Upregulated expression of leukocyte immunoglobulin‑like receptor A3 in patients with severe aplastic anemia

Abstract

Severe aplastic anemia (SAA) is a rare and potentially life-threatening disease characterized by pancytopenia and bone marrow (BM) hypoplasia. In a previous study by our group, increased expression of leukocyte immunoglobulin-like receptors A (LILRA), LILRA3 in myeloid dendritic cells (mDCs) and LILRA5 in CD34 + cells in SAA was detected using proteomics techniques, highlighting their potential role in disease pathogenesis. In the present study, the expression of LILRA1-6 mRNA was assessed in the BM mononuclear cells of patients with SAA using reverse transcription-quantitative (RT-q)PCR. The expression of homogenic LILRA3 and LILRA5 isoform on mDCs, as well as CD34 + , CD3 + CD8 + , CD19 + and CD14 + cells, was detected using flow cytometry. mDCs were then induced, cultured and sorted. The expression of LILRA3 was confirmed using RT-qPCR and western blot analyses. The serum levels of soluble LILRA3 were measured using ELISA. Furthermore, the relationship between LILRA3 expression and disease severity was assessed. The results indicated increased LILRA3 mRNA expression in patients with SAA. The percentage of LILRA3 + in BM mDCs and CD34 + cells was increased. Compared with controls, the relative LILRA3 mRNA expression and the relative protein intensity were highly increased in SAA mDCs. The serum LILRA3 levels in patients with SAA were also increased. The proportion of LILRA3 + CD11C + human leukocyte antigen (HLA)-DR + /CD11C + HLA-DR + cells was positively correlated with the ratio of LILRA3 + CD34 + /CD34 + cells and the expression of LILRA3 mRNA. Taken together, the expression of LILRA3 on mDCs of patients with SAA was increased, which may affect the function of mDCs. LILRA3 may have a significant role in the immune pathogenesis of SAA.

Single-cell RNA Sequencing Reveals Novel Cellular Factors for Response to Immunosuppressive Therapy in Aplastic Anemia

“…On the contrary, immune‐regulatory interactions, such as LILRB1/HLA‐F, 58 were inactivated in AA patients (Figure 8C). 59 IST responders, in particular, were featured by costimulatory interaction between CD86 and CD28 when compared with non‐responders (Figure 8D). 60–62 …”

“…Furthermore, the interaction between immunosuppressive receptor LILRB1 on memory B cells and HLA-F from CD4 + T cells was absent in AA patients (Figure 8C). 58,59 IST responders in particular were characterized by the enhanced interaction between CD86 and CD28, which enhances T cell survival through the upregulation of Bcl-x L , an antiapoptotic molecule (Figure 8D). 61,62 In summary, our findings demonstrate that various cellular factors are related to the immune-stimulating microenvironment in the BM of AA patients, and the IST response is significantly correlated with the level of immune activation.…”

Ferritin Light Chain: A Candidate Autoantigen in Immuno-Related Pancytopenia

“…Western blot was performed as described previously ( 22 ). The primary reagents were used: rabbit anti-FTL (dilution, 1:1,000; Abcam, UK), rabbit anti-GAPDH antibodies (dilution, 1:1,000; Cell Signaling Technology, Inc., USA), horseradish peroxidase (HRP)–conjugated anti-rabbit IgG (dilution, 1:2,000; Cell Signaling Technology, Inc., USA), ECL Chemiluminescent HRP Substrate (Merck Millipore, USA), and BCA Protein Assay Kit (Beijing Biosynthesis Biotechnology Co., China).…”

When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms

“…AA and hypoplastic MDS (hMDS) are typical forms of immune-mediated AHF, and they share similar cytological and immunological landscapes ( 39 , 40 ). In AHF, autoimmune CTLs ( 43 – 45 ) and natural killer (NK)/NKT cells ( 46 – 48 ) become activated and expanded. Trained CTLs [effector memory CTLs (emCTLs)] and NK/NKT cells (effector memory NK/NKT cells) exhibit elevated killing activities ( 43 – 48 ), increased secretory capacities ( 49 – 51 ), and enhanced sensitivities to antigen stimulation ( 52 , 53 ).…”

“…In AHF, autoimmune CTLs ( 43 – 45 ) and natural killer (NK)/NKT cells ( 46 – 48 ) become activated and expanded. Trained CTLs [effector memory CTLs (emCTLs)] and NK/NKT cells (effector memory NK/NKT cells) exhibit elevated killing activities ( 43 – 48 ), increased secretory capacities ( 49 – 51 ), and enhanced sensitivities to antigen stimulation ( 52 , 53 ). The oligoclonal feature of expanded emCTL infiltrating the BM suggests the presence of chronic stimulation that is driven by an antigen from the BME ( 43 , 50 ).…”