Impact Of Early Disease Factors On Metabolic Syndrome In Systemic Lupus Erythematosus: Data From An International Inception Cohort,
2015
Zucker School of Medicine at Hofstra/Northwell
Impact Of Early Disease Factors On Metabolic Syndrome In Systemic Lupus Erythematosus: Data From An International Inception Cohort, B. Parker, M. B. Urowitz, D. D. Gladman, M. Lunt, R. Donn, S. C. Bae, J. Sanchez-Guerrero, C. Aranow, M. Mackay, I. N. Bruce, +30 Additional Authors
Journal Articles
BACKGROUND: The metabolic syndrome (MetS) may contribute to the increased cardiovascular risk in systemic lupus erythematosus (SLE). We examined the association between MetS and disease activity, disease phenotype and corticosteroid exposure over time in patients with SLE. METHODS: Recently diagnosed (<15 >months) patients with SLE from 30 centres across 11 countries were enrolled into the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort from 2000 onwards. Baseline and annual assessments recorded clinical, laboratory and therapeutic data. A longitudinal analysis of factors associated with MetS in the first 2 years of follow-up was performed using random effects logistic regression. RESULTS: We …
Association Of Valine And Leucine At Hla-Drb1 Position 11 With Radiographic Progression In Rheumatoid Arthritis, Independent Of The Shared Epitope Alleles But Not Independent Of Anti-Citrullinated Protein Antibodies,
2015
Zucker School of Medicine at Hofstra/Northwell
Association Of Valine And Leucine At Hla-Drb1 Position 11 With Radiographic Progression In Rheumatoid Arthritis, Independent Of The Shared Epitope Alleles But Not Independent Of Anti-Citrullinated Protein Antibodies, H. W. Van Steenbergen, S. Raychaudhuri, L. Rodriguez-Rodriguez, S. Rantapaa-Dahlqvist, E. Berglin, R. E. M. Toes, T. W. J. Huizinga, B. Fernandez-Gutierrez, P. K. Gregersen, A. H. M. Van Der Helm-Van Mil
Journal Articles
Objective. For decades it has been known that the HLA-DRB1 shared epitope (SE) alleles are associated with an increased risk of development and progression of rheumatoid arthritis (RA). Recently, the following variations in the peptide-binding grooves of HLA molecules that predispose to RA development have been identified: Val and Leu at HLA-DRB1 position 11, Asp at HLA-B position 9, and Phe at HLA-DPB1 position 9. This study was undertaken to investigate whether these variants are also associated with radiographic progression in RA, independent of SE and anti-citrullinated protein antibody (ACPA) status. Methods. A total of 4,911 radiograph sets from 1,878 …
Crossing The Atlantic: The Euro-Lupus Nephritis Regimen In North America,
2015
Zucker School of Medicine at Hofstra/Northwell
Crossing The Atlantic: The Euro-Lupus Nephritis Regimen In North America, D. Wofsy, B. Diamond, F. A. Houssiau
Journal Articles
No abstract provided.
Dna-Containing Immunocomplexes Promote Inflammasome Assembly And Release Of Pyrogenic Cytokines By Cd14+ Cd16+ Cd64high Cd32low Inflammatory Monocytes From Malaria Patients,
2015
Zucker School of Medicine at Hofstra/Northwell
Dna-Containing Immunocomplexes Promote Inflammasome Assembly And Release Of Pyrogenic Cytokines By Cd14+ Cd16+ Cd64high Cd32low Inflammatory Monocytes From Malaria Patients, I. C. Hirako, C. Gallego-Marin, M. A. Ataide, W. A. Andrade, H. Gravina, B. C. Rocha, R. B. De Oliveira, D. B. Pereira, B. Diamond, R. T. Gazzinelli, +3 Additional Authors
Journal Articles
High levels of circulating immunocomplexes (ICs) are found in patients with either infectious or sterile inflammation. We report that patients with either Plasmodium falciparum or Plasmodium vivax malaria have increased levels of circulating anti-DNA antibodies and ICs containing parasite DNA. Upon stimulation with malaria-induced ICs, monocytes express an NF-kappaB transcriptional signature. The main source of IC-induced proinflammatory cytokines (i.e., tumor necrosis factor alpha [TNF-alpha] and interleukin-1beta [IL-1beta])in peripheral blood mononuclear cells from acute malaria patients was found to be a CD14(+) CD16 (FcgammaRIIIA)(+) CD64 (FcgammaRI)(high) CD32 (FcgammaRIIB)(low) monocyte subset. Monocytes from convalescent patients were predominantly of the classical phenotype (CD14(+) …
Genome-Wide Association Study Identifies Hla 8.1 Ancestral Haplotype Alleles As Major Genetic Risk Factors For Myositis Phenotypes,
2015
Zucker School of Medicine at Hofstra/Northwell
Genome-Wide Association Study Identifies Hla 8.1 Ancestral Haplotype Alleles As Major Genetic Risk Factors For Myositis Phenotypes, F. W. Miller, W. Chen, T. P. O'Hanlon, R. G. Cooper, J. Vencovsky, L. G. Rider, K. Danko, A. Lee, P. K. Gregersen, C. I. Amos, +17 Additional Authors
Journal Articles
Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (P10-8) in GWAS were identified in the major histocompatibility complex (MHC) region for all myositis phenotypes together, as well as for …
A Genetic Study On C5-Traf1 And Progression Of Joint Damage In Rheumatoid Arthritis,
2015
Zucker School of Medicine at Hofstra/Northwell
A Genetic Study On C5-Traf1 And Progression Of Joint Damage In Rheumatoid Arthritis, H. W. Van Steenbergen, L. Rodriguez-Rodriguez, E. Berglin, A. Zhernakova, R. Knevel, J. Ivorra-Cortes, T. W. J. Huizinga, B. Fernandez-Gutierrez, P. K. Gregersen, A. H. M. Van Der Helm-Van Mil, +1 Additional Author
Journal Articles
Introduction: The severity of joint damage progression in rheumatoid arthritis (RA) is heritable. Several genetic variants have been identified, but together explain only part of the total genetic effect. Variants in Interleukin-6 (IL-6), Interleukin-10 (IL-10), C5-TRAF1, and Fc-receptor-like-3 (FCRL3) have been described to associate with radiographic progression, but results of different studies were incongruent. We aimed to clarify associations of these variants with radiographic progression by evaluating six independent cohorts. Methods: In total 5,895 sets of radiographs of 2,493 RA-patients included in six different independent datasets from the Netherlands, Sweden, Spain and North-America were studied in relation to rs1800795 (IL-6), …
Genome-Wide Association Analysis Of Psoriatic Arthritis And Cutaneous Psoriasis Reveals Differences In Their Genetic Architecture,
2015
Zucker School of Medicine at Hofstra/Northwell
Genome-Wide Association Analysis Of Psoriatic Arthritis And Cutaneous Psoriasis Reveals Differences In Their Genetic Architecture, P. E. Stuart, R. P. Nair, L. C. Tsoi, T. Tejasvi, S. Das, H. M. Kang, E. Ellinghaus, V. Chandran, K. Callis-Duffin, R. Ike, Y. Li, X. Wen, C. Enerback, J. E. Gudjonsson, S. Koks, K. Kingo, J. Winkelmann, P. K. Gregersen, J. T. Elder, +30 Additional Authors
Journal Articles
Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with …
A Large-Scale Genetic Analysis Reveals A Strong Contribution Of The Hla Class Ii Region To Giant Cell Arteritis Susceptibility,
2015
Zucker School of Medicine at Hofstra/Northwell
A Large-Scale Genetic Analysis Reveals A Strong Contribution Of The Hla Class Ii Region To Giant Cell Arteritis Susceptibility, F. D. Carmona, S. L. Mackie, J. E. Martin, J. C. Taylor, A. Vaglio, S. Eyre, L. Bossini-Castillo, S. Castaneda, P. K. Gregersen, G. C. A. Grp Spanish, +64 Additional Authors
Journal Articles
We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 x 10(-40), OR = 1.73). A multivariate model including class II amino acids of HLA-DR beta 1 and …
Robotics: A Rehabilitation Modality,
2015
Zucker School of Medicine at Hofstra/Northwell
Robotics: A Rehabilitation Modality, H. I. Krebs, B. T. Volpe
Journal Articles
No abstract provided.
Stat5a/B Contribute To Sex Bias In Vascular Disease: A Neuroendocrine Perspective,
2015
Zucker School of Medicine at Hofstra/Northwell
Stat5a/B Contribute To Sex Bias In Vascular Disease: A Neuroendocrine Perspective, P.B. Sehgal, Y. Yang, H. Yuan, E.J. Miller
Journal Articles
No abstract provided.
Deletion Of Stat5a/B In Vascular Smooth Muscle Abrogates The Male Bias In Hypoxic Pulmonary Hypertension In Mice: Implications In The Human Disease,
2015
Northwell Health
Deletion Of Stat5a/B In Vascular Smooth Muscle Abrogates The Male Bias In Hypoxic Pulmonary Hypertension In Mice: Implications In The Human Disease, Y. M. Yang, H. Yuan, J. G. Edwards, Y. Skayian, K. Ochani, E. J. Miller, P. B. Sehgal
Journal Articles
Chronic hypoxia typically elicits pulmonary hypertension (PH) in mice with a male-dominant phenotype. There is an opposite sex-bias in human PH with higher prevalence in women, but greater survival (the "estrogen paradox"). We investigated the involvement of STAT5a/b species, previously established to mediate sexual dimorphism in other contexts, in the sex-bias in PH. Mice with heterozygous or homozygous deletions of the STAT5a/b locus in vascular smooth muscle cells (SMC) were generated in crosses between STAT5a/bfl/fl and transgelin (SM22alpha)-Cre+/+ parents. Wild-type (wt) males subjected to chronic hypoxia showed significant PH and pulmonary arterial remodeling, with wt females showing minimal changes (a …
Age-Dependent Alterations In The Inflammatory Response To Pulmonary Challenge,
2015
Northwell Health
Age-Dependent Alterations In The Inflammatory Response To Pulmonary Challenge, H. M. Linge, K. Ochani, K. Lin, J. Y. Lee, E. J. Miller
Journal Articles
The aging lung is increasingly susceptible to infectious disease. Changes in pulmonary physiology and function are common in older populations, and in those older than 60 years, pneumonia is the major cause of infectious death. Understanding age-related changes in the innate and adaptive immune systems, and how they affect both pulmonary and systemic responses to pulmonary challenge are critical to the development of novel therapeutic strategies for the treatment of the elderly patient. In this observational study, we examined age-associated differences in inflammatory responses to pulmonary challenge with cell wall components from Gram-positive bacteria. Thus, male Sprague-Dawley rats, aged 6 …
Antibodies As Mediators Of Brain Pathology,
2015
Zucker School of Medicine at Hofstra/Northwell
Antibodies As Mediators Of Brain Pathology, L. Brimberg, S. Mader, Y. Fujieda, Y. Arinuma, C. Kowal, B. T. Volpe, B. Diamond
Journal Articles
No abstract provided.
Autoantibodies In Systemic Autoimmune Diseases: Specificity And Pathogenicity,
2015
Northwell Health
Autoantibodies In Systemic Autoimmune Diseases: Specificity And Pathogenicity, J. Suurmond, B. Diamond
Journal Articles
In this Review we focus on the initiation of autoantibody production and autoantibody pathogenicity, with a special emphasis on the targeted antigens. Release of intracellular antigens due to excessive cell death or to ineffective clearance of apoptotic debris, modification of self-antigens during inflammatory responses, and molecular mimicry contribute to the initiation of autoantibody production. We hypothesize that those autoreactive B cells that survive and produce pathogenic autoantibodies have specificity for self-antigens that are TLR ligands. Such B cells experience both B cell receptor (BCR) activation and TLR engagement, leading to an escape from tolerance. Moreover, the autoantibodies they produce form …
B Cells In The Aging Immune System: Time To Consider B-1 Cells,
2015
Northwell Health
B Cells In The Aging Immune System: Time To Consider B-1 Cells, N. E. Holodick, T. L. Rothstein
Journal Articles
The investigation of immune senescence has uncovered many changes in B cell development, maintenance, and function with increasing age. However, most of these studies have focused on conventional B cell subsets in the spleen. The B-1 cell subset is an essential arm of the innate immune system, which in general has been understudied in terms of immune senescence. Here, we review what is currently known about B cells during aging and go on to describe why B-1 cell biology is an important component of the aging immune system in the context of diseases that most affect the aged population.
Brain Metabolism And Autoantibody Titres Predict Functional Impairment In Systemic Lupus Erythematosus,
2015
Zucker School of Medicine at Hofstra/Northwell
Brain Metabolism And Autoantibody Titres Predict Functional Impairment In Systemic Lupus Erythematosus, M. Mackay, C. C. Tang, B. T. Volpe, C. Aranow, P. J. Mattis, R. A. Korff, B. Diamond, D. Eidelberg
Journal Articles
OBJECTIVE: We investigated whether systemic lupus erythematosus (SLE) disease duration or serology associate with abnormal regional glucose metabolism as measured with [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and deficits on neuropsychological testing. METHODS: Subjects with SLE with stable disease activity, without brain damage or clinical symptoms of neuropsychiatric (NP) SLE, stratified by disease duration (short-term (ST)-SLE=disease/=10 years), underwent clinical assessments, neuropsychological testing, resting FDG-PET scan imaging and measurement of serum titres of antibody to N-methyl-d-aspartate receptor (DNRAb). FDG-PET scans were compared with age-matched and gender-matched healthy controls. RESULTS: Subjects with LT-SLE demonstrated hypometabolism in the prefrontal and premotor cortices that correlated …
The Brighter (And Evolutionarily Older) Face Of The Metabolic Syndrome: Evidence From Trypanosoma Cruzi Infection In Cd-1 Mice,
2015
Northwell Health
The Brighter (And Evolutionarily Older) Face Of The Metabolic Syndrome: Evidence From Trypanosoma Cruzi Infection In Cd-1 Mice, W. Brima, D. J. Eden, S. F. Mehdi, M. Bravo, M. M. Wiese, J. Stein, V. Almonte, D. Zhao, J. Roth, F. Nagajyothi, +5 Additional Authors
Journal Articles
BACKGROUND: Infection with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, results in chronic infection that leads to cardiomyopathy with increased mortality and morbidity in endemic regions. In a companion study, our group found that a high-fat diet (HFD) protected mice from T. cruzi-induced myocardial damage and significantly reduced post-infection mortality during acute T. cruzi infection. METHODS: In the present study metabolic syndrome was induced prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated with anti-diabetic drug metformin. RESULTS: In the present study, the lethality of T. cruzi (Brazil strain) infection in CD-1 …
Calhm1 Deletion In Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, And Life Span,
2015
Northwell Health
Calhm1 Deletion In Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, And Life Span, G. Hellekant, J. Schmolling, P. Marambaud, T. A. Rose-Hellekant
Journal Articles
Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1), which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have previously demonstrated with chorda tympani nerve recordings and two-bottle preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO]) have severely impaired perception of sweet, bitter, and umami compounds, whereas their sour and salty tasting ability is unaltered. Here, we present data from KO mice of effects on glossopharyngeal (NG) nerve responses, TBP, …
The Cation Channel Trpv2 Is A New Suppressor Of Arthritis Severity, Joint Damage, And Synovial Fibroblast Invasion,
2015
Northwell Health
The Cation Channel Trpv2 Is A New Suppressor Of Arthritis Severity, Joint Damage, And Synovial Fibroblast Invasion, T. Laragione, K. F. Cheng, M. R. Tanner, M. He, C. Beeton, Y. Al-Abed, P. S. Gulko
Journal Articles
Little is known about the regulation of arthritis severity and joint damage in rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) have a central role in joint damage and express increased levels of the cation channel Trpv2. We aimed at determining the role of Trpv2 in arthritis. Treatment with Trpv2-specific agonists decreased the in vitro invasiveness of FLS from RA patients and arthritic rats and mice. Trpv2 stimulation suppressed IL-1beta-induced expression of MMP-2 and MMP-3. Trpv2 agonists, including the new and more potent LER13, significantly reduced disease severity in KRN serum- and collagen-induced arthritis, and reduced histologic joint damage, synovial inflammation, and …
Defects In Germinal Center Selection In Sle,
2015
Zucker School of Medicine at Hofstra/Northwell
Defects In Germinal Center Selection In Sle, M. Woods, Y. R. Zou, A. Davidson
Journal Articles
Germinal centers (GCs) are the primary site at which clonal expansion and affinity maturation of B cells occur. B cells encounter antigen and receive T cell help in the GC light zone (LZ) and then migrate to the dark zone where they proliferate and undergo somatic mutation before cycling back to the LZ for further rounds of selection. Tolerance to autoantigens is frequently lost de novo as GC B cells undergo class switching and somatic mutation. This loss of tolerance is regulated by a variety of mechanisms including cell death, failure to compete for T cell help, and failure to …
