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https://www.readbyqxmd.com/read/28219888/cd74-deficiency-mitigates-systemic-lupus-erythematosus-like-autoimmunity-and-pathological-findings-in-mice
#1
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Lijun Zhang, Vasileios C Kyttaris, George C Tsokos, Isaac E Stillman, Takaharu Ichimura, Joseph V Bonventre, Peter Libby, Guo-Ping Shi
CD74 mediates MHC class-II antigenic peptide loading and presentation and plays an important role in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus. C57BL/6 Fas(lpr) mice that develop spontaneous lupus-like autoimmunity and pathology showed elevated CD74 expression in the inflammatory cell infiltrates and the adjacent tubular epithelial cells (TECs) in kidneys affected by lupus nephritis but negligible levels in kidneys from age-matched wild-type mice. The inflammatory cytokine IFN-γ or IL-6 induced CD74 expression in kidney TECs in vitro...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28219887/disruption-of-pathogenic-cellular-networks-by-il-21-blockade-leads-to-disease-amelioration-in-murine-lupus
#2
Jin-Young Choi, Abhinav Seth, Michael Kashgarian, Sonia Terrillon, Emma Fung, Lili Huang, Li Chun Wang, Joe Craft
Systemic lupus erythematosus (lupus) is characterized by autoantibody-mediated organ injury. Follicular Th (Tfh) cells orchestrate physiological germinal center (GC) B cell responses, whereas in lupus they promote aberrant GC responses with autoreactive memory B cell development and plasma cell-derived autoantibody production. IL-21, a Tfh cell-derived cytokine, provides instructional cues for GC B cell maturation, with disruption of IL-21 signaling representing a potential therapeutic strategy for autoantibody-driven diseases such as systemic lupus erythematosus...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28217966/pathogenesis-of-diffuse-alveolar-hemorrhage-in-murine-lupus
#3
Haoyang Zhuang, Shuhong Han, Pui Y Lee, Ravil Khaybullin, Stepan Shumyak, Li Lu, Amina Chatha, Anan Afaneh, Yuan Zhang, Chao Xie, Dina Nacionales, Lyle Moldawer, Xin Qi, Li-Jun Yang, Westley H Reeves
OBJECTIVE: Diffuse alveolar hemorrhage (DAH) in lupus patients is >50% fatal. The cause is unknown. The pathogenesis of DAH in C57BL/6 mice with pristane-induced lupus, a model of human lupus-associated DAH, was examined. METHODS: Clinical/pathological and immunological manifestations DAH in pristane-lupus were compared with human DAH. Tissue distribution of pristane was examined by mass spectrometry. Cell types responsible for disease were determined by in vivo depletion using clodronate liposomes (CloLip) and anti-neutrophil monoclonal antibodies (GR1)...
February 19, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28215100/targeting-baff-and-april-in-systemic-lupus-erythematosus-and-other-antibody-associated-diseases
#4
Eileen Samy, Stephen Wax, Bertrand Huard, Henry Hess, Pascal Schneider
The B cell-stimulating molecules, BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand), are critical factors in the maintenance of the B cell pool and humoral immunity. In addition, BAFF and APRIL are involved in the pathogenesis of a number of human autoimmune diseases, with elevated levels of these cytokines detected in the sera of patients with systemic lupus erythematosus (SLE), IgA nephropathy, Sjögren's syndrome, and rheumatoid arthritis. As such, both molecules are rational targets for new therapies in B cell-driven autoimmune diseases, and several inhibitors of BAFF or BAFF and APRIL together have been investigated in clinical trials...
January 2, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28215033/anti-mutated-citrullinated-vimentin-antibodies-in-antiphospholipid-syndrome-diagnostic-value-and-relationship-with-clinical-features
#5
Cristiano Alessandri, Nancy Agmon-Levin, Fabrizio Conti, Carlo Perricone, Elena Ortona, Monica Pendolino, Antonella Capozzi, Federica Delunardo, Riccardo Mancini, Simona Truglia, Francesca Romana Spinelli, Fulvia Ceccarelli, Maurizio Sorice, Yehuda Shoenfeld, Guido Valesini
: Antiphospholipid antibodies (aPLs) are a heterogeneous group of autoantibodies essential for the diagnosis of antiphospholipid syndrome (APS) but do not predict clinical manifestations or disease progression. Hence, the co-presence of other antibodies may prove useful. Autoimmunity directed toward vimentin and other citrullinated peptides was established in rheumatoid arthritis (RA) and in other autoimmune conditions including systemic lupus erythematosus (SLE). We have previously described the presence of autoantibodies directed against vimentin/cardiolipin complex in patients with antiphospholipid syndrome (APS), but there are no data on the role of citrullinated vimentin in APS...
February 18, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28207493/treatment-of-lupus-nephritis-current-paradigms-and-emerging-strategies
#6
Maria Dall'Era
PURPOSE OF REVIEW: Lupus nephritis is the most common organ-threatening manifestation of lupus and continues to result in end-stage renal disease. This review describes the contemporary treatment of lupus nephritis as well as emerging therapeutic strategies. RECENT FINDINGS: Lupus nephritis management consists of an initial (induction) phase and a maintenance (extended) phase in which steroids are used in combination with another immunosuppressive medication. Current treatments are incompletely effective and associated with substantial toxicity...
February 15, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28205373/pulmonary-hypertension-in-connective-tissue-diseases-an-update
#7
REVIEW
Ramya Aithala, Anoop G Alex, Debashish Danda
Pulmonary hypertension (PH) is a relatively commoner complication of systemic sclerosis (SSc) with estimated prevalence ranging between 8% and 12% as compared to much lower figures in other connective tissue diseases (CTD). It is a major cause of morbidity and mortality in CTDs. PH is classified into five major groups. CTD-associated PH belongs to group 1 PH, also known as pulmonary arterial hypertension (PAH). Around 30% of scleroderma-related deaths are due to PAH. Underlying pathogenesis is related to pulmonary vasculopathy involving small vessels...
February 16, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28198796/carbonic-anhydrase-i-and-ii-autoantibodies-in-beh%C3%A3-et-s-disease
#8
Ahmet Mentese, Ahmet Alver, Selim Demir, Aysegul Sumer, Serap Ozer Yaman, Murat Karkucak, Arzu Aydin Capkin, Diler Us Altay, Ibrahim Turan
BACKGROUND: Behçet's disease is a vasculitis, seen more frequently around the Mediterranean and the Far East, and evinces with oral and genital ulcerations, skin lesions and uveitis. Carbonic anhydrase (CA) is a metalloenzyme which is widely distributed in the living world, and it is essential for the regulation of acid-base balance. Anti-CA antibodies have been reported in many disorders, such as systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, endometriosis, idiopathic chronic pancreatitis, type 1 diabetes and Graves' disease...
December 3, 2016: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28191680/friends-or-foes-host-defense-antimicrobial-peptides-and-proteins-in-human-skin-diseases
#9
REVIEW
François Niyonsaba, Chanisa Kiatsurayanon, Panjit Chieosilapatham, Hideoki Ogawa
Host defense peptides/proteins (HDPs), also known as antimicrobial peptides/proteins (AMPs), are key molecules in the cutaneous innate immune system. AMPs/HDPs historically exhibit broad-spectrum killing activity against bacteria, enveloped viruses, fungi and several parasites. Recently, AMPs/HDPs were shown to have important biological functions, including inducing cell proliferation, migration and differentiation; regulating inflammatory responses; controlling the production of various cytokines/chemokines; promoting wound healing; and improving skin barrier function...
February 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28185016/association-between-paraoxonase-1-gene-q192r-and-l55m-polymorphisms-in-systemic-lupus-erythematosus-sle-and-anti-phospholipid-syndrome-aps-in-a-population-from-cairo-of-egypt
#10
Alshaymaa Ahmed Ibrahim, Dalia El-Lebedy, Ingy Ashmawy, Maha Abdel Hady
Paraoxonase-1 (PON1) is involved in the oxidative stress process that cause tissue damage observed in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). The aim of the present study was to investigate the association of PON1 Q192R and L55M polymorphisms with risk of SLE and associated APS among Egyptian sample. The study included 120 SLE patients (45 without APS and 75 with APS) and 120 healthy subjects. PON1 Q192R and L55M polymorphisms were genotyped by real-time PCR. No significant differences in Q192R genotypes or allele frequencies were found between patients and controls (p = 0...
February 9, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28183532/growth-factor-midkine-promotes-nuclear-factor-of-activated-t-cells-regulated-t-cell-activation-and-th1-cell-differentiation-in-lupus-nephritis
#11
Tomohiro Masuda, Kayaho Maeda, Waichi Sato, Tomoki Kosugi, Yuka Sato, Hiroshi Kojima, Noritoshi Kato, Takuji Ishimoto, Naotake Tsuboi, Kenji Uchimura, Yukio Yuzawa, Shoichi Maruyama, Kenji Kadomatsu
Activated T cells play crucial roles in the pathogenesis of autoimmune diseases, including lupus nephritis (LN). The activation of calcineurin/nuclear factor of activated T cells (NFAT) and STAT4 signaling is essential for T cells to perform various effector functions. Here, we identified the growth factor midkine (MK; gene name, Mdk) as a novel regulator in the pathogenesis of 2,6,10,14-tetramethylpentadecane-induced LN via activation of NFAT and IL-12/STAT4 signaling. Wild-type (Mdk(+/+)) mice showed more severe glomerular injury than MK-deficient (Mdk(-/-)) mice, as demonstrated by mesangial hypercellularity and matrix expansion, and glomerular capillary loops with immune-complex deposition...
February 7, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28168401/dyslipidemia-in-systemic-lupus-erythematosus
#12
Melinda Zsuzsanna Szabó, Peter Szodoray, Emese Kiss
Cardiovascular disease is one of the major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Accelerated atherosclerosis is related to traditional (age, hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, and positive family history) and non-traditional, disease-related factors. Traditional risk factors are still more prominent in patients with lupus, as both hypertension and hypercholesterinemia were independently associated with premature atherosclerosis in several SLE cohorts...
February 7, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28162788/pathways-of-impending-disease-flare-in-african-american-systemic-lupus-erythematosus-patients
#13
Melissa E Munroe, Evan S Vista, Joan T Merrill, Joel M Guthridge, Virginia C Roberts, Judith A James
Immune dysregulation in systemic lupus erythematosus (SLE) contributes to increased disease activity. African-American (AA) SLE patients have an increased prevalence of complications from disease flares and end-organ damage that leads to increased morbidity and early mortality. We previously reported alterations in inflammatory and regulatory immune mediator levels prior to disease flare in European American (EA) SLE patients. In the current study, we assessed baseline and follow-up plasma levels of 52 soluble mediators, including innate, adaptive, chemokine, and TNF superfamily members, in AA SLE patients who developed SELENA-SLEDAI defined flare 6 or 12 weeks after baseline assessment...
February 2, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28154472/autoantibodies-to-nr2a-peptide-of-the-glutamate-nmda-receptor-in-patients-with-seizure-disorders-in-neuropsychiatric-systemic-lupus-erythematosus
#14
Yan Yang, Chao Yuan, Shu-Qun Shen, Xue-Er Wang, Qing-Hua Mei, Wen-Qing Jiang, Qin Huang
Objective. Seizure disorders are one of the most disabling, life-threatening, and the least understood syndromes associated with neuropsychiatric SLE (NPSLE). N-Methyl-D-aspartate (NMDA) receptors are a subgroup of the glutamate receptor family, whose NR2A subunit was found on neuronal cells (anti-NR2A) in NPSLE patients with different types of epilepsy. The present study was conducted to determine the serum levels of anti-NR2A antibodies in a large group of SLE patients, to investigate the possible correlation between the presence of the NR2A specific antibodies and NPSLE-related seizure disorders...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28153882/activated-platelets-induce-endothelial-cell-activation-via-an-interleukin-1%C3%AE-pathway-in-systemic-lupus-erythematosus
#15
Sokha Nhek, Robert Clancy, Kristen A Lee, Nicole M Allen, Tessa J Barrett, Emanuela Marcantoni, Janet Nwaukoni, Sara Rasmussen, Maya Rubin, Jonathan D Newman, Jill P Buyon, Jeffrey S Berger
OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with the premature development of cardiovascular disease. The platelet-endothelium interaction is important in the pathogenesis of cardiovascular disease. In this study, we investigated the platelet phenotype from patients with SLE and matched controls, and their effect on endothelial cells. APPROACH AND RESULTS: Platelet aggregability was measured in 54 SLE subjects off antiplatelet therapy (mean age 40...
February 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28152213/melatonin-signaling-in-t-cells-functions-and-applications
#16
REVIEW
Wenkai Ren, Gang Liu, Shuai Chen, Jie Yin, Jing Wang, Bie Tan, Guoyao Wu, Fuller W Bazer, Yuanyi Peng, Tiejun Li, Russel J Reiter, Yulong Yin
Melatonin affects a variety of physiological processes including circadian rhythms, cellular redox status and immune function. Importantly, melatonin significantly influences T cell-mediated immune responses, which are crucial to protect mammals against cancers and infections, but are associated with pathogenesis of many autoimmune diseases. This review focuses on our current understanding of the significance of melatonin in T cell biology and the beneficial effects of melatonin in T cell response-based diseases...
February 2, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28150814/p-selectin-preserves-immune-tolerance-in-mice-and-is-reduced-in-human-cutaneous-lupus
#17
Rafael González-Tajuelo, Javier Silván, Alicia Pérez-Frías, María de la Fuente-Fernández, Reyes Tejedor, Marina Espartero-Santos, Esther Vicente-Rabaneda, Ángeles Juarranz, Cecilia Muñoz-Calleja, Santos Castañeda, Carlos Gamallo, Ana Urzainqui
Mice deficient in P-Selectin presented altered immunity/tolerance balance. We have observed that the absence of P-Selectin promotes splenomegaly with reduced naïve T cell population, elevated activated/effector T cell subset, increased germinal center B and Tfh populations and high production of autoreactive antibodies. Moreover, 1.5-3-month-old P-selectin KO mice showed reduced IL-10-producing leukocytes in blood and a slightly reduced Treg population in the skin. With aging and, coinciding with disease severity, there is an increase in the IL17(+) circulating and dermal T cell subpopulations and reduction of dermal Treg...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28150518/chloroquine-attenuates-tlr3-ifn-%C3%AE-signaling-in-cultured-normal-human-mesangial-cells-a-possible-protective-effect-against-renal-damage-in-lupus-nephritis
#18
Tadaatsu Imaizumi, Ryo Hayakari, Tomoh Matsumiya, Hidemi Yoshida, Kazushi Tsuruga, Shojiro Watanabe, Shogo Kawaguchi, Hiroshi Tanaka
BACKGROUND: Chloroquine has been reported to protect against renal damage in lupus nephritis (LN), however, its detailed mechanism in glomerular inflammation remains unclear. Upregulation of the type I interferon (IFN) system plays a pivotal role in LN pathogenesis, therefore, we examined whether chloroquine inhibits Toll-like receptor 3 (TLR3)/IFN-β signaling in cultured normal human mesangial cells (MCs). METHODS: We examined chloroquine effect on the representative TLR3/IFN-β signaling axis, TLR3/IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5 in MCs treated with polyinosinic-polycytidylic acid (poly IC), a synthetic viral dsRNA analog and analyzed the expression of these molecules using reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay...
February 2, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28148586/systemic-lupus-erythematosus
#19
Maliha F Shaikh, Natasha Jordan, David P D'Cruz
Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease that is highly heterogeneous in its presentation. This can pose significant challenges for physicians responsible for the diagnosis and treatment of such patients. SLE arises from a combination of genetic, epigenetic and environmental factors. Pathologically, the disease is primarily driven by loss of immune tolerance and abnormal B- and T-cell function. Major organ involvement may lead to significant morbidity and mortality. Classification criteria for SLE have been developed largely for research purposes; however, these are also widely used in clinical practice...
February 2017: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/28147328/autoantibody-to-mdm2-a-potential-serological-marker-of-primary-sjogren-s-syndrome
#20
Yuan Liu, Xining Liao, Ying Wang, Shiju Chen, Yuechi Sun, Qingyan Lin, Guixiu Shi
INTRODUCTION: Primary Sjogren's Syndrome (pSS) is one of the autoimmune diseases characterized by polyclonal autoantibody production. The human homologue of the mouse double minute 2 (MDM2) is an important negative regulator of p53. Our previous study indicated that autoantibody to MDM2 can be detected in systemic lupus erythematosus patients. The purpose of this study is to study anti-MDM2 autoantibody in pSS patients. METHODS: Anti-MDM2 autoantibody in sera from 100 pSS patients and 74 normal controls was investigated by ELISA...
January 28, 2017: Oncotarget
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