A5019245481- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Rheumatoid Arthritis Research and Therapies
- Chronic Lymphocytic Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Autoimmune and Inflammatory Disorders Research
- Immune Response and Inflammation
- CAR-T cell therapy research
- Cytokine Signaling Pathways and Interactions
- Diabetes and associated disorders
- Multiple Sclerosis Research Studies
- Lymphoma Diagnosis and Treatment
- Salivary Gland Disorders and Functions
- Atherosclerosis and Cardiovascular Diseases
- Autoimmune Bullous Skin Diseases
- Pregnancy and preeclampsia studies
- Ocular Surface and Contact Lens
- Cancer Immunotherapy and Biomarkers
- Toxin Mechanisms and Immunotoxins
- Reproductive System and Pregnancy
- Birth, Development, and Health
- Galectins and Cancer Biology
University of Southern California
2015-2024
New York State Psychiatric Institute
2024
Los Angeles Medical Center
1992-2021
Eli Lilly (United States)
2017
Ronald Reagan UCLA Medical Center
2017
UCLA Medical Center
2017
Child Neurology Associates
2017
Harbor–UCLA Medical Center
2017
Keck Hospital of USC
2010-2015
Weatherford College
2014
To assess the efficacy/safety of B lymphocyte stimulator inhibitor belimumab plus standard therapy compared with placebo in active systemic lupus erythematosus (SLE).In a phase III, multicenter, randomized, placebo-controlled trial, 819 antinuclear antibody-positive or anti-double-stranded DNA-positive SLE patients scores ≥6 on Safety Estrogens Lupus Erythematosus National Assessment (SELENA) version Disease Activity Index (SLEDAI) were randomized 1:1:1 ratio to receive 1 mg/kg belimumab, 10...
To determine whether serum levels of B lymphocyte stimulator (BLyS) are elevated in patients with systemic immune-based rheumatic diseases and correlate Ig and/or autoantibody titers.Sera from 185 various (95 lupus erythematosus [SLE], 67 rheumatoid arthritis [RA], 23 other diagnoses) were assayed for BLyS Ig. In 7 who required arthrocentesis a swollen knee, coincident synovial fluid samples BLyS. Medical charts retrospectively reviewed titers proteinuria within 1-month period before or...
Abstract Objective To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard care therapy (SOC) patients active systemic lupus erythematosus (SLE). Methods Patients a Safety Estrogens Lupus Erythematosus: National Assessment (SELENA) version Systemic Erythematosus Disease Activity Index (SLEDAI) score ≥4 (n = 449) were randomly assigned to (1, 4, or 10 mg/kg) placebo 52‐week study. Coprimary end points percent change SELENA–SLEDAI at week...
Abstract Objective To assess the overexpression of B lymphocyte stimulator (BLyS) over time in patients with systemic lupus erythematosus (SLE). Methods Sixty‐eight SLE were followed up longitudinally for a median 369 days. At each physician encounter, disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index, and blood collected determination serum BLyS level, messenger RNA (mRNA) cell surface expression. Twenty normal control subjects underwent similar laboratory...
Abstract Objective To describe a new systemic lupus erythematosus (SLE) responder index (SRI) based on belimumab phase II SLE trial and demonstrate its potential utility in clinical trials. Methods Data from randomized, double‐blind, placebo‐controlled study 449 patients of 3 doses (1, 4, 10 mg/kg) or placebo plus standard care therapy (SOC) over 56‐week period were analyzed. The Safety Estrogens Lupus Erythematosus: National Assessment (SELENA) version the Systemic Erythematosus Disease...
Abstract Objective To determine the association of plasma B lymphocyte stimulator (BLyS) levels, immunosuppressive therapy, and other clinical parameters with disease activity in systemic lupus erythematosus (SLE). Methods Two hundred forty‐five SLE patients were evaluated prospectively over a 2‐year period at 4 centers. Assessments performed every 3–6 months. Univariate analysis was used to among Safety Estrogens Lupus Erythematosus: National Assessment (SELENA) version Systemic...
To assess the effects of B lymphocyte stimulator (BLyS)-specific inhibitor belimumab on immunologic biomarkers, including cell and T populations, maintenance antibody titers to prior vaccines in autoantibody-positive systemic lupus erythematosus (SLE) patients.Pooled data from 2 phase III trials, Study Belimumab Subjects with SLE 52-week (BLISS-52) 76-week (BLISS-76) comparing 1 mg/kg or 10 versus placebo (plus standard therapy for each group) were analyzed changes autoantibody,...
To assess the efficacy and safety of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE).Patients moderate-to-severe SLE (score ≥8 on Safety Estrogens Lupus Erythematosus National Assessment [SELENA] version Disease Activity Index [SLEDAI]) were randomized 2:1 to receive weekly SC 200 mg or placebo by prefilled syringe addition standard therapy for 52 weeks. The primary end point was Responder (SRI4) at week 52. Secondary points reduction corticosteroid dosage...
<h3>Objectives</h3> Rituximab is an effective treatment in patients with established rheumatoid arthritis (RA). The objective of the IMAGE study was to determine efficacy rituximab prevention joint damage and its safety combination methotrexate (MTX) initiating MTX. <h3>Methods</h3> In this double-blind randomised controlled phase III study, 755 MTX-naïve active RA were randomly assigned MTX alone, 2×500 mg + or 2×1000 primary end point at week 52 change measured using a Genant-modified...
<h3>Objectives</h3> To evaluate the efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that neutralises membrane soluble B-cell activating factor (BAFF). <h3>Methods</h3> This randomised, placebo-controlled study enrolled 1124 patients with moderate-to-severe systemic lupus erythematosus (SLE) (Safety Estrogens in Lupus Erythematosus National Assessment- SLE Disease Activity Index ≥6 at baseline). Patients received standard care plus subcutaneous drug, starting loading dose...
Objectives To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) limited or no prior methotrexate (MTX) exposure. Methods This 52-week, phase 3, multicentre, double-blind clinical trial ( NCT02886728 ) evaluated once-daily oral 1252 RA randomised 2:1:1:2 to 200 mg MTX (FIL200 +MTX), 100 (FIL100 monotherapy (FIL200), MTX. The primary endpoint was proportion achieving 20% improvement American College Rheumatology...
Abstract Although positive CD28 costimulation is needed for the generation of natural CD4+CD25+ regulatory T cells, we report that negative CTLA-4 necessary generating phenotypically and functionally similar adaptive suppressor cells. TGF-β could not induce CD4+CD25− cells from CTLA-4−/− mice to express normal levels FoxP3 or develop activity. Moreover, blockade following activation wild-type CD4+ abolished ability FoxP3-expressing mouse accelerated expression CTLA-4, time course studies...
Abstract Objective To assess the effects of B lymphocyte depletion on serum stimulator (BLyS; trademark Human Genome Sciences, Rockville, MD) levels in patients with rheumatoid arthritis (RA), and to relationship BLyS peripheral blood cell depletion, autoantibodies antimicrobial antibodies, return cells, clinical relapse. Methods Fifteen active RA underwent rituximab‐based therapy (BCDT). Disease activity was assessed clinically, CD19+ counts were determined by flow cytometry, BLyS, IgM,...
Abstract BLyS and APRIL are two members of the TNF superfamily that secreted by activated myeloid cells have costimulatory activity on B cells. share receptors, TACI BCMA, whereas a third receptor, BAFF-R, specifically binds BLyS. Both been described as homotrimeric molecules, feature common to superfamily. In this study, we show can form active heterotrimeric molecules when coexpressed circulating heterotrimers present in serum samples from patients with systemic immune-based rheumatic...
Abstract Introduction This trial evaluated the safety, biologic activity, and pharmacokinetics of belimumab, a fully human monoclonal antibody that inhibits activity soluble form essential B-cell survival factor B-lymphocyte stimulator (BLyS) in patients with systemic lupus erythematosus (SLE). Methods Seventy mild-to-moderate SLE were enrolled phase I, double-blind, randomized study treated placebo ( n = 13) or belimumab 57) at four different doses (1.0, 4.0, 10, 20 mg/kg) as single...
Abstract Objective To determine whether synovial fluid (SF) levels and cell‐surface expression of B lymphocyte stimulator (BLyS) protein SF APRIL are elevated in patients with inflammatory arthritis (IA). Methods Same‐day blood samples from 89 103 knee effusions (81 knees IA 22 noninflammatory [NIA]) were evaluated for BLyS by enzyme‐linked immunosorbent assay. Blood mononuclear cells double‐stained surface CD14 (monocyte marker) analyzed flow cytometry. Complete cell counts nucleated...
To assess the relationships between serum B lymphocyte stimulator (BLyS) levels, autoantibody profile and clinical response in patients with systemic lupus erythematosus (SLE) following rituximab-based cell depletion therapy (BCDT).A total of 25 active refractory SLE were followed for >or=1 year BCDT. Disease activity was assessed using British Isles Lupus Assessment Group (BILAG) system, levels BLyS autoantibodies to dsDNA extractable nuclear antigens (ENA) measured by ELISA. Serum...
TNF-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator chronic inflammatory processes via prolonged activation the NF-kappaB pathway in several tissues, including kidney. Evidence for importance TWEAK pathogenesis lupus nephritis (LN) recently introduced. Thus, levels may serve an indication LN presence and activity.Multicenter cohorts systemic erythematosus (SLE) patients controls were recruited cross-sectional longitudinal analysis urinary (uTWEAK) and/or serum...
Objective. To evaluate the efficacy/safety of belimumab plus standard therapy in patients (n = 449) with active systemic lupus erythematosus (SLE) treated up to 7 years 177 currently ongoing). Methods. Patients 345) who completed a double-blind, placebo-controlled, 52-week study 1, 4, or 10 mg/kg and 24-week extension (placebo switched mg/kg; same dose mg/kg) could receive an open-label continuation 296). Disease activity was analyzed SLE at baseline initial study. Biomarker medication...
Engagement of the low-affinity Ab receptor FcγRIIb downregulates B cell activation, and its dysfunction is associated with autoimmunity in mice humans. We engineered Fc domain an anti-human CD19 to bind high affinity, promoting coengagement BCR complex. This (XmAb5871) stimulated phosphorylation ITIM suppressed BCR-induced calcium mobilization, proliferation, costimulatory molecule expression human cells from healthy volunteers systemic lupus erythematosus (SLE) patients, as well...
Objective The diagnosis of Sjögren's syndrome (SS) in routine practice is largely a clinical one and requires high index suspicion by the treating physician. This great dependence on judgment frequently leads to delayed or misdiagnosis. Tear protein profiles have been proposed as simple reliable biomarkers for SS. Given that cathepsin S activity increased lacrimal glands tears NOD mice (a murine model SS), aim this study was explore utility using tear (CTSS) biomarker Methods A method...
We have assessed the role of B lymphocyte stimulator (BLyS) and its receptors in germinal center (GC) reaction affinity maturation. Despite ample BLyS retention on cells follicular (FO) regions, GC microenvironment lacks substantial BLyS. This reflects IL-21–mediated down-regulation receptor TACI (transmembrane activator calcium modulator cyclophilin ligand interactor) cells, thus limiting their capacity for binding retention. Within GC, FO helper T (TFH cells) provide a local source Whereas...
To investigate the long-term safety and efficacy of intravenous (IV) belimumab plus standard care (SOC) therapy for systemic lupus erythematosus (SLE) in patients with active, autoantibody-positive SLE.The study was designed as a multicenter, open-label, continuation IV given every 4 weeks conjunction SOC SLE who completed phase II, double-blind study. Adverse events (AEs) laboratory data were monitored from first dose (in either study) until 24 after final dose. Efficacy assessments...