scholarly journals High-dimensional analysis reveals abnormal B cell subsets associated with specific changes to circulating T and myeloid cell populations in patients with idiopathic inflammatory myopathies

2021 ◽  
Author(s):  
Erin Marie Wilfong ◽  
Todd Bartkowiak ◽  
Katherine N. Vowell ◽  
Camille S. Westlake ◽  
Jonathan M. Irish ◽  
...  
Keyword(s):  
B Cell ◽  
Mononuclear Cells ◽  
Clinical Manifestations ◽  
Myeloid Cell ◽  
Cell Phenotype ◽  
Idiopathic Inflammatory Myopathies ◽  
Healthy Controls ◽  
Inflammatory Myopathies ◽  
Inflammatory Myositis ◽  
Immune Signatures

Objectives: The idiopathic inflammatory myopathies (IIM) are a clinically heterogeneous group of conditions affecting the skin, muscle, joint, and lung in various combinations. This study aims to investigate the immunologic heterogeneity through detailed immunophenotyping of peripheral blood mononuclear cells (PBMCs) in IIM patients and healthy controls. Methods: We collected PBMCs from 17 patients with a clinical diagnosis of inflammatory myositis in the inpatient or outpatient setting and performed immunophenotyping using mass cytometry by time of flight (CyTOF) to simultaneously characterize B, T, and myeloid cell subsets. Data were analyzed using a combination of supervised biaxial gating and unsupervised clustering algorithms including t-distributed stochastic neighbor embedding (tSNE), cluster identification, characterization, and regression (CITRUS), and marker enrichment modeling (MEM). Results: We identified two distinct immune signatures amongst IIM patients. In one signature, increased CD19+CXCR4hiCCR7hi cells correlated with increased CD3+CXCR4hiCD38hi (r=0.62, p=0.009) and CD14+CD16-CXCR4+CD38+HLADR- (r=0.61, p=0.01) populations. In the second signature, increased CD19+CD21loCD11c+ cells correlated with an increased CD3+CD4+PD1+ (r=0.60, p=0.01) population. Other shared immunologic features amongst IIM patients compared to healthy controls included decreased surface expression of RP105/CD180 on B cells (median mass intensity 39.9 ± 16.0 v. 60.9 ± 20.1, p=0.002). In the T cell compartment, all circulating CD3+CXCR3+ subsets (2.7 ± 2.4 v. 9.6 ± 8.1% of all PBMCs, p=0.0004) were reduced. Conclusion: Based on circulating B cell phenotype, we identified two distinct immunologic signatures in IIM patients. Future work is needed to determine the significance of these immune signatures for clinical manifestations and treatment responses.

scholarly journals A study on demographic pattern of idiopathic inflammatory myopathies in a tertiary care hospital

2019 ◽  
Vol 6 (2) ◽  
pp. 236
Author(s):  
Srujith C. H. ◽  
Kavitha Mohanasundaram ◽  
Jagadeesan M. ◽  
Halleys Kumar E. ◽  
Kannan R. ◽  
...  
Keyword(s):  
Tertiary Care ◽  
Lactic Dehydrogenase ◽  
Idiopathic Inflammatory Myopathies ◽  
Care Hospital ◽  
Inflammatory Myopathies ◽  
Muscle Enzymes ◽  
Cross Sectional ◽  
Inflammatory Myositis ◽  
Idiopathic Inflammatory Myositis

Background: Idiopathic inflammatory myopathies (IIMs) are a group of chronic systemic autoimmune diseases characterized by proximal muscle weakness and elevated muscle enzymes. Aim and Objective was to analyze the demographic profile of patients with idiopathic inflammatory myopathies (IIM).Methods: This was a cross sectional observational study conducted over a period of two years (2016-2018). After obtaining institutional ethical committee clearance, informed consent from patients. 16 patients who fulfilled the criteria were included in the study. The demographic and the clinical data were analysed.Results: The mean age was 47.3±11.2 years. The study showed female predominance. ANA was positive in 11(68.7%) patients. Among the 16 patients, 5 (31.25%) had polymyositis and 11 (68.7%) had dermatomyositis. The median enzymes levels were creatinine kinase 1134 U/L, lactic dehydrogenase 477U/L, ALT (alanine aminotransferase) 154 IU/L, AST (aspartate aminotransferase) 236IU/L. Raynaud's phenomenon was seen in 37.5%. In our study, 31.25% had hypothyroidism and 6.25% had diabetic mellitus. On follow up 37.5% developed interstitial lung disease (ILD) and 18.75% were found to have malignancy.Conclusions: Steroids and immunomodulators are the mainstay of treatment in patients with idiopathic inflammatory myositis. All our patients improved with steroids. It is important to evaluate these patients during early stages and follow up to prevent complications.

scholarly journals Development of a New Classification System for Idiopathic Inflammatory Myopathies Based on Clinical Manifestations and Myositis-Specific Autoantibodies

2018 ◽  
Vol 75 (12) ◽  
pp. 1528 ◽  
Author(s):  
Kubéraka Mariampillai ◽  
Benjamin Granger ◽  
Damien Amelin ◽  
Marguerite Guiguet ◽  
Eric Hachulla ◽  
...  
Keyword(s):  
Classification System ◽  
Clinical Manifestations ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
New Classification

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

Rheumatology ◽  
2019 ◽  
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.

scholarly journals THU0522 CLINICAL MANIFESTATIONS AND COMPARISON OF SUBTYPES OF JUVENILE IDIOPATHIC INFLAMMATORY MYOPATHIES: DATA FROM THE REMICAM REGISTRY

2019 ◽  
Author(s):  
Jesús Loarce-Martos ◽  
Carmen Larena ◽  
M. Ángeles Blázquez ◽  
Beatriz Joven-Ibáñez ◽  
Patricia Carreira ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies

SAT0288 CHARACTERIZATION OF ANTI-AMINOACYL TRNA SYNTHETASE AUTOANTIBODIES IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1088.1-1089
Author(s):  
C. Preger ◽  
A. Notarnicola ◽  
C. Hellström ◽  
E. Wigren ◽  
C. Cerqueira ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Clinical Manifestations ◽  
Trna Synthetase ◽  
University Hospital ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Research Support ◽  
Mortality And Morbidity

Background:Idiopathic inflammatory myopathies (IIM) are rare chronic inflammatory diseases associated with high mortality and morbidity [1]. One sub-group of IIM, anti-synthetase syndrome (ASS), is characterized by the presence of autoantibodies that target aminoacyl transfer(t) RNA synthetases (aaRS), together with specific clinical manifestations such as myositis, interstitial lung disease (ILD), arthritis, mechanic’s hand, Raynaud’s syndrome and fever [2]. The most common anti-aaRS autoantibody, anti-Jo1 targeting histidyl tRNA synthetase (HisRS), is present in up to 20-30% of patients with IIM, and up to 90% of patients with myositis and ILD [3, 4]. Besides Jo1, there are today seven other identified autoantigens within the aaRS family.Objectives:A large part of patients with IIM, including individuals with clinical manifestations indicating ASS, test seronegative to all known myositis specific autoantibodies. However, these patients could potentially harbor autoantibodies against targets not tested for in clinic. In this study, we aimed at extending the detection of autoantibodies by including all cytoplasmic aaRS in the analysis of patients with IIM. We hypothesized the existence of new potential autoantigens within this protein family.Methods:The presence of anti-aaRS autoantibodies was determined using a multiplex suspension bead array assay on 242 IIM patients from the Karolinska University Hospital myositis cohort. A panel of 186 recombinant constructs, representing 57 proteins that included full-length or partial sequence overlaps between constructs of all cytoplasmic aaRS as well as other myositis related proteins, were coupled to magnetic color-coded beads and each plasma sample was tested against the complete antigen panel.Results:By the use of this multiplex method we identified patients with autoantibodies against many of the tested aaRS. Autoantibodies binding to HisRS have previously been shown to bind with higher reactivity to the WHEP domain of HisRS and this was also confirmed in this study. We confirmed reactivity against three of the other aaRS tested for in the clinic (PL-12, PL-7, and EJ). In addition, we identified patients positive for anti-Zo, -KS and -HA, autoantibodies usually not screened for in routine. Finally, our data indicates that there are autoantibodies binding to other aaRS than the previously known eight autoantigens, which will be presented.Conclusion:In this study, we could detect autoantibodies in plasma from patients with IIM, both against the most common aaRS autoantigens, but also against other aaRS that are usually not tested for in clinic. We conclude that it is important to continue the studies of anti-aaRS autoantibodies, and their correlation to clinical manifestations, and in the long run also include more aaRS autoantigens in clinical practice.References:[1]Dobloug, G.C., et al., Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study. Ann Rheum Dis, 2018. 77(1): p. 40-47.[2]Barsotti, S. and I.E. Lundberg, Myositis an evolving spectrum of disease. Immunol Med, 2018. 41(2): p. 46-54.[3]Vencovsky, J., H. Alexanderson, and I.E. Lundberg, Idiopathic Inflammatory Myopathies. Rheum Dis Clin North Am, 2019. 45(4): p. 569-581.[4]Richards, T.J., et al., Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum, 2009. 60(7): p. 2183-92.Disclosure of Interests:Charlotta Preger: None declared, Antonella Notarnicola: None declared, Cecilia Hellström: None declared, Edvard Wigren: None declared, Catia Cerqueira: None declared, Peter Nilsson: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Helena Persson: None declared, Susanne Gräslund: None declared, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Grant/research support from: Gesynta Pharma, AstraZeneca,

Acquired Muscle Disorders

2021 ◽  
pp. 779-784
Author(s):  
Teerin Liewluck ◽  
Margherita Milone
Keyword(s):  
Skeletal Muscle ◽  
Inclusion Body Myositis ◽  
Inflammatory Diseases ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Overlap Syndrome ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Muscle Disorders ◽  
Diagnostic Pathways

Muscle diseases consist of various disorders that primarily affect skeletal muscle, but they can also affect cardiac or smooth muscle. The disorders may be inherited or acquired. The pathophysiology, clinical manifestations, diagnostic pathways, and treatment options will vary for each disorder. This chapter reviews common acquired muscle disorders. Inflammatory myopathies are characterized by muscle weakness and inflammatory reaction in muscle, and often, but not always, are accompanied by elevated creatine kinase values. They can occur with infections, systemic inflammatory diseases, or they may be idiopathic. On the basis of clinical, histologic, and immunopathologic criteria, idiopathic inflammatory myopathies can be distinguished as dermatomyositis, polymyositis, or inclusion body myositis. When dermatomyositis or polymyositis occurs in association with a connective tissue disease, the disorder is called overlap syndrome.

scholarly journals Diagnostic criteria of lymphoproliferative diseases from the peripheral blood samples using a cell biochip

2021 ◽  
Vol 49 ◽  
Author(s):  
O. S. Fedyanina ◽  
Yu. Yu. Chuksina ◽  
A. N. Khmelevskaya ◽  
A. N. Khvastunova ◽  
Yu. N. Matveev ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
B Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Lymphoproliferative Disorders ◽  
Lower Proportion ◽  
Healthy Controls ◽  
Lymphoproliferative Diseases ◽  
Healthy Donors ◽  
A Cell

Background: At present, the diagnosis of lymphoproliferative disorders is based on the combination of blood or bone marrow smear morphology and immunophenotyping by flow cytometry. Immunophenotypic testing by flow cytometry technique is available only in big medical centers, which is not always convenient for a  patient. Therefore, development of an available method for preliminary diagnosis of lymphoproliferative diseases not requiring special equipment seems relevant.Materials and methods: Peripheral blood mononuclear cells from 17  patients admitted to the hospital with suspicion of a  lymphoproliferative disorder, and 17  healthy donors were studied on a cell biochip for determination of proportions of cells positive for various surface CD antigens. The diagnosis was verified by flow cytometry.Results: Compared to healthy controls and patients with T-cell lymphoproliferative disorders (TCLPD), the patients with B-cell lymphoproliferative disorders (BCLPD) had significantly lower proportion of CD7+ cells (medians, 7% and 73% respectively, p=2×10-6 for comparison with healthy controls; median  7% and 93% for comparison with TCLPD, p=0.032). In addition, the patients with BCLPD had higher proportion of peripheral СD19+ mononuclear cells, compared to that in the patients with TCLPD and healthy donors (medians 84% and 13% for comparison between BCLPD and healthy control, p=2×10-5; 84% and 3% for comparison of BCLPD and TCLPD, p=0.033). The patients with B-cell chronic lymphocytic leukemia had significantly higher CD5+ cells in the cell biochip compared to the patients with other BCLPD (medians 72% and 9%, p=0.024). The patients with TCLPD had significantly lower proportion of CD19+ cells than the healthy controls (medians, 3% and 13%, respectively, р=0.042).Conclusion: The study has demonstrated the potential to use the previously developed cell biochip for diagnosis of lymphoproliferative diseases. The biochip makes it possible to sort out white blood cells according to their surface differentiation antigen for their further morphological analysis. The cell biochip allows for the differential diagnosis between BCLPD and TCLPD and determination the lymphocyte clones based on the expression of immunoglobulin light chains.

Aberrant DNA methylation ofp57KIP2 gene in the promoter region in lymphoid malignancies of B-cell phenotype

Blood ◽  
2002 ◽  
Vol 100 (7) ◽  
pp. 2572-2577 ◽  
Author(s):  
Yinghua Li ◽  
Hirokazu Nagai ◽  
Toshihito Ohno ◽  
Masaaki Yuge ◽  
Sonoko Hatano ◽  
...  
Keyword(s):  
Dna Methylation ◽  
B Cell ◽  
Cell Lines ◽  
Promoter Region ◽  
Mononuclear Cells ◽  
B Cell Lymphoma ◽  
Cell Phenotype ◽  
Sequencing Analysis ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood

The cyclin-dependent kinase inhibitorp57KIP2 is thought to be a potential tumor suppressor gene (TSG). The present study examines this possibility. We found that the expression ofp57KIP2 gene is absent in various hematological cell lines. Exposing cell lines to the DNA demethylating agent 5-aza-2′-deoxycytidine restoredp57KIP2 gene expression. Bisulfite sequencing analysis of its promoter region showed thatp57KIP2 DNA was completely methylated in cell lines that did not express thep57KIP2 gene. Thus, DNA methylation of its promoter might lead to inactivation of thep57KIP2 gene. DNA methylation of this region is thought to be an aberrant alteration, since DNA was not methylated in normal peripheral blood mononuclear cells or in reactive lymphadenitis. Methylation-specific polymerase chain reaction analysis found frequent DNA methylation of thep57KIP2 gene in primary diffuse large B-cell lymphoma (54.9%) and in follicular lymphoma (44.0%), but methylation was infrequent in myelodysplastic syndrome and adult T-cell leukemia (3.0% and 2.0%, respectively). These findings directly indicate that the profile of the p57KIP2gene corresponds to that of a TSG.

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