scholarly journals TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C

2021 ◽  
Vol 219 (2) ◽  
Author(s):  
Levi Hoste ◽  
Lisa Roels ◽  
Leslie Naesens ◽  
Victor Bosteels ◽  
Stijn Vanhee ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Potential Role ◽  
Type I ◽  
Cytokine Release ◽  
Epithelial Injury ◽  
Hla Dr ◽  
Inflammatory Syndrome ◽  
Classical Monocytes ◽  
Patrolling Monocytes

In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRβ repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis.

scholarly journals Polyclonal expansion of TCR Vbeta 21.3+ CD4+ and CD8+ T cells is a hallmark of Multisystem Inflammatory Syndrome in Children

2021 ◽  
Vol 6 (59) ◽  
pp. eabh1516
Author(s):  
Marion Moreews ◽  
Kenz Le Gouge ◽  
Samira Khaldi-Plassart ◽  
Rémi Pescarmona ◽  
Anne-Laure Mathieu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Expansion ◽  
Healthy Children ◽  
Antigenic Peptides ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Hla Dr ◽  
T Cell Expansion ◽  
Inflammatory Syndrome

Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vβ21.3 T cell receptor β chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vβ21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro. Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vβ21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.

scholarly journals Superantigenic TCR Vbeta 21.3 signature in Multisystem Inflammatory Syndrome in Children

2021 ◽  
Author(s):  
Marion Moreews ◽  
Kenz Le Gouge ◽  
Alicia Bellomo ◽  
Christophe Malcus ◽  
Rémi Pescarmona ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Kawasaki Disease ◽  
T Cell Activation ◽  
Toxic Shock Syndrome ◽  
Healthy Children ◽  
Toxic Shock ◽  
Hla Dr ◽  
Inflammatory Syndrome

AbstractObjectivesMultiple Inflammatory Syndrome in Children (MIS-C) is the most severe pediatric form of COVID-19 and occurs in previously healthy children. MIS-C combines features of Kawasaki disease and Toxic Shock Syndrome (TSS).MethodsChildren with suspected MIS-C were included within the first week of diagnosis and a large scale immunoassay was performed to determein the immunologic signature of these patients.ResultsWe characterized the immunological profile of 27 MIS-C cases in comparison with 4 KD and 4 TSS cases. Similarly to TSS, an increase of serum inflammatory cytokines (IL-6, TNF-a, CD25s) was observed in MIS-C contrasting with low expression of HLA-DR monocytes, a feature often associated with immune paralysis. Expansions of T cells expressing the Vβ21.3 T cell receptor β chain variable region were detected in both CD4 and CD8 subsets in almost 50% of patients and Vβ21.3-positive T cells expressed high level of HLA-DR highlighting their specific activation. TCR sequencing uncovered the polyclonal nature of the Vβ 21.3+ population. SARS-CoV2 antigene-specific production of interferon gamma in T cells was not increased in MIS-C T cells compared to COVID-19 patients suggesting the antigen-specific immune response in MIS-C patients is not pivotal to the manifestation.ConclusionsOur findings argue in favor of a strong activation of the immune system related to a superantigenic immune response in MIS-C with a specific polyclonal Vβ21.3 T cell expansion.Key messagesWhat is already known about this subject ?MIS-C occurs 3-5 weeks after acute SARS-CoV2 infection and overlap features of Toxic Shock syndrome and Kawasaki disease.MIS-C appears different in term of cytokine and autoantibodies generation from KD with subtle signs of T cells activationWhat does this study add?This study demonstrates that Vβ21.3+ CD4 and CD8 T cells are highly increased in about 50% of MIS-C and distinctive of the Vβ2+ expansion observed in toxic shock syndrome in This reflects a specific T cell activation and cytokine release syndrome similar to toxic shock syndromeHow mich this impact on clinical practice or future developments?Vβ21.3+ signature can be available on a short term basis by flowcytometry and represents a signature of the MIS-C.As for TSS, immunomodulating therapies may revert the superantigenic activation and resolve this life threatening pediatric condition.

scholarly journals P03.24 Calreticulin exposure on malignant blasts correlates with improved NK cell-mediated cytotoxicity in AML patients

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A32.1-A32
Author(s):  
I Truxova ◽  
L Kasikova ◽  
C Salek ◽  
M Hensler ◽  
D Lysak ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cell Activation ◽  
Nk Cell ◽  
Type I ◽  
Danger Signals ◽  
Hla Dr ◽  
Patient Prognosis ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

In some settings, cancer cells responding to treatment undergo an immunogenic form of cell death that is associated with the abundant emission of danger signals in the form of damage-associated molecular patterns. Accumulating preclinical and clinical evidence indicates that danger signals play a crucial role in the (re-)activation of antitumor immune responses in vivo, thus having a major impact on patient prognosis. We have previously demonstrated that the presence of calreticulin on the surface of malignant blasts is a positive prognostic biomarker for patients with acute myeloid leukemia (AML). Calreticulin exposure not only correlated with enhanced T-cell-dependent antitumor immunity in this setting but also affected the number of circulating natural killer (NK) cells upon restoration of normal hematopoiesis. Here, we report that calreticulin exposure on malignant blasts is associated with enhanced NK cell cytotoxic and secretory functions, both in AML patients and in vivo in mice. The ability of calreticulin to stimulate NK-cells relies on CD11c+CD14high cells that, upon exposure to CRT, express higher levels of IL-15Rα, maturation markers (CD86 and HLA- DR) and CCR7. CRT exposure on malignant blasts also correlates with the upregulation of genes coding for type I interferon. This suggests that CD11c+CD14high cells have increased capacity to migrate to secondary lymphoid organs, where can efficiently deliver stimulatory signals (IL-15Rα/IL- 15) to NK cells. These findings delineate a multipronged, clinically relevant mechanism whereby surface-exposed calreticulin favors NK-cell activation in AML patients.Disclosure InformationI. Truxova: None. L. Kasikova: None. C. Salek: None. M. Hensler: None. D. Lysak: None. P. Holicek: None. P. Bilkova: None. M. Holubova: None. X. Chen: None. R. Mikyskova: None. M. Reinis: None. M. Kovar: None. B. Tomalova: None. J.P. Kline: None. L. Galluzzi: None. R. Spisek: None. J. Fucikova: None.

Innate Immunity in Idiopathic Thrombocytopenic Purpura (ITP)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4907-4907
Author(s):  
Akio Saito ◽  
Akihiko Yokohama ◽  
Hirotaka Nakahashi ◽  
Kohtaro Toyama ◽  
Takeki Mitsui ◽  
...  
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Nk Cells ◽  
Th17 Cells ◽  
Inkt Cells ◽  
Thrombocytopenic Purpura ◽  
Hla Dr ◽  
H Pylori

Abstract Background: Dendritic cells (DCs), natural killer (NK) cells, and invariant NKT (iNKT) cells play important roles in innate immune systems. These cells have recently been shown to be involved in immunoregulation, and some studies have suggested associations with various kinds of autoimmune disease. Conversely, regulatory T cells (Tregs) that are important for peripheral tolerance and Th17 cells that play a central role in maintenance of chronic inflammation are also associated with the pathogenesis of several autoimmune diseases. Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies, but relationships to innate immunity are unclear. In addition, the pathogenesis of ITP associated with Helicobacter pylori remains obscure. In particular, the regulation of immune responses by these cells in patients infected with H. pylori has not been investigated. This study analyzed DCs, NK cells, iNKT cells, Tregs and Th17 cells in patients with ITP. Methods: Subjects comprised 31 patients with ITP and 22 healthy donors. Study protocols were approved by the Institutional Review Board of Gunma University Hospital, and written informed consent was obtained from all subjects. Flow cytometry was used to investigate amounts of circulating plasmacytoid DCs (pDCs) (CD123+ HLA−DR+) and myeloid DCs (mDCs) (CD11c+ HLA−DR+) from whole white blood cells, and NK cells (CD3− CD56+), iNKT cells (Vα24+ Vβ11+), Tregs (CD4+ CD25+ Foxp3+) and Th17 cells (CD4+ IL−17A+) from mononuclear cells. The intracellular interleukin (IL)-17A production in CD4+ T-cells activated by phorbol 12-myristate 13-acetate (PMA) and ionomycin was assessed to detect Th17 cells. Results: Both the percentage and numbers of pDCs were significantly reduced in patients compared to healthy controls (p<0.001), while those of mDCs tended to be lower in patients than in controls, but with no significant differences. NK cell counts tended to be higher in patients than in controls and counts of iNKT cells tended to be lower in patients than in controls, but again no significant differences were demonstrated. Notably, Treg levels were comparable between patients and controls, while Th17 cells were significantly increased in patients compared with controls (p<0.002). In all cases, no significant differences were demonstrated between patients with H. pylori-positive and -negative results. Conclusion: These results suggest that alterations in innate immunity as a reduction of pDCs could be associated with the pathogenesis of ITP. Furthermore, as in some autoimmune diseases that have been considered as Th1 diseases, Th17 cells may play an important role in ITP.

Influence of Lenalidomide Treatment on Immune Effector Cells From High-Risk Smoldering Multiple Myeloma (SMM) Patients,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3944-3944
Author(s):  
Bruno Paiva ◽  
Maria Victoria Mateos ◽  
Lucía López-Corral ◽  
María-Belén Vidriales ◽  
Miguel T. Hernandez ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Nk Cell ◽  
Γδ T Cells ◽  
Activation Markers ◽  
Hla Dr ◽  
Activation Profile ◽  
Immunomodulatory Properties

Abstract Abstract 3944 Lenalidomide is an immunomodulatory agent that enhances T and NK cell activation, being this consideration as a major player in its anti-myeloma effect. However, in MM lenalidomide is usually combined with the immunosuppressant dexamethasone, which has raised questions regarding a potential abrogation of this immunomodulatory effect. In fact, this may be a dilemma upon treating early stage MM patients with lenalidomide +/− dexamethasone. Moreover, our current knowledge of the immune system in SMM is limited. Herein we evaluated by multiparameter flow cytometry (MFC) immunophenotyping peripheral blood (PB) T and NK cells from high-risk SMM patients (N=33), treated according to the QUIREDEX trial (NCT 00480363): an induction phase of 9 four-week cycles of LenDex followed by maintenance with lenalidomide until disease progression. To evaluate the immune status of T and NK cells of SMM patients, we compared them at baseline vs healthy adults (HA) aged over 60 years (N=10). To assess the effect of LenDex on T and NK cells of SMM patients, we compared baseline samples vs those studied after 3 and 9 cycles of LenDex. To address the question whether dexamethasone antagonizes the immunomodulatory properties of lenalidomide, we compared in 11 of the 33 patients, the PB T and NK cells at the end of induction (9th cycle of LenDex) vs during maintenance (lenalidomide alone and at least 3 months after dexamethasone discontinuation). The percentage of PB T cells in high-risk SMM patients at baseline was increased when compared to HA (23% vs 17%; P=.02), mainly due to expansion of CD8 T cells (P=.03). Of note, γδ T cells were also increased in SMM (0.8% vs 0.3%; P=.003). In turn, no differences (P>.05) were noted for both the CD56dim and CD56bright NK cell compartments. However, when a more detailed immunophenotypic characterization was carried out, CD4 and/or CD8 T cells from SMM patients showed decreased expression of activation markers (CD25, P≤.04; CD54, P<.001 and CD154, P=.002), as well as decreased production of the Th1 related cytokines (IFNγ, P=.03; TNFα, P≤.003; and IL-2, P=.02). We then investigated the effect of LenDex treatment. After 3 and 9 cycles of LenDex both CD4 and/or CD8 T cells showed up-regulation of Th1related chemokines (CCR5; p<.001) and cytokine production (IFNγ, P=.03; TNFα, P=.03 and IL-2, P=.02), as well as increased expression of activation markers (CD69, P≤.005; CD25, P<.001; CD28, P≤.04; CD54, P<.001 and HLA-DR, P<.001). Similarly, CD56dim and CD56bright NK cells showed up-regulation of HLA-DR (P<.001), the antibody-dependent cell-mediated cytotoxicity associated receptor CD16 (p≤.005), and the adhesion molecules CD11a (p≤.001) and CD11b (p≤.005). Concerning cell cycle analysis, the percentage of cells in S-phase was significantly increased from baseline vs. 3 vs. 9 cycles of LenDex for T CD4 (0.04% vs 0.13% vs 0.13%; p<.001), CD8 (0.05% vs 0.13% vs 0.18%; p<.001) and NK cells (0.07% vs 0.16% vs 0.15%; p<.001). Interestingly, an unsupervised cluster analysis of the overall immunophenotypic expression profile obtained after 9 cycles of LenDex was able to discriminate two groups of patients with different activation profiles particularly on T CD8 cells, with differences (P<.05) in both their percentage in PB and expression of activation, Th1 and maturation markers. Patients displaying a higher activation profile showed a trend towards increased depth of response after 9 cycles of LenDex (sCR+CR: 31% vs 15%; p=.229), as well as time-to progression (TTP) to symptomatic MM (TTP at 2-years: 100% vs 79%; P=.177). Finally, we explored whether the immunomodulatory properties of lenalidomide could be increased when dexamethasone was removed for the maintenance phase. Regarding T and NK cell distribution, only an increase in the percentage of CD4 T cells was found (9% vs. 12%, P=.04), whereas no differences (P>.05) were noted regarding the immunophenotypic expression profile of T and NK cells studied. In summary, we show that in high-risk SMM patients at baseline CD8 and γδ T cells are increased but overall T cells show an impaired activation profile. Treatment with LenDex induces an activation and proliferation of T and NK cells which may contribute to disease control. Finally, our results do not show an inhibition of the immunomodulatory effects of lenalidomide by the concomitant use of dexamethasone. Disclosures: Paiva: Celgene: Honoraria; Janssen: Honoraria. Off Label Use: lenalidomide is not approved for smoldering myeloma. Mateos:Janssen: Honoraria; Celgene: Honoraria. Rosiñol:Janssen: Honoraria; Celgene: Honoraria. Lahuerta:Janssen: Honoraria; Celgene: Honoraria. Blade:Janssen: Honoraria; Celgene: Honoraria. San Miguel:Janssen-Cilag: Honoraria; Celgene: Honoraria.

scholarly journals Modeling PPRV pathogenesis in mice to assess the contribution of innate cells and anti-viral T cells

2020 ◽  
Author(s):  
Yashu Sharma ◽  
Roman Sarkar ◽  
Ayush Jain ◽  
Sudhakar Singh ◽  
Chander Shekhar ◽  
...  
Keyword(s):  
Animal Model ◽  
T Cells ◽  
Nk Cells ◽  
Immune Cells ◽  
Laboratory Animal ◽  
Inoculum Size ◽  
Interferon Response ◽  
Type I ◽  
Rapid Induction ◽  
The Way

AbstractWe demonstrate a rapid induction of type I IFN response in PPRV stimulated cells and the susceptibility of mice, genetically ablated of interferon response, to PPRV infection. Following PPRV infection, IFNR KO mice gradually reduced their body weights and succumbed to the infection within 10 days. While the infecting inoculum size did not alter the outcome of infection, the nature of the induced disease was qualitatively different. Immunopathological lesions were characterized by the expansion and infiltration of innate immune cells distinctly evident at the lower infecting dose of PPRV infection. The replicating virus particles as well as the viral antigens were abundant in most of the critical organs of PPRV infected IFNR KO mice. Neutrophils and macrophages transported the replicating virus to central nervous system and contributed to pathology while the NK cells and T cells were protective against the virus. Using an array of fluorescently labeled H-2Kb tetramers PPRV specific CD8+ T cells responses were identified and measured in the infected as well as the peptide immunized mice. Our study therefore established and employed a laboratory animal model for investigating PPRV pathogenesis and the contribution of virus specific CD8+ T cells during the virus infection to pave the way for elucidating protective or pathological roles of immune cells during PPRV infection.ImportanceWe developed a laboratory animal model for investigating the pathogenesis and immunity induced by PPRV. IFNR KO animals succumbed to the infection irrespective of the dose and the route of infection. Neutrophils and macrophages served as the Trojan horse and helped transport the virus to CNS to cause encephalitis while the NK cells and CD8+ T cells provided the protection against PPRV infection. We additionally identified class I restricted immunogenic epitopes of PPRV in C57BL/6 mice. Our study therefore paves the way for an optimal utilization of this model to unravel PPRV pathogenesis and assessing the host correlates of protection.

scholarly journals Granulocyte Colony-Stimulating Factor Effectively Mobilizes TCR γδ and NK Cells Providing an Allograft Potentially Enhanced for the Graft-Versus-Leukemia Effect for Allogeneic Stem Cell Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Lia Minculescu ◽  
Henrik Sengelov ◽  
Hanne Vibeke Marquart ◽  
Lars Peter Ryder ◽  
Anne Fischer-Nielsen ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Cell Compartment ◽  
Effector Cells ◽  
Graft Versus Leukemia ◽  
Hla Dr

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potential cure for patients with hematological malignancies but substantial risks of recurrence of the malignant disease remain. TCR γδ and NK cells are perceived as potent innate effector cells in HSCT and have been associated with post-transplant protection from relapse in clinical studies. Immunocompetent cells from the donor are crucial for patient outcomes and peripheral blood stem cells (PBSC) are being increasingly applied as graft source. G-CSF is the preferential mobilizing agent in healthy donors for PBSC grafts, yet effects of G-CSF on TCR γδ and NK cells are scarcely uncovered and could influence the graft composition and potency of these cells. Therefore, we analyzed T and NK cell subsets and activation markers in peripheral blood samples of 49 donors before and after G-CSF mobilization and—for a subset of donors—also in the corresponding graft samples using multicolor flowcytometry with staining for CD3, CD4, CD8, TCRαβ, TCRγδ, Vδ1, Vδ2, HLA-DR, CD45RA, CD197, CD45RO, HLA-DR, CD16, CD56, and CD314. We found that TCR γδ cells were mobilized and harvested with an efficiency corresponding that of TCR αβ cells. For TCR γδ as well as for TCR αβ cells, G-CSF preferentially mobilized naïve and terminally differentiated effector (TEMRA) cells over memory cells. In the TCR γδ cell compartment, G-CSF preferentially mobilized cells of the nonVδ2 types and increased the fraction of HLA-DR positive TCR γδ cells. For NK cells, mobilization by G-CSF was increased compared to that of T cells, yet NK cells appeared to be less efficiently harvested than T cells. In the NK cell compartment, G-CSF-stimulation preserved the proportion of CD56dim NK effector cells which have been associated with relapse protection. The expression of the activating receptor NKG2D implied in anti-leukemic responses, was significantly increased in both CD56dim and CD56bright NK cells after G-CSF stimulation. These results indicate differentiated mobilization and altering properties of G-CSF which could improve the effects of donor TCR γδ and NK cells in the processes of graft-versus-leukemia for relapse prevention after HSCT.

scholarly journals The Study of the Association between Immune Monitoring and Pneumonia in Kidney Transplant Recipients Through Machine Learning Models

2020 ◽  
Author(s):  
Bo Peng ◽  
Hang Gong ◽  
Han Tian ◽  
Quan Zhuang ◽  
Junhui Li ◽  
...  
Keyword(s):  
Machine Learning ◽  
T Cells ◽  
Nk Cells ◽  
Kidney Transplant ◽  
Immune Monitoring ◽  
Learning Models ◽  
Kidney Transplant Recipients ◽  
Cell Counts ◽  
Hla Dr ◽  
Machine Learning Models

Abstract Background: Kidney transplantation is the optimal treatment to cure the patients with end-stage renal disease (ESRD). However, the infectious complication, especially pneumonia, is the main cause of mortality in the early stage. Immune monitoring by relevant biomarkers provides direct evidence of immune status. We aimed to study the association between immune monitoring and pneumonia in kidney transplant patients through machine learning models. Methods: A total of 146 patients receiving the immune monitoring panel in our center, including 46 pneumonia recipients and 100 stable recipients, were retrospectively reviewed to develop the models. All the models were validated by external data containing 10 pneumonia recipients and 32 stable recipients. The immune monitoring panel consisted of the percentages and absolute cell counts of CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+ B cells and natural killer (NK) cells, and median fluorescence intensity (MFI) of human leukocyte antigen (HLA)-DR on monocytes and CD64 on neutrophils. The machine learning models of support vector machine (SVM), logistic regression (LR), multi-layer perceptron (MLP) and random forest (RF) were applied for analysis.Results: The pneumonia and stable groups showed significant difference in cell counts of each subpopulation and MFI of monocyte HLA-DR and neutrophil CD64. The SVM model by monocyte HLA-DR (MFI), neutrophil CD64 (MFI), CD8+ T cells (cells/μl), NK cells (cell/μl) and TBNK (T cells, B cells and NK cells, cells/μl) had the best performance with the average area under the curve (AUC) of 0.940. The RF model best predicted the patients who would progress into severe pneumonia, with the average AUC of 0.760. All the models had good performance validated by external data.Conclusions: The immune monitoring panel was tightly associated with pneumonia in kidney transplant recipients. The models developed by machine learning techniques identified patients at risk and predicted the prognosis. Based on the results of immune monitoring, better individualized therapy might be achieved.

scholarly journals Immune characterization of a Colombian familiar cluster of SARS-CoV-2 infection

Biomédica ◽  
2021 ◽  
Vol 41 (Sp. 2) ◽  
Author(s):  
Wbeimar Aguilar-Jiménez ◽  
Lizdany Flórez-Álvarez ◽  
Daniel S. Rincón ◽  
Damariz Marín-Palma ◽  
Alexandra Sánchez-Martínez ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
K562 Cells ◽  
Neutralization Assay ◽  
Immunological Markers ◽  
Hla Dr ◽  
Immune Alterations ◽  
And Function

Introduction: Immunological markers have been described during COVID-19 and persist after recovery. Those immune alterations are associated with clinical features among SARS-CoV-2 infected individuals. Although, studies reporting a comprehensive analysis of these immune alterations are still limited. Objective: To evaluate the production of pro-inflammatory cytokines, antibody response, and phenotype and function of NK cells and T cells in a Colombian familiar cluster of SARS-CoV-2 infection. Materials and methods: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. Frequency, phenotype and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with Spike/RdRp peptides) were assessed by flow cytometry; anti-SARS-CoV-2 antibodies were determined by indirect immunofluorescence and plaque reduction neutralization assay. Results: During COVID-19, we observed a high pro-inflammatory cytokine production and reduced CD56bright NK cells and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by a high IL-10 production. Nevertheless, during recovery, a bifunctional response was observed, characterized by the co-expression of CD107a and Granzyme B or Perforin. Conclusion: Although pro-inflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells could be associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and, to guide future immunotherapy strategies. 

scholarly journals The study of the association between immune monitoring and pneumonia in kidney transplant recipients through machine learning models

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Bo Peng ◽  
Hang Gong ◽  
Han Tian ◽  
Quan Zhuang ◽  
Junhui Li ◽  
...  
Keyword(s):  
Machine Learning ◽  
T Cells ◽  
Nk Cells ◽  
Kidney Transplant ◽  
Immune Monitoring ◽  
Learning Models ◽  
Kidney Transplant Recipients ◽  
Cell Counts ◽  
Hla Dr ◽  
Machine Learning Models

Abstract Background Kidney transplantation is the optimal treatment to cure the patients with end-stage renal disease (ESRD). However, the infectious complication, especially pneumonia, is the main cause of mortality in the early stage. Immune monitoring by relevant biomarkers provides direct evidence of immune status. We aimed to study the association between immune monitoring and pneumonia in kidney transplant patients through machine learning models. Methods A total of 146 patients receiving the immune monitoring panel in our center, including 46 pneumonia recipients and 100 stable recipients, were retrospectively reviewed to develop the models. All the models were validated by external data containing 10 pneumonia recipients and 32 stable recipients. The immune monitoring panel consisted of the percentages and absolute cell counts of CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+ B cells and natural killer (NK) cells, and median fluorescence intensity (MFI) of human leukocyte antigen (HLA)-DR on monocytes and CD64 on neutrophils. The machine learning models including support vector machine (SVM), logistic regression (LR), multi-layer perceptron (MLP) and random forest (RF) were applied for analysis. Results The pneumonia and stable groups showed significant difference in cell counts of each subpopulation and MFI of monocyte HLA-DR and neutrophil CD64. The SVM model by monocyte HLA-DR (MFI), neutrophil CD64 (MFI), CD8+ T cells (cells/μl), NK cells (cell/μl) and TBNK (T cells, B cells and NK cells, cells/μl) had the best performance with the average area under the curve (AUC) of 0.940. The RF model best predicted the patients who would progress into severe pneumonia, with the average AUC of 0.760. All the models had good performance validated by external data. Conclusions The immune monitoring panel was tightly associated with pneumonia in kidney transplant recipients. The models developed by machine learning techniques identified patients at risk and predicted the prognosis. Based on the results of immune monitoring, better individualized therapy might be achieved.

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