POS0413 COMPREHENSIVE IMMUNE PROFILING OF PERIPHERAL BLOOD IN PSORIATIC ARTHRITIS (PsA) PATIENTS: EXPANSION OF INTERMEDIATE MONOCYTES AND DECREASED T REG AND CD8 T CELLS

Background:Psoriatic arthritis (PsA) is a heterogeneous inflammatory arthritis that develops in a subset of patients with psoriasis. According to the current paradigm, cells of the innate and adaptive immunity interact with resident tissue fibroblasts mounting an inflammatory response via complex cytokine networks in the skin and joints in which type 1 and type 17 T cells play a dominant role. The abundance and relative contribution of other peripheral blood immune cells to disease pathogenesis as well the molecular signature of peripheral blood mononuclear cells and tissue fibroblasts remain ill defined.Objectives:To comprehensively characterize immune cell subsets driving inflammation in the peripheral blood of patients with active PsA and their impact on psoriatic skin fibroblasts.Methods:Peripheral blood was collected from PsA patients (n=31) and age-/sex-matched healthy individuals (HI) (n=9), after informed consent. Psoriatic skin biopsies were acquired from a subset of 5 patients and 3 HI. All patients fulfilled the CASPAR criteria for the diagnosis and displayed peripheral polyarthritis of moderate- to high-disease activity. Patients’ demographic and clinical data were recorded at time of sampling. Disease activity was assessed using the Disease Activity Index for Psoriatic arthritis (DAPSA) score. Skin psoriasis activity indices, enthesitis and dactylitis were also recorded. Peripheral blood mononuclear cells (PBMCs) were isolated by ficoll density gradient centrifugation. Flow cytometry was performed using a BD FACS-Aria-III and analyzed using FlowJo software. The antibody staining panel utilized aimed at the identification of the following immune cell subsets: Monocyte subsets (HLA-DR+ CD14+/- CD16+/-), Plasmacytoid dendritic cells (HLA- DR+ CD123+), T helper (CD4+), cytotoxic T (CD8+), regulatory T (CD4+ CD25+ CD127-) and B cells (CD19+). Statistical analyses were performed using GraphPad Prism software. Differences between groups were compared using unpaired T test for parametric data; Mann-Whitney and Kruskal Wallis tests for non-parametric data. The level of significance was set at P<0.05.Results:9 males and 22 females PsA patients are included (mean age 50 years and the mean disease duration 19.2 years for skin disease and 5.9 years for arthritis). The mean DAPSA score was 43.4, suggestive of high disease activity, while 8 (26%) patients displayed clinical enthesitis at time of sampling. Flow cytometry analysis revealed aberrancies in peripheral blood immune cell populations. More specifically, PsA patients displayed a significant increase in intermediate monocyte subset (HLA-DR+ CD14+ CD16+) compared to HI with patients with clinical enthesitis demonstrating a more exaggerated expansion of intermediate monocytes compared to patients without enthesitis. A trend towards increased patrolling monocytes (HLA-DR+ CD14- CD16+) was also noted although this did not reach statistical significance. In contrast, both regulatory T cells and cytotoxic CD8+ T cells were significantly decreased probably due to their selective migration at the sites of inflammation. RNA-seq from whole blood and skin fibroblasts from affected skin are in progress.Conclusion:These data demonstrate significant expansion of intermediate monocytes -more pronounced in the enthesitis affected individuals- and decrease in T regulatory cells and T cytotoxic cells in PsA peripheral blood. Increased antigen presentation and co-stimulation mediated via intermediate monocytes in combination with their proangiogenic properties may contribute to disease pathogenesisReferences:[1]Veale, D. J. & Fearon, U. The pathogenesis of psoriatic arthritis. The Lancet (2018) doi:10.1016/S0140-6736(18)30830-4.Disclosure of Interests:None declared

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IRF5 Acts as a Potential Therapeutic Marker in Inflammatory Bowel Diseases

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa200 ◽

2020 ◽

Author(s):

Yonghong Yang ◽

Cui Zhang ◽

Dehuai Jing ◽

Heng He ◽

Xiaoyu Li ◽

...

Keyword(s):

T Cells ◽

Disease Activity ◽

Inflammatory Bowel Diseases ◽

Peripheral Blood ◽

Cd4 T Cells ◽

Mononuclear Cells ◽

Orphan Receptor ◽

Peripheral Blood Mononuclear ◽

Bowel Diseases ◽

Inflammatory Bowel

Abstract Background Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic inflammatory disorders. As is well known, interferon regulatory factor (IRF) 5 is closely associated with the pathogenesis of various inflammatory diseases. But the exact role of IRF5 in IBD remains unclear. Methods In this study, we detected IRF5 expression in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa from IBD patients by immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction. Peripheral blood CD4+ T cells were stimulated with inflammatory cytokines and transfected by lentivirus. Results In active IBD patients, the expression of IRF5 in PBMCs and inflamed colonic tissues was obviously increased and significantly associated with disease activity. Ectopic overexpression of IRF5 could promote the differentiation of IBD CD4+ T cells into Th1 and Th17 cells by regulating T-bet and RAR related orphan receptor C, whereas knockdown of IRF5 had the opposite effects. Tumor necrosis factor (TNF)-α upregulated expression of IRF5 in CD4+ T cells, but anti-TNF treatment with infliximab could markedly reduce IRF5 expression in CD4+ T cells and intestinal mucosa of CD patients. Conclusion Our study reveals a novel mechanism that IRF5 levels are correlated with disease activity in IBD and might function as a possible marker for the management of IBD via regulating Th1 and Th17 immune responses and cytokine production.

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Using peripheral blood immune signatures to stratify patients with adult and juvenile inflammatory myopathies

Rheumatology ◽

10.1093/rheumatology/kez252 ◽

2019 ◽

Cited By ~ 1

Author(s):

Meredyth G Ll Wilkinson ◽

Anna Radziszewska ◽

Chris Wincup ◽

Yiannis Ioannou ◽

David A Isenberg ◽

...

Keyword(s):

T Cell ◽

B Cells ◽

Disease Activity ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Assessment Tool ◽

Immune Cell ◽

Memory B Cells ◽

Healthy Controls ◽

Immune Signatures

AbstractObjectiveThe inflammatory idiopathic myopathies (IIM) are a group of rare autoimmune diseases defined by muscle weakness and characterized by pro-inflammatory infiltrates in muscle. Little is known about the immunological profile in peripheral blood of these patients and how this relates to IIM subtypes. This study aimed to stratify adult and juvenile-onset IIM patients according to immune cell profile.MethodsPeripheral blood mononuclear cells from 44 patients with adult myositis (AM), 15 adolescent-onset juvenile dermatomyositis (a-JDM), and 40 age-matched healthy controls were analysed by flow cytometry to quantify 33 immune cell subsets. Adult myositis patients were grouped according to myositis subtype; DM and polymyositis; and also autoantibody specificity. Disease activity was determined by the myositis disease activity assessment tool and clinicians’ decision on treatment.ResultsUnique immune signatures were identified for DM, polymyositis and a-JDM compared with healthy controls. DM patients had a T-cell signature comprising increased CD4+ and TH17 cell frequencies and increased immune cell expression of IL-6. Polymyositis patients had a B-cell signature with reduced memory B cells. A-JDM had decreased naïve B cells and increased CD4+T cells. All patient groups had decreased CD8+central memory T-cell frequencies. The distinct immune signatures were also seen when adult myositis patients were stratified according to auto-antibody expression; patients with anti-synthetase-antibodies had reduced memory B cells and patients with autoimmune rheumatic disease overlap had an elevated Th17 profile.ConclusionUnique immune signatures were associated with adult vs juvenile disease. The Th17 signature in DM patients supports the potential use of IL-17 inhibitors in treatment of IIMs.

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Immune profiling of circulating T cells and TILs following neoadjuvant ipilimumab and chemotherapy in non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.7_suppl.26 ◽

2017 ◽

Vol 35 (7_suppl) ◽

pp. 26-26

Author(s):

John Yi ◽

Jeffrey Melson Clarke ◽

Patrick Healy ◽

Xiaofei F. Wang ◽

Debra Shoemaker ◽

...

Keyword(s):

T Cells ◽

T Cell Activation ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Objective Response ◽

Study Objective ◽

Cd8 Cells ◽

Hla Dr ◽

Circulating T Cells ◽

Immune Profiling

26 Background: Ipilimumab (Ipi) is a humanized CTLA-4 antibody that blocks binding of CTLA-4 to B7, permitting T cell activation through CD28. Phased in Ipi added to chemotherapy (C) may enhance efficacy in NSCLC. Methods: Patients with stage 2 or 3A NSCLC received neoadjuvant carboplatin AUC6 plus paclitaxel 200 mg/m2 every 21 days for 3 cycles and Ipi (10 mg/kg) was given on day 1 for cycles 2 and 3. Blood for immune profiling of circulating T cells was collected at baseline, after chemotherapy alone, and after chemotherapy plus Ipi. Tumor infiltrating lymphocytes (TIL) were derived from 7 available tumors. Polychromatic flow cytometry (PFC) analyses were performed on peripheral blood mononuclear cells (PBMC) and TIL. Objective response rates were assessed according to RECIST 1.1 criteria. Results: Of the 24 patients enrolled on this study, objective responses after 3 cycles of neoadjuvant C plus ipi included 2 PD, 8 SD, and 14 PR. Phenotypic analyses revealed that PBMC from all 24 patients were highly activated following two cycles of Ipi (cycle 3) as evidenced by significantly increased frequencies of CD28, ICOS, HLA-DR, PD-1, and CTLA-4 expressing CD4+ cells; and ICOS, HLA-DR, and CTLA-4 expressing CD8+ cells. The frequencies of Tregs were highly variable among the 24 participants. Two of the 24 participants had levels of MDSC cells above 15%. TIL contained far greater frequencies of activated CD4+ and CD8+ cells than found in the PBMC at cycle 3. Tumor associated antigen (TAA)-specific CD4+ or CD8+ cells were detected at baseline in 4 patients (24%), but their relative frequencies remained unaltered by Ipi therapy. No patients developed detectable de novo TAA reactivities while on Ipi therapy. Conclusions: Combined neoadjuvant Ipi plus chemotherapy produced significantly increased frequencies of highly activated CD4+ and CD8+ populations in the peripheral blood and the tumor microenvironment. TAA-specific CD4+ or CD8+ cells were detected in PBMC at baseline in a subset of patients. No TAA-reactive T cells were detected among the 7 TIL samples analyzed. Analysis for predictive or pharmacodynamic biomarkers is ongoing. Clinical trial information: NCT01820754.

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Longitudinal Peripheral Blood Lymphocyte Subsets Correlate with Decreased Disease Activity in Juvenile Dermatomyositis

The Journal of Rheumatology ◽

10.3899/jrheum.121031 ◽

2013 ◽

Vol 40 (7) ◽

pp. 1200-1211 ◽

Cited By ~ 10

Author(s):

Floranne C. Ernste ◽

Cynthia S. Crowson ◽

Consuelo Lopez de Padilla ◽

Molly S. Hein ◽

Ann M. Reed

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Disease Activity ◽

Nk Cells ◽

Peripheral Blood ◽

Juvenile Dermatomyositis ◽

Plasmacytoid Dendritic Cells ◽

Myeloid Dendritic Cells ◽

Hla Dr ◽

Vas Scores

Objective:To determine the clinical characteristics and subsets of peripheral blood lymphocytes (PBL), which correlate with decreased disease activity in patients with juvenile dermatomyositis (JDM).Methods.Peripheral blood mononuclear cells from 24 patients with JDM were collected at Mayo Clinic Rochester between 2007 and 2011. These were analyzed using fluorescence-activated cell sorting and flow cytometry. Clinical disease activity was determined by visual analog scales (VAS) collected in 2 consecutive visits and correlated with PBL subsets.Results.The change in CD3+CD69+ T cells correlated with the change in global VAS scores. The change in HLA-DR- CD11c+ myeloid dendritic cells also correlated with the change in extramuscular VAS scores. There were trends toward decreased levels of HLA-DR- CD11c+ cells with decreased muscle and global VAS scores, but these did not reach significance. The change in HLA-DR- CD123+ plasmacytoid dendritic cells negatively correlated with the change in muscle VAS scores. Although not statistically significant, decreased levels of CD3-CD16- CD56+ natural killer (NK) cells and HLA-DR- CD86+ myeloid dendritic cells, and increased levels of CD16+CD56- NK cells, correlated with decreased VAS scores.Conclusion.Changes in CD3+CD69+ T cells, HLA-DR- CD11c+ myeloid dendritic cells, and HLA-DR- CD123+ plasmacytoid dendritic cells are associated with improved clinical course in JDM and could be used as markers for disease activity, but findings need to be verified in a larger, independent cohort. Lack of significant differences among most of our PBL subsets suggests that lymphocyte phenotyping may be difficult to definitively correlate with disease activity in JDM.

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Invasion of Bovine Peripheral Blood Mononuclear Cells and Erythrocytes by Mycoplasma bovis

Infection and Immunity ◽

10.1128/iai.00707-10 ◽

2010 ◽

Vol 78 (11) ◽

pp. 4570-4578 ◽

Cited By ~ 46

Author(s):

Jacques van der Merwe ◽

Tracy Prysliak ◽

Jose Perez-Casal

Keyword(s):

T Cells ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Immune Cell ◽

Γδ T Cells ◽

Mycoplasma Bovis ◽

Immune Cell Population ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

ABSTRACT Mycoplasma bovis is a small, cell wall-less bacterium that contributes to a number of chronic inflammatory diseases in both dairy and feedlot cattle, including mastitis and bronchopneumonia. Numerous reports have implicated M. bovis in the activation of the immune system, while at the same time inhibiting immune cell proliferation. However, it is unknown whether the specific immune-cell population M. bovis is capable of attaching to and potentially invading. Here, we demonstrate that incubation of M. bovis Mb1 with bovine peripheral blood mononuclear cells (PBMC) resulted in a significant reduction in their proliferative responses while still remaining viable and capable of gamma interferon secretion. Furthermore, we show that M. bovis Mb1 can be found intracellularly (suggesting a role for either phagocytosis or attachment/invasion) in a number of select bovine PBMC populations (T cells, B cells, monocytes, γδ T cells, dendritic cells, NK cells, cytotoxic T cells, and T-helper cells), as well as red blood cells, albeit it at a significantly lower proportion. M. bovis Mb1 appeared to display three main patterns of intracellular staining: diffuse staining, an association with the intracellular side of the cell membrane, and punctate/vacuole-like staining. The invasion of circulating immune cells and erythrocytes could play an important role in disease pathogenesis by aiding the transport of M. bovis from the lungs to other sites.

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POS1001 CLINICAL AND SURROGATE CARDIOVASCULAR RISK ASSESSMENT AND ITS RELATIONSHIP WITH PSORIATIC ARTHRITIS PATHOGENESIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2990 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 769.1-769

Author(s):

N. Barbarroja Puerto ◽

I. Arias de la Rosa ◽

C. Román-Rodriguez ◽

I. Gómez García ◽

C. Perez-Sanchez ◽

...

Keyword(s):

Risk Factors ◽

Psoriatic Arthritis ◽

Disease Activity ◽

Surface Area ◽

Body Surface Area ◽

Body Surface ◽

Peripheral Blood ◽

Molecular Mechanisms ◽

Mononuclear Cells ◽

Cv Disease

Background:Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with an increased prevalence of cardiovascular (CV) events. Traditional CV risk factors do not account for the increased CV disease mortality in PsA. Inflammation seems to have a key role in the development of this comorbidity, however the specific molecular mechanisms involved are not defined yet.Objectives:To evaluate clinical CV risk factors and surrogate markers and their relationship with inflammation, disease activity and metabolic comorbidities in PsA patientsMethods:This is a cross-sectional study including 100 PsA patients without CV disease recruited in the routine clinical practice at the Rheumatology Department, Reina Sofia Hospital of Cordoba and 100 age-matched healthy donors (HDs). Different parameters related to the cardiometabolic risk were analyzed. Clinical and analytical parameters were collected: lipid profile (cholesterol, HDL, LDL, TG, ApoA and ApoB), glucose and insulin, body surface area (BSA) affected by psoriasis, number of tender and swollen joints, DAPSA, VAS, CRP and ESR. To measure the persistence of inflammation, CRP levels were recorded retrospectively once, twice, or three times during the 5 years prior to study and at the moment of the study. Increased levels of CRP in at least 50% of the determinations was considered as persistent inflammation. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood of patients and HDs. A panel of 92 proteins involved in CV disease and an adipocytokine profile was measured in plasma and PBMCs. In addition, activation of 18 intracellular pathways involved in cell activation was also measured in PBMCs. In vitro experiments in adipocytes treated with serum from PsA patients were also carried out.Results:Traditional CV risk factors including atherogenic risk, insulin resistance (IR), metabolic syndrome, smoking, obesity, arterial hypertension, apolipoprotein B/A risk, type 2 diabetes mellitus and the levels of SCORE were significantly increased in PsA patients. The presence of IR was associated with disease activity markers (DAPSA, ESR and CRP). In fact, the HOMA-IR index was related to the CRP persistence. PsA patients with obesity had significantly increased the number of tender and swollen joints, the levels of DAPSA and CRP. Twenty-eight proteins involved in CV disease and six adipocytokines were significantly elevated in the plasma of PsA patients. Several of these cardiovascular molecules were associated with higher levels of DAPSA (CTSD, GAL3, CD163, FABP4, IL6 and IL1RT2), acute phase reactants (GAL3, TNFα, Adiponectin, TNFR1 and IL6), affected body surface area (IL2RA, GAL3, CCL15, TRAP, CSTB, CD163, OPG and CNTN1) and onychopaty (TRAP, VWF, MCP-1, GAL3, LTBR, TFPI, CHI3L1, CTSZ and JAM-A). In addition, the mRNA expression of most of those 28 CV molecules were significantly increased in PBMCs from PsA patients. At intracellular level, the activation of 11 kinases (ERK1/2, AKT, S6 Ribosomal, mTOR, HSP27, Bad, p70 S6 kinase, PRAS40, p53 and caspase-3) involved in insulin signaling, inflammation, cell survival and apoptosis were altered in PBMCs. Finally, serum from PsA patients was able to modify the expression of these molecules in adipocytes.Conclusion:1) Disease activity and inflammatory burden are closely associated with the presence of metabolic alterations, specifically obesity and IR in patients with PsA. 2) The development of IR is extremely related to the persistence of CRP levels in the previous 5 years. 3) Inflammation is closely associated to the adipose tissue dysfunction in PsA and 4) FABP4, CD163 and GAL3 are surrogate CV markers commonly associated with clinical features of PsA, suggesting the role of these molecules linking CVD and PsA pathogenesis.Funded by ISCIII (PI17/01316 and RIER RD16/0012/0015) co-funded with FEDER.Disclosure of Interests:None declared.

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Abnormal B-Cell and Tfh-Cell Profiles in Patients With Parkinson Disease

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000001125 ◽

2021 ◽

Vol 9 (2) ◽

pp. e1125

Author(s):

Rui Li ◽

Thomas Francis Tropea ◽

Laura Rosa Baratta ◽

Leah Zuroff ◽

Maria E. Diaz-Ortiz ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

Parkinson Disease ◽

B Cell ◽

Immune Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Immune Cell ◽

Ex Vivo ◽

Cell Counts

Background and ObjectivesThere has been growing interest in potential roles of the immune system in the pathogenesis of Parkinson disease (PD). The aim of the current study was to comprehensively characterize phenotypic and functional profiles of circulating immune cells in patients with PD vs controls.MethodsPeripheral blood was collected from patients with PD and age- and sex-matched neurologically normal controls (NCs) in 2 independent cohorts (discovery and validation). Comprehensive multicolor flow cytometry was performed on whole blood leukocytes and peripheral blood mononuclear cells to characterize different immune subsets and their ex vivo responses.ResultsThe discovery cohort included 17 NCs and 12 participants with PD, and the validation cohort included 18 NCs and 18 participants with PD. Among major immune cell types, B cells appeared to be preferentially affected in PD. Proliferating B cell counts were decreased in patients with PD compared with controls. Proportions of B-cell subsets with regulatory capacity such as transitional B cells were preferentially reduced in the patients with PD, whereas proportions of proinflammatory cytokine-producing B cells increased, resulting in a proinflammatory shift of their B-cell functional cytokine responses. Unsupervised principal component analysis revealed increased expression of TNFα and GM-CSF by both B cells and T cells of patients with PD. In addition, levels of follicular T cells, an important B-cell helper T-cell population, decreased in the patients with PD, correlating with their B-cell abnormality.DiscussionOur findings define a novel signature of peripheral immune cells and implicate aberrant Tfh:B-cell interactions in patients with PD.

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Immunological correlates of response to immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (mUC) patients (pts).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.454 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 454-454

Author(s):

Alice Tzeng ◽

C. Marcela Diaz-Montero ◽

Patricia A. Rayman ◽

Jin Sub Kim ◽

Paul G Pavicic ◽

...

Keyword(s):

T Cells ◽

Peripheral Blood ◽

Mixed Model ◽

Mononuclear Cells ◽

Immune Cell ◽

Checkpoint Inhibitors ◽

Suppressor Cells ◽

Peripheral Blood Mononuclear ◽

Blood Samples ◽

Never Smokers

454 Background: Identification of biomarkers predictive of response to ICI could help guide treatment (tx) decisions. We assessed the correlation between PD1/PDL1 expression in key immunomodulatory subsets (myeloid-derived suppressor cells [MDSC]; CD8+ T cells) and tx response in mUC pts treated with ICI. Methods: Serial peripheral blood samples were collected from mUC pts treated with ICI. Flow cytometry was used to quantify PD1/PDL1 expression in MDSC (CD33+HLADR−) and CD8+ T cells (CD8+CD4−) from live peripheral blood mononuclear cells. MDSC were subdivided into monocytic (M)-MDSC (CD14+CD15−), polymorphonuclear (PMN)-MDSC (CD14− CD15+), and immature (I)-MDSC (CD14− CD15−). Mixed-model regression and Wilcoxon rank-sum tests were performed to assess post-ICI changes in immune marker expression and identify correlations between PD1/PDL1 expression and best overall response (BOR) to ICI. Results: Of 36 ICI-treated pts with ≥2 blood samples, 24 received anti-PDL1 (22 atezolizumab/2 avelumab; [A]) and 12 received anti-PD1 (pembrolizumab [P]). 78% were men, median age 69 (46–81), 28% never smokers, 19% had prior intravesical BCG, 39% prior neoadjuvant chemotherapy, and 64% prior cystectomy. BOR to ICI included 3 PR/14 SD/7 PD (A) and 1 CR/2 PR/6 SD/3 PD (P). Successive doses of A correlated with decreased %PDL1+ M-MDSC (mean change −5.26/dose; p = 0.009), while those of P correlated with decreased %PD1+ M- and I- MDSC (mean change −1.55 and −1.14/dose; p = 0.04 and 0.02, respectively). Though pre-tx %PD1+ CD8+ T cells did not predict BOR, greater PD1 expression by CD8+ T cells within 12 weeks after ICI initiation correlated with BOR (Table). Conclusions: ICI tx correlated with distinct changes in PD1/PDL1 expression by specific peripheral immune cell subsets. Responders to ICI had higher % of PD1+ CD8+ T cells after ICI than non-responders, though pre-tx % were comparable between groups. Further validation of these and other potential blood/tissue biomarkers is ongoing. [Table: see text]

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Changes in T-Cell and Monocyte PhenotypesIn VitrobySchistosoma mansoniAntigens in Cutaneous Leishmaniasis Patients

Journal of Parasitology Research ◽

10.1155/2012/520308 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Aline Michelle Barbosa Bafica ◽

Luciana Santos Cardoso ◽

Sérgio Costa Oliveira ◽

Alex Loukas ◽

Alfredo Góes ◽

...

Keyword(s):

T Cells ◽

Cutaneous Leishmaniasis ◽

T Lymphocyte ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Hla Dr ◽

Lymphocyte Phenotypes ◽

Intermediate Monocytes ◽

Activation Status

High levels of proinflammatory cytokines such as IFN-γand TNF are associated with tissue lesions in cutaneous leishmaniasis (CL). We previously demonstrated thatSchistosoma mansoniantigens downmodulate thein vitrocytokine response in CL. In the current study we evaluated whetherS. mansoniantigens alter monocyte and T-lymphocyte phenotypes in leishmaniasis. Peripheral blood mononuclear cells of CL patients were cultured withL. braziliensisantigen in the presence or absence of theS. mansoniantigens rSm29, rSmTSP-2- and PIII. Cells were stained with fluorochrome conjugated antibodies and analyzed by flow cytometry. The addition of rSm29 to the cultures decreased the expression of HLA-DR in nonclassical (CD14+CD16++) monocytes, while the addition of PIII diminished the expression of this molecule in classical (CD14++CD16-) and intermediate (CD14++CD16+) monocytes. The addition of PIII and rSmTSP-2 resulted in downmodulation of CD80 expression in nonclassical and CD86 expression in intermediate monocytes, respectively. These two antigens increased the expression of CTLA-4 in CD4+T cells and they also expanded the frequency of CD4+CD25highFoxp3+T cells. Taken together, we show thatS. mansoniantigens, mainly rSmTSP-2 and PIII, are able to decrease the activation status of monocytes and also to upregulate the expression of modulatory molecules in T lymphocytes.

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OP0128 DISTINCT FEATURES OF HLA-DR+ AND HLA-DR- PD-1HI CXCR5- T PERIPHERAL HELPER CELLS IN SEROPOSITIVE RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5552 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 84.2-84

Author(s):

H. Yamada ◽

T. Sasaki ◽

K. Suzuki ◽

M. Takeshita ◽

S. Tanemura ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

Disease Activity ◽

Plasma Cells ◽

Immune Cell ◽

Effector Memory ◽

Chugai Pharmaceutical ◽

Effector Memory T Cells ◽

Hla Dr ◽

Immune Cell Subsets

Background:PD-1hi CXCR5- T peripheral helper (Tph) cells are newly identified pathogenic CD4+ helper T cells in rheumatoid arthritis (RA). Since Tph cells have been emerged quite recently, the characteristics of Tph cells as a biomarker of RA are not fully understood.Objectives:The aim of the study is to evaluate how useful Tph cells in peripheral bloods are when compared to other immune cell subsets, and to clarify which Tph subset most accurately reflects the disease activity of RA.Methods:The RA patients who visited our rheumatology department between January 2000 and February 2017, and met the 2010 ACR/European League Against Rheumatism (EULAR) classification criteria were included. We first assessed correlation with 40 immune cell subsets and the disease activity of RA. Next, the proportions of these immune cells were compared between RA and healthy controls (HCs). We also investigated the immune cell subsets which reflected the time course change of the disease activity after the methotrexate (MTX) treatment. The study protocol was approved by the ethics committee at Keio University School of Medicine.Results:Thirty-four seropositive RA, 12 seronegative RA and 34 HCs were included. The Immune cell subsets which showed correlation with DAS28-ESR (r> 0.2 or r> -0.2) were activated CD4 T cells (r= 0.31), HLA-DR+Th1 cells (r= 0.20), HLA-DR+Th1-17 cells (r= 0.25), Tfh1-17 cells (r= -0.25), HLA-DR+Tph cells (r= 0.22), CD3+CD8+naïve T cells (r= -0.25), CD3+CD8+effector memory T cells (r= -0.26), plasma cells (r= 0.40) and CD14++CD16+intermediate monocyte (r= 0.23). The proportions of HLA-DR+Th1 cells (2.3% vs. 5.7%), HLA-DR+Th1-17 cells (0.7% vs. 2.2%), Tfh1-17 cells (1.7% vs. 2.0%), HLA-DR+Tph cells (0.02% vs. 0.1%), CD3+CD8+effector memory T cells (16.6% vs 25.7%), plasma cells (0.04% vs. 0.17%) were statistically higher in the patients with RA compared to HCs. While the proportion of Tph cells showed weak correlation with DAS28-ESR (r= 0.18), that was extremely higher in RA (0.08% vs. 0.25%). Interestingly, when assessing the correlations with the disease activity in seropositive and seronegative RA separately, the proportions of Tph cells (r= 0.52) and HLA-DR+Tph cells (r= 0.50) were highly reflected in seropositive RA, but not in seronegative RA. Regarding the disease activity after the MTX treatment, the change of proportion of Tph cells between week 0 and 52 significantly reflected the change of DAS28-ESR (r= 0.75, p= 0.025), but not HLA-DR+Tph cells because of the non-specific reduction by the MTX treatment. Rather, HLA-DR-Tph cells significantly reflected the change of DAS28-ESR while receiving the MTX treatment (r= 0.76, p= 0.021).Conclusion:Tph cells and HLA-DR+Tph cells highly reflected the disease activity of seropositive RA. However, after the treatment, the proportion of HLA-DR+Tph cells decreased independent from the disease activity, and that of HLA-DR-Tph cells more accurately reflected the change of the disease activity during the treatment.References:[1]Rao DA, et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature. 2017;542:110-114.Disclosure of Interests:Hiroki Yamada: None declared, Takanori Sasaki: None declared, Katsuya Suzuki: None declared, Masaru Takeshita: None declared, Shuhei Tanemura Employee of: I am employed by Mitsubishi Tanabe Pharma Corporation, Noriyasu Seki Employee of: I am employed by Mitsubishi Tanabe Pharma Corporation, Hideto Tsujimoto Employee of: I am employed by Mitsubishi Tanabe Pharma Corporation, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd.

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