CTLA-4 Expression Inversely Correlates with Kidney Function and Serum Immunoglobulin Concentration in Patients with Primary Glomerulonephritides

• Published in: Archivum Immunologiae et Therapiae Experimentalis 2019-10, Vol.67 (5), p.335-349
• Main Authors: Grywalska, Ewelina, Smarz-Widelska, Iwona, Mertowski, Sebastian, Gosik, Krzysztof, Mielnik, Michał, Podgajna, Martyna, Abramiuk, Monika, Drop, Bartłomiej, Roliński, Jacek, Załuska, Wojciech
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens, CD - metabolism; Biomedical and Life Sciences; Biomedicine; CD19 antigen; CD4 antigen; CD8 antigen; Cell activation; Cell membranes; CTLA-4 Antigen - blood; CTLA-4 Antigen - genetics; CTLA-4 Antigen - metabolism; CTLA-4 protein; Cytotoxicity; Enzyme-linked immunosorbent assay; Female; Flow cytometry; Gene Expression Regulation; Glomerulonephritis - immunology; Glomerulonephritis - physiopathology; Humans; Immunoglobulins; Immunoglobulins - blood; Immunology; Kidney - physiopathology; Kidney diseases; Lymphocyte Activation; Lymphocyte Count; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Middle Aged; Monoclonal antibodies; Original; Original Article; Pathogenesis; Peripheral blood; Pharmacology/Toxicology; Proliferative kidney disease; ROC Curve; Young Adult
• ISSN: 0004-069X; 1661-4917; 1661-4917
• DOI: 10.1007/s00005-019-00548-3

Major causes of chronic kidney disease are primary proliferative and nonproliferative glomerulonephritides (PGN and NPGN). However, the pathogenesis of PGN and NPGN is still not fully understood. Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is a T-cell membrane receptor that plays a key role in T-cell inhibition. Despite its role in autoimmunological diseases, little is known about the involvement of CTLA-4 in the pathogenesis of PGN and NPGN. The objective of this study was to determine the role of CTLA-4 in the pathogenesis of PGN and NPGN by evaluating the frequencies of T and B lymphocytes expressing CTLA-4 and the serum concentration of the sCTLA-4 isoform in patients with PGN and NPGN in relation to clinical parameters. The study included peripheral blood (PB) samples from 40 PGN and NPGN patients and 20 healthy age- and sex-matched volunteers (control group). The viable PB lymphocytes were labeled with fluorochrome-conjugated monoclonal anti-CTLA-4 antibodies and analyzed using flow cytometry. The serum concentration of sCTLA-4 was measured using ELISA. The frequencies and absolute counts of CD4 + /CTLA-4 + T lymphocytes, CD8 + /CTLA-4 + T lymphocytes and CD19 + /CTLA-4 + B lymphocytes and the serum sCTLA-4 concentration were lower in PGN and NPGN patients that in the control group. Reduced sCTLA-4 expression was associated with a lower concentration of serum immunoglobulins. Our results indicate that deregulation of CTLA-4 expression may result in continuous activation of T cells and contribute to the pathogenesis of PGN and NPGN.