scholarly journals An Update for Mesenchymal Stem Cell Therapy in Lupus Nephritis

2021 ◽  
Vol 7 (2) ◽  
pp. 79-89
Author(s):  
Wenchao Li ◽  
Weiwei Chen ◽  
Lingyun Sun
Keyword(s):  
Stem Cell ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Mesangial Cells ◽  
Treatment Options ◽  
Novel Therapy ◽  
Mesenchymal Stem Cell Therapy ◽  
Allogeneic Mscs ◽  
Senescent Phenotype ◽  
Organ Manifestations

Background: Lupus nephritis (LN) is the most severe organ manifestations of systemic lupus erythematosus (SLE). Although increased knowledge of the disease pathogenesis has improved treatment options, outcomes have plateaued as current immunosuppressive therapies have failed to prevent disease relapse in more than half of treated patients. Thus, there is still an urgent need for novel therapy. Mesenchymal stem cells (MSCs) possess a potently immunosuppressive regulation on immune responses, and intravenous transplantation of MSCs ameliorates disease symptoms and has emerged as a potential beneficial therapy for LN. The objective of this review is to discuss the defective functions of MSCs in LN patients and the application of MSCs in the treatment of both LN animal models and patients. Summary: Bone marrow MSCs from SLE patients exhibit impaired capabilities of migration, differentiation, and immune regulation and display senescent phenotype. Allogeneic MSCs suppress autoimmunity and restore renal function in mouse models and patients with LN by inducing regulatory immune cells and suppressing Th1, Th17, T follicular helper cell, and B-cell responses. In addition, MSCs can home to the kidney and integrate into tubular cells and differentiate into mesangial cells. Key Messages: The efficacy of MSCs in the LN treatment remains to be confirmed, and future advances from stem cell science can be expected to pinpoint significant MSC subpopulations, as well as specific mechanisms of action, leading the way to the use of more potent stimulated or primed pretreated MSCs to treat LN.

scholarly journals Systemic lupus erythematosus and diffuse alveolar hemorrhage, etiology and novel treatment strategies

Lupus ◽  
2020 ◽  
Vol 29 (4) ◽  
pp. 355-363 ◽  
Author(s):  
N K Al-Adhoubi ◽  
J Bystrom
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Factor Vii ◽  
Systemic Lupus ◽  
Mesenchymal Stem Cell Therapy

Diffuse alveolar hemorrhage is a severe respiratory complication of systemic lupus erythematosus. The illness develops over hours to a few days and is the systemic lupus erythematosus-associated syndrome with highest mortality. Although no specific symptoms have been identified, a number of features are associated with diffuse alveolar hemorrhage, with a drop in blood hemoglobin the most prominent. Dyspnea, blood-stained sputum, diffuse infiltrates identified by chest imaging, elevated single breath-diffusing capacity for monoxide, thrombocytopenia and C3 hypocomplementemia are other commonly reported signs of diffuse alveolar hemorrhage. The etiology is not completely understood but many patients develop diffuse alveolar hemorrhage concomitant with lupus nephritis, suggesting immune complex-driven pathology. Biopsy studies have identified both cases with capillaritis and a bland non-inflammatory phenotype. An animal model of diffuse alveolar hemorrhage has indicated requirement of B lymphocytes and complement receptor-mediated apoptotic body phagocytosis by monocytes as part of the pathogenesis. This review will discuss considerations when diagnosing the condition and available therapies. Infections and other causes of hemorrhage have to be excluded as these require different treatment strategies. Methylprednisolone and cyclophosphamide remain the most commonly used therapies. Plasmapheresis and rituximab are other beneficial treatment options. A few studies have also considered intrapulmonary Factor VII therapy, extracorporeal membrane oxygenation and mesenchymal stem cell therapy. There is an unmet need of better definition of diffuse alveolar hemorrhages etiology and pathology for development of improved treatment strategies.

Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for lupus nephritis

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2161-2165 ◽  
Author(s):  
J Barbado ◽  
S Tabera ◽  
A Sánchez ◽  
J García-Sancho
Keyword(s):  
Lupus Nephritis ◽  
Mesenchymal Stromal Cells ◽  
Lupus Erythematosus ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Activity Index ◽  
Disease Activity Index ◽  
Controlled Clinical Trial ◽  
Allogeneic Mscs

Animal and human studies have suggested the potential of mesenchymal stromal cells (MSCs) to treat systemic lupus erythematosus (SLE). Here, we present the results of compassionate MSC treatments for three SLE patients to provide the proof of concept for a randomized and controlled clinical trial. Three patients of different ethnicities who suffer from chronic SLE, and who presented with class IV active proliferative nephritis confirmed by biopsy, were treated with allogeneic MSCs from healthy donors. Ninety million cells were infused intravenously into each patient during high and very high activity disease flare-ups and follow-up was continued for 9 months. Multi-organic affectation was quantified by the SLE disease activity index (SLEDAI), and indicators of lupus nephritis activity, such as proteinuria, as well as lymphocyte and monocyte antigens and anti-HLA antibodies were measured at 1, 3, 6, and 9 months after treatment. Proteinuria levels improved dramatically during the 1st month after treatment and the ameliorations were sustained throughout the follow-up period. SLEDAI scores revealed early, durable, and substantial remissions that were complete for two patients and partial for the third patient and that permitted medication doses to be reduced 50–90%. These favourable outcomes support completion of the randomized and controlled MSC trial for SLE.

scholarly journals Radical Improvement of Signs and Symptoms in Systemic Lupus Erythematosus when Treated with Hemodiafiltration with Endogenous Reinfusion Dialysis

2015 ◽  
Vol 5 (1) ◽  
pp. 106-112 ◽  
Author(s):  
Francesco Giuseppe Solano ◽  
Elisa Bellei ◽  
Aurora Cuoghi ◽  
Marialuisa Caiazzo ◽  
Francesco Bruni
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Joint Pain ◽  
Mesangial Cells ◽  
Skin Lesions ◽  
Dialysis Session ◽  
Skin Damage ◽  
Systemic Lupus ◽  
Conjunctival Hyperemia

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). In the kidney, immune complexes and autoantibodies activate mesangial cells that secrete cytokines that can further amplify inflammatory processes. We present the case of a 42-year-old woman with lupus nephritis accompanied by periods of exacerbation of SLE, with necrotic-like skin lesions, psoriatic arthritis without skin psoriasis, purpura of the lower limb, petechial rash, joint pain, fever, eyelid edema with bilateral conjunctival hyperemia and itching. The patient underwent a dialytic treatment of hemodiafiltration with endogenous reinfusion. The technique uses the super-high-flux membrane Synclear 02 (SUPRA treatment) coupled with an adsorbent cartridge that has affinity for many toxins and mediators. Fever and joint pain were immediately reduced after treatment and, subsequently, there was a notable reduction of the skin damage. Prednisone and immunosuppressive drugs were gradually reduced until complete suspension. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer was performed for identification of proteins captured by a resin bed during a dialysis session of the patient. This technique identified several biomarkers of kidney injuries, uremic toxins, fragments of immunoglobulins, antigens involved in antiphospholipid syndrome and a new marker (α-defensin) that correlated significantly with disease activity. The removal of these different proteins could possibly provide an explanation of the improvement in the patient's symptoms and the normalization of her SLE. SUPRA coupled with an adsorption may be a promising new technique for the treatment of lupus nephritis.

Lupus Nephritis

2019 ◽  
pp. 309-318
Author(s):  
Aisha Shaikh ◽  
Kirk N. Campbell
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Disease Entity ◽  
Disease Remission ◽  
Renal Histology ◽  
Single Disease Entity ◽  
Histological Remission ◽  
Common Manifestation ◽  
Histological Form

Lupus nephritis (LN) is common manifestation of systemic lupus erythematosus and is associated with significant morbidity and mortality. LN is a not a single-disease entity; on the contrary, it encompasses a wide array of renal histological patterns. The treatment options and outcomes vary with the type of renal histology. Proliferative LN remains the most aggressive histological form of LN and requires aggressive treatment. The goal of therapy for LN is to achieve clinical and histological remission and avoid progression to chronic kidney disease. Remission of LN not only improves renal outcomes but also results in significant improvement in overall patient mortality. Though much progress has been made in this arena, there is still a need for therapeutic agents that are less toxic and more effective than the currently available therapies.

P0346THE EFFECTS OF RITUXIMAB MAINTENANCE THERAPY ON LUPUS NEPHRITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Matthias Cassia ◽  
Rachel B Jones ◽  
Daniele Cagna ◽  
Rona Smith ◽  
Giovanni Casazza ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Maintenance Therapy ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Complete Response ◽  
Immunosuppressive Drugs ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Urinary Sediment ◽  
Renal Flare

Abstract Background and Aims Lupus Nephritis (LN) is the organ manifestation with the most severe prognosis in Systemic Lupus Erythematosus (SLE). Treatment options are limited due to partial efficacy, intolerance or side effects; moreover 10% of patients reach ESRD despite treatments. Rituximab (RTX) in LN is recommended as second line drug for induction of the remission after failure of Cyclophosphimide or Mycophenolate Mofetil. We have shown a role for RTX as maintenance therapy (RMT) in SLE however the effects of such approach on LN are still unclear. Aim of this study was a sub-analyses of a cohort of SLE patients treated with RTX focusing on the ones with active LN at the moment of the first RTX administration. Methods Patients with active LN at the time of the first RTX administration within a cohort of 147 patients with SLE were identified. Patients with SLE and a flare of LN were classified as treated with a “Single RTX course” (any RTX regimen administered within a single month) (SRC) or with RMT. Patients receiving at least three SRCs with the aim of relapse prevention and within 4 to 8 months between consecutive treatments, were classified as receiving RMT. LN activity was determined according to creatinine, proteinuria and haematuria; complete response (CR) was defined as a decrease of proteinuria to <0.5 g/day, normal creatinine and negative urinary sediment; partial response (PR) was defined as ≥50% improvement in creatinine and proteinuria, treatment failure (TF) was any other condition. A renal flare (RF) was defined as an increase of creatinine and/or proteinuria >30% or the detection of an active urinary sediment due, according to the treating physician, to active disease. Results 33 patients were identified; a renal biopsy had been performed in 76% with prevalence of class IV lupus nephritis in 16/33 (48%). Six months after RTX the rate of CR, PR and TF was respectively 36%, 27% and 36%; proteinuria and the prednisolone dose reduced significantly compared to baseline (respectively from a median of 2200 mg/day (IQR 499-5400) to 850 mg/day (IQR 400-1700) (p=0.005)) and from 25 mg (IQR 11-25) to 10 mg (IQR 6.125-15) (p<0.0001)). At univariate analyses the only factor associate to the risk of TF was a high number of immunosuppressive drugs employed before RTX (p=0.0077). Of the 33 patients, 11 received RMT with a median duration of 18 months (IQR 12,6-23,4) and a median RTX dose of 5 g (IQR 4-6). During the RMT 3 patients experienced a renal flare. The median follow-up after the last RTX administration within the SRC and the RMT groups was respectively 15 months (IQR 13,5-18,4) and 16 months (IQR 3,5-23). Comparing the RF free-survival of the two subgroups after the last RTX infusion, there was a trend towards a longer relapse free survival after the RMT (p=0.057) (figure, left panel). Of interest, the renal relapse free-survival of the 11 patients treated with RMT after the last RTX infusion was significantly longer compared to the one of the same group after the first RTX (p=0.0271) (figure, right panel). The incidence of SAEs per 100 patient years was 0.31 in the SRC group and 0.74 in the RMT group. Conclusion RTX is confirmed as an effective option for patients with LN. A RMT may have a role in improving LN disease control compared to a single RTX administration.

scholarly journals Mesangial cells are key contributors to the fibrotic damage seen in the lupus nephritis glomerulus

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Rachael D. Wright ◽  
Paraskevi Dimou ◽  
Sarah J. Northey ◽  
Michael W. Beresford
Keyword(s):  
Lupus Nephritis ◽  
Inflammatory Cytokines ◽  
Lupus Erythematosus ◽  
In Vitro Model ◽  
Mesangial Cells ◽  
Vitro Model ◽  
Tgf Β1 ◽  
Onset Systemic Lupus Erythematosus ◽  
Pro Inflammatory Cytokines

Abstract Background Lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus patients. Mesangial cells (MCs) comprise a third of the glomerular cells and are key contributors to fibrotic changes within the kidney. This project aims to identify the roles of MCs in an in vitro model of LN. Methods Conditionally immortalised MCs were treated with pro-inflammatory cytokines or with patient sera in an in vitro model of LN and assessed for their roles in inflammation and fibrosis. Results MCs were shown to produce pro-inflammatory cytokines in response to a model of the inflammatory environment in LN. Further the cells expressed increased levels of mRNA for extracellular matrix (ECM) proteins (COL1A1, COL1A2, COL4A1 and LAMB1), matrix metalloproteinase enzymes (MMP9) and tissue inhibitors of matrix metalloproteinases (TIMP1). Treatment of MCs with serum from patients with active LN was able to induce a similar, albeit milder phenotype. Treatment of MCs with cytokines or patient sera was able to induce secretion of TGF-β1, a known inducer of fibrotic changes. Inhibition of TGF-β1 actions through SB-431542 (an activin A receptor type II-like kinase (ALK5) inhibitor) was able to reduce these responses suggesting that the release of TGF-β1 plays a role in these changes. Conclusions MCs contribute to the inflammatory environment in LN by producing cytokines involved in leukocyte recruitment, activation and maturation. Further the cells remodel the ECM via protein deposition and enzymatic degradation. This occurs through the actions of TGF-β1 on its receptor, ALK5. This may represent a potential therapeutic target for treatment of LN-associated fibrosis.

Stem cells for lupus nephritis: a concise review of current knowledge

Lupus ◽  
2018 ◽  
Vol 27 (12) ◽  
pp. 1881-1897 ◽  
Author(s):  
P D Sattwika ◽  
R Mustafa ◽  
A Paramaiswari ◽  
E H Herningtyas
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Lupus Nephritis ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Lupus Erythematosus ◽  
Current Knowledge ◽  
Secondary Effects ◽  
Hematopoietic Stem ◽  
Future Direction

Lupus nephritis (LN), a common manifestation of systemic lupus erythematosus (SLE), accounts for significant morbidity and mortality in SLE patients. Since the available standard therapies and biologic agents for LN are yet to achieve the desired response and have considerable secondary effects, stem cell therapy has now emerged as a new approach. This therapy involves the transplantation of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Our current review will highlight the progress of stem cell therapy for LN, along with the challenges encountered and the future direction of this approach.

scholarly journals Mesenchymal Stem Cell Therapy for rheumatic diseases

2016 ◽  
Vol 16 (1) ◽  
pp. 6-10
Author(s):  
Winnie Wan-Yin Yeung ◽  
Chak-Sing Lau
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Therapy ◽  
Rheumatic Diseases ◽  
Stem Cell Therapy ◽  
Lupus Erythematosus ◽  
Underlying Mechanism ◽  
Human Studies ◽  
Small Scale ◽  
Mesenchymal Stem Cell Therapy

AbstractMesenchymal stem cell therapy (MSCT) is an innovative treatment for rheumatic diseases. Underlying mechanism of how MSCT works in rheumatic diseases are still uncertain and with various hypotheses. Animal studies in MSCT show conflicting results mainly attributed by the differences in administration methods of MSCT, types of MSC use and randomization procedures. Human studies of MSCT are so far small scale but with satisfactory results in patients with systemic lupus erythematosus (SLE). Human studies of MSCT, however, showed less rewarding results in patients with rheumatoid arthritis (RA) and systemic sclerosis (SSc). Larger scale studies are needed to confirm the efficiency of MSCT as well as the safety profile in human use.

scholarly journals Susceptibility of BAFF-var allele carriers to severe SLE with occurrence of lupus nephritis

2019 ◽  
Author(s):  
Justa Friebus-Kardash ◽  
Marten Trendelenburg ◽  
Ute Eisenberger ◽  
Camillo Ribi ◽  
Carlo Chizzolini ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Immunosuppressive Agents ◽  
Disease Activity Index ◽  
University Hospital ◽  
Study Entry ◽  
Organ Manifestations ◽  
The University

Abstract Background: Dysregulation of the B-cell activating factor (BAFF) system is involved in the pathogenesis of systemic lupus erythematosus (SLE). Increased serum concentrations of BAFF are related to lupus nephritis and disease activity among SLE patients. Recently, a variant of the BAFF-encoding gene, BAFF-var, was identified to be associated with autoimmune diseases, in particular SLE, and to promote the production of soluble BAFF. The present study aimed to assess the prevalence of BAFF-var in a cohort of 195 SLE patients and to analyze the association of the BAFF-var genotype (TNSF13B) with various manifestations of SLE. Methods: A cohort of 195 SLE patients from Central Europe, including 153 patients from the Swiss SLE Cohort Study and 42 patients from the University Hospital Essen, Germany, underwent genotyping for detection of BAFF-var allele. Results: Of the 195 patients, 18 (9.2%) tested positive for BAFF-var variant according to the minor allele frequency of 4.6%. The presence of BAFF-var was associated with the occurrence of lupus nephritis (p=0.038) (p=0.03 and p=0.003). Among various organ manifestations of SLE, the presence of BAFF-var was associated with the occurrence of lupus nephritis (p=0.038; odds ratio [OR], 2.4; 95% confidence interval [CI], 0.89-6.34) and renal activity markers such as proteinuria and hematuria (p=0.03; OR, 2.4; 95% CI, 0.9-6.4 for proteinuria; p=0.003; OR, 3.9; 95% CI, 1.43-10.76 for hematuria). SLE patients carrying the BAFF-var allele exhibited increased disease activity at study entry, as determined by the physician's global assessment (PGA: p=0.002; OR, 4.8; 95% CI, 1.54-14.93) and the SLE Disease Activity Index (p=0.012; OR, 3.5; 95% CI, 1.12-11.18). Consistent with that, the percentage of patients treated with immunosuppressive agents at study entry was higher among those carrying the BAFF-var allele than among those tested negative for BAFF-var (p=0.006; OR, 3.7; 95% CI, 1.27-10.84). Conclusions: Our results indicate an association between the BAFF-var genotype and increased severity of SLE. Determining the BAFF-var status of SLE patients may improve the risk stratification of patients for whom the development of lupus nephritis is more likely and thus may be helpful in the follow-up care and treatment of SLE patients.

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