scholarly journals The DNA co-vaccination using Sm antigen and IL-10 as prophylactic experimental therapy ameliorates nephritis in a model of lupus induced by pristane

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0259114
Author(s):  
Beatriz Teresita Martín-Márquez ◽  
Minoru Satoh ◽  
Rogelio Hernández-Pando ◽  
Erika Aurora Martínez-García ◽  
Marcelo Heron Petri ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Lupus Erythematosus ◽  
Renal Damage ◽  
K562 Cells ◽  
Experimental Therapy ◽  
Direct Immunofluorescence ◽  
Ifn Γ ◽  
Models Of Lupus ◽  
Specific Tolerance ◽  
Sm Antigen

Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies such as anti-Sm. Studies in patients with SLE and murine models of lupus reveal that the most critical anti-Sm autoantibodies are predominantly direct against D1(83–119), D2, and B´/B epitopes. Objectives The present study aimed to analyze the induction of antigen-specific tolerance after prophylactic immunization with a DNA vaccine encoding the epitopes: D183-119, D2, B´/B, and B´/BCOOH in co-vaccination with IFN-γ or IL-10 in a murine model of lupus induced by pristane. Material and methods To obtain endotoxin-free DNA vaccines, direct cloning techniques using pcDNA were performed: D183-119, D2, B´/B, B´/BCOOH, IFN-γ, or IL-10. Lupus was induced by 0.5 mL of pristane via intraperitoneal in BALB/c female mice. Immunoprecipitation with K562 cells was metabolically labeled with 35S and ELISA to detect serum antibodies or mice IgG1, IgG2a isotypes. ELISA determined IL-10 and IFN-γ from splenocytes supernatants. Proteinuria was assessed monthly, and lupus nephritis was evaluated by immunofluorescence, and electron microscopy. Results The prophylactic co-vaccination with D2/IL-10 reduced the expression of kidney damage observed by electron microscopy, direct immunofluorescence, and H & E, along with reduced level of anti-nRNP/Sm antibodies (P = 0.048). Conclusion The prophylactic co-vaccination of IL-10 with D2 in pristane-induced lupus ameliorates the renal damage maybe by acting as prophylactic DNA tolerizing therapy.

scholarly journals Correlations of Expression Levels of a Panel of Genes (IRF5, STAT4, TNFSF4, MECP2, and TLR7) and Cytokine Levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, and TNF-α) with Systemic Lupus Erythematosus Outcomes in Jordanian Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Amal H. Uzrail ◽  
Areej M. Assaf ◽  
Shtaywy S. Abdalla
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Renal Damage ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Expression Levels ◽  
Cardiovascular Damage ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ

Systemic lupus erythematosus (SLE) is characterized by systemic end-organ damage. We investigated the involvement of IRF5, TLR-7, MECP2, STAT4, and TNFSF4 genes and TNF-α, IFN-γ, IL-2, IL-12, IL-6, and IL-10 cytokines in SLE pathogenesis and in organ damage in Jordanian patients. Blood was collected from 51 patients and 50 controls. Expression levels of SLE genes in PBMCs and cytokine levels were determined using RT-PCR and ELISA, respectively. Expression levels of all genes and levels of TNF-α, IL-12, IL-6, and IL-10 were higher in SLE patients than those in controls (p<0.05), whereas IL-2 level was lower. High STAT4 (α), TNFSF4, and IL-10 levels correlated with cardiovascular damage, and high MECP2 (α) and TNF-α correlated with renal damage. Pulmonary and musculoskeletal damages correlated with high levels of TNFSF4. We concluded that STAT4 and TNFSF4 genes with TNF-α and IL-10 cytokines could be used as biomarkers to assess SLE activity and manage treatment.

scholarly journals Predictors of renal damage in systemic lupus erythematous patients: data from a multiethnic, multinational Latin American lupus cohort (GLADEL)

RMD Open ◽  
2020 ◽  
Vol 6 (3) ◽  
pp. e001299
Author(s):  
Cristina Reátegui-Sokolova ◽  
Manuel F Ugarte-Gil ◽  
Guillermina B Harvey ◽  
Daniel Wojdyla ◽  
Guillermo J Pons-Estel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Latin American ◽  
Lupus Erythematosus ◽  
Renal Damage ◽  
Cox Regression ◽  
Damage Index ◽  
Early Response ◽  
Male Gender ◽  
Systemic Lupus

AimA decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria.MethodsWe included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed.ResultsFive hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence.ConclusionsEarly response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.

Association of microRNA-125a with the clinical features, disease activity and inflammatory cytokines of juvenile-onset lupus patients

Lupus ◽  
2021 ◽  
pp. 096120332110103
Author(s):  
Eman Eissa ◽  
Botros Morcos ◽  
Rania Fawzy Mahmoud Abdelkawy ◽  
Hanan H Ahmed ◽  
Naglaa M Kholoussi
Keyword(s):  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Plasma Levels ◽  
Clinical Manifestations ◽  
Juvenile Onset ◽  
Expression Levels ◽  
Ifn Γ ◽  
Chronic Autoimmune Disease ◽  
Normal Controls

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with marked variation in its clinical presentation. Juvenile-onset SLE (jSLE) exhibits an aggressive clinical phenotype and severe complications. Dysregulated expression of microRNAs (miRs) in immune cells from patients with SLE has been found. We aim to evaluate the association of miR-125a with the clinical and laboratory characteristics, disease activity and inflammatory cytokines of jSLE patients. Methods 60 jSLE patients and 25 normal controls were involved in the study. The expression pattern of miR-125a was determined in plasma of all subjects using qRT-PCR. In addition, plasma levels of IL-17 and IFN-γ were examined using ELISA. The correlation of miR-125a expression with the clinical manifestations and disease activity of jSLE patients was analyzed. Also, its association with the inflammatory cytokines was investigated in jSLE patients. Results Our findings showed that miR-125a expression levels were significantly reduced in jSLE patients compared to normal controls ( p < 0.01) and these expression levels differed based on the clinical variability of patients. In addition, plasma levels of IL-17 and IFN-γ in jSLE patients were significantly higher than healthy controls ( p < 0.01). Finally, miR-125a expression had significant negative associations with each of SLEDAI-2K ( p < 0.01), SLICC ( p < 0.01), ESR ( p < 0.05), proteinuria ( p < 0.01) and IL-17 levels ( p < 0.01) in jSLE patients. Conclusion Our findings postulate that miR-125a could act as a candidate therapeutic target for its possible regulation of inflammation in jSLE patients.

EBV load is associated with cfDNA fragmentation and renal damage in SLE patients

Lupus ◽  
2021 ◽  
pp. 096120332110103
Author(s):  
Anna Truszewska ◽  
Agnieszka Wirkowska ◽  
Kamila Gala ◽  
Piotr Truszewski ◽  
Łucja Krzemień-Ojak ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Lupus Erythematosus ◽  
Epstein Barr Virus ◽  
Renal Damage ◽  
Healthy Individuals ◽  
Pcr Assay ◽  
Barr Virus ◽  
Fragmentation Index ◽  
Epstein Barr

Background For long Epstein–Barr virus (EBV) has been suspected to be involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to verify the association between EBV, cell-free DNA (cfDNA) and kidney disease in SLE. Methods Blood samples were obtained from 43 SLE patients and 50 healthy individuals. EBV load was measured via real-time PCR assay. Sizing and quantification of plasma cfDNA was performed on Bioanalyzer. We proposed that the uniformity of cfDNA fragmentation can be described using cfDNA fragmentation index. Results SLE patients with chronic kidney disease (CKD +) had higher EBV load compared to CKD(–) patients (P = 0.042). Patients with high cfDNA level had higher EBV load (P = 0.041) and higher cfDNA fragmentation index (P < 0.001) compared to patients with low cfDNA level. Among patients with high cfDNA level, EBV load was higher in CKD(+) group compared to CKD(–) group (P = 0.035). EBV load was positively correlated with the fragmentation index in all SLE patients (P = 0.028, R2 = 0.13), and the correlation was even more pronounced in CKD (+) patients (P < 0.001, R2 = 0.20). Conclusions We showed that EBV load was associated with non-uniform cfDNA fragmentation, higher cfDNA levels, and kidney disease in SLE patients. Although the causality of this relationship could not be determined with the current study, it brings rationale for further investigations on the role of EBV and cfDNA interplay in SLE pathogenesis.

scholarly journals Serum biomarker profile orchestrating the seroconversion status of patients with autoimmune diseases upon planned primary 17DD Yellow fever vaccination

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ismael Artur da Costa-Rocha ◽  
Ketty Lysie Libardi Lira Machado ◽  
Ana Carolina Campi-Azevedo ◽  
Andréa Teixeira-Carvalho ◽  
Vanessa Peruhype-Magalhães ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Neutralizing Antibody ◽  
Serum Biomarkers ◽  
Serum Biomarker ◽  
Time Points ◽  
Inflammatory Status ◽  
Biomarker Response ◽  
Ifn Γ ◽  
A Prospective Study

AbstractThe present study aimed to investigate whether the serum biomarkers of immune response orchestrate the seroconversion status in patients with autoimmune diseases (AID) upon planned primary 17DD-YF vaccination. For this purpose a total of 161 individuals were enrolled in a prospective study, including patients with Rheumatoid Arthritis (RA = 38), Spondyloarthritis (SpA = 51), Systemic Lupus Erythematosus (SLE = 21) and Sjögren’s Syndrome (SS = 30) along with a group of healthy controls (HC = 21). Analysis of plaque reduction neutralization test (PRNT) titers and seropositivity rates along with the 17DD-YF viremia and serum biomarkers were carried out at distinct time points (D0/D3–4/D5–6/D7/D14–28). The results demonstrated an overall lower PRNT titer and seropositivity rate (170 vs. 448; 77 vs. 95%) in AID as compared to HC, especially in SpA and SLE subgroups. No significant differences were observed in the viremia levels amongst groups. In general, a more prominent serum biomarker response was observed in AID as compared to HC, throughout the timeline kinetics. Remarkably, AID/PRNT(−) exhibited higher levels of several biomarkers at baseline as compared to AID/PRNT+. Moreover, while AID/PRNT(+) exhibited earlier increase in serum biomarkers at D3–4/D5–6, the AID/PRNT(−) displayed higher response at later time points (D7/D14–D28). Of note, a synchronic increase of IFN-γ at the peak of viremia (D5–6) was observed in HC and AID/PRNT(+) groups, whereas a later asynchronous IFN-γ response was reported for AID/PRNT(−) at D7. The biomarker profile tends to deflate at post-vaccination timeline, highlighting a putative immunomodulatory effect of live attenuated 17DD-YF vaccine in AID/PRNT(+), but not in AID/PRNT(−). Altogether these data suggested that inflammatory status prior vaccination, low IFN-γ at viremia peak and the occurrence of asynchronous biomarker storm after 17DD-YF vaccination may orchestrate the lack of neutralizing antibody response γ.

AB0440 Serum Uric Acid Levels Predict New Renal Damage in Systemic Lupus Erythematosus Patients

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 1057.3-1057
Author(s):  
C. Reátegui-Sokolova ◽  
M. Ugarte-Gil ◽  
R. Gamboa-Cardenas ◽  
F. Zevallos ◽  
J.M. Cucho-Venegas ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Lupus Erythematosus ◽  
Renal Damage ◽  
Systemic Lupus

scholarly journals Diffuse Bullous Eruptions in an Elderly Woman: Late-Onset Bullous Systemic Lupus Erythematosus

2016 ◽  
Vol 8 (3) ◽  
pp. 278-282 ◽  
Author(s):  
Prajwal Boddu ◽  
Mojtaba Nadiri ◽  
Owais Malik
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Late Onset ◽  
Clinical History ◽  
The Elderly ◽  
Direct Immunofluorescence ◽  
Systemic Lupus ◽  
Diverse Range ◽  
American College Of Rheumatology ◽  
Type Vii Collagen

Vesiculobullous eruptions in the elderly represent a diverse range of varying pathophysiologies and can present a significant clinical dilemma to the diagnostician. Diagnosis requires a careful review of clinical history, attention to detail on physical and histomorphological examination, and appropriate immunofluorescence testing. We describe the case of a 73-year-old female who presented to our hospital with a painful blistering skin rash developed over 2 days. Examination of the skin was remarkable for numerous flaccid hemorrhagic bullae on a normal-appearing nonerythematous skin involving both the upper and lower extremities. Histopathology of the biopsy lesion showed interface change at the epidermo-dermal region with subepidermal blister formation, mild dermal fibrosis, and sparse interstitial neutrophilic infiltrate. Immunohistological analysis was significant for positive IgG basement membrane zone antibodies with a dermal pattern of localization on direct immunofluorescence and positive IgG antinuclear antibodies on indirect immunofluorescence. Evidence of antibodies to type VII collagen suggested the diagnosis of epidermolysis bullosa acquisita versus bullous systemic lupus erythematosus (BSLE). A diagnosis of BSLE was made based on positive American College of Rheumatology criteria, acquired vesiculo-bullous eruptions with compatible histopathological and immunofluorescence findings. This case illustrates one of many difficulties a physician encounters while arriving at a diagnosis from a myriad of immunobullous dermatoses. Also, it is important for internists and dermatologists alike to be aware of and differentiate this uncommon and nonspecific cutaneous SLE manifestation from a myriad of disorders presenting with vesiculobullous skin eruptions in the elderly.

CUTANEOUS LUPUS ERYTHEMATOSUS: DIRECT IMMUNOFLUORESCENCE AND EPIDERMAL BASAL MEMBRANE STUDY

1992 ◽  
Vol 31 (4) ◽  
pp. 260-264 ◽  
Author(s):  
SOLEDAD A. SUGAI ◽  
ANDREA B. GERBASE ◽  
SELMA S. CERNEA ◽  
MIRIAN N. SOTTO ◽  
ZILDA N.P. OLIVEIRA ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Cutaneous Lupus Erythematosus ◽  
Basal Membrane ◽  
Direct Immunofluorescence ◽  
Cutaneous Lupus

scholarly journals CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice

2021 ◽  
Vol 22 (21) ◽  
pp. 11977
Author(s):  
Jocelyn C. Pérez-Lara ◽  
Enrique Espinosa ◽  
Leopoldo Santos-Argumedo ◽  
Héctor Romero-Ramírez ◽  
Gabriela López-Herrera ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Activation ◽  
Lupus Erythematosus ◽  
Clinical Signs ◽  
Foxp3 Expression ◽  
Cell Receptor ◽  
Treg Cells ◽  
Transmembrane Glycoprotein ◽  
Ifn Γ

CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38+CD25+ T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency in murine models has shown enhanced autoimmunity development. Recent studies have suggested that CD38+ regulatory T-cells are more suppressive than CD38− regulatory T-cells. Thus, we have suggested that CD38 overexpression in SLE patients could play a role in regulating immune activation cells instead of enhancing it. This study found a correlation between CD38 with FoxP3 expression and immunosuppressive molecules (CD69, IL-10, CTLA-4, and PD-1) in T-cells from lupus-prone mice (B6.MRL-Faslpr/J). Additionally, B6.MRL-Faslpr/J mice showed a decreased proportion of CD38+ Treg cells regarding wild-type mice (WT). Furthermore, Regulatory T-Cells (Treg cells) from CD38-/- mice showed impairment in expressing immunosuppressive molecules and proliferation after stimulation through the T-cell receptor (TCR). Finally, we demonstrated an increased ratio of IFN-γ/IL-10 secretion in CD38-/- splenocytes stimulated with anti-CD3 compared with the WT. Altogether, our data suggest that CD38 represents an element in maintaining activated and proliferative Treg cells. Consequently, CD38 could have a crucial role in immune tolerance, preventing SLE development through Treg cells.

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