaga, Ieva et al. "Association of human leukocyte antigen class II alleles with epithelial cell apoptosis and extracellular matrix production in acute COVID-19." Central European Journal of Immunology, vol. 48, no. 4, 2023, pp. 322-329. doi:10.5114/ceji.2023.133684.

Vancouver

Vanaga I, Kolesova O, Kolesovs A, Sture G, Hagina E, Storozenko J et al. Association of human leukocyte antigen class II alleles with epithelial cell apoptosis and extracellular matrix production in acute COVID-19. Central European Journal of Immunology. 2023;48(4):322-329. doi:10.5114/ceji.2023.133684.

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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:

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

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

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}