scholarly journals AB0496 AUTOANTIBODIES TARGETING COMPLEMENT RECEPTORS 3A AND 5A1 ARE DECREASED IN ANCA-ASSOCIATED VASCULITIS AND CORRELATE WITH HIGHER RELAPSE RATE.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1546.1-1546
Author(s):  
S. Klapa ◽  
A. Müller ◽  
A. Koch ◽  
A. Kerstein-Staehle ◽  
W. Kaehler ◽  
...  
Keyword(s):  
T Cells ◽  
Disease Activity ◽  
Plasma Levels ◽  
Granulomatosis With Polyangiitis ◽  
Phase Iii ◽  
Clinical Aspects ◽  
Complement Receptors ◽  
C5a Receptor ◽  
Vascular Walls ◽  
Anca Associated Vasculitis

Background:Activation of the alternative and final common pathways have been shown in ANCA-associated vasculitis (AAV) (1). Circulating titers of C5a are elevated and correlate with disease activity in AAV. Binding to the corresponding G protein-coupled receptor (GPCR) C5aR1 enhances the influx of neutrophils, leading to ROS generation and severe necrotizing of vascular walls (2). Moreover, subsequent interaction of C5a with C5aR1 may represent a proinflammatory amplification loop (3). Blocking of the receptor is protective in a murine model in AAV (4). In humans, avacopan, a C5aR1-inhibitor showed promising results as glucocorticoid-sparing agent in two randomized phase II and one ongoing phase III clinicals trials in AAV (NCT02994927). Notably, disease-specific anti-GPCR autoantibody (aab) signatures have been found in different autoimmune diseases (5).Objectives:The aim of the present study was to examine whether (patho)physiological anti-C3aR and anti-C5aR1 aabs correlate with clinical findings in AAV, and whether this is linked to the clinical outcome.Methods:Sera and plasma of AAV patients [granulomatosis with polyangiitis (GPA), n=64; microscopic polyangiitis (MPA), n=26; eosinophilic granulomatosis with polyangiitis (EGPA), n=11] were measured by Elisa for circulating autoantibodies against complement receptors C3a (anti-C3aR aab) and C5a (anti-C5aR1 aab) and plasma levels of C3a and C5a. Expression of C3aR and C5aR1 on T-cells was determined using flow cytometry. Clinical data were assessed at the time of serum sampling and during follow-up for 48 monthsResults:GPA displayed low titers of anti-C3aR aab (GPA:5.33±2.54vs. HD:6.47±2.61, P=0.0031). Anti-C5aR1 aab were decreased in AAV, especially in GPA (GPA:1.02±1.07vs. HD:6.63±2.91, P=<0.0001). Plasma levels of C5a and anti-C5aR aab yielded an inverse correlation in AAV (r=-0.6813, P=0.0127). C5aR1 expression was increased on T-cells in GPA (CD4+C5aR1+T-cells: GPA:10.76±2.55%vs. HD:3.44±0.68%, P=0.0021; CD8+C5aR1+T-cells GPA:9.74±2.10%vs.HD:4.11±0.92%, P=0.0198). Reduced titers of anti-C5aR1 aab <0.45U/ml displayed an increased relapse risk for major organ involvement in GPA (HR 12.85, P=0.0014).Conclusion:As potential diagnostic marker, anti-C5aR1 aab titer may additionally be useful to monitor disease activity in AAV.References:[1]Chen M et al.Complement deposition in renal histopathology of patients with ANCA-associated pauci-immune glomerulonephritis.Nephrol Dial Transpl. 2009;24:1247-1252[2]Schreiber A et al.C5a receptor mediates neutrophil activation an ANCA-induced glomerulonephritis.J Am Soc Nephrol. 2009; 20:289-298[3]Lamprecht P et al.: Pathogenetic and clinical aspects of Anti-Neutrophil Cytoplasmic Autoantibody-associated vasculitides.Front Immunol.2018 Apr 9;9-680[4]Xiao H et al.C5a receptor (CD88) blockade protects against MPO-ANCA GN.J Am Soc Nephrol. 2014;25(2):225-31[5]Klapa S et al. Decreased endothelin receptor A autoantibody levels are associated with early ischaemic events in patients with giant-cell arteritis.Ann Rheum Dis2019 Oct;78(19):1443-1444Disclosure of Interests:Sebastian Klapa Grant/research support from: Actelion, Consultant of: Pfizer, Abbvie, Antje Müller: None declared, Andreas Koch: None declared, Anja Kerstein-Staehle: None declared, Wataru Kaehler: None declared, Harald Heidecke Shareholder of: Cell Trend GmbH, Employee of: Cell Trend GmbH, Speakers bureau: Cell Trend GmbH, Susanne Schinke Speakers bureau: Pfizer, Markus Huber-Lang: None declared, Martin Nitschke: None declared, Silke Pitann: None declared, Christian Karsten: None declared, Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Peter Lamprecht: None declared

scholarly journals POS0830 FACTORS INFLUENCING PATIENT-REPORTED OUTCOMES IN ANCA-ASSOCIATED VASCULITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 668.2-669
Author(s):  
S. Monti ◽  
P. Delvino ◽  
C. Klersy ◽  
G. Coppa ◽  
A. Milanesi ◽  
...  
Keyword(s):  
Disease Activity ◽  
Global Assessment ◽  
Patient Reported Outcomes ◽  
Granulomatosis With Polyangiitis ◽  
Disease Duration ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Anca Associated Vasculitis ◽  
Organ Systems ◽  
Damage Accrual ◽  
Patient Reported

Background:Patient-reported outcomes (PROs) are currently poorly integrated in the clinical evaluation of disease activity in patients with ANCA-associated vasculitis (AAV).Objectives:To assess the distribution of the Patient Global Assessment (PtGA) in patients with AAV in stable remission, and to identify correlates of PtGA; to assess the discordance between PtGA score and PhGA.Methods:Patients with a diagnosis of AAV [eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, microscopic polyangiitis] in stable, complete remission (defined by a BVAS=0) and with a Physician Global Assessment (PhGA)=0 were included. A questionnaire including several aspects of disease captured by PROs was collected. PtGA on a 0-100 mm visual analogue scale (VAS) was assessed, with higher scores representing higher/worse levels of disease activity. Similarly, VAS for pain, chronic damage according to the patient’s opinion, general health (GH), fatigue, and sleep quality were collected. The worst symptom in the patient’s opinion affecting the overall assessment of disease activity was recorded. The Cragg Hurdle model was used to assess the predictors of PtGA.Results:65 patients were included, female 57%, mean age 61±12 years. Mean disease duration at enrollment was 8±6 years. Mean vasculitis damage index (VDI) was 4.4 ±2.3, with 45% of patients having a VDI ≥ 5. Despite having been classified as being in remission, PtGA was elevated in 37% of patients. We explored several correlates of PtGA. Higher degree of damage accrual (VDI) did not influence the patient’s evaluation of current disease activity. Similarly, we did not identify a correlation between older age, educational level, number of organ-systems involved, number of comorbidities, the number of previous major or minor relapses, higher disease duration, nor the type of AAV diagnosis (figure 1, panel A). Only sex significantly correlated with PtGA scores: 19 (51%) of female patients reported an elevated PtGA compared to only 5 (18%) of male (p=0.009). PtGA resulted to be significantly correlated with other (mostly modifiable) PROs including VAS pain, perception of the level of chronic damage accrual, GH, and fatigue (figure 1, panel B). The agreement between patients’ and physicians’ assessments of disease activity was 63%. Patients reported pain, followed by chronic respiratory symptoms to be the worst-experienced ongoing manifestations affecting their evaluation of disease activity.Conclusion:A significant proportion of patients with AAV considered to be in remission by the physician still declares to have persistent aspects of uncontrolled disease. PtGA is significantly influenced by persistent pain and fatigue, which warrant better assessment in the future.Disclosure of Interests:None declared

Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis

2007 ◽  
Vol 293 (6) ◽  
pp. F1927-F1934 ◽  
Author(s):  
Jan-Stephan F. Sanders ◽  
Minke G. Huitema ◽  
Roeland Hanemaaijer ◽  
Harry van Goor ◽  
Cees G. M. Kallenberg ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Disease Activity ◽  
Plasma Levels ◽  
Renal Damage ◽  
Healthy Controls ◽  
Anca Associated Vasculitis ◽  
Tubulointerstitial Damage ◽  
Relationship Of ◽  
The Relationship ◽  
Renal Expression

Renal expression of MMP-2, -9, and tissue inhibitor of MMP-1 (TIMP-1) correlates with histological disease activity in anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV). We studied whether urinary and plasma levels of MMP-2, -9, and TIMP-1 reflect renal expression of these proteins and renal disease-activity in AAV. Urine and plasma samples of patients with AAV who underwent a renal biopsy were collected ( n = 32). Urinary activity of MMP-2 and -9 was measured by activity assays. Urinary and plasma levels of MMP-2, MMP-9, and TIMP-1 proteins were measured by ELISA. Healthy controls provided plasma and urine for comparison ( n = 31). In patients, the relationship of urinary and plasma levels with renal expression of MMP-2 and MMP-9 and clinical and histological disease activity was studied. Renal MMP expression was compared between patients and controls ( n = 8). Urinary MMP-2 and MMP-9 activity and urinary and plasma TIMP-1 levels were significantly higher in patients than in controls. In glomeruli of patients, both MMP-2 and MMP-9 expression reflected active glomerular inflammation. Urinary activity of MMP-2 and MMP-9 did not correlate with renal MMP expression or plasma levels. Urinary MMP activity correlated negatively with glomerular inflammation, but positively with fibrous crescents. Urinary MMP-2 and TIMP-1 levels showed a positive correlation with tubulointerstitial damage and a negative correlation with creatinine clearance. Urinary MMP-2, MMP-9, and TIMP-1 are elevated in AAV but do not reflect renal MMP expression and glomerular inflammation. However, urinary MMP-2 activity and TIMP-1 levels reflect tubulointerstitial damage and correlate negatively with creatinine clearance at biopsy.

AB0500 CLINICAL CHARACTERISTICS AND POTENTIAL BIOMARKERS FOR DISEASE ACTIVITY OF PATIENTS WITH ANCA ASSOCIATED VASCULITIS: A MONOCENTER STUDY IN CHINA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1548-1548
Author(s):  
Y. Liu ◽  
L. MA ◽  
L. Jiang
Keyword(s):  
Disease Activity ◽  
Granulomatosis With Polyangiitis ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Chinese Patients ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
American College Of Rheumatology ◽  
Chapel Hill ◽  
Anca Associated Vasculitis ◽  
Incident Cases

Background:Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are a group of multisystem, autoimmune, inflammatory disease characterized by pauci- necrotizing vasculitis affecting small blood vessels. The clinical manifestations of the AAV are diverse and can be confined to one organ, or multiple organs and even life-threatening. However, there has been no specific index for assessing the activity of AAV at diagnosis.Objectives:The aim of this study was to describe the clinical and serological features of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in eastern China using data from a hospital-based study. And looking for indicators that can predict disease activity.Methods:We retrospectively studied patients with newly diagnosed AAV evaluated from January 1, 2009, to December 31, 2018. In total, 219 patients diagnosed were classified according to the American College of Rheumatology classification criteria and/or revised Chapel Hill 2012 definitions, and their clinical and serological features were evaluated. The association of laboratory data with disease activity was assessed via regression models.Results:Of 219 incident cases of AAV, 37/219 (16.9%) had granulomatosis with polyangiitis (GPA), 172/219 (78.5%) were microscopic polyangiitis (MPA), and 10/219 (4.6%) had eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis of patients with GPA were 51.5 years MPA were 61.7 years, and EGPA were 49.8 years, respectively. Patients with MPA were significantly older than GPA and EGPA at diagnosis (p<0.001). ANCAs tested positive in 207 (94.5%) of cases: 167 (80.7%) were MPO-ANCA and 40 (19.3%) were PR3-ANCA. Lung, skin, nervous system symptoms were the most common in EGPA. For GPA, ear–nose–throat (ENT) symptoms and lungs involvement were the most common. Renal and lung involvement occurs most frequently in MPA. In the multivariable logistic regression analysis, higher anti-MPO antibody (149.4 IU/ml), higher hypersensitive c-reactive protein (hs-CRP, 62.5 mg/L), lower hemoglobin (113.5g/L), and higher complement 4 (C4, >0.215 g/L) were proved to be independent risk factors for active disease. Further research showed that C4 had higher sensitivity (70.0%) and specificity (83.4%) than the other three indicators.Conclusion:MPO-ANCA-positive MPA is the most common form of AAV in Chinese patients. Serum C4 concentrations at diagnosis might be a useful biomarker of disease activity in AAV.References:[1]Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.Arthritis Rheum2013, 65:1-11.[2]Choi H, Kim Y, Jung SM, Song JJ, Park Y-B, Lee S-W. Low serum complement 3 level is associated with severe ANCA-associated vasculitis at diagnosis.Clinical and Experimental Nephrology2018, 23:223-230.[3]Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis.Arthritis Rheum1990, 33:1101-1107.[4]Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis).Arthritis Rheum1990, 33:1094-1100.[5]Mukhtyar C, Lee R, Brown D, Carruthers D, Dasgupta B, Dubey S, et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3).Ann Rheum Dis2009, 68:1827-1832.[6]Markiewski MM, Lambris JD. The role of complement in inflammatory diseases from behind the scenes into the spotlight.Am J Pathol2007, 171:715-727.Disclosure of Interests:None declared

scholarly journals POS0248 PSYCHOMETRIC PROPERTIES OF OUTCOME MEASUREMENT INSTRUMENTS FOR ANCA-ASSOCIATED VASCULITIS: A SYSTEMATIC LITERATURE REVIEW

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 345.1-346
Author(s):  
A. Berti ◽  
G. Boleto ◽  
P. A. Merkel ◽  
G. Tomasson ◽  
S. Monti ◽  
...  
Keyword(s):  
Disease Activity ◽  
Psychometric Properties ◽  
Patient Reported Outcomes ◽  
Granulomatosis With Polyangiitis ◽  
Outcome Measurement ◽  
Patient Reported Outcome ◽  
Measurement Instruments ◽  
Anca Associated Vasculitis ◽  
Patient Reported ◽  
Disease Damage

Background:The OMERACT Vasculitis Working Group has defined a Core Domain Set of outcome measures for ANCA-associated vasculitis (AAV). However, the psychometric properties of available outcome measurement instruments in AAV, an essential consideration when choosing among instruments, have not been summarized.Objectives:To systematically review and summarize the psychometric properties of outcome measurement instruments used in AAV.Methods:A comprehensive search of several databases (Medline, EMBASE, Cochrane, Scopus, among others) from inception to July 14, 2020 and without language limitations was conducted. Articles were included if they covered psychometric properties of instruments used in AAV (granulomatosis with polyangiitis, GPA; microscopic polyangiitis, MPA; eosinophilic granulomatosis with polyangiitis, EGPA); articles encompassing other systemic vasculitides and not presenting the data for AAV separately were excluded. Following the COSMIN and OMERACT frameworks, different psychometric properties (validity, inter- and intra-observer reliability, sensitivity to change, and feasibility) of outcome measurement instruments used in AAV were assessed. Risk of bias was assessed according to the COSMIN checklist.Results:From 2505 articles identified, 20 met the predefined criteria. Three were identified as development studies, 14 were validation studies, and 3 pursued both objectives.These studies provided information on 16 instruments: 8 assessing disease activity, 1 assessing disease damage, 3 assessing patient-reported outcome, 4 assessing function (Figure 1). Overall, a few psychometric properties have been considered in each study, ranging from one to five. Most of the instruments were tested in GPA only (n=7), followed by AAV as a group (GPA, MPA and EGPA; n=5), MPA and GPA (n=3), and EGPA only (n=1). Sample sizes of the studies ranged between 27 and 626 patients. The studies with a higher risk of bias, according to COSMIN definitions, were those assessing RAPID3, MVIA, ENT/GPA DAS, and ODSS.There was a wide heterogeneity of the psychometric proprieties assessed for each instrument. Validity was the most frequently assessed domain in 88% of the instruments, and few properties other than construct validity were reported (Figure 1).Within each domain, BVAS/WG for activity, VDI for damage, AAV-PRO for patient-reported outcomes, and ODSS for function were the instruments with more psychometric features assessed. For the disease activity domain, BVAS/WG showed a good validity having the highest correlation with physician global assessment (r=0.90), a good reliability (intra-observer ICC=0.62; inter-observer ICC=0.97), and good feasibility and responsiveness. For disease damage, VDI showed moderate validity (correlations with BVAS/WG at 5-year with r=0.20 and BVAS/WG at 1-year with r=0.40) and good feasibility. Among patient-reported outcomes, AAV-PRO had the best performance in terms of validity (construct validity: correlations of the 6 disease domains and EQ-5D-5L, with r ranging between -0.78 and -0.55; discriminating validity between active disease versus remission of the 6 disease domains, p<0.0001 for all comparisons). The performance of instruments assessing function domain was low-to-moderate.Conclusion:Sixteen instruments covering the OMERACT domains of disease activity, damage, patient-reported outcome, and function had their psychometric properties assessed in the study of AAV. The majority were developed or validated for GPA only or AAV as a group. Overall, validity was the domain most frequently assessed. BVAS/WG, VDI, AAV-PRO, and ODSS were the instruments with more psychometric features assessed. More rigorous studies aimed at estimating a wider range of psychometric properties in larger numbers of patients with AAV are warranted.References:[1]Castrejon I, et al. Clin Exp Rheumatol. 2015[2]Merkel PA, Journal of Rheumatology, July 2011Disclosure of Interests:None declared

Significant association between clinical characteristics and immuno-phenotypes in patients with ANCA-associated vasculitis

Rheumatology ◽  
2019 ◽  
Author(s):  
Kotaro Matsumoto ◽  
Katsuya Suzuki ◽  
Keiko Yoshimoto ◽  
Noriyasu Seki ◽  
Hideto Tsujimoto ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
T Cells ◽  
Cytotoxic Activity ◽  
Antibody Production ◽  
Clinical Characteristics ◽  
Granulomatosis With Polyangiitis ◽  
Healthy Controls ◽  
Anca Associated Vasculitis ◽  
Kidney Involvement ◽  
Related Group

Abstract Objectives To elucidate the association between clinical characteristics and immuno-phenotypes in patients with ANCA-associated vasculitis (AAV). Methods Peripheral blood from 36 patients with active AAV and 18 healthy controls was examined for numbers of circulating T cells, B cells, NK cells, dendritic cells, monocytes and granulocytes using flow cytometry. These immuno-phenotyping data were subjected to cluster analysis and principal components analysis to divide AAV patients into subgroups. Associated organ involvement or therapeutic prognosis were assessed for each subgroup. Results AAV patients had higher proportions of plasma cells, plasmablasts, activated T cells, CD14++ CD16+ monocytes, eosinophils and neutrophils than healthy controls. Immuno-phenotyping findings were similar between patients with microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis. Cluster analysis indicated that AAV patients could be divided into three subgroups according to peripheral immune cell numbers: antibody production-related (n = 9), cytotoxic activity-related (n = 4) and neutrocytosis/lymphocytopenia-related (n = 23). The antibody production-related or cytotoxic activity-related group was associated with CNS involvement, and the neutrocytosis/lymphocytopenia-related group was associated with high incidence of kidney involvement. Incidence of severe infection was markedly higher in the neutrocytosis/lymphocytopenia-related group than the other two groups. Incidence of disease relapse was comparable among the three groups. Conclusion Patients with active AAV can be divided into three subgroups based on immuno-phenotyping. These results may provide a hint to understanding disease pathophysiology and prognosis, and determining appropriate treatment.

scholarly journals Clinical characteristics and potential biomarkers for disease activity of patients with ANCA associated vasculitis: a monocenter study in China

2020 ◽  
Author(s):  
Yun Liu ◽  
Lili Ma ◽  
Zongfei Ji ◽  
Rongyi Chen ◽  
Xiufang Kong ◽  
...  
Keyword(s):  
Disease Activity ◽  
Granulomatosis With Polyangiitis ◽  
Eastern China ◽  
Laboratory Data ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Chinese Patients ◽  
Multivariable Logistic Regression Analysis ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Anca Associated Vasculitis ◽  
Incident Cases

Abstract Objective: The aim of this study was to describe the clinical and serological features of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in eastern China using data from a hospital-based study. And looking for indicators that can predict disease activity. Methods: We retrospectively studied patients with newly diagnosed AAV evaluated from January 1, 2009, to December 31, 2018 . In total, 219 patients diagnosed were classified according to the American College of Rheumatology classification criteria and/or revised Chapel Hill 2012 definitions, and their clinical and serological features were evaluated. The association of laboratory data with disease activity was assessed via regression models. Results: Of 219 incident cases of AAV, 37/219 (16.9%) had granulomatosis with polyangiitis (GPA), 172/219 (78.5%) were microscopic polyangiitis (MPA), and 10/219 (4.6%) had eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis of patients with GPA were 51.5 years (male/female, 18/19), MPA were 61. 7 years (male/female, 84/88), and EGPA were 49.8 years ( male/female, 7/3), respectively. Patients with MPA were significantly older than GPA and EGPA at diagnosis ( p <0.001). ANCAs tested positive in 207 (94.5%) of cases: 167 (80.7%) were MPO-ANCA and 40 (19.3%) were PR3-ANCA. Lung, skin, nervous system symptoms were the most common in EGPA. For GPA, ear–nose–throat (ENT) symptoms and lungs involvement were the most common. Renal and lung involvement occurs most frequently in MPA. In the multivariable logistic regression analysis, higher anti-MPO antibody ( 149.4 IU/ml), higher hypersensitive c-reactive protein (hs-CRP, 62.5 mg/L), lower hemoglobin ( 113.5g/L), and higher complement 4 (C4, >0.215 g/L) were proved to be independent risk factors for active disease. Further research showed that C4 had higher sensitivity (70.0%) and specificity (83.4%) than the other three indicators. Conclusion: MPO-ANCA-positive MPA is the most common form of AAV in Chinese patients. Serum C4 concentrations at diagnosis might be a useful biomarker of disease activity in AAV.

scholarly journals Increased Circulating PD-1 hi CXCR5 – Peripheral T Helper Cells are Associated with Disease Activity of ANCA-Associated Vasculitis

2022 ◽  
Author(s):  
Zhenyu Liu ◽  
Xueqin Li ◽  
Ningning Fan ◽  
Hong Wang ◽  
Wenli Xia ◽  
...  
Keyword(s):  
T Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Rheumatic Arthritis ◽  
Neutrophil Lymphocyte Ratio ◽  
Reactive Protein ◽  
Anca Associated Vasculitis ◽  
Cellular Crescent ◽  
Programmed Death 1 ◽  
Factor Α

Abstract Newly identified PD-1 hiCXCR5 –CD4 + T cells, termed as peripheral helper T cells (Tph), have been found elevated and playing pathogenic role in some autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatic arthritis (RA). However, the potential role of Tph cells in Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains unclear. Here, we explored the potential clinical significance of circulating Tph cells in the pathogenesis of AAV. Comparing 32 active AAV patients and 18 age- and sex-matched healthy controls (HCs), we found that the frequency of circulating Tph cells was significantly expanded in active AAV patients. Besides, programmed death 1 (PD-1) expression on the surface of Tph cells was significantly up-regulated in active AAV patients. Importantly, the frequency of circulating Tph cells was greatly decreased in AAV patients after receiving treatment. Tph cells frequency was positively correlated with the Birmingham Vasculitis Activity Score (BVAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil lymphocyte ratio (NLR) and cellular crescent in active AAV patients, but negatively correlated with fibrosus crescent. Tph cells frequency was also positively correlated with naïve B cells, serum concentration of MPO-ANCAs, serum tumor necrosis factor-α (TNF-α), IL-4, IL-21 and IL-12. However, serum IL-10 exhibited negative correlation with circulating Tph cells in active AAV patients. These results demonstrated that circulating Tph cells are greatly expanded in active AAV patients and are positively associated with serum MPO-ANCAs and disease activity, thus contributing to the pathogenesis of AAV.

Clinical Impact of Interferon-γ in Anti-Citrullinated Protein Antibody-Positive Rheumatoid Arthritis

2020 ◽  
Author(s):  
Kijun Lee ◽  
Hong Ki Min ◽  
Seong-Hee Ko ◽  
Sang-Heon Lee ◽  
Hae-Rim Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
T Cells ◽  
Disease Activity ◽  
Plasma Levels ◽  
Control Group ◽  
Clinical Biomarkers ◽  
Reduction Group ◽  
Ifn Γ ◽  
Citrullinated Protein

Abstract Background: CD4+ T cells are crucial for the pathogenesis of rheumatoid arthritis (RA). The roles of gene overexpression in CD4+ T cells and the predictive roles of Th1- and Th17-related cytokines have not been clearly defined in patients with RA. Here, we investigated gene expression levels in CD4+ T cells in methotrexate (MTX)-naïve early RA (eRA) and evaluated changes in CD4+ T-cell-related cytokines during eRA. Methods: Patients with anti-citrullinated protein antibody (ACPA)-positive MTX-naïve eRA were recruited. Patients with osteoarthritis were evaluated as controls. Microarray analysis was used to identify overexpressed genes in CD4+ T cells, and reverse transcription quantitative polymerase chain reaction was used to validate the identified genes. Plasma cytokine levels were measured, and correlations with disease activity were assessed.Results: Thirty-four genes showed overexpression in CD4+ T cells from patients with ACPA-positive MTX-naïve eRA compared with controls. Nineteen were related to interferon (IFN)-γ, and nine were related to interleukin (IL)-17A; five were related to both IFN-γ and IL-17A. Plasma levels of five cytokines were elevated in the ACPA-positive MTX-naïve eRA group compared with those in the control group, and C-X-C motif chemokine ligand 10 was significantly elevated in the ACPA-positive MTX-naïve eRA group compared with that in the established active RA and OA groups. In established RA with low disease activity, the drug-free remission group/drug reduction group showed significantly lower IFN-γ and IL-17A levels than the drug maintenance group and relapse after drug reduction group. Conclusion: Our T2 research of IFN-γ emphasized that, not only the Th17 immune response, but the Th1 immune response is also very important for the RA pathogenesis. Concurrent increase in IFN-γ and IL-17 were observed in active stage of ACPA-positive MTX-naïve eRA, and the plasma levels of them could be useful for new clinical biomarkers before and/or after treatment of RA.

Expansions of CD4+CD28– and CD8+CD28– T cells in Granulomatosis with Polyangiitis and Microscopic Polyangiitis Are Associated with Cytomegalovirus Infection But Not with Disease Activity

2012 ◽  
Vol 39 (9) ◽  
pp. 1840-1843 ◽  
Author(s):  
PER ERIKSSON ◽  
CHRISTINA SANDELL ◽  
KARIN BACKTEMAN ◽  
JAN ERNERUDH
Keyword(s):  
T Cells ◽  
Disease Activity ◽  
Granulomatosis With Polyangiitis ◽  
Multivariate Analyses ◽  
Microscopic Polyangiitis ◽  
T Helper ◽  
Cmv Infection ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
Cmv Status

Objective.T helper cells lacking CD28 (CD4+CD28–) have been implicated in the pathogenesis of granulomatosis with polyangiitis (Wegener; GPA) and microscopic polyangiitis (MPA). Expansions of CD4+CD28– and CD8+CD28– T cells have also been associated with latent cytomegalovirus (CMV) infection. We assessed these T cells with and without coexpression of CD56 and CD57 in relation to vasculitis as well as CMV status.Methods.Blood from 16 patients in remission (12 GPA, 4 MPA), 18 patients with active vasculitis (12 GPA, 6 MPA), and 20 healthy controls was examined by flow cytometry for expression of CD4, CD8, CD56, CD57, and CD28 on T cells. The influence of age, CMV status, presence of disease, and disease activity on T cell subpopulations was tested with multiple regression analyses.Results.In active vasculitis, the total numbers and proportion of lymphocytes were decreased. Total numbers of CD4+, CD8+, CD4+CD28–, CD8+CD28–, CD4+CD57+, and CD8+CD57+ T subpopulations were decreased to the same extent, implying unchanged proportions. Multivariate analyses showed no associations between vasculitis and CD28– or CD57+ T subpopulations, whereas immunoglobulin G antibodies to CMV were associated with expanded proportions of CD28– and CD57+ T cells, in both the CD4+ and the CD8+ compartments.Conclusion.CD28– and CD57+ T cells were associated with latent CMV infection and not with a diagnosis of GPA or MPA. Vasculitis assessment should include CMV status.

scholarly journals Avacopan, a Selective C5a Receptor Antagonist, for Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

2022 ◽  
Author(s):  
Masayoshi Harigai ◽  
Hideto Takada
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Microscopic Polyangiitis ◽  
The United States ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
C5a Receptor ◽  
Primary Endpoints ◽  
Free Treatment ◽  
Secondary Endpoints ◽  
Improvement Score

Abstract Avacopan, an orally administered C5a receptor (C5aR) antagonist, has been approved for the treatment of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in Japan and the United States. In ADVOCATE Phase III clinical trial, patients with active MPA or GPA received either 30 mg avacopan twice daily or prednisone on a tapering schedule in combination with rituximab or cyclophosphamide (followed by azathioprine). The trial met its two primary endpoints: avacopan showed non-inferiority to prednisone for achieving remission at week 26 (avacopan, 72.3%; prednisone, 70.1%; p &lt; 0.001 for non-inferiority and p = 0.24 for superiority) and superiority for maintaining remission at week 52 (65.7% for avacopan, 54.9% prednisone, p &lt; 0.001 for non-inferiority and p = 0.007 for superiority). Of several key secondary endpoints tested, the glucocorticoid toxicity index (GTI)-cumulative worsening score and GTI-aggregate improvement score were significantly lower in the avacopan group than in the prednisone group at both weeks 26 and 52. Serious adverse events related and unrelated to the worsening vasculitis were reported at 10.2% and 37.3% in the avacopan group and at 14.0% and 39.0% in the prednisone group, respectively. Avacopan has set the stage for the semi-glucocorticoid-free or glucocorticoid-free treatment of MPA and GPA.

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