scholarly journals P0185ROLE OF THE COMPLEMENT SYSTEM IN PROLIFERATIVE LUPUS NEPHRITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Andres Ribas ◽  
Isabel Galcerán ◽  
Sara Outón ◽  
Tarek Salman ◽  
Javier Gimeno ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Complement System ◽  
Analytical Data ◽  
Kidney Tissue ◽  
Classical Pathway ◽  
Strong Intensity ◽  
Native Kidney ◽  
Weak Intensity ◽  
C4d Staining

Abstract Background and Aims Lupus Nephritis (LN) is a serious complication in patients with Systemic Lupus Erythematosus (SLE) which confers a worse prognosis in patients that develop this condition. It is well known that histological lesions correlate poorly with the prognosis of the disease, but little is known about the role of complement proteins deposition in kidney tissue. The aim of this study was to evaluate the effect on renal manifestations of the deposition in renal tissue of C3, as a marker of alternative pathway, C4 as a marker of the classical pathway and C1q representing the lectin pathway. Method A retrospective observational study was performed, including native kidney biopsies with a diagnosis of lupus proliferative nephritis (class III/IV) (ISN/RPS 2003). Direct immunofluorescence microscopy was performed in -80ºC frozen sections to evaluate IgA, IgG, IgM, C4d, C1q and C3, and LES activity and chronicity scores were calculated according to NIH disease activity scoring system. The intensity of staining was graded as 0 (no staining), +1 (stainvisible at 40X magnification), +2 (at 20X), +3 (at X10), and +4 (at 2-4X). For statistical purpose we considered weak staining: 0, +1, +2 and strong staining: +3, +4. Patient´s files were retrospectively reviewed and clinical and analytical data were collected using a standardized form. Results 64 native kidney biopsies from 56 patients with a diagnosis of lupus proliferative nephritis were included, basal characteristics are described in attached Table. Activity index was significantly higher in biopsies showing strong intensity C3 staining compared to biopsies showing weak intensity C3 staining [(n=25) 10±1 vs (n=13) 5±1; p=0.002 respectively], alb/creat was significantly higher in patients in whom biopsy showed strong intensity C3 staining, compared to biopsies showing weak intensity C3 staining [(n=10) 1964.4±585.2 mg/gr vs (n=6) 823.6±58 mg/gr; p<0.001, respectively], prot/creat was significantly higher in biopsies that showed strong C3 staining intensity [(n=27) 2302.5±325 mg/gr vs (n=12) 1287.7±235 mg/gr, p<0.005, respectively], haematuria at NL diagnosis was more frequently in patients whose biopsy showed strong intensity C3 staining (n=21, 80.8%), compared to biopsies showing weak intensity C3 staining (n=5, 19.5%, p<0.001); most of the patients without haematuria at diagnosis showed a weak intensity C3 staining or not C3 staining (n=13, 62%). Endocapillary proliferation was significantly higher in biopsies showing strong intensity C3 staining (90.9% vs 9.1%, p<0.001).Time to proteinuria response is higher in patients showing strong intensity C4d stainingcompared with biopsies showing weak intensity C4d staining (15.2±2.4 vs 6.4±1.8 months; p=0.001), time to haematuria response is higher inbiopsies showing strong intensity C4d staining (19.5±5.5 vs 7.5±2.3 months, p=0.003). Time to proteinuria response is higher in patients showing strong intensity C1q stainingcompared to biopsies showing weak intensity C1q staining (14.0±9 vs 3.3±2.6 months, p <0.001). Conclusion Our results suggest that complement system is activated in kidney tissue of proliferative LN patients; C3 staining is associated with clinical, analytical and histological data related to acute lupus activity, whereas C4d and C1q staining are related with long-term outcomes like treatment response. Further studies are needed to elucidate the role of complement system in LN.

scholarly journals Role of the Classical Pathway of Complement Activation in Experimentally Induced Polymicrobial Peritonitis

2001 ◽  
Vol 69 (12) ◽  
pp. 7304-7309 ◽  
Author(s):  
Ilhan Celik ◽  
Cordula Stover ◽  
Marina Botto ◽  
Steffen Thiel ◽  
Sotiria Tzima ◽  
...  
Keyword(s):  
Complement System ◽  
Complement Activation ◽  
Immune Defense ◽  
Classical Pathway ◽  
Complement Factor ◽  
Wild Type ◽  
Factor B ◽  
The Complement System ◽  
Deficient Mice

ABSTRACT The complement system and the natural antibody repertoire provide a critical first-line defense against infection. The binding of natural antibodies to microbial surfaces opsonizes invading microorganisms and activates complement via the classical pathway. Both defense systems cooperate within the innate immune response. We studied the role of the complement system in the host defense against experimental polymicrobial peritonitis using mice lacking either C1q or factor B and C2. The C1q-deficient mice lacked the classical pathway of complement activation. The factor B- and C2-deficient mice were known to lack the classical and alternative pathways, and we demonstrate here that these mice also lacked the lectin pathway of complement activation. Using inoculum doses adjusted to cause 42% mortality in the wild-type strain, none of the mice deficient in the three activation routes of complement (factor B and C2 deficient) survived (mortality of 100%). Mortality in mice deficient only in the classical pathway of complement activation (C1q deficient) was 83%. Application of further dilutions of the polymicrobial inoculum showed a dose-dependent decrease of mortality in wild-type controls, whereas no changes in mortality were observed in the two gene-targeted strains. These results demonstrate that the classical activation pathway is required for an effective antimicrobial immune defense in polymicrobial peritonitis and that, in the infection model used, the remaining antibody-independent complement activation routes (alternative and lectin pathways) provide a supporting line of defense to gain residual protection in classical pathway deficiency.

Emerging Role of Circular RNAs in Kidney Diseases in Nephrology

2021 ◽  
Vol 22 ◽  
Author(s):  
Cong Ma ◽  
Junjun Luan ◽  
Jeffrey B. Kopp ◽  
Hua Zhou
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Kidney Diseases ◽  
Kidney Tissue ◽  
Current Status ◽  
Renal Diseases ◽  
Circular Rnas ◽  
Systemic Lupus

Background: Circular RNAs (circRNAs) have been identified to be involved in a variety of human diseases such as cancers, cardiovascular diseases, and autoimmune diseases. In recent years, the role of circRNAs in the development of kidney diseases in nephrology has been gradually recognized. Objective: We updated and described the current status of circRNAs in kidney diseases in nephrology. We particularly focused on the roles and mechanisms of circRNAs in systemic lupus erythematosus and lupus nephritis. Methods: We summarized recent reports published on PubMed, Web of Science, Scopus, Scielo databases using key words circRNAs, kidney diseases or renal diseases, or systemic lupus erythematosus. Results: Studies of circRNAs in certain kidney diseases such as acute kidney injury, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, IgA nephropathy, diabetic nephropathy, hypertensive renal damage and particular lupus nephritis address the function and pathogenesis of circRNAs in these diseases. Mechanisms of circRNAs in the above human kidney diseases so far have focused on the role of sponging microRNAs and regulating the expression of target genes. Moreover, circRNAs have been detected in blood, urine, and kidney tissue samples. These results suggest that circRNAs can serve as biomarkers for the diagnosis and monitoring the progression of kidney diseases. Conclusion: CircRNAs play important roles in the pathogenesis, diagnosis, and treatment of kidney diseases emphasizing lupus nephritis in nephrology.

Correlation Between Serological Makers and Immunofluorescence Deposits i n Kidney Tissue of Patients with Lupus Nephritis

2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Haider S Al-Hadad ◽  
Aqeel Abbas Matrood ◽  
Maha Abdalrasool Almukhtar ◽  
Haider Jabur Kehiosh ◽  
Riyadh Muhi Al-Saegh
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Kidney Biopsy ◽  
Pearson Correlation ◽  
Standard Procedure ◽  
Kidney Tissue ◽  
P Value ◽  
American College Of Rheumatology ◽  
Immune Deposits ◽  
Number Of Patients

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease. Few biomarkers for SLE have been validated and widely accepted for the laboratory follow-up of inflammatory activity. In SLE patients, with lupus nephritis (LN), complement activation leads to fluctuation of serum C3 and C4 that are frequently used as clinicalm biomarker of disease activity in SLE. Patients and Methods: In this study the number of patients were 37, seven patients were excluded for incomplete data collection, 28 were females ,2 were males. The duration of the study is two years from 2015 to 2017. Patients were considered to have SLE and LN according to American College of Rheumatology (ACR) criteria, and International Society of Nephrology/ Renal Pathology Society (ISN/RPS). All patients were evaluated withm clinical presentation, laboratory investigations. Our patients underwent kidney biopsy according to standard procedure by Kerstin Amann, and their tissue specimens were studied in the laboratory with light microscope (LM) and immunofluorescence microscope reagents. The relationship between the serological markers and immunofluorescence deposits in kidney biopsy of all patients were studied using the statistical analysis of Pearson correlation and single table student's T test. A P value 0.05 was considered statistically significant. Results: The granular pattern of IF deposits was present in all LN patients, and in more than two third of patients these IF deposits presented in glomerular, tubular, and mesangium sites. While less than one third of patients had IF deposits in the mesangium only. There was no statistically significant correlation between serum ANA, anti-dsDNA, and IF deposits of different types. There was significant correlation between serum C3 and C4 hypocomplementemia and IgG immune deposits in kidney biopsy, and there was significant relationship between serum C3 hypocomplementemia and full house immunofluorescence (FHIF) deposits inm kidney biopsy.Conclusions:Immunofluorescence deposits is mainly granular pattern in LN patients. There was no significant association between serum ANA, anti-dsDNA, and immune deposits in kidney tissue. Immunofluorescence deposits of IgG type correlates significantly with serum C3 and C4 hypocomplemetemia, and these immune deposits in association with low complement levels correlates with LN flare. There was significant correlation between C3 hypocomplementemia and FHIF.

INTERPRETATIONAL FIELD OF THE CONCEPT “WOMAN” IN ENGLISH AND KYRGYZ LINGUOCULTURES

2019 ◽  
pp. 54-56
Author(s):  
Баяманова М.С.
Keyword(s):  
Comparative Study ◽  
Key Words ◽  
Analytical Data ◽  
Semantic Field ◽  
Traditional Values ◽  
Lexical Unit ◽  
Semantic Fields ◽  
Field Culture

Summary: The article deals with the analysis of the interpretational field of the basic lexical units which represent the meaning of the concept “woman” in English and Kyrgyz languages and cultures. Comparative – contrastive analytical data of the most frequently used in both languages variants of the interpretation of the concept “woman” have been given. The semantic fields of nuclear and nearnuclear meanings of the lexical units, transforming the notion of “woman” in English and Kyrgyz languages and also the place and role of these notions in cultures and philosophy of the nations on the basis of mentality and traditional values have been studied and described. The situations of the use of this or that variant of the meaning of lexical unit. A comparative study of the definitions of the word “woman’ in English and Kyrgyz languages have been given. Key words: concept, woman, interpretational field, notion, definition, semantic field, culture, language, linguoculture, transformation Аннотация: В статье рассматриваются интерпретационные поля основных лексических единиц, репрезентирующих значение концепта «женщина» в английской и кыргызской лингвокультурах. Приводятся сравнительно-сопоставительные аналитические данные наиболее употребительных в речи обоих языков вариантов интерпретации концепта «женщина». Изучены и описаны семантические поля ядерных и околоядерных значений лексических единиц, трансформирующих понятие «женщина» в английском и кыргызском языке, а также роль и место этих понятий в культурах и философии народов на основе менталитета и традиционных ценностей. Приводятся ситуации использования того или ино- го варианта значения лексической единицы, проведено сравнительное изучение определений слова «женщина» в английском и кыргызском языках. Ключевые слова: концепт, женщина, интерпретационное поле, понятие, определение, семантическое поле, культура, язык, лингвокультура, трансформация Аннотация: Макалада англис жана кыргыз тилдеринде жана маданияттарында «аял» концептинин маанисин репрезентациалаган негизги лексикалык бирдиктер каралат. «Аял» концептин эки тилдеги кѳп колдонулуучу интерпретациялоо варианттарынын аналитикалык салыштырма маалыматтары изил- делип берилген. Англис жана кыргыз тилдеринде «аял» түшүнүгүн трансформациялаган лексикалык бирдиктердин түп нуска жана ага жакындашкан маанилери иликтелип каралган. Берилген түшүнүктѳрдүн элдик философиясында жана маданиятында, менталитеттин жана салттын негизинде эл арасына кеӊири тараган, элдик тилде жана маданиятта ойногон ролу менен орду чагылдырылган. Ар түрдү ситацияларда колдонулуучу тиги же бул лексикалык бирдиктердин маанисинин варианттары каралган, «аял» деген сѳздун англис жана кыргыз тилдериндеги түшүндүрмѳлѳрү салыштырылып изилделген. Түйүндүү сѳздѳр: концепт, аял, интерпретациялоо мейкиндиги, түшүнүк, түшүндүрмѳ, семантикалык чѳйрѳ, маданият, тил, лингвомаданият, трансформациялоо

A Comparative Study on the Incidence, Aggravation, and Remission of Lupus Nephritis Based on iTRAQ Technology

2020 ◽  
Vol 23 (7) ◽  
pp. 649-657
Author(s):  
Dong-Jiang Liao ◽  
Xi-Ping Cheng ◽  
Nan Li ◽  
Kang-Li Liang ◽  
Hui Fan ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Kidney Tissue ◽  
Quantitative Information ◽  
Enzyme Linked Immunosorbent Assay ◽  
Absolute Quantitation ◽  
Western Blot Method ◽  
Close Relationship ◽  
Polymerase Chain ◽  
Isobaric Tags

Aim and Objective: Lupus nephritis (LN) is one of the major complications of systemic lupus erythematosus (SLE). The specific mechanisms of pathogenesis, aggravation, and remission processes in LN have not been clarified but is of great need in the clinic. Using isobaric tags for relative and absolute quantitation (iTRAQ) technology to screen the functional proteins of LN in mice. Especially under intervention factors of lipopolysaccharide (LPS) and dexamethasone. Methods: Mrl-lps mice were intervened with LPS, dexamethasone, and normal saline (NS) using intraperitoneal injection, and c57 mice intervened with NS as control. The anti-ANA antibody enzyme-linked immunosorbent assay (ELISA) was used to verify disease severity. Kidney tissue is collected and processed for iTRAQ to screen out functional proteins closely related to the onset and development of LN. Western blot method and rt-PCR (real-time Polymerase Chain Reaction) were used for verification. Results: We identified 136 proteins that marked quantitative information. Among them, Hp, Igkv8-27, Itgb2, Got2, and Pcx proteins showed significant abnormal manifestations. Conclusion: Using iTRAQ methods, the functional proteins Hp, Igkv8-27, Itgb2, Got2, and Pcx were screened out for a close relationship with the pathogenesis and development of LN, which is worth further study.

YAP1 Overexpression Is Associated with Kidney Dysfunction in Lupus Nephritis

Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Ying Xie ◽  
Yuanyuan Ruan ◽  
Huimei Zou ◽  
Yixin Wang ◽  
Xin Wu ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Tissue ◽  
Mouse Kidney ◽  
Experimental Comparison ◽  
Control Group ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Protein Levels

<b><i>Objective:</i></b> The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis. <b><i>Methods:</i></b> C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson’s trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman’s analysis. <b><i>Results:</i></b> Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury. <b><i>Conclusion:</i></b> YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.

scholarly journals Special Issue: The Role of Complement in Cancer Immunotherapy

Antibodies ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 29
Author(s):  
Ronald P. Taylor
Keyword(s):  
Cancer Immunotherapy ◽  
Complement System ◽  
Immune Defense ◽  
Special Issue ◽  
The Complement System ◽  
Critical Aspects

The complement system plays an important role in critical aspects of immune defense and in the maintenance of homeostasis in the bloodstream, as well as in essentially all tissues and organs [...]

scholarly journals T cell–specific STAT3 deficiency abrogates lupus nephritis

Lupus ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 1468-1472 ◽  
Author(s):  
N Yoshida ◽  
F He ◽  
V C Kyttaris
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Cell Responses ◽  
Cytokines And Chemokines ◽  
Novel Approach ◽  
Cell Tissue ◽  
External Stimuli

Signal transducer and activator of transcription (STAT) 3 is a regulator of T-cell responses to external stimuli, such as pro-inflammatory cytokines and chemokines. We have previously shown that STAT3 is activated (phosphorylated) at high levels in systemic lupus erythematosus (SLE) T cells and mediates chemokine-induced migration and T:B cell interactions. Stattic, a small molecular STAT3 inhibitor, can partially ameliorate lupus nephritis in mice. To understand the role of STAT3 better in T-cell pathophysiology in lupus nephritis and its potential as a treatment target, we silenced its expression in T cells using a cd4-driven CRE-Flox model. We found that lupus-prone mice that do not express STAT3 in T cells did not develop lymphadenopathy, splenomegaly, or glomerulonephritis. Moreover, the production of anti-dsDNA antibodies was decreased in these mice compared to controls. To dissect the mechanism, we also used a nephrotoxic serum model of nephritis. In this model, T cell–specific silencing of STAT3 resulted in amelioration of nephrotoxic serum-induced kidney damage. Taken together, our results suggest that in mouse models of autoimmune nephritis, T cell–specific silencing of STAT3 can hamper their ability to help B cells to produce autoantibodies and induce cell tissue infiltration. We propose that STAT3 inhibition in T cells represents a novel approach in the treatment of SLE and lupus nephritis in particular.

scholarly journals Chronic complement dysregulation drives neuroinflammation after traumatic brain injury: a transcriptomic study

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Amer Toutonji ◽  
Mamatha Mandava ◽  
Silvia Guglietta ◽  
Stephen Tomlinson
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Complement System ◽  
Classical Pathway ◽  
Post Injury ◽  
Complement Inhibition ◽  
Time Points ◽  
Complement Gene ◽  
The Complement System

AbstractActivation of the complement system propagates neuroinflammation and brain damage early and chronically after traumatic brain injury (TBI). The complement system is complex and comprises more than 50 components, many of which remain to be characterized in the normal and injured brain. Moreover, complement therapeutic studies have focused on a limited number of histopathological outcomes, which while informative, do not assess the effect of complement inhibition on neuroprotection and inflammation in a comprehensive manner. Using high throughput gene expression technology (NanoString), we simultaneously analyzed complement gene expression profiles with other neuroinflammatory pathway genes at different time points after TBI. We additionally assessed the effects of complement inhibition on neuropathological processes. Analyses of neuroinflammatory genes were performed at days 3, 7, and 28 post injury in male C57BL/6 mice following a controlled cortical impact injury. We also characterized the expression of 59 complement genes at similar time points, and also at 1- and 2-years post injury. Overall, TBI upregulated the expression of markers of astrogliosis, immune cell activation, and cellular stress, and downregulated the expression of neuronal and synaptic markers from day 3 through 28 post injury. Moreover, TBI upregulated gene expression across most complement activation and effector pathways, with an early emphasis on classical pathway genes and with continued upregulation of C2, C3 and C4 expression 2 years post injury. Treatment using the targeted complement inhibitor, CR2-Crry, significantly ameliorated TBI-induced transcriptomic changes at all time points. Nevertheless, some immune and synaptic genes remained dysregulated with CR2-Crry treatment, suggesting adjuvant anti-inflammatory and neurotropic therapy may confer additional neuroprotection. In addition to characterizing complement gene expression in the normal and aging brain, our results demonstrate broad and chronic dysregulation of the complement system after TBI, and strengthen the view that the complement system is an attractive target for TBI therapy.

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