Rheumatology Commons^™

Sputum Lautropia Is Decreased In Rheumatoid Arthritis-Associated Pulmonary Fibrosis, Timothy M. Wilson, Brendan Allen, J. Kirk Harris, Kristine A. Kuhn, Kevin D. Deane, Stephen M. Humphries, Joyce S. Lee, Joshua J. Solomon, M. Kristen Demoruelle

Division of Rheumatology Faculty Papers

OBJECTIVE: To investigate whether lung microbial composition differs between individuals with rheumatoid arthritis and pulmonary fibrosis (RA-PF) compared to those without fibrosis (RA-no-PF).

METHODS: We enrolled 54 RA patients (22 RA-PF, 32 RA-no-PF) from rheumatology and pulmonary clinics. PF was defined by high-resolution computed tomography (HRCT) findings. Induced sputum was analyzed using 16 S rRNA sequencing to identify the relative abundance of sputum bacteria. Taxonomic differences between groups were evaluated using three independent analytic approaches: Mann-Whitney U, DESeq2, and EdgeR, with false discovery rate correction. Logistic regression examined associations between Lautropia abundance and clinical variables.

RESULTS: Individuals with RA-PF were …

Patient Perceptions And Knowledge Of Corticosteroid Injections: A Cross-Sectional Survey Study, Juliet Chung, Sina Ramtin, Philip Koehler, Stephen Stache, Charles Langman, Bryan Hozack, Asif M. Ilyas

Rothman Institute Papers

INTRODUCTION: Although cortisone injections are commonly used, patient understanding of cortisone is variable and often affected by misconceptions. This study explores patient perspectives, identifies misconceptions, and emphasizes the importance of improved patient education to enhance patient-centered care.

METHODS: A cross-sectional survey study was conducted from April to August 2024 among patients aged 18 and older presenting to an orthopedic physicians' office. Patients completed a novel anonymous questionnaire designed to assess their knowledge and perceptions of cortisone injections. A total of 246 patients participated, with responses collected electronically via SurveyMonkey.

RESULTS: Among 246 respondents, individuals with history of prior cortisone infections …

Hand Swelling And Other Non-Raynaud Phenomenon Symptoms As The Initial Presentation Of Systemic Sclerosis: Prevalence And Clinical Associations In Two Us Cohorts, Iqtidar Hanif, Shervin Assassi, Maureen D Mayes, Zsuzsanna H Mcmahan, Meng Zhang, Julio Charles, John M Vanburen, Jessica S Alvey, Kimia Ghaffari, Elana J Bernstein, Flavia V Castelino, Lorinda Chung, Luke Evnin, Tracy M Frech, Jessica K Gordon, Faye N Hant, Laura K Hummers, Dinesh Khanna, Kimberly S Lakin, Dorota Lebiedz-Odrobina, Yiming Luo, Ashima Makol, Jerry A Molitor, Duncan F Moore, Carrie Richardson, Nora Sandorfi, Ami A Shah, Ankoor Shah, Victoria K Shanmugam, Virginia D Steen, Elizabeth R Volkmann, Carleigh Zahn, Brian Skaug

Faculty, Staff and Student Publications

Objective: Raynaud phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts.

Methods: All patient data in the Genetics vs Environment in Scleroderma Outcomes Study (GENISOS) and Collaborative National Quality and Efficacy Registry (CONQUER) cohorts were reviewed. Both studies enrolled patients within five years of the first non-RP symptom.

Results: In GENISOS and CONQUER, respectively, 194 (44.2%) of 439 and 292 …

Continued Nintedanib In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease: 3-Year Data From Senscis-On, Yannick Allanore, Madelon C Vonk, Oliver Distler, Arata Azuma, Maureen D Mayes, Alexandra James, Veronika Kohlbrenner, Margarida Alves, Dinesh Khanna, Kristin B Highland

Faculty, Staff and Student Publications

Objective: We assessed adverse events and changes in forced vital capacity (FVC) in patients treated with open-label nintedanib over 148 weeks of SENSCIS-ON, the extension of the SENSCIS trial.

Methods: Adverse events and changes in FVC over 148 weeks of SENSCIS-ON were assessed in patients who received nintedanib in SENSCIS and continued nintedanib in SENSCIS-ON ('continued nintedanib' group) and in patients who received placebo in SENSCIS or received nintedanib for ≤28 days in a drug-drug interaction study and then received nintedanib in SENSCIS-ON ('initiated nintedanib' group).

Results: The continued nintedanib group comprised 197 patients, and the initiated nintedanib group comprised …

Patient And Parent Knowledge, Understanding, And Concerns After A New Diagnosis Of Ehlers Danlos Syndrome., Jordan T. Jones, Lora L. Black, William R. Black

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: After diagnosis of Ehlers Danlos Syndrome (EDS), it is unclear what information patients and parents need and understand about EDS. The objective of this study is to characterize patient and parent knowledge and concerns about EDS after a diagnosis of EDS is made to determine patient and parent concerns and identify barriers that cause discomfort with the diagnosis.6 METHODS: A convenience sample of patient and parent dyads were recruited after new diagnosis of EDS. Patients and parents completed questionnaires that assessed knowledge, comfort, and barriers of EDS before and after diagnosis, EDS education materials accessed, and additional clinical needs …

Transforming Growth Factor-Beta Is Increased In Sputum From Individuals With Rheumatoid Arthritis-Associated Pulmonary Fibrosis, Timothy M. Wilson, Matthew Bolt, Andrew Stahly, Joyce S. Lee, Tami J. Bang, Peter B. Sachs, Kevin D. Deane, Stephen M. Humphries, Joshua J. Solomon, M. Kristen Demoruelle

Division of Rheumatology Faculty Papers

BACKGROUND: Interstitial lung disease (ILD) develops in 5-10% of patients with RA and contributes significantly to morbidity and mortality, particularly in those with a fibrotic phenotype. Yet, biomarkers to reliably identify RA patients with underlying pulmonary fibrosis are inadequate. Herein, we used sputum to identify lung-based biomarkers that distinguish RA patients with underlying pulmonary fibrosis and may better inform underlying pathogenesis in RA-ILD.

METHODS: We included 37 RA patients with pulmonary fibrosis (RA-PF) and 30 RA patients without ILD (RA-no-ILD). Induced sputum and serum were tested for TGF-β levels by immunoassay. DNA was extracted to determine presence of the MUC5B …

Trends In The Use Of Biologic Disease-Modifying Antirheumatic Drugs In Patients With Rheumatoid Arthritis And Recently Diagnosed Colorectal, Lung, Or Prostate Cancer, Maria E Suarez-Almazor, Juan I Ruiz, Xiudong Lei, Chi-Fang Wu, Hui Zhao, Suja S Rajan, Sharon H Giordano

Faculty, Staff and Student Publications

INTRODUCTION: Biologic disease-modifying antirheumatic drugs (bDMARD) are often discontinued when a patient with rheumatoid arthritis (RA) is diagnosed with cancer. Our aim was to determine trends in bDMARD utilization in patients with RA and recently diagnosed cancer.

METHOD: We examined two national claims databases to identify adults with RA and recently diagnosed colorectal, lung, or prostate cancer (Optum's de-identified Clinformatics® Data Mart Database 2008-2022, and Surveillance, Epidemiology, and End Results Program (SEER) Medicare-linked 2008-2017). We determined time trends in bDMARD and tumor necrosis factor inhibitor (TNFi) prescriptions during the first 3 years after cancer with Cochram-Armitage tests and multivariable logistic …

Racial Variability In Immune Responses Only Partially Explains Differential Systemic Sclerosis Disease Severity, Kamini E Kuchinad, Ji Soo Kim, Adrianne Woods, Gwen Leatherman, Laura Gutierrez-Alamillo, Maureen D Mayes, Robyn Domsic, Paula S Ramos, Richard M Silver, John Varga, Lesley Ann Saketkoo, Suzanne Kafaja, Victoria K Shanmugan, Jessica Gordon, Lorinda Chung, Elana J Bernstein, Pravitt Gourh, Francesco Boin, Daniel L Kastner, Scott L Zeger, Livia Casciola-Rosen, Fredrick M Wigley, Ami A Shah

Faculty, Staff and Student Publications

Objective: To understand if autoantibodies account for racial variation in disease severity, we compared autoantibody distribution and associated phenotype between self-identified black and white systemic sclerosis (SSc) patients.

Methods: 803 black and 2178 white SSc patients had systematic testing for autoantibodies using Euroimmun (centromere (ACA), RNA-polymerase III (POLR3), Scl70, PM/Scl, NOR90, Th/To, Ku, U3RNP and Ro52) and commercial ELISA (U1RNP). In this observational study, logistic regression was performed to assess the association between self-identified race and outcomes, adjusting for autoantibodies. To estimate whether the effect of race was mediated by autoantibody status, race coefficients from multivariate models including and excluding …

Successful Management Of Pre-Existing Psoriatic Arthritis Through Targeting The Il-23/Il-17 Axis In Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy: A Case Series, Yuanteng Jeff Li, Pavlos Msaouel, Matthew Campbell, Patrick Hwu, Adi Diab, Sang T Kim

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with cancer. However, these therapies are associated with adverse events including de novo immune-related adverse events or flare of pre-exiting autoimmune disorders. Up to 80% of patients with cancer and pre-existing psoriasis (PsO) or psoriatic arthritis (PsA) experience PsO/PsA flare after initiating ICIs. Targeting the interleukin (IL)-17/IL-23 axis is a mainstream of the PsO/PsA treatment. However, whether this treatment can effectively control PsO/PsA with ICI exposure while preserving anti-tumour efficacy remains unknown.

CASE REPORTS: We report three patients with PsA and cancer, who received ICIs for their cancer treatment. …

Longitudinal Program Evaluation Of An Inter-Institutional Mentorship Network For Pediatric Rheumatology Using A Quality Improvement Framework, Kristen Hayward, Alexi Grom, Eyal Muscal, Peter A Nigrovic, Kelly A Rouster-Stevens, Kaveh Ardalan, Linda Hiraki, L Nandini Moorthy

Faculty, Staff and Students Publications

BACKGROUND: The American College of Rheumatology (ACR)/Childhood Arthritis and Rheumatology Research Alliance (CARRA) Mentoring Interest Group (AMIGO) is an inter-institutional mentorship program launched to target mentorship gaps within pediatric rheumatology. Initial program evaluation indicated increased mentorship access. Given the small size of the pediatric rheumatology workforce, maintaining a consistent supply of mentors was a potential threat to the longevity of the network. Our aims were to: (i) describe the sustainability of AMIGO over the period 2011-2018, (ii) highlight ongoing benefits to participants, and (iii) describe challenges in the maintenance of a mentorship network.

METHODS: A mixed-methods approach centered on a …

A Prospective Observational Study Of Disease Severity And Mortality In Hispanic American Patients With Systemic Sclerosis, Bochra Jandali, Marka Lyons, Julio Charles, Meng Zhang, Samuel Theodore, Claudia Pedroza, Maureen D Mayes, Shervin Assassi

Faculty, Staff and Student Publications

Objective: To characterize disease manifestations in Hispanic American patients with systemic sclerosis (SSc) in comparison with non-Hispanic White and Black patients.

Methods: Longitudinal clinical characteristics were collected prospectively in the Genetics versus Environment in Scleroderma Outcome Study cohort. All patients fulfilled the classification criteria for SSc and had a disease duration less than five years at enrollment.

Results: A cohort of 427 patients, consisting of 124 Hispanic, 220 non-Hispanic White, and 83 non-Hispanic Black participants were examined. At enrollment, Hispanic patients were significantly younger but had longer disease duration, higher frequency of U1-RNP positivity as well as concurrent systemic lupus …

Utilization Of Biologic Disease-Modifying Antirheumatic Therapy In Patients With Rheumatoid Arthritis And Recently Diagnosed Breast Cancer, Juan I Ruiz, Xiudong Lei, Chi-Fang Wu, Hui Zhao, Sharon H Giordano, Suja S Rajan, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

Objective: Biologic disease-modifying antirheumatic drugs (bDMARDs) are immunosuppressants, and there have been concerns that they might impact tumor immunity in patients with cancer with rheumatoid arthritis (RA). The purpose of this study was to describe the utilization trends of bDMARD in patients with RA after breast cancer (BC) diagnosis.

Methods: We performed a retrospective cohort study of adults with RA and BC (2008 onward) from Optum's de-identified Clinformatics® Data Mart Database (CDM); the Surveillance, Epidemiology, and End Results Program (SEER) Medicare; and the Texas Cancer Registry (TCR) Medicare databases. We evaluated bDMARD utilization trends during the first three years after …

Effect Of Aspirin Versus Low-Molecular-Weight Heparin Thromboprophylaxis On Medication Satisfaction And Out-Of-Pocket Costs: A Secondary Analysis Of A Randomized Clinical Trial, Nathan N O'Hara, Katherine P Frey, Deborah M Stein, Joseph F Levy, Gerard P Slobogean, Renan Castillo, Reza Firoozabadi, Madhav A Karunakar, Joshua L Gary, William T Obremskey, Rachel B Seymour, Joseph Cuschieri, C Daniel Mullins, Robert V O'Toole, Metrc

Faculty, Staff and Student Publications

BACKGROUND: Current guidelines recommend low-molecular-weight heparin for thromboprophylaxis after orthopaedic trauma. However, recent evidence suggests that aspirin is similar in efficacy and safety. To understand patients' experiences with these medications, we compared patients' satisfaction and out-of-pocket costs after thromboprophylaxis with aspirin versus low-molecular-weight heparin.

METHODS: This study was a secondary analysis of the PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT) trial, conducted at 21 trauma centers in the U.S. and Canada. We included adult patients with an operatively treated extremity fracture or a pelvic or acetabular fracture. Patients were randomly assigned to receive 30 mg of low-molecular-weight heparin (enoxaparin) …

A Randomized Controlled Trial Evaluating The Effects Of Social Networking On Chronic Disease Management In Rheumatoid Arthritis, Maria A Lopez-Olivo, Jessica T Foreman, Cheuk Leung, Heather Y Lin, Tiffany Westrich-Robertson, Catherine Hofstetter, Jude K A Des Bordes, Anne Lyddiatt, Amye Leong, Irmgard U Willcockson, Susan K Peterson, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

OBJECTIVE: Social networking has been shown to improve health outcomes in certain patient populations. While patients with rheumatoid arthritis (RA) increasingly use social networking to communicate with peers, the effects of these interactions are largely unknown.

METHODS: In a randomized controlled trial, we compared RA patients who participated in a social networking group moderated by peer leaders and who had access to a static website offering RA materials with a control group, who only had access to the website. The primary outcomes were patients' RA knowledge, self-efficacy and empowerment. Secondary outcomes included participation in desired health behaviors, and satisfaction with …

Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko

Faculty, Staff and Students Publications

OBJECTIVE: Inhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease-modifying activity in OA.

METHODS: Primary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee …

Clinical Mortality In A Large Covid-19 Cohort: Observational Study., M. Jarrett, S. Schultz, J. Lyall, J. Wang, L. Stier, M. De Geronimo, K. Nelson

Journal Articles

BACKGROUND: Northwell Health, an integrated health system in New York, has treated more than 15,000 inpatients with COVID-19 at the US epicenter of the SARS-CoV-2 pandemic.

OBJECTIVE: We describe the demographic characteristics of patients who died of COVID-19, observation of frequent rapid response team/cardiac arrest (RRT/CA) calls for non-intensive care unit (ICU) patients, and factors that contributed to RRT/CA calls.

METHODS: A team of registered nurses reviewed the medical records of inpatients who tested positive for SARS-CoV-2 via polymerase chain reaction before or on admission and who died between March 13 (first Northwell Health inpatient expiration) and April 30, 2020, …

A Head-To-Head Comparison Of The Efficacy And Safety Of Ixekizumab And Adalimumab In Biological-Naïve Patients With Active Psoriatic Arthritis: 24-Week Results Of A Randomised, Open-Label, Blinded-Assessor Trial., Philip Mease, Josef S Smolen, Frank Behrens, Peter Nash, Soyi Liu Leage, Lingnan Li, Hasan Tahir, Melinda Gooderham, Eswar Krishnan, Hong Liu-Seifert, Paul Emery, Sreekumar G Pillai, Philip S Helliwell

Articles, Abstracts, and Reports

OBJECTIVES: To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs).

METHODS: Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the …

Secukinumab Efficacy On Resolution Of Enthesitis In Psoriatic Arthritis: Pooled Analysis Of Two Phase 3 Studies., Laura C Coates, Johan K Wallman, Dennis Mcgonagle, Georg A Schett, Iain B Mcinnes, Philip Mease, Lawrence Rasouliyan, Erhard Quebe-Fehling, Darren L Asquith, Andreas E R Fasth, Luminita Pricop, Corine Gaillez

Articles, Abstracts, and Reports

BACKGROUND: Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies.

METHOD: Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3-6) to full resolution (FR), stable (similar or reduction …

Sustained Efficacy, Safety And Patient-Reported Outcomes Of Certolizumab Pegol In Axial Spondyloarthritis: 4-Year Outcomes From Rapid-Axspa., Désirée Van Der Heijde, Maxime Dougados, Robert Landewé, Joachim Sieper, Walter P Maksymowych, Martin Rudwaleit, Filip Van Den Bosch, Jürgen Braun, Philip Mease, Alan J Kivitz, Jessica Walsh, Owen Davies, Lars Bauer, Bengt Hoepken, Luke Peterson, Atul Deodhar

Articles, Abstracts, and Reports

Objective: The aim was to assess the long-term safety and efficacy of certolizumab pegol over 4 years of continuous treatment in patients with axial spondyloarthritis (axSpA), including both AS and non-radiographic (nr-) axSpA.

Methods: RAPID-axSpA was a phase 3 randomized trial, double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204. Patients had a clinical diagnosis of axSpA, meeting Assessment of SpondyloArthritis international Society (ASAS) criteria, and had active disease. The assessed outcomes included ASAS20, ASAS40, AS DAS (ASDAS), BASDAI, BASFI and BASMI scores, along with selected measures of remission. Further …

Efficacy And Safety Of Abatacept, A T-Cell Modulator, In A Randomised, Double-Blind, Placebo-Controlled, Phase Iii Study In Psoriatic Arthritis., Philip Mease, Alice B Gottlieb, Désirée Van Der Heijde, Oliver Fitzgerald, Alyssa Johnsen, Marleen Nys, Subhashis Banerjee, Dafna D Gladman

Articles, Abstracts, and Reports

OBJECTIVES: To assess the efficacy and safety of abatacept, a selective T-cell costimulation modulator, in a phase III study in psoriatic arthritis (PsA).

METHODS: This study randomised patients (1:1) with active PsA (~60% with prior exposure to a tumour necrosis factor inhibitor) to blinded weekly subcutaneous abatacept 125 mg (n=213) or placebo (n=211) for 24 weeks, followed by open-label subcutaneous abatacept. Patients without ≥20% improvement in joint counts at week 16 were switched to open-label abatacept. The primary end point was the proportion of patients with ≥20% improvement in the American College of Rheumatology (ACR20) criteria at week 24.

RESULTS: …

Endothelial Cells Expressing Endothelial And Mesenchymal Cell Gene Products In Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease., Fabian A. Mendoza, Sonsoles Piera-Velazquez, John L. Farber, Carol Feghali-Bostwick, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT).

METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed …

Effect Of Mycophenolate Mofetil On The White Blood Cell Count And The Frequency Of Infection In Systemic Lupus Erythematosus., Ananta Subedi, Laurence S. Magder, Michelle Petri

Department of Medicine Faculty Papers

Leukopenia is a common manifestation of SLE. Addition of immunosuppressive therapy in a SLE patient who is already leukopenic is a clinical concern. It could worsen leukopenia, increase the risk of infection, or both. The aim of this study was to analyze the immediate effect of mycophenolate mofetil on the white blood cell count and the rate of infection in SLE patients. Two hundred and forty-four patients within the Hopkins Lupus Cohort who were newly started on mycophenolate mofetil were included in the study. The white blood cell count and interval infection history on the day mycophenolate mofetil was started …

A Prospective Observational Study Of Mycophenolate Mofetil Treatment In Progressive Diffuse Cutaneous Systemic Sclerosis Of Recent Onset., Fabian A. Mendoza, Md, Sarah J. Nagle, Jason B. Lee, Md, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

OBJECTIVE: A prospective observational study of mycophenolate mofetil (MMF) treatment in patients with diffuse progressive cutaneous systemic sclerosis (SSc) of recent onset.

METHODS: Twenty-five previously untreated consecutive patients with recent-onset (< 24 mo) diffuse progressive cutaneous SSc received MMF as the only disease-modifying therapy. Modified Rodnan skin score (mRSS) and affected body surface area (BSA) were compared from initiation of MMF to study end. Pulmonary function tests performed at the same institution before therapy and at study end were available in 15 patients. Histopathology and real-time PCR assessment of fibrosis-related gene expression were performed before and after treatment in skin biopsies from 3 patients.

RESULTS: At 18.2 ± 8.73 months of MMF therapy (median 2000 mg/day) the mRSS decreased from 24.56 ± 8.62 to 14.52 ± 10.9 (p = 0.0004) and the affected BSA from 36% ± 16% to 14% ± 13.3% (p = 0.00001). Pulmonary function tests remained stable from initiation of MMF to the end of the study. Skin histopathology showed a remarkable reduction in accumulation of fibrotic tissue. Real-time PCR …

Modulation Of Tgf-Beta Signaling By Proinflammatory Cytokines In Articular Chondrocytes., Jorge A. Roman-Blas, David G. Stokes, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways …

Regulation Of Human Lung Fibroblast Alpha 1(I) Procollagen Gene Expression By Tumor Necrosis Factor Alpha, Interleukin-1 Beta, And Prostaglandin E2., Arturo Diaz, Elena Munoz, Rosemary Johnston, Joseph H. Korn, Sergio A. Jimenez

Department of Medicine Faculty Papers

We investigated the participation of prostaglandin (PG) E2 in the regulation of the alpha 1(I) procollagen gene expression by tumor necrosis factor alpha (TNF alpha), and interleukin-1 beta (IL-1 beta) in normal adult human lung fibroblasts. TNF alpha (100 units/ml) and IL-1 beta (100 units/ml) stimulated the production of PGE2 and caused a dose-dependent inhibition of up to 54 and 66%, respectively, of the production of type I procollagen. Preincubation of cultures with indomethacin partially reversed the inhibition of procollagen production induced by the cytokines. Cytokine-stimulated endogenous fibroblast PG accounted for 35 and 68% of the inhibition induced by TNF …