scholarly journals TLR2 Expression on Select Lymphocyte Subsets as a New Marker in Glomerulonephritis

2020 ◽  
Vol 9 (2) ◽  
pp. 541 ◽  
Author(s):  
Sebastian Mertowski ◽  
Ewelina Grywalska ◽  
Krzysztof Gosik ◽  
Iwona Smarz-Widelska ◽  
Anna Hymos ◽  
...  

Toll-like receptor (TLR) signaling may be involved in autoimmune kidney disorders and has been implicated in proliferative and non-proliferative glomerulonephritis (PGN and NPGN). In this study, we investigated the expression of TLR2 on T and B lymphocytes in relation to selected clinical parameters in patients with PGN and NPGN. We collected peripheral blood from the ulnar vein of patients with PGN (n = 15) or NPGN (n = 22) and healthy volunteers (n = 20). The percentage of peripheral blood mononuclear cells expressing TLR2 was determined with flow cytometry. TLR2 expression on T and B lymphocytes was increased in PGN patients compared with NPGN patients and controls (p ≤ 0.001). In patients with PGN, TLR2 expression correlated negatively with the serum concentrations of IgG and albumin and positively with urine protein excretion. Receiver operating characteristic (ROC) analysis indicated that TLR2 expression is a highly specific marker to distinguish PGN patients from NPGN patients and controls, especially on CD4+ T lymphocytes. Its use as a non-invasive marker of disease should be further investigated.

Blood ◽  
1996 ◽  
Vol 88 (4) ◽  
pp. 1473-1478 ◽  
Author(s):  
N Yamamoto ◽  
VR Naraparaju ◽  
PJ Orchard

Generation of macrophage-activating factor requires a precursor protein, Gc protein (serum vitamin D3-binding protein), as well as participation of beta-galactosidase of inflammation-primed B lymphocytes and sialidase of T lymphocytes. The treatment of human peripheral blood mononuclear cells with an inflammatory lysophospholipid induced beta-galactosidase and sialidase activity of lymphocytes, leading to the generation of macrophage-activating factor and activation of monocytes/macrophages. However, lysophospholipid treatment of peripheral blood mononuclear cells from three infantile patients with osteopetrosis resulted in no significant activation of monocytes/macrophages. The lysophospholipid-inducible beta- galactosidase activity of B lymphocytes as well as that of the sialidase of T lymphocytes was found to be defective in these patients.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2912-2912
Author(s):  
Xiao Ni ◽  
Lisa Shiue ◽  
Paola Arias-Mendoza ◽  
Erin Aakhus ◽  
Chitra Hosing ◽  
...  

Abstract Anti-tumor immunity mediated by cytotoxic CD8+ T lymphocytes (CTL) is thought to underlie the efficacy of extracorporeal photopheresis (ECP) for cutaneous T cell lymphoma (CTCL). In contrast, induction of immune tolerance mediated by regulatory T cells (Treg) is hypothesized to underlie the effect of ECP for graft-versus-host disease (GVHD). In this translational research study, peripheral blood mononuclear cells (PBMC) from patients (Pt) with Sézary Syndrome (SS), a leukemic form of CTCL, and GVHD pre- and post-ECP were studied for expression of the CTL cytokine IFN-gamma and of the nuclear transcription factor forkhead box P3 (Foxp3), a specific marker of Treg. Total RNA from PBMCs at pre-ECP, 2 day, 1 month, 3 months, and 6 months post- ECP were quantitated by real-time quantitative reverse transcript-PCR (RT-Q-PCR) for Foxp3 and IFN-gamma mRNA expression levels, normalized to endogenous control gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Foxp3 levels at baseline varied but increased at 2 day and 1 month post-ECP in GVHD by 9.5-fold and 27.6-fold, respectively (Fig.1). Similarly,foxp3 also increased in 3 of 4 CTCL patients (Pt#1, #2 and #4). Foxp3 levels rose steadily in clinical responders, Pt#1 and Pt#2, during the treatment course, and highest levels were detected at 6 months post-ECP with 13.1-fold and 17.4-fold increase, respectively. Pt#1 and #2 experienced partial clinical response and decreased circulating tumor cells with ECP. The levels of interferon-gamma had only < 2-fold up or down over the treatment course from baseline among CTCL post-ECP samples. While the level of IFN-gamma was decreased by half at 2 day and 1 month post-ECP in GVHD compared to that in pre-ECP (Fig.2). These results suggest that Tregs (detected by Foxp3) but not IFN-gamma are induced during ECP in responding CTCL patients as in GVHD. ECP might thus have common mechanisms in these two T cell mediated diseases. The study will continue to enroll patients to further study the effects of ECP. Fig. 1 Foxp3 expression in PBMCs from CTCL and GVHD pre- and post ECP Fig. 1. Foxp3 expression in PBMCs from CTCL and GVHD pre- and post ECP Fig. 2 IFN-gamma expression in PBMCs from CTCL and GVHD pre- and post ECP Fig. 2. IFN-gamma expression in PBMCs from CTCL and GVHD pre- and post ECP


2020 ◽  
Vol 21 (7) ◽  
pp. 2379
Author(s):  
Anna Hymos ◽  
Ewelina Grywalska ◽  
Janusz Klatka ◽  
Maria Klatka ◽  
Izabela Korona-Głowniak ◽  
...  

Recurrent infection with human alphaherpesvirus 1 (HHV-1) may be associated with immune exhaustion that impairs virus elimination. Thymic peptides enhance immune function and thus could overcome immune exhaustion. In this study, we investigated whether reactivation of herpes infections was associated with immune exhaustion. Moreover, we examined the impact of treatment with thymostimulin on the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on T and B lymphocytes in patients suffering from recurrent HHV-1 reactivation. We also assessed the effector function of peripheral blood mononuclear cells (PBMCs) after stimulation with thymic peptides. We enrolled 50 women with reactivated HHV-1 infections and healthy volunteers. We measured the expression of various activation and exhaustion markers on the surface of PBMCs using flow cytometry. In ex vivo experiments, we measured the secretion of inflammatory cytokines by PBMCs cultured with thymostimulin. Compared with controls, patients with reactivated HHV-1 infections had increased percentages of CD3+ co-expressing CD25, an activation marker (p < 0.001). Moreover, these patients had increased percentages of CD4+ and CD8+ cells co-expressing the inhibitory markers PD-1 and PD-L1. In cultures of PBMCs from the patients, thymostimulin increased the secretion of interferon gamma (p < 0.001) and interleukin (IL)-2 (p = 0.023), but not IL-4 or IL-10.Two-month thymostimulin therapy resulted in no reactivation of HHV-1 infection during this period and the reduction of PD-1 and PD-L1 expression on the surface of T and B lymphocytes (p < 0.001). In conclusion, reactivation of herpes infection is associated with immune exhaustion, which could be reversed by treatment with thymic peptides.


Immunobiology ◽  
1993 ◽  
Vol 188 (4-5) ◽  
pp. 323-329 ◽  
Author(s):  
Ying-Hua Chen ◽  
Günther Bock ◽  
Rolf Vornhagen ◽  
Franz Steindl ◽  
Hermann Katinger ◽  
...  

2019 ◽  
Author(s):  
Tao Huang ◽  
Jun Zhang ◽  
Wujian Ke ◽  
Xiaohui Zhang ◽  
Wentao Chen ◽  
...  

Abstract Background Treponema pallidum (T. pallidum Tp) infection evokes vigorous immune responses, resulting in tissue damage. The immune mechanism after Treponema pallidum infection is still not clear. MicroRNAs (miRNAs) have been shown, however, to influence immune cell function and consequently the generation of antibody responses during other microbe infections, but these values are unknown for Tp. Methods In this study, we performed a comprehensive analysis of differentially expressed miRNAs in healthy persons, untreated patients with syphilis, patients in the serofast state, and serologically cured patients. MiRNAs were profiled from patient peripheral blood obtained at the time of serological diagnosis. Then both the target sequence analysis on these different miRNAs and pathway analysis were performed to identify important immune and cell signaling pathways. Quantitative RT-PCR for analysis of microRNA Results There were 89 differentially regulated miRNA identified in total. Following RT-qPCR confirmation, three miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p) showed significant difference among serofast state, and serological cure (P<0.05). A miRNAs (hsa-miR-195-5p) showed significant differences among untreated patients and healthy individuals. Conclusions This is the first study of miRNA expression difference in PBMCs in different stages of T. pallium infection. Our study suggests that the combination of three miRNAs has great potential to serve as non-invasive biomarkers of Treponema pallidum infections, which will facilitate better diagnosis and treat of T. pallium infections.


2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
M. L. Kowalski ◽  
A. Wolska ◽  
J. Grzegorczyk ◽  
J. Hilt ◽  
M. Jarzebska ◽  
...  

Background. Cell signaling via Toll-like receptors (TLRs) leads to synovial inflammation in rheumatoid arthritis (RA). We aimed to assess effects of TLR2 and TLR4 stimulation on proinflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with recent-onset RA, osteoarthrosis (OA), and healthy control (HC).Methods. PBMCs were stimulated with LPS, biglycan and cytokine mix. Cytokines were analyzed in supernatants with ELISA. Expression of toll-like receptors mRNA in leukocytes was analyzed using real-time qPCR.Results. PBMCs from RA patients spontaneously produced less IL-6 and TNFαthan cells from OA and HC subjects. LPS increased cytokines' production in all groups. In RA patients increase was dramatic (30 to 48-fold and 17 to 31-fold, for respective cytokines) compared to moderate (2 to 8-fold) in other groups. LPS induced 15-HETE generation in PBMCs from RA (mean 251%) and OA patients (mean 43%), although only in OA group, the increase was significant. TLR2 and TLR4 gene expressions decreased in response to cytokine mix, while LPS enhanced TLR2 expression in HC and depressed TLR4 expression in OA patients.Conclusion. PBMCs from recent-onset RA patients are overresponsive to stimulation with bacterial lipopolysaccharide. TLR expression is differentially regulated in healthy and arthritic subjects.


2020 ◽  
Vol 21 (21) ◽  
pp. 8001
Author(s):  
Ewelina Grywalska ◽  
Iwona Smarz-Widelska ◽  
Izabela Korona-Głowniak ◽  
Sebastian Mertowski ◽  
Krzysztof Gosik ◽  
...  

Alterations to the programmed cell death protein-1 (PD-1) pathway were previously shown to be involved in a poorer prognosis for patients with proliferative glomerulonephritis (PGN). Here, we investigated the association between several infectious agents and the expression of PD-1 and its ligand (PD-L1) on T and B lymphocytes in patients with PGN and nonproliferative glomerulonephritis (NPGN). A cohort of 45 newly-diagnosed patients (23 with PGN and 22 with NPGN) and 20 healthy volunteers was enrolled. The percentage of peripheral blood mononuclear cells expressing PD-1 and PD-L1 antigens was determined by flow cytometry. We found PD-1 and PD-L1 expression on T and B lymphocytes was higher in PGN patients than in NPGN patients and controls. We also found that reactivation of the Epstein-Barr virus (EBV) correlated with the expression of PD-1/PD-L1 antigens in patients with PGN. Further receiver operating characteristic analysis indicated that PD-1 expression could distinguish EBV-positive PGN patients from those with NPGN or healthy controls. The use of PD-1 expression as a non-invasive marker of PGN should be further investigated.


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