Differential effects of treatment with a small-molecule VLA-4 antagonist before and after onset of relapsing EAE

Blood ◽  
2003 ◽  
Vol 102 (13) ◽  
pp. 4464-4471 ◽  
Author(s):  
Bradley E. Theien ◽  
Carol L. Vanderlugt ◽  
Cheryl Nickerson-Nutter ◽  
Mark Cornebise ◽  
Daniel M. Scott ◽  
...  
Keyword(s):  
T Cells ◽  
Small Molecule ◽  
Clinical Symptoms ◽  
Severe Disease ◽  
Disease Onset ◽  
Proteolipid Protein ◽  
Clinical Disease ◽  
Disease Remission ◽  
Before And After ◽  
Late Antigen

AbstractInteraction of very late antigen-4 (VLA-4) with its ligand vascular cell adhesion molecule-1 (VCAM-1) is required for central nervous system (CNS) migration of encephalitogenic T cells in relapsing experimental autoimmune encephalomyelitis (R-EAE). Anti-VLA-4 monoclonal antibody (mAb) treatment prior to EAE onset inhibits disease induction; however, treatment initiated after the appearance of clinical symptoms increases relapse rates, augments Th1 responses, and enhances epitope spreading perhaps due to the activation of costimulatory signals. To negate the potential costimulatory activity of intact anti-VLA-4, we examined the ability of BIO 5192, a small-molecule VLA-4 antagonist, to regulate active proteolipid protein 139-151 (PLP139-151)-induced R-EAE. BIO 5192 administered one week after peptide priming (ie, before clinical disease onset) delayed the clinical disease onset but led to severe disease exacerbation upon treatment removal. BIO 5192 treatment initiated during disease remission moderately enhanced clinical disease while mice were on treatment and also resulted in posttreatment exacerbation. Interestingly, BIO 5192 treatment begun at the peak of acute disease accelerated entrance into disease remission and inhibited relapses, but treatment removal again exacerbated disease. Enhanced disease was caused by the release of encephalitogenic cells from the periphery and the rapid accumulation of T cells in the CNS. Collectively, these results further demonstrate the complexity of VLA-4/VCAM interactions, particularly in a relapsing-remitting autoimmune disease. (Blood. 2003;102:4464-4471)

scholarly journals Differences in Clinical Characteristics Between Delta Variant and Wild-Type SARS-CoV-2 Infected Patients

2022 ◽  
Vol 8 ◽  
Author(s):  
Zhenkui Hu ◽  
Xing Huang ◽  
Jianguo Zhang ◽  
Shixiang Fu ◽  
Daoyin Ding ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Clinical Symptoms ◽  
Hematological Parameters ◽  
Severe Disease ◽  
Disease Onset ◽  
Smoking History ◽  
Time Interval ◽  
Wild Type ◽  
Disease Condition ◽  
The Difference

Background: As delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevailed in the current coronavirus disease 2019 (COVID-19) pandemic, its clinical characteristics with the difference from those of wild-type strains have been little studied.Methods: We reported one cohort of 341 wild-type patients with COVID-19 admitted at Wuhan, China in 2020 and the other cohort of 336 delta variant patients with COVID-19 admitted at Yangzhou, China in 2021, with comparisons of their demographic information, medical history, clinical manifestation, and hematological data. Furthermore, within the delta variant cohort, patients with none, partial, and full vaccination were also compared to assess vaccine effectiveness.Findings: For a total of 677 patients with COVID-19 included in this study, their median age was 53.0 years [interquartile range (IQR): 38.0–66.0] and 46.8% were men. No difference was found in age, gender, and percentage of patients with the leading comorbidity between wild-type and delta variant cohorts, but delta variant cohort showed a lessened time interval between disease onset to hospitalization, a reduced portion of patients with smoking history, and a lowered frequency of clinical symptoms. For hematological parameters, most values demonstrated significant differences between wild-type and delta variant cohorts, while full vaccination rather than partial vaccination alleviated the disease condition. This reflected the viremic effect of delta variant when vaccination succeeds or fails to protect.Interpretation: Delta variant of SARS-CoV-2 may cause severe disease profiles, but timely diagnosis and full vaccination could protect patients with COVID-19 from worsened disease progression.

scholarly journals POS1307 ULTRASOUND-DETECTED TENOSYNOVITIS IN ANKLES WITH CLINICALLY ACTIVE DISEASE OF CHILDREN WITH NEW-ONSET JUVENILE IDIOPATHIC ARTHRITIS DOES NOT AFFECT THE CHANCE TO ACHIEVE DISEASE REMISSION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 935.2-936
Author(s):  
S. Lanni ◽  
O. De Lucia ◽  
S. Orsi ◽  
S. Costi ◽  
G. Beretta ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Disease Onset ◽  
Clinical Disease ◽  
Common Finding ◽  
Disease Remission ◽  
Tendon Pathology ◽  
Active Disease ◽  
New Onset

Background:The ankle is one of the most commonly affected sites in juvenile idiopathic arthritis (JIA). This region has a complex anatomical structure owing to the presence of multiple joint recesses and surrounding tendons. While the prognostic value of ultrasound (US)-detected arthritis has been investigated in recent studies, the role of tenosynovitis in JIA remains still unexplored.Objectives:To investigate: 1) US features of ankle involvement in JIA at disease onset; 2) the predictive value of US-detected tenosynovitis in ankles with clinically active disease of children with new-onset JIA.Methods:The clinical charts of all consecutive patients with new-onset JIA between May 2018 and January 2020 at study centres (Policlinico and G.Pini Hospitals of Milan) and with clinically active ankle disease among the joints affected were reviewed retrospectively. Data on ankle US assessment were retrieved and patients were then stratified as follows: 1) patients with detection on US of isolated arthritis in at least one of the joint recesses of the ankle region; 2) patients with detection on US of tenosynovitis in at least one of the tendon compartments of the ankle irrespective of the presence of concomitant arthritis. For each of these two categories, estimation of patients who were able to achieve clinical disease remission at 12 months since disease onset was evaluated.Results:Twenty-seven new-onset JIA patients were found to have clinical involvement of the ankle among the joints affected. Nine of them (33.3%) showed on US isolated arthritis of the ankle, whereas US-detected tenosynovitis was found in 18 (66.7%) patients. The amount of patients who were able to achieve disease remission at 12-months was the same (66.7%) for both patients with and without US-detected tenosynovitis in the ankle (12/18 and 6/9 patients, respectively). In patients with US-detected tenosynovitis and clinical disease remission at 12 months, the lateral tendon compartment (LTC) was the tendon site more frequently affected by pathology (75.0%). Patients with US-detected tenosynovitis that did not achieve clinical disease remission at follow-up had the highest frequency of tendon pathology on US in the medial tendon compartment (MTC) (83.3%). The anterior tendon compartment was the less frequently affected tendon compartment of the ankle in all patients (33.3% in both patients with and without clinical remission of disease at the 12-months follow-up visit).Conclusion:US-detected tenosynovitis of the ankle is a common finding in patients with new-onset JIA with clinically ankle disease activity and is more frequent than the detection on US of isolated arthritis. The MTC and LTC are the tendon compartments more commonly affected on US. The detection on US of tenosynovitis at disease onset in ankles with clinical disease activity did not seem to affect the change to achieve the overall clinical disease remission compared to patients without tendon pathology but with joint disease in the ankle region.Disclosure of Interests:None declared

scholarly journals Cytolytic memory CD4+ T cell clonotypes are expanded during Plasmodium falciparum infection

2021 ◽  
Author(s):  
Raquel Furtado ◽  
Fabien Delahaye ◽  
Jinghang Zhang ◽  
Joowhan Sung ◽  
Paul Karell ◽  
...  
Keyword(s):  
T Cells ◽  
Plasmodium Falciparum ◽  
T Cell ◽  
Malaria Infection ◽  
Clinical Symptoms ◽  
Severe Disease ◽  
Cd4 T Cell ◽  
Effective Vaccine ◽  
T Helper 1 ◽  
Endemic Region

Plasmodium falciparum (Pf) malaria causes high rates of morbidity and mortality and lacks a sufficiently effective vaccine. Clinical immunity develops in residents of malaria endemic regions which confers reduced clinical symptoms during infection and protection against severe disease. We hypothesized that understanding the immune mechanisms of clinical immunity could inform vaccine design to improve efficacy. We compared the peripheral blood cellular and humoral immune responses during a mild episode of Pf malaria infection. Participants were classified as either clinically susceptible or clinically protected, based on the number of recurrent clinical infections over an 18-month longitudinal study in a malaria endemic region in Malawi. Susceptible participants had three or more recurrent clinical episodes while clinically immune individuals had one or none. Protected participants exhibited higher plasma immunoglobulin G (IgG) breadth and titers against Pf antigens, and greater antibody (Ab)-dependent Pf opsonization compared to susceptible participants. Using high dimensional mass cytometry (CyTOF), spectral flow cytometry and single-cell transcriptomic analyses, we identified expanded memory CD4+ T cell clones sharing identical T cell receptor clonotypes in the blood of protected participants during malaria infection. These cells express a strong cytolytic T helper 1 effector program with transcripts encoding granzymes (A, B, H, M), granulysin, NKG7 and the Zeb2 master transcriptional regulator of terminally differentiated effector T cells. Memory CD4+ T cells expressing Zeb2+ were CD39hiTIGIThi and expressed multiple chemotactic and checkpoint inhibitory receptors, although the cellular levels of several of these receptors were reduced in protected compared to susceptible individuals. We propose that clonally expanded Zeb2+ cytolytic memory CD4+ Th1 cells could represent essential contributors to clinical immunity against Pf malaria.

scholarly journals 519. Immune responses and COVID-19 severity

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S325-S325
Author(s):  
mirella salvatore ◽  
Charles K Vorkas ◽  
Harjot Sing ◽  
Ayana Morales ◽  
Rosemary Soave ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Disease Severity ◽  
Severe Disease ◽  
Laboratory Data ◽  
Disease Onset ◽  
Disease Evolution ◽  
Igm Antibody ◽  
Immune Correlates ◽  
Over Time

Abstract Background The coronavirus-19-disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to >200 countries and surpassed 7 million cases. There is a broad range of COVID-19 illness, ranging from milder disease to a rapidly progressive respiratory disease and ARDS. The causes of this different clinical course and the drivers for severe disease are currently unknown. A fulminant increase of pro-inflammatory cytokines is thought to play a role in causing a rapid disease evolution, however the immune correlates of severe COVID-19 remain unclear. Methods To gain insight into relationship between immune responses and disease severity we built a longitudinal cohort of 40 adult patients with known COVID-19. Samples were collected at diagnosis and every 7 days until hospital discharge or death. As controls we also included a group of convalescent patients, and subjects who tested negative for COVID-19 by PCR. Clinical and laboratory data and were also collected. Multicolor flow cytometry was used to determine the presence and phenotype of B, T and natural killer (NK) cells. We also identified specific sub-populations (Tfh, activated/cytotoxic CD8 and NK) and assessed lymphoid exhaustion of different cell types such as naïve, memory T cells, or NK over time. Anti-Sars-CoV2 IgG and IgM antibody were detected using lateral flow method. Results We found that the absolute number of lymphocytes and monocytes was decreased starting at diagnosis and correlated with disease severity. Disease severity correlated with decreased NK and T cell. In severe COVID-19 cases, NK cell populations were strongly decreased over time in intubated patients while they recovered in patients who improved and were discharged. CD8+ were also decreased at disease onset and seemed to correlate with disease severity. A high percentage of CD4+ and CD8+ T cells showed an exhausted phenotype. All patients tested at admission had IgM antibody responses irrespective of the course of the disease. Further analyses are ongoing. Conclusion The characterization and role of the immune responses in COVID-19 evolution is still under investigation. Further characterization of viral and immune factors will help in identifying subjects at high risk of severe disease and targets for intervention. Disclosures All Authors: No reported disclosures

scholarly journals Therapeutic Use of Cerebellar Intermittent Theta Burst Stimulation (iTBS) in a Sardinian Family Affected by Spinocerebellar Ataxia 38 (SCA 38)

2021 ◽  
Author(s):  
Angela Sanna ◽  
Paolo Follesa ◽  
Paolo Tacconi ◽  
Mariangela Serra ◽  
Maria Giuseppina Pisu ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Rating Scale ◽  
Clinical Symptoms ◽  
Therapeutic Use ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Motor Cortex Excitability ◽  
Before And After ◽  
Theta Burst ◽  
Serum Bdnf

AbstractSpinocerebellar ataxia 38 (SCA 38) is an autosomal dominant disorder caused by conventional mutations in the ELOVL5 gene which encodes an enzyme involved in the synthesis of very long fatty acids, with a specific expression in cerebellar Purkinje cells. Three Italian families carrying the mutation, one of which is of Sardinian descent, have been identified and characterized. One session of cerebellar intermittent theta burst stimulation (iTBS) was applied to 6 affected members of the Sardinian family to probe motor cortex excitability measured by motor-evoked potentials (MEPs). Afterwards, patients were exposed to ten sessions of cerebellar real and sham iTBS in a cross-over study and clinical symptoms were evaluated before and after treatment by Modified International Cooperative Ataxia Rating Scale (MICARS). Moreover, serum BDNF levels were evaluated before and after real and sham cerebellar iTBS and the role of BDNF Val66Met polymorphism in influencing iTBS effect was explored. Present data show that one session of cerebellar iTBS was able to increase MEPs in all tested patients, suggesting an enhancement of the cerebello-thalamo-cortical pathway in SCA 38. MICARS scores were reduced after ten sessions of real cerebellar iTBS showing an improvement in clinical symptoms. Finally, although serum BDNF levels were not affected by cerebellar iTBS when considering all samples, segregating for genotype a difference was found between Val66Val and Val66Met carriers. These preliminary data suggest a potential therapeutic use of cerebellar iTBS in improving motor symptoms of SCA38.

scholarly journals AB0858 SUCCESSFUL TERM PREGNANCY IN A PATIENT WITH GRANULOMATOSIS WITH POLYANGIITIS AFTER UNDERGOING RITUXIMAB THERAPY - CASE REPORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1452.2-1453
Author(s):  
O. Sirenko ◽  
O. Kuryata ◽  
T. Lysunets ◽  
A. Legkobyt ◽  
H. Mostova
Keyword(s):  
Case Report ◽  
Granulomatosis With Polyangiitis ◽  
Disease Onset ◽  
Biological Agents ◽  
Term Pregnancy ◽  
Aseptic Necrosis ◽  
Azathioprine Therapy ◽  
Disease Remission ◽  
Obstetric Medicine ◽  
Patient Reported

Background:Granulomatosis with polyangiitis (GWP) is a relatively rare disease with the lack of experience in the management of pregnancy currently. Potentially negative factors of pregnancy prognosis are both disease-related and teratogenic effects of specific vasculitis therapy [1].Objectives:To describe a clinical case of Successful term pregnancy in a patient with Granulomatosis with polyangiitis after undergoing rituximab therapy.Methods:19 years-old woman was admitted to the rheumatology department of Clinical Regional Hospital After Mechnicov in 2013 with the debut of Granulomatosis with polyangiitis. Her disease course included recurrent rhinitis and sinusitis, Granulomatosis of the eye orbits. Positive ANCA titers were present in the disease onset. In the preceding 7 years she had been treated with corticosteroids, cyclophospan (discontinuated in 2017 because of lack of efficiency), than azathioprine. Aseptic necrosis of the both femoral head was estimated on fifth disease year. In 2018 azathioprine therapy had been discontinued owing to the disease progression and biological agents were prescribed – rituximab with positive effect. The disease remission was achived by rituximab therapy, the patient was warned about the need for contraception. The last dose of rituximab was introduced in February 2020. However, in March 2020, the patient reported pregnancy and therapy was discontinued. At the onset of pregnancy she was treated with 6 mg oral methylprednisolone. Daily and this dose was stable till all pregnancy period. Fetal growth assessment, congenital abnormalities screening test, and laboratory tests for gestational diabetes and preeclampsia were unremarkable during all gestational trimesters. The ANCA titers remained negative and renal function was normal and there was no flare during all pregnancy period.Results:At 38 weeks’ gestation a spontataneous labor started without induction. A 3270-g healthy boy delivered with APGAR score of 9 at 1 minute and 5 minutes. Postpartum the disease remained in remission, and the patient was maintained on corticosteroids. The infant was healthy, with normal development.Conclusion:Thus, the use of biological agents therapy in patients with GWP shows possible ways to safe reproductive potential with disease remission achievement.References:[1]Daher A, Sauvetre G, Girszyn N, Verspyck E, Levesque H, Le Besnerais M. Granulomatosis with polyangiitis and pregnancy: A case report and review of the literature. Obstetric Medicine. 2020;13(2):76-82. doi:10.1177/1753495X18822581Disclosure of Interests:None declared

scholarly journals Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David S. Fischer ◽  
Meshal Ansari ◽  
Karolin I. Wagner ◽  
Sebastian Jarosch ◽  
Yiqi Huang ◽  
...  
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Rna Sequencing ◽  
Ex Vivo ◽  
Severe Disease ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Single Cell Rna Sequencing

AbstractThe in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we use single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients. To do so, we induce transcriptional shifts by antigenic stimulation in vitro and take advantage of natural T cell receptor (TCR) sequences of clonally expanded T cells as barcodes for ‘reverse phenotyping’. This allows identification of SARS-CoV-2-reactive TCRs and reveals phenotypic effects introduced by antigen-specific stimulation. We characterize transcriptional signatures of currently and previously activated SARS-CoV-2-reactive T cells, and show correspondence with phenotypes of T cells from the respiratory tract of patients with severe disease in the presence or absence of virus in independent cohorts. Reverse phenotyping is a powerful tool to provide an integrated insight into cellular states of SARS-CoV-2-reactive T cells across tissues and activation states.

scholarly journals Endoscopically controlled surgery with open hemilaminectomy for the treatment of intradural extramedullary tumors: an operative technique and short-term outcomes of 20 consecutive cases

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaorong Yan ◽  
Huiqing Wang ◽  
Cai Li ◽  
Yuanxiang Lin ◽  
Lin Lin ◽  
...  
Keyword(s):  
Surgical Technique ◽  
Spinal Deformity ◽  
Tumor Recurrence ◽  
Clinical Symptoms ◽  
Short Term ◽  
Before And After ◽  
Intradural Extramedullary ◽  
Controlled Surgery

Abstract Background To present a surgical technique for the treatment of intradural extramedullary (IDEM) tumors by using endoscopically controlled surgery with open hemilaminectomy technique. Methods In this study, 20 patients with 22 IDEM tumors were enrolled. An endoscopically controlled surgery with open hemilaminectomy was employed to remove the tumors. Data related to clinical symptoms and medical images before and after surgery were collected for perioperative evaluation and follow-up analysis. Results All the tumors in 20 patients were well removed. The clinical symptoms were significantly reduced in all the patients as well. The short-term follow-up data showed that there was no tumor recurrence or spinal deformity. Conclusion The endoscopically controlled surgery with open hemilaminectomy technique provided favorable exposure and satisfactory resection to the IDEM tumors. It may be an effective surgical method for treating IDEM tumors. Larger samples and longer follow-up data are needed to verify its long-term effectiveness.

scholarly journals THU0351 MUSCLE INVOLVEMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS AND ANTI-PM/SCL+ ANTIBODIES IS ASSOCIATED WITH CARDIAC AND PULMONARY INVOLVEMENT. ANALYSIS OF THE MULTICENTRE EUSTAR COHORT.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 407.1-407
Author(s):  
M. G. Lazzaroni ◽  
S. Zingarelli ◽  
P. Airò ◽  
Y. Allanore ◽  
O. Distler
Keyword(s):  
Systemic Sclerosis ◽  
Cardiac Involvement ◽  
Severe Disease ◽  
Disease Onset ◽  
Pulmonary Involvement ◽  
Left Ventricular ◽  
Research Support ◽  
Muscle Involvement ◽  
Group A ◽  
Tendon Friction Rubs

Background:Anti-PM/Scl antibodies positivity has been associated with frequent skeletal muscle involvement in patients with Systemic Sclerosis (SSc) in different studies, including the EUSTAR cohort (1). Moreover, although myositis has been previously associated with heart involvement in SSc patients (2), this issue has never been explored among anti-PM/Scl+ patients.Objectives:To evaluate the cardiac involvement in anti-PM/Scl patients with SSc in the large multicentre EUSTAR database, with focus on the subgroup of patients with muscle involvement.Methods:Patients from the EUSTAR database were included when the item anti-PM/Scl was fulfilled in at least one visit.Results:Anti-PM/Scl status was available in 7,353 SSc patients from EUSTAR database: 295 were anti-PM/Scl+. After exclusion of 151 patients with multiple autoantibody positivity, 144 anti-PM/Scl + patients were compared with 7,058 anti-PM/Scl- patients. Among them, 3,120 (44.2%) were positive for ACA, 2,361 (33.5%) for anti-Topo I and 274 (3.88%) for anti-RNAP3.Regarding the specific cardiac outcomes, in the anti-PM/Scl+ as compared to the anti-PM/Scl- group, a decreased rate of elevated sPAP at ECHO was recorded (12.8% vs 25.0%, p:0.001), while no differences were observed in the frequency of conduction blocks (26.2% vs 23.7%, p:0.526), abnormal diastolic function (33.9% vs 36.4%, p:0.582), pericardial effusion (10.2% vs 10.9%, p:1.000) and LVEF ≤50% (4.76% vs 6.11%, p:0.818). In multivariate analysis, adjusted for age at disease onset, sex, and disease duration, the negative association of anti-PM/Scl with elevated sPAP was not confirmed (p:0.061).When comparing anti-PM/Scl+ patients with (n=47) and without (n=87) CK elevation, the former group had a higher frequency of conduction blocks (43.2% vs 17.5%, p:0.005; OR 95% CI 3.47, 1.51-7.97) and left ventricular dysfunction, both diastolic (45.6% vs 27.2%, p:0.050; OR 95% CI 2.25, 1.05-4.81) and systolic (LVEF ≤50% 13.3% vs 0%, p:0.018; OR 95% CI 16.8, 0.87-324). Moreover, anti-PM/Scl+ patients with CK elevation had significantly increased rate of lung fibrosis on HRCT (p:0.045), intestinal symptoms (p:0.017), joint contractures (p:0.045) and tendon friction rubs (p:0.034).Conclusion:In the largest series of anti-PM/Scl positive SSc patients so far reported, muscle involvement in anti-PM/Scl+ patients (defined as increased serum CK) seems to represent a marker of a more severe disease phenotype, including a higher frequency of cardio-pulmonary involvement.References:[1]Lazzaroni MG, et al. Ann Rheum Dis 2018. 77 (2), 421-2.[2]Follansbee WP, et al. Am Heart J 1993. 125: 194-203.Acknowledgments:Authors would like to thank the patients’ association GILS (Gruppo Italiano Lotta Sclerodermia) for the grant that supported the project.Disclosure of Interests:Maria Grazia Lazzaroni: None declared, Stefania Zingarelli: None declared, Paolo Airò: None declared, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

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