AB0026 DECREASE OF ANGIOGENIC T CELLS IN CONNECTIVE TISSUE DISEASE-ASSOCIATED INTERSTITIAL LUNG DISEASE

Background:Interstitial lung disease (ILD) is one of the most significant complications of connective tissue diseases (CTD), leading to an increase of the morbidity and mortality in patients with CTD [1]. A specific T cell subset termed angiogenic T cells (TAng), that promote endothelial repair and revascularization, have been involved in the pathogenesis of CTD [2-4]. However, to the best of our knowledge, no information regarding the role of TAng in CTD-ILD+ is available.Objectives:To study, for the first time, the potential role of TAng related to vascular damage in CTD-ILD+.Methods:Peripheral venous blood was collected from 40 patients with CTD-ILD+ and three comparative groups: 44 CTD-ILD- patients, 21 idiopathic pulmonary fibrosis (IPF) patients and 20 healthy controls (HC). All subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Quantification of TAng was performed by flow cytometry. TAng were considered as triple-positive for CD3, CD31 and CXCR4.Results:Patients with CTD-ILD+ exhibited a significantly lower TAng frequency than CTD-ILD- patients (p<0.001). Similar results were obtained when patients with CTD-ILD+ were compared with HC (p=0.004) although no difference was observed between CTD-ILD+ and IPF. In addition, a significant increase of TAng frequency was shown in patients with CTD-ILD- in relation to IPF patients (p<0.001), while no difference was observed between CTD-ILD- and HC.Conclusion:Our results reveal a decrease of TAng frequency related to vascular damage in CTD-ILD+. Furthermore, we disclose that the presence of ILD is associated with lower TAng frequency.References:[1]Expert Rev Clin Immunol 2018;14(1):69-82.[2]Circulation 2007;116(15):1671-82.[3]Ann Rheum Dis 2015 74(5):921-7.[4]PLoS One 2017;12(8):e0183102.Acknowledgements:Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: INNVAL20/06 (IDIVAL); RP-F: START PROJECT (FOREUM); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).Disclosure of Interests:Verónica Pulito-Cueto: None declared, Sara Remuzgo Martinez: None declared, Fernanda Genre: None declared, Belén Atienza-Mateo: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe-Fernández: None declared, Leticia Lera-Gómez: None declared, Raquel Pérez-Fernández: None declared, Pilar Alonso Lecue: None declared, Javier Rodriguez Carrio: None declared, Diana Prieto-Peña: None declared, Virginia Portilla: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Alfonso Corrales: None declared, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Speakers bureau: Pfizer, Abbvie, MSD, Grant/research support from: Pfizer, Abbvie, MSD

Download Full-text

Bronchoalveolar Lavage Fluid Reflects a TH1-CD21low B-Cell Interaction in CVID-Related Interstitial Lung Disease

Frontiers in Immunology ◽

10.3389/fimmu.2020.616832 ◽

2021 ◽

Vol 11 ◽

Author(s):

David Friedmann ◽

Susanne Unger ◽

Baerbel Keller ◽

Mirzokhid Rakhmanov ◽

Sigune Goldacker ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Interstitial Lung Disease ◽

Bronchoalveolar Lavage ◽

Lung Disease ◽

B Cell ◽

Cell Subset ◽

Immune Dysregulation

BackgroundAbout 20% of patients with common variable immunodeficiency (CVID) suffer from interstitial lung disease (ILD) as part of a systemic immune dysregulation. Current understanding suggests a role of B cells in the pathogenesis based on histology and increased levels of BAFF and IgM associated with active disease corroborated by several reports which demonstrate the successful use of rituximab in CVID-ILD. It is debated whether histological confirmation by biopsy or even video-assisted thoracoscopy is required and currently not investigated whether less invasive methods like a bronchoalveolar lavage (BAL) might provide an informative diagnostic tool.ObjectiveTo gain insight into potential immune mechanisms underlying granulomatous and lymphocytic interstitial lung disease (GLILD) and to define biomarkers for progressive ILD by characterizing the phenotype of B- and T-cell populations and cytokine profiles in BAL fluid (BALF) of CVID-ILD compared to sarcoidosis patients and healthy donors (HD).MethodsSixty-four CVID, six sarcoidosis, and 25 HD BALF samples were analyzed by flow cytometric profiling of B- and T-cells and for cytokines by ELISA and Multiplexing LASER Bead technology.ResultsBoth sarcoidosis and CVID-ILD are characterized by a predominantly T-cell mediated lymphocytosis in the BALF. There is an increase in T follicular helper (TFH)-like memory and decrease of regulatory T cells in CVID-ILD BALF. This TFH-like cell subset is clearly skewed toward TH1 cells in CVID-ILD. In contrast to sarcoidosis, CVID-ILD BALF contains a higher percentage of B cells comprising mostly CD21low B cells, but less class-switched memory B cells. BALF analysis showed increased levels of APRIL, CXCL10, and IL-17.ConclusionUnlike in sarcoidosis, B cells are expanded in BALF of CVID-ILD patients. This is associated with an expansion of TFH- and TPH-like cells and an increase in APRIL potentially supporting B-cell survival and differentiation and proinflammatory cytokines reflecting not only the previously described TH1 profile seen in CVID patients with secondary immune dysregulation. Thus, the analysis of BALF might be of diagnostic value not only in the diagnosis of CVID-ILD, but also in the evaluation of the activity of the disease and in determining potential treatment targets confirming the prominent role of B-cell targeted strategies.

Download Full-text

AB0094 INCREASE OF ENDOTHELIAL PROGENITOR CELLS IN SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2350 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1076.1-1076

Author(s):

V. Pulito-Cueto ◽

S. Remuzgo Martinez ◽

F. Genre ◽

B. Atienza-Mateo ◽

V. M. Mora-Cuesta ◽

...

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Potential Role ◽

Type I ◽

Research Support ◽

Endothelial Progenitor

Background:Endothelial progenitor cells (EPC), involved in vasculogenesis and endothelial tissue repair, have been described as relevant players in vascular and connective tissue diseases [1-2]. In this regard, a previous study of our group disclosed that the degree of EPC frequency may help to identify the presence of interstitial lung disease (ILD) in rheumatoid arthritis patients [3]. Given that ILD is the main cause of mortality in patients with systemic sclerosis (SSc) [1, 4-6], the understanding of the role of EPC in the mechanism of SSc-ILD+ vasculopathy is crucial.Objectives:To assess the potential role of EPC on vascular dysfunction associated with the presence of ILD in patients with SSc.Methods:Peripheral venous blood was collected from a total of 39 patients with SSc, 20 with ILD (SSc-ILD+) and 19 without ILD (SSc-ILD-). All subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Quantification of EPC was analyzed by flow cytometry. EPC were considered as CD34+, CD45Low, CD309+ and CD133+.Results:Statistically significant differences in EPC frequency between patients with SSc-ILD+ and patients with SSc-ILD- were disclosed. Specifically, an increase of EPC frequency was observed in SSc-ILD+ patients when compared to patients with SSc-ILD- (mean ± standard deviation: 0.033 ± 0.012 versus 0.021 ± 0.017, respectively, p=0.012).Conclusion:Our results suggest a potential role of EPC on vascular damage associated with the manifestation of ILD in patients with SSc.References:[1]Eur J Rheumatol 2020;7(Suppl 3):S139-S146.[2]Arthritis Rheum 2009;60(11):3168-79.[3]J Clin Med 2020;9(12):4098.[4]Ann Rheum Dis 2007;66(7):940-4.[5]Rheumatology (Oxford) 2010;49(12):2375-80.[6]Eur Respir Rev 2015;24(135):102-14.Acknowledgements:Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: INNVAL20/06 (IDIVAL); RP-F: START PROJECT (FOREUM); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).Disclosure of Interests:Verónica Pulito-Cueto: None declared, Sara Remuzgo Martinez: None declared, Fernanda Genre: None declared, Belén Atienza-Mateo: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe-Fernández: None declared, Leticia Lera-Gómez: None declared, Raquel Pérez-Fernández: None declared, Diana Prieto-Peña: None declared, Virginia Portilla: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Alfonso Corrales: None declared, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Speakers bureau: Pfizer, Abbvie, MSD, Grant/research support from: Pfizer, Abbvie, MSD

Download Full-text

SAT0014 ENDOTHELIAL PROGENITOR CELLS: ROLE IN ENDOTHELIAL DAMAGE OF INTERSTITIAL LUNG DISEASE ASSOCIATED TO RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3228 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 937.1-937

Author(s):

V. Pulito-Cueto ◽

S. Remuzgo-Martínez ◽

F. Genre ◽

V. M. Mora-Cuesta ◽

D. Iturbe Fernández ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Potential Role ◽

Endothelial Damage ◽

Research Support ◽

Endothelial Progenitor

Background:Interstitial lung disease (ILD) is one of the most significant comorbidities of rheumatoid arthritis (RA), increasing the mortality in these patients [1,2]. Although the pathogenesis of ILD associated to RA (RA-ILD+) remains poorly defined [1], it is known that vascular tissue plays a crucial role in lung physiology [3]. In this context, a population of cells termed endothelial progenitor cells (EPC) are involved in vasculogenesis and endothelial tissue repair [4]. Previous reports suggest the implication of EPC in different conditions such as RA and idiopathic pulmonary fibrosis (IPF), the most common and destructive ILD [5,6]. Nevertheless, little is known about their specific role in RA-ILD+.Objectives:The purpose of this study was to shed light on the potential role of EPC in endothelial damage in RA-ILD+.Methods:Peripheral venous blood was collected from a total of 68 individuals (18 with RA-ILD+, 17 with RA-ILD-, 19 with IPF and 14 healthy controls). All subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Quantification of EPC was analyzed by the expression of surface antigens by flow cytometry. The combination of antibodies against the stem cell marker CD34, the immature progenitor marker CD133, the endothelial marker VEGF receptor 2 (CD309) and the common leukocyte antigen CD45 was used. EPC were considered as CD34+, CD45Low, CD309+and CD133+. All statistical analyses were performed using Prism software 5 (GraphPad).Results:EPC frequency was significantly increased in patients with RA-ILD+, RA-ILD-and IPF compared to controls (p=0.001, p=0.002, p< 0.0001, respectively). Nevertheless, patients with RA, both RA-ILD+and RA-ILD-, showed a lower frequency of EPC than those with IPF (p= 0.048, p= 0.006, respectively).Conclusion:Our results provide evidence for a potential role of EPC as a reparative compensatory mechanism related to endothelial damage in RA-ILD+, RA-ILD-and IPF patients. Interestingly, EPC frequency may help to establish a differential diagnostic between patients with IPF and those who have an underlying autoimmune disease (RA-ILD+).References:[1] J Clin Med 2019; 8: 2038;[2] Arthritis Rheumatol 2015; 67: 28-38;[3] Nat Protoc 2015; 10: 1697-1708;[4] Science 1997; 275: 964-966;[5] Rheumatology (Oxford) 2012; 51: 1775-1784;[6] Angiogenesis 2013; 16: 147-157.Acknowledgments:Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: PI18/00042 (ISCIII-ERDF); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).Disclosure of Interests:Verónica Pulito-Cueto: None declared, Sara Remuzgo-Martínez: None declared, Fernanda Genre: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe Fernández: None declared, Sonia Fernández-Rozas: None declared, Leticia Lera-Gómez: None declared, Pilar Alonso Lecue: None declared, Javier Rodriguez Carrio: None declared, Belén Atienza-Mateo: None declared, Virginia Portilla: None declared, David Merino: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD, Alfonso Corrales Speakers bureau: Abbvie, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD

Download Full-text

Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37132013000600012 ◽

2013 ◽

Vol 39 (6) ◽

pp. 728-741 ◽

Cited By ~ 4

Author(s):

Daniel Antunes Silva Pereira ◽

Alexandre de Melo Kawassaki ◽

Bruno Guedes Baldi

Keyword(s):

Interstitial Lung Disease ◽

Connective Tissue ◽

Lung Disease ◽

Connective Tissue Disease ◽

Current Knowledge ◽

Pulmonary Involvement ◽

Pathophysiological Role ◽

History Of

The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.

Download Full-text

Role of gastroesophageal reflux in interstitial lung disease associated to connective tissue disease.

10.1183/13993003.congress-2018.pa2967 ◽

2018 ◽

Author(s):

Carolina Diaz Cuña ◽

Sandra Consani ◽

Veronica Torres ◽

Fernanda Alonso ◽

Adriana Bérez

Keyword(s):

Interstitial Lung Disease ◽

Connective Tissue ◽

Gastroesophageal Reflux ◽

Lung Disease ◽

Connective Tissue Disease

Download Full-text

The role of biologics in treatment of connective tissue disease-associated interstitial lung disease

QJM ◽

10.1093/qjmed/hcv007 ◽

2015 ◽

Vol 108 (9) ◽

pp. 683-688 ◽

Cited By ~ 4

Author(s):

C. Sharp ◽

N. Dodds ◽

L. Mayers ◽

A.B. Millar ◽

H. Gunawardena ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Connective Tissue ◽

Lung Disease ◽

Connective Tissue Disease

Download Full-text

POS1449 SEGMENTED SHORT-FORMAT ONLINE EDUCATION SIGNIFICANTLY INCREASES PREDICTION, PROGNOSIS, AND MANAGEMENT OF FIBROSING INTERSTITIAL LUNG DISEASE ASSOCIATED WITH CONNECTIVE TISSUE DISEASE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1510 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1008.1-1009

Author(s):

C. Rohani-Montez ◽

M. Calle ◽

C. Allen ◽

T. Maher ◽

V. Smith ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Connective Tissue ◽

Online Education ◽

Lung Disease ◽

Disease Progression ◽

Correct Response ◽

Response Rate ◽

Research Support ◽

Post Assessment ◽

Correct Response Rate

Background:Identifying fibrosing interstitial lung disease (ILD) at the earliest opportunity remains one of the most urgent challenges for the effective management of this potentially rapidly progressive and burdensome condition, which is frequently associated with several connective tissue diseases (CTDs). However, knowledge on how to identify early hallmarks and predictors of fibrosing ILD, as well as knowing which steps to take next is frequently lacking in clinical practice.Objectives:This study was conducted to determine whether online independent medical education could improve rheumatologists’ and pulmonologists’ knowledge and competence in identifying and managing progressive fibrosing ILDs earlier in the disease course.Methods:Rheumatologists and pulmonologists participated in five ~10-min presentations about the early identification of fibrosing ILD in patients with or without CTDs and completed all pre- and post-questions.1 The effects of the education on knowledge and competence were assessed using a 3-question, repeated pairs, pre-assessment/post-assessment study design. For all questions combined, the chi-square test assessed differences from pre- to post-assessment. P values <.05 are statistically significant. The activity launched on October 9, 2020, and data were collected through December 18, 2020.Results:Overall significant improvements were seen after participation for both rheumatologists (average correct response rate of 28% at pre-assessment vs 74% at post-assessment; P<.001, representing a 165% relative percentage change [RPC]; N=39), and pulmonologists (average correct response rate of 39% at pre-assessment vs 67% at post-assessment; P<.001, representing a 72% RPC; N=102). Specifically, significant improvements were observed in clinicians’ knowledge of predictors of fibrosing ILD in patients with CTD, as well as competence in selecting the right HRCT parameters to assess prognosis and select a treatment approach to reduce the risk of disease progression (Figure 1).Figure 1.After participating in the activity, 59% of rheumatologists and 50% of pulmonologists had measurable improved confidence related to identifying early disease progression in patients with progressive fibrosing ILDs.Given the very low rates of correct responses at baseline regarding predictors of fibrosing ILD and assessing prognosis, it will be important to continue to reinforce these learnings in ongoing educational programs.Conclusion:This study demonstrates the success of segmented online education in improving rheumatologists’ and pulmonologists’ knowledge and competence in evaluating risk and prognosis of fibrosing ILD and managing patients with CTD-ILDs. This could lead to earlier changes in therapeutic approach for those with signs of progression and result in improved overall outcomes for these patients.References:[1]Kolb M, Maher T, Smith V, Jacob J, Rimekasten G. Catching and Managing Progressive Fibrosing Interstitial Lung Disease Progression Earlier. Launched: Oct 9, 2020. Data as of Dec 18, 2020. Available at www.medscape.org/viewarticle/938826Disclosure of Interests:Christy Rohani-Montez: None declared, Marinella Calle: None declared, Chris Allen: None declared, Toby Maher Speakers bureau: Astra Zeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Galapagos, Galecto, GlaxoSmithKline R&D, Indalo, IQVIA, Pliant, Respivant, Roche and Theravance, Consultant of: Astra Zeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Galapagos, Galecto, GlaxoSmithKline R&D, Indalo, IQVIA, Pliant, Respivant, Roche and Theravance, Grant/research support from: Astra Zeneca and GlaxoSmithKline R&D, Vanessa Smith Speakers bureau: Boehringer-Ingelheim Pharma GmbH&Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH&Co, Grant/research support from: Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer-Ingelheim, Pharma GmbH&Co, and Janssen-Cilag NV, Joseph Jacob Speakers bureau: Boehringer-Ingelheim; Roche, Consultant of: Boehringer-Ingelheim, Grant/research support from: GlaxoSmithKline, Gabriela Riemekasten Speakers bureau: AbbVie; Actelion; Boehringer-Ingelheim, Consultant of: Actelion; CellTrend; Janssen, Grant/research support from: AbbVie; Actelion, Martin Kolb Speakers bureau: AstraZeneca; Boehringer-Ingelheim; Novartis; Roche, Consultant of: AbbVie Inc.; Algernon Pharma; AstraZeneca;, Boehringer-Ingelheim; Cipla; Covance; EPG Health; Galapagos NV; Gilead; GlaxoSmithKline; Indalo; MitoImmune Therapeutics Inc; Novartis; Pieris; Prometic (now Liminal Biosciences); Roche; Third Pole Inc.; TwoXAR Inc., Grant/research support from: Boehringer-Ingelheim; GlaxoSmithKline; Novartis; Prometic; Roche; Avalyn

Download Full-text