scholarly journals Circulating and Pulmonary T-cell Populations Driving the Immune Response in Non-HIV Immunocompromised Patients with Pneumocystis jirovecii Pneumonia

2019 ◽  
Vol 16 (9) ◽  
pp. 1221-1230 ◽  
Author(s):  
Nan-Nan Zhang ◽  
Xu Huang ◽  
Hui-Ying Feng ◽  
Lin-Na Huang ◽  
Jin-Gen Xia ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Pneumocystis Jirovecii ◽  
Cell Populations ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Immunocompromised Patients

scholarly journals OP0083 INFECTIOUS AND AUTOINFLAMMATORY MODIC TYPE 1 CHANGES HAVE DIFFERENT PATHOMECHANISMS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 45.2-45
Author(s):  
I. Heggli ◽  
R. Schüpbach ◽  
N. Herger ◽  
T. A. Schweizer ◽  
A. Juengel ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
T Cell ◽  
Cell Populations ◽  
Gene Set ◽  
Go Enrichment ◽  
Modic Type ◽  
And Control ◽  
Infectious Etiology

Background:Modic type 1 changes (MC1) are vertebral bone marrow (BM) edema that associate with non-specific low back pain (LBP). Two etiologies have been described. In the infectious etiology the anaerobic aerotolerant Cutibacterium acnes (C. acnes) invades damaged intervertebral discs (IVDs) resulting in disc infection and endplate damage, which leads to the evocation of an immune response. In the autoinflammatory etiology disc and endplate damage lead to the exposure of immune privileged disc cells and matrix to leukocytes, thereby evoking an immune response in the BM. Different etiologies require different treatment strategies. However, it is unknown if etiology-specific pathological mechanisms exist.Objectives:The aim of this study was to identify etiology-specific dysregulated pathways of MC1 and to perform in-depth analysis of immune cell populations of the autoinflammatory etiology.Methods:BM aspirates and biopsies were obtained from LBP patients with MC1 undergoing spinal fusion. Aspirates/biopsies were taken prior screw insertion through the pedicle screw trajectory. From each patient, a MC1 and an intra-patient control aspiration/biopsy from the adjacent vertebral level was taken. If C. acnes in IVDs adjacent to MC1 were detected by anaerobic bacterial culture, patients were assigned to the infectious, otherwise to the autoinflammatory etiology.Total RNA was isolated from aspirates and sequenced (Novaseq) (infectious n=3 + 3, autoinflammatory n=5 + 5). Genes were considered as differentially expressed (DEG) if p-value < 0.01 and log2fc > ± 0.5. Gene ontology (GO) enrichment was performed in R (GOseq), gene set enrichment analysis (GSEA) with GSEA software.Changes in cell populations of the autoinflammatory etiology were analyzed with single cell RNA sequencing (scRNAseq): Control and MC1 biopsies (n=1 + 1) were digested, CD45+CD66b- mononuclear cells isolated with fluorescence activated cell sorting (FACS), and 10000 cells were sequenced (10x Genomics). Seurat R toolkit was used for quality-control, clustering, and differential expression analysis.Transcriptomic changes (n=5 + 5) of CD45+CD66b+ neutrophils isolated with flow cytometry from aspirates were analyzed as for total bulk RNAseq. Neutrophil activation (n=3 + 3) was measured as CD66b+ expression with flow cytometry. CD66bhigh and CD66blow fractions in MC1 and control neutrophils were compared with paired t-test.Results:Comparing MC1 to control in total bulk RNAseq, 204 DEG in the autoinflammatory and 444 DEG in the infectious etiology were identified with only 67 shared genes (Fig. 1a). GO enrichment revealed “T-cell activation” (p = 2.50E-03) in the autoinflammatory and “complement activation, classical pathway” (p=1.1E-25) in the infectious etiology as top enriched upregulated biological processes (BP) (Fig 1b). ScRNAseq of autoinflammatory MC1 showed an overrepresentation of T-cells (p= 1.00E-34, OR=1.54) and myelocytes (neutrophil progenitor cells) (p=4.00E-05, OR=2.27) indicating an increased demand of these cells (Fig. 1c). Bulk RNAseq analysis of neutrophils from the autoinflammatory etiology revealed an activated, pro-inflammatory phenotype (Fig 1d), which was confirmed with more CD66bhigh neutrophils in MC1 (+11.13 ± 2.71%, p=0.02) (Fig. 1e).Figure 1.(a) Venn diagram of DEG from total bulk RNAseq (b) Top enriched upregulated BP of autoinflammatory (left) and infectious (right) etiology (c) Cell clustering of autoinflammatory MC1 BM (d) Enrichment of “inflammatory response” gene set in autoinflammatory MC1 neutrophils (e) Representative histogram of CD66b+ expression in MC1 and control neutrophils.Conclusion:Autoinflammatory and infectious etiologies of MC1 have different pathological mechanisms. T-cell and neutrophil activation seem to be important in the autoinflammatory etiology. This has clinical implication as it could be explored for diagnostic approaches to distinguish the two MC1 etiologies and supports developing targeted treatments for both etiologies.Disclosure of Interests:None declared

Introduction to Clinical Immunology: Overview of the Immune Response, Autoimmune Conditions, and Immunosuppressive Therapeutics for Rheumatic Diseases

2016 ◽  
Author(s):  
Steven K. Lundy ◽  
Alison Gizinski ◽  
David A. Fox
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Cell ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Adaptive Immunity ◽  
Cell Populations ◽  
Hematopoietic Stem ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune

The immune system is a complex network of cells and mediators that must balance the task of protecting the host from invasive threats. From a clinical perspective, many diseases and conditions have an obvious link to improper functioning of the immune system, and insufficient immune responses can lead to uncontrolled acute and chronic infections. The immune system may also be important in tumor surveillance and control, cardiovascular disease, health complications related to obesity, neuromuscular diseases, depression, and dementia. Thus, a working knowledge of the role of immunity in disease processes is becoming increasingly important in almost all aspects of clinical practice. This review provides an overview of the immune response and discusses immune cell populations and major branches of immunity, compartmentalization and specialized immune niches, antigen recognition in innate and adaptive immunity, immune tolerance toward self antigens, inflammation and innate immune responses, adaptive immune responses and helper T (Th) cell subsets, components of the immune response that are important targets of treatment in autoimmune diseases, mechanisms of action of biologics used to treat autoimmune diseases and their approved uses, and mechanisms of other drugs commonly used in the treatment of autoimmune diseases. Figures show the development of erythrocytes, platelets, lymphocytes, and other immune system cells originating from hematopoietic stem cells that first reside in the fetal liver and later migrate to the bone marrow, antigen–major histocompatibility complex recognition by T cell receptor control of T cell survival and activation, and Th cells as central determinants of the adaptive immune response toward different stimuli. Tables list cell populations involved in innate and adaptive immunity, pattern recognition receptors with known ligands, autoantibody-mediated human diseases: examples of pathogenic mechanisms, selected Food and Drug Administration–approved autoimmune disease indications for biologics, and mechanism of action of biologics used to treat autoimmune diseases.   This review contains 3 highly rendered figures, 5 tables, and 64 references.

scholarly journals P54 Pneumocystis jirovecii prophylaxis in patients on rituximab

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_4) ◽  
Author(s):  
Kishore Warrier1 ◽  
Catherine Salvesani ◽  
Samundeeswari Deepak
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Pneumocystis Jirovecii ◽  
Current Evidence ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Number Of Patients ◽  
Increased Risk

Abstract Background Rituximab is a chimeric monoclonal antibody that depletes the B cell population by targeting cells bearing the CD20 surface marker and is used widely in the management of paediatric rheumatological conditions like juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), mixed connective tissue disease (MCTD) and juvenile idiopathic arthritis (JIA). Pneumocystis jirovecii pneumonia (PCP) is a potentially fatal opportunistic infection associated with congenital and acquired defects in T cell–mediated immunity. Our guideline did not recommend prophylaxis against PCP for patients on rituximab, unlike patients on cyclophosphamide, who are on cotrimoxazole until three months after cessation of the treatment. Cyclophosphamide is an alkylating agent which affects both B and T lymphocytes. Following the death of 16 year-old girl with JSLE due to PCP, the team reviewed the possible contributing factors, undertook a review of literature and discussed this at multi-disciplinary meetings involving the microbiology and immunology teams. This patient was found to have other risk factors for PCP – low CD4 T cells, concomitant use of corticosteroids and hypogammaglobulinaemia (IgG 3.0g/L). Although there is limited evidence that rituximab on its own increases the risk of PCP, there is emerging data that B cells may have a role in the protection against pneumocystis. Following the review, it was concluded that children on rituximab and an additional immunosuppressant (including corticosteroids) should receive prophylactic cotrimoxazole to cover PCP. Methods Retrospective audit carried out by the team to look at adherence to the new guideline regarding the use of cotrimoxazole for PCP prophylaxis in patients who have had rituximab between August 2017 and May 2019. Results P54 Table 1 Total number of patients who had rituximab 10 Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months) 7 Number of patients on rituximab monotherapy 2 Number of patients who are 6 months post-treatment 1 Number of patients with other risk factors for PCP 1 (hypogammaglobulinaemia) Number of patients who are eligible for prophylaxis, as per the guideline 8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia) Number of patients on cotrimoxazole 7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole We achieved 87.5% compliance in prescribing cotrimoxazole for PCP prophylaxis to all rheumatology patients receiving rituximab alongside another immunosuppressant agent; the one patient who this was not adhered to was due to potential adverse drug pharmacodynamic interaction between cotrimoxazole and methotrexate. Conclusion Although the current evidence points to increased risk of PCP in patients with inherited and iatrogenic defect of T cell function, there is emerging evidence that B cells may have a role too. Hence more work is required to determine the risk of PCP in patients on B cell targeted therapy (BCTT) and the need for prophylaxis. Conflicts of Interest The authors declare no conflicts of interest.

scholarly journals Point-Counterpoint: Should Serum β-d-Glucan Testing Be Used for the Diagnosis of Pneumocystis jirovecii Pneumonia?

2019 ◽  
Vol 58 (1) ◽  
Author(s):  
Gabriela Corsi-Vasquez ◽  
Luis Ostrosky-Zeichner ◽  
Edward F. Pilkington ◽  
Paul E. Sax
Keyword(s):  
High Risk ◽  
Prophylactic Antibiotics ◽  
Induced Sputum ◽  
Pneumocystis Jirovecii ◽  
Outpatient Clinics ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Immunocompromised Patients ◽  
Content Type ◽  
Aids Epidemic

Despite the widespread use of prophylactic antibiotics in high-risk individuals, Pneumocystis jirovecii remains an important cause of pneumonia in immunocompromised patients. During the peak of the AIDS epidemic, many hospitals and outpatient clinics were very proficient at collecting induced sputum specimens for the diagnosis of Pneumocystis jirovecii pneumonia (PJP).

scholarly journals Impact of Low-Dose Occupational Exposure to Ionizing Radiation on T-Cell Populations and Subpopulations and Humoral Factors Included in the Immune Response

Dose-Response ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. 155932581878556 ◽  
Author(s):  
Ilona Gyuleva ◽  
Jana Djounova ◽  
Ivanka Rupova
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Occupational Exposure ◽  
Low Dose ◽  
Dose Range ◽  
Interleukin 2 ◽  
Cell Populations ◽  
Control Group ◽  
T Helper ◽  
Humoral Factors

The aim of the present study is to assess the effects of low-dose occupational exposure on T helper response. One Hundred five employees working in Nuclear Power Plant, Kozloduy, Bulgaria and control group of 32 persons are included in this investigation. Flow cytometry measurements of T-cell populations and subpopulations and natural killer T cells are performed and levels of G, A, and M immunoglobulins and interleukin 2 (IL-2), IL-4, and interferon γ were determined. The data interpreted with regard to cumulative doses, length of service, and age. The results of the present study are not enough to outline a clear impact of occupational radiation exposure on T helper populations. Nevertheless, the observed even slight trends in some lymphocyte’s populations and in cytokines profile give us the reason to assume a possibility of a gradual polarization of T helper 1 to T helper 2 immune response at dose range 100 to 200 mSv. The results of the present study indicate the need to perform a more detailed epidemiological survey including potential confounding and misclassifying factors and possible selection bias that could influence the results.

scholarly journals Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies.

2021 ◽  
Author(s):  
Daniel Re ◽  
barbara Seitz-Polski ◽  
Michel Carles ◽  
Vesna Brglez ◽  
Daisy Graca ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cellular Response ◽  
Vaccine Dose ◽  
Cellular Responses ◽  
Double Negative ◽  
Immunocompromised Patients ◽  
Ifn Gamma ◽  
Lymphoid Malignancies ◽  
Anti Cd20

Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies. BACKGROUND: Immunocompromised patients such as patients with hematological malignancies have impaired immune response to two doses of BNT162b2 (Pfizer / BioNtech) vaccine against SARS-CoV-2. Evaluation of a repeated immune stimulation with a third vaccine dose is needed. METHODS: a vaccine monitoring observatory was conducted in outpatients who were treated for lymphoid malignancies (LM) to monitor both immune and cellular response measured the day of administration of the dose 3 of the mRNA vaccine BNT162b2 and again three to four weeks. Elecsys Anti-SARS-CoV-2 immunoassay was used to asses to the level of SARS-CoV-2 anti-Spike (S) antibodies (Abs) titer and SARS-CoV-2-specific T-cell responses were assessed by a whole blood Interferon-Gamma Release Immuno Assay (IGRA) (QuantiFERON Human IFN-gamma SARS-CoV-2, Qiagen). RESULTS: Among the 43 assessable patients (suffering from chronic lymphocytic leukemia (CLL) (n=15), indolent and aggressive B cell non-Hodgkin lymphoma (NHL) (n=14), and multiple myeloma (MM) (n=16)), 18 (41,8%) had no anti-S Abs before the dose 3 of BNT162b2 vaccine (n=9 CLL, n=8 NHL, n=1 MM), and they all 18 remained negative after the dose 3. Amongst the 25 patients with positive anti-S titers before dose 3, all patients remained positive and 23 patients increased their anti-S titer after dose 3. Patients with CLL and/or with previous anti-CD20 therapy treated within 12 months of administration of dose 3 had no significant increase of the humoral response. Among 22 available patients, dose 3 of BNT162b2 vaccine significantly increased the median IFN-gamma secretion. On eight (36.4%) patients who were double-negative for both immune and cellular response, five (22.7%) patients remained double-negative after dose 3. CONCLUSIONS Dose 3 of BNT162b2 vaccine stimulated humoral immune response among patients with LM, in particular patients with MM (who had higher anti-S baseline titer after dose 2) and those with no anti-CD20 treatment history within a year. T-cell response was increased among patients in particular with no active chemotherapy regimen. Our data support the use of an early third vaccine dose among immunocompromised patients followed for LM though some of them will still have vaccine failure.

scholarly journals Is It Possible to Differentiate Pneumocystis jirovecii Pneumonia and Colonization in the Immunocompromised Patients with Pneumonia?

2021 ◽  
Vol 7 (12) ◽  
pp. 1036
Author(s):  
Yudy A. Aguilar ◽  
Zulma Vanessa Rueda ◽  
María Angélica Maya ◽  
Cristian Vera ◽  
Jenniffer Rodiño ◽  
...  
Keyword(s):  
Qpcr Assay ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Rrna Gene ◽  
Immunocompromised Patients ◽  
Lung Cancer Patients ◽  
Molecular Tests ◽  
Cancer Group ◽  
Diagnostic Characteristics ◽  
Immunosuppressed Patients

Respiratory sample staining is a standard tool used to diagnose Pneumocystis jirovecii pneumonia (PjP). Although molecular tests are more sensitive, their interpretation can be difficult due to the potential of colonization. We aimed to validate a Pneumocystis jirovecii (Pj) real-time PCR (qPCR) assay in bronchoscopic bronchoalveolar lavage (BAL) and oropharyngeal washes (OW). We included 158 immunosuppressed patients with pneumonia, 35 lung cancer patients who underwent BAL, and 20 healthy individuals. We used a SYBR green qPCR assay to look for a 103 bp fragment of the Pj mtLSU rRNA gene in BAL and OW. We calculated the qPCR cut-off as well as the analytical and diagnostic characteristics. The qPCR was positive in 67.8% of BAL samples from the immunocompromised patients. The established cut-off for discriminating between disease and colonization was Ct 24.53 for BAL samples. In the immunosuppressed group, qPCR detected all 25 microscopy-positive PjP cases, plus three additional cases. Pj colonization in the immunocompromised group was 66.2%, while in the cancer group, colonization rates were 48%. qPCR was ineffective at diagnosing PjP in the OW samples. This new qPCR allowed for reliable diagnosis of PjP, and differentiation between PjP disease and colonization in BAL of immunocompromised patients with pneumonia.

scholarly journals A case report describing the immune response of an infant with congenital heart disease and severe COVID-19

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Danielle Wurzel ◽  
Melanie R. Neeland ◽  
Jeremy Anderson ◽  
Yara-Natalie Abo ◽  
Lien Anh Ha Do ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Acute Infection ◽  
Young Infant ◽  
Immune Memory ◽  
Future Research ◽  
Cell Populations ◽  
Initial Increase ◽  
Immune Correlates ◽  
Cytokine Analysis

Abstract Background Children with SARS-CoV-2 infection generally present with milder symptoms or are asymptomatic in comparison with adults, however severe disease occurs in a subset of children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterised. Methods We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19 using high-dimensional flow cytometry and multiplex cytokine analysis. Results Systemic cellular and cytokine profiling show an initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8 + T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4 + T (but not CD8 + T) cells occurred over time, with a predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Substantial in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory. Conclusions These findings provide important insights into the immune response of a young infant with severe COVID-19 and will help to inform future research into therapeutic targets for high-risk groups.

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