Abstract Number: 124 • 2019 ACR/ARP Annual Meeting
Treatment with Abatacept but Not with TNF Blockers, Is Associated with a Reduction of Constitutively Elevated Circulating Follicular Helper T Cells in Rheumatoid Arthritis
Background/Purpose: Circulating CD4 T cells that express CXCR5 together with PD-1 and/or ICOS are considered as counterparts of bona fide Tfh cells and function as…Abstract Number: 2791 • 2018 ACR/ARHP Annual Meeting
Characterization of Monoclonal Anti-PAD4 Autoantibodies from Rheumatoid Arthritis Patients: Functional Implications for Citrullination and Disease Progression
Background/Purpose: Anti-citrullinated protein antibodies (ACPA) are present in two-thirds of patients with rheumatoid arthritis (RA), and target proteins that have been post-translationally modified by the…Abstract Number: 2947 • 2018 ACR/ARHP Annual Meeting
Peripheral Helper T Cells in Systemic Lupus Erythematosus
Background/Purpose: Autoreactive T-B cell interactions in lymphoid tissue have been thought to play a crucial role in the autoantibody production in systemic lupus erythematosus (SLE).…Abstract Number: 30 • 2017 ACR/ARHP Annual Meeting
Specificity of Salivary Gland-Derived Monoclonal Antibodies from Sjogren’s Syndrome Patients Using Human Proteome Arrays
Background/Purpose: Sjögren’s syndrome (SS) is a rheumatic autoimmune disease characterized by focal lymphocytic infiltrations in the lacrimal and salivary glands, autoantibodies to the ubiquitous Ro…Abstract Number: 1882 • 2017 ACR/ARHP Annual Meeting
Thymus and Activation-Regulated Chemokine (TARC) As Biomarker for IgG4-Related Disease
Background/Purpose: TARC, also known as chemokine ligand 17 (CCR17), is expressed in the thymus and is produced by dendritic cells, endothelial cells, keratinocytes and fibroblasts.…Abstract Number: 2426 • 2017 ACR/ARHP Annual Meeting
Altered Frequencies of Circulating Follicullar T Helper Cell Counterparts and Their Subsets but Not of Peripheral Helper T Cells, Are Associated with Increased Circulating Plasmablasts in Seropositive Early RA Patients
Background/Purpose: Follicular T helper (Tfh) cells are typically located in lymphoid organs where they promote B cell differentiation and function. Circulating CD4 T cells expressing…Abstract Number: 2639 • 2017 ACR/ARHP Annual Meeting
Pathological Relevance of T Follicular Helper Cell and Plasmablast in Patients with Systemic Lupus Erythematosus
Background/Purpose: Increasing evidence points to immunological heterogeneity in the pathogenesis of SLE. Indeed, targeted therapy for SLE showed considerable variability of efficacy. Thus, it seems…Abstract Number: 666 • 2016 ACR/ARHP Annual Meeting
Immunoglobulin N-Glycosylation Acquired By Somatic Hypermutation As a Potential Mechanism for Non-Specific B Cell Activation in Sjogren’s Syndrome
Background/Purpose: Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands resulting in tissue destruction, pathological dry…Abstract Number: 1286 • 2016 ACR/ARHP Annual Meeting
Inflammatory Activity of IgG4-Related Disease Lesions Assessed By Quantitative Positron Emission Tomography Correlates with Circulating Plasmablasts Levels
Background/Purpose: 18-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan is emerging as a promising imaging technique for diagnosis and staging of IgG4-RD. We aim to correlate…Abstract Number: 2861 • 2016 ACR/ARHP Annual Meeting
Proportions of Circulating Follicular Helper T Cells and Complement Levels, White Blood Cell Counts, and Skin Manifestations in Patients with Active Systemic Lupus Erythematosus
Background/Purpose: Although circulating B cells and T cells, including follicular helper T (Tfh) cells, are reported to be involved in systemic lupus erythematosus (SLE) 1,2),…Abstract Number: 2040 • 2015 ACR/ARHP Annual Meeting
T Follicular Helper like CD4+CXCR5+pd-1+ Cells and T Follicular Helper like Type 2 Cells Subsets Are Increased in IgG4-Related Disease Patients
Background/Purpose: IgG4 related disease (IgG4-RD) is associated with characteristic pathological changes including lymphoplasmocytic infiltration with abundant IgG4 positive plasma cells, storiform fibrosis and obliterative phlebitis.…Abstract Number: 1120 • 2015 ACR/ARHP Annual Meeting
Analysis of SLE Plasmablasts By High Throughput Pairing of the Immunoglobulin Heavy and Light Chain (VH-VL)
Background/Purpose: In-depth analysis of the molecular and antigenic properties of antibody secreting cells (ASC) is critical for our understanding of autoimmune diseases. This goal however…Abstract Number: 1953 • 2014 ACR/ARHP Annual Meeting
Circulating Plasmablasts from Patients with Systemic Lupus Erythematosus Produce Autoantibodies Reactive to Epstein-Barr Virus
Background/Purpose: Systemic lupus erythematosus (SLE) is characterized by the over-production of high affinity autoantibodies. It is not clear how such autoantibodies are generated during the…Abstract Number: 1238 • 2014 ACR/ARHP Annual Meeting
Proportion of Peripheral Plasmacytoid Dendritic Cells and Plasmablasts Reflects Disease Activity in IgG4-related Disease
Background/Purpose Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disease with multi-organ system involvement. Affected patients frequently have a history of bronchial asthma and allergic rhinitis. The reported pathogenesis of IgG4-RD describes the clear involvement of excessive Th2 cells and regulatory immune reaction in addition to plasma cells 1). However, peripheral immune cell phenotype, which reflects disease status, has not been comprehensively evaluated. Our aim was to definitively determine peripheral blood cell abnormalities and their correlation with disease activity in patients with IgG4-RD.Methods Peripheral blood samples were obtained from active untreated IgG4-RD patients (n=11) and healthy controls (n=16). Comprehensive immunophenotyping assay with information on activation status was done by multi-color flow cytometry, and the proportion of peripheral blood mononuclear cells (PBMCs), including T cells (naïve/memory, Th1/2/17, Treg, and Tfh), B cells (naïve/memory, plasmablast, Breg), monocytes (classical, intermediate, non-classical) and dendritic cells (myeloid, plasmacytoid), and their activity status were precisely defined. Disease activity was measured using the IgG4-RD responder index (RI). Statistical analysis was done using the Mann-Whitney U test and Spearman rank correlation coefficient test.Results The proportion of plasmablasts (CD19+CD20-CD27+CD38+), memory Th2 cells (CD3+CD4+CXCR3-CCR6-CD45RA-), Tregs (CD3+CD4+CD25+CD127low), Tfh (CD3+CD4+CXCR5+), and mDCs (CD3-CD19-CD14-HLA-DR+CD1c+CD303-) in peripheral blood was significantly increased in IgG4-RD patients compared with HC, whereas the proportion of pDCs (CD3-CD19-CD14-HLA-DR+CD1c-CD303+)was significantly decreased. Interestingly, the proportion of pDCs in total DCs was negatively correlated with IgG4-RD RI (r=-0.778, p=0.005) while the proportion of plasmablasts in CD19+cells was positively correlated with RI (r=0.701, p=0.016). Further, the increased proportion of plasmablasts was positively correlated with serum IgG4 level (r=0.718, p=0.013) while the decreased proportion of pDCs tended to be negatively correlated with the number of affected organs (r=-0.518, p=0.061). Conclusion Our comprehensive analysis identified distinct proportional changes in PBMCs in IgG4-RD. In particular, the decrease in pDCs and increase in plasmablasts were strongly linked with disease activity. These combined measurements are expected to be clinically useful surrogate cell markers. This newly identified decrease in circulating pDCs may be involved in the pathogenesis in IgG4-RD via the recently described role in the enhancement of Th2 response 2).References: 1) Stone JH et.al. N Engl J Med 2012;366:539-51 2) Maazi H et.al. Allergy 2013;68:695-701Abstract Number: 605 • 2014 ACR/ARHP Annual Meeting
Decreased Frequencies of Circulating Follicular Helper T Cell Counterparts and Plasmablasts in Ankylosing Spondylitis Patients Naïve for TNF Blockers
Background/Purpose: Follicular helper T cells (Tfh), localized in lymphoid organs, promote B cell differentiation and function. Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1…