Abstract
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.
Highlights
Chronic kidney disease affects 13.4% of the population worldwide (Hill et al 2016), leading to millions of deaths each year (Krata et al 2018)
Frequencies and Absolute Counts of CTLA‐4+ Lymphocytes are Lower in Patients with proliferative GN (PGN) and nonproliferative GN (NPGN) than in Controls
The frequencies of C D4+/Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)+ T lymphocytes were lower among patients with PGN [1.549 ± 1.327%; median 1.265% (0.11–3.96%)] and NPGN [1.886 ± 1.397%; median 1.905% (0.02–5.45%)] than in the control group [6.793 ± 1.280%; median 6.665% (4.37–9.16%)] (Fig. 1a)
Summary
Chronic kidney disease affects 13.4% of the population worldwide (Hill et al 2016), leading to millions of deaths each year (Krata et al 2018). Major causes of chronic kidney disease and end-stage renal disease (MD 2013) are primary glomerulonephritides (GN). Primary GN are categorized into proliferative GN (PGN), characterized by an increased number of cells in glomeruli, and nonproliferative GN (NPGN), characterized by a lack of proliferation of cells in glomeruli. Primary GN are a heterogeneous group of glomerular diseases characterized by local inflammation of glomeruli. Local glomerular inflammation is caused by dysregulated humoral and cellular immune responses to different etiologic agents (Floege 2013; Rodrigues et al 2014). B cells are activated, immunoglobulin (Ig) deposited, and complement activated.
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