New-onset Systemic Lupus Erythematosus Research Articles

Aberrant phenotypes of circulating γδ-T cells may be involved in the onset of systemic lupus erythematosus.

Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.

Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies.

The coronavirus disease 2019 (COVID-19) pandemic triggered an unprecedented concentration of economic and research efforts to generate knowledge at unequalled speed on deregulated interferon type I signalling and nuclear factor kappa light chain enhancer in B-cells (NF-κB)-driven interleukin (IL)-1β, IL-6, IL-18 secretion causing cytokine storms. The translation of the knowledge on how the resulting systemic inflammation can lead to life-threatening complications into novel treatments and vaccine technologies is underway. Nevertheless, previously existing knowledge on the role of cytoplasmatic or circulating self-DNA as a pro-inflammatory damage-associated molecular pattern (DAMP) was largely ignored. Pathologies reported 'de novo' for patients infected with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 to be outcomes of self-DNA-driven inflammation in fact had been linked earlier to self-DNA in different contexts, e.g., the infection with Human Immunodeficiency Virus (HIV)-1, sterile inflammation, and autoimmune diseases. I highlight particularly how synergies with other DAMPs can render immunogenic properties to normally non-immunogenic extracellular self-DNA, and I discuss the shared features of the gp41 unit of the HIV-1 envelope protein and the SARS-CoV 2 Spike protein that enable HIV-1 and SARS-CoV-2 to interact with cell or nuclear membranes, trigger syncytia formation, inflict damage to their host's DNA, and trigger inflammation - likely for their own benefit. These similarities motivate speculations that similar mechanisms to those driven by gp41 can explain how inflammatory self-DNA contributes to some of most frequent adverse events after vaccination with the BNT162b2 mRNA (Pfizer/BioNTech) or the mRNA-1273 (Moderna) vaccine, i.e., myocarditis, herpes zoster, rheumatoid arthritis, autoimmune nephritis or hepatitis, new-onset systemic lupus erythematosus, and flare-ups of psoriasis or lupus. The hope is to motivate a wider application of the lessons learned from the experiences with COVID-19 and the new mRNA vaccines to combat future non-COVID-19 diseases.

New-onset Systemic Lupus Erythematosus Manifestation Following COVID-19: A Case Report and Literature Review.

Coronavirus disease 2019 (COVID-19) is a respiratory viral disease, and several cases of autoimmune diseases have been reported after infection. This report presents the case of a 38-year-old Japanese woman who developed systemic lupus erythematosus (SLE) following COVID-19. Clinical manifestations included dermatological complications, joint pain, and positive autoantibodies. The patient met the SLE classification criteria, and renal involvement was observed. Her symptoms improved with immunosuppressive therapy. A literature review identified 10 similar cases, those with lymphopenia and renal involvement. SLE should be considered in patients with persistent nonspecific symptoms after COVID-19 infection, particularly when hematologic and renal involvement are present.

Serological and clinical associations of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus

To study the clinical significance of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus (SLE), we enrolled 526 new-onset patients who met the 1997 Updated American College of Rheumatology SLE Classification Criteria for a retrospective cohort study. Chi-square test and Wilcoxon rank-sum test were used to detect the relationship of autoantibodies with clinical manifestations and serological results respectively. Our results demonstrated that the positive rate of anti-ribosomal P protein (anti-P) antibody in female patients was higher than that in male patients (41.2% vs. 22%, P = 0.008). Patients with anti-SSB (43.95 ± 73.12 vs. 40.92 ± 75.75, P = 0.004; 63.93 ± 103.56 vs. 55.06 ± 120.84, P = 0.008 respectively) antibodies had higher levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), whereas those with anti-P antibody (28.90 ± 25.70 vs. 50.08 ± 93.00, P = 0.014; 38.51 ± 48.19 vs. 69.95 ± 142.67, P = 0.047, respectively) had lower levels of them. Anti-dsDNA antibody (P = 0.021) was associated with pulmonary arterial hypertension (PAH). The patients with anti-Ro60 (P = 0.044), anti-P (P = 0.012) and anti-dsDNA (P = 0.013) antibodies were less likely to develop Interstitial lung disease. Anti-SmRNP antibody was correlated to lower prevalence of neuropsychiatric symptoms (P = 0.037), and patients with anti-centromere antibody (ACA) were more likely to develop serositis (P = 0.016).We identified five clusters of SLE-related autoantibodies, confirmed previously reported associations of autoantibodies, and discovered new associations.

EZH2 inhibition dampens autoantibody production in lupus by restoring B cell immune tolerance.

The aim of this study was to elucidate the role of enhancer of zeste homolog 2 (EZH2) in the breakdown of B cell immune tolerance and production of autoantibodies in systemic lupus erythematosus (SLE), and to explore the therapeutic effects of EZH2 inhibition on lupus. Peripheral blood mononuclear cells (PBMCs) were collected from new-onset SLE patients for flow cytometric analysis. Pristane-induced lupus mice were constructed, and the EZH2 inhibitor was administrated by intraperitoneal injection to treat lupus mice. Blood and urine were collected from lupus mice to detect autoantibodies and proteinuria, and renal pathology scores were assessed. Mouse spleen B cells were sorted with magnetic beads and subjected to flow cytometric apoptosis detection, real time quantitative PCR (RT-qPCR), and western blotting (WB). EZH2 expression was elevated in diverse B-cell subsets in both SLE patients and pristane-induced lupus mice. The EZH2 inhibitor attenuated lupus-like symptoms and dampened autoantibody production in pristane-induced lupus mice. Inhibition of EZH2 also reduced autoantibody secretion by plasma cells from lupus patients. Mechanistically, EZH2 mediated the impaired apoptosis of autoreactive B cells and the differentiation of autoantibody producing plasma cells by inhibiting multiple cyclin-dependent kinase inhibitor (CKI) genes. EZH2 mediated the breakdown of B-cell peripheral immune tolerance by inhibiting CKI genes and participated in the generation of autoantibodies in SLE. EZH2 inhibition could serve as a promising drug intervention for the treatment of SLE.

Hsa_circ_0044235 and hsa_circ_0001947 as novel biomarkers in plasma of patients with new-onset systemic lupus erythematosus

Circular RNA (circRNA) are novel types of non-coding RNA that may be used as non-invasive noninvasive biomarkers in clinical plasma samples. However, the role of circRNA in plasma samples from patients with new-onset systemic lupus erythematosus (SLE) has not been extensively investigated. In the present study, reverse transcription-quantitative PCR was used to screen differentially-expressed circRNA (hsa_circ_0000175, hsa_circ_0044235, hsa_circ_0068367, hsa_circ_0002316, hsa_circ_0104871, hsa_circ_0001947, hsa_circ_0001481, hsa_circ_0008675, hsa_circ_0082689 and hsa_circ_0082688) in plasma samples isolated from 22 patients with new-onset SLE and 22 healthy control (HC). The results indicated hsa_circ_0000175, hsa_circ_ 0044235, hsa_circ_0068367, and hsa_circ_0001947 expression levels were significantly lower in plasma samples from new-onset SLE patients compared with corresponding levels in HC subjects and patients with new-onset rheumatoid arthritis (RA). Multivariate analysis indicated expression levels of hsa_circ_0044235 and hsa_circ_0001947 in plasma were independent risk factors for SLE. ROC curve analysis suggested that the combination of hsa_circ_0044235 and hsa_circ_0001947 indicated significant value in discriminating new-onset SLE from HC subjects and patients with RA. Moreover, the levels of hsa_circ_0044235 in plasma samples from patients with new-onset SLE were associated with platelet count, platelet-crit, and platelet distribution width; the expression of hsa_circ_0001947 in plasma from patients with SLE was associated with treatment. Thus, the present study demonstrated a promise for the combination of plasma hsa_circ_0044235 and hsa_circ_0001947 expression as potential diagnostic and prognostic biomarkers in patients with new-onset SLE.

Chorioretinal Findings in a Patient with New-Onset Systemic Lupus Erythematosus and Antiphospholipid Syndrome after Stillbirth Associated with Pre eclampsia

ABSTRACT Purpose To describe chorioretinal findings in a patient with new-onset systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) after a stillbirth associated with preeclampsia. Study design Case report. Results We report a patient with new-onset SLE and APS after pregnancy, who had a history of preeclampsia and intrauterine death that presented with bilateral visual loss after a seizure. Clinical findings of a unilateral vaso-occlusive retinopathy and choroidopathy associated with intraocular inflammation, serous retinal detachment, and vasculitis are presented, which responded well to immunosuppressive therapy. Conclusion New-onset systemic lupus erythematosus (SLE) during or after pregnancy could occur, especially when complicated with preeclampsia, making it difficult to diagnose accurately. Pregnancy-induced hypertension retinopathy and choroidopathy, as well as chorioretinal manifestations of SLE and APS, can share similar ocular manifestations that can overlap and coexist in the same patient, and it is important to recognize them for an adequate management and follow-up.

Hashimoto’s thyroiditis increases the risk of new-onset systemic lupus erythematosus: a nationwide population-based cohort study

BackgroundPrevious studies have shown systemic lupus erythematosus (SLE) patients had a significantly higher prevalence of thyroid diseases and hypothyroidism than matched controls, and some case reports showed SLE may occur after Hashimoto’s thyroiditis (HT).ObjectiveThis study aimed to investigate the subsequent risk of SLE in patients with HT.MethodsIn this retrospective cohort study done by the Taiwan National Health Insurance Research Database, the HT group (exposure group) and the non-HT group (comparator group) were propensity score matched at a ratio of 1:2 by demographic data, comorbidities, medications, and the index date. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Several sensitivity analyses were done for cross-validation of our findings.ResultsWe identified 15,512 HT patients and matched 31,024 individuals. The incidence rate ratio of SLE was 3.58 (95% CI, 2.43–5.28; p < 0.01). Several sensitivity analyses show adjusted hazard ratio (aHR) (CIs) of 4.35 (3.28–5.76), 4.39 (3.31–5.82), 5.11 (3.75–6.98), and 4.70 (3.46–6.38), consistent with the results of the main model.ConclusionOur study showed an increased risk of SLE in the HT group after adjustment for baseline characteristics, comorbidities, and medical confounders compared with the reference group.

The association of serum magnesium with infection in new-onset systemic lupus erythematosus patients.

To assess the association of serum magnesium with infection in new-onset systemic lupus erythematosus (SLE) patients. We conducted a single-center retrospective cohort study of new-onset SLE patients from 2012 to 2021. The hospitalized SLE patients were divided into infection and noninfection groups. Logistic regression analysis was conducted to examine the association of hypomagnesemia with infection. A total of 476 new-onset SLE patients were included, with 299 cases in the infection group and 177 cases in the noninfection group. The patients were mostly females (81.7%). The average age at diagnosis was 43.7years. The median duration was 1.0month. The prevalence of hypomagnesemia (<0.70), normomagnesemia (0.70-1.10), and hypermagnesemia (>1.10) in new-onset SLE patients was 14.3%, 83.4%, and 2.3%, respectively. The prevalence of hypomagnesemia was 18.4% in the infection group and 7.3% in the noninfection group (p = .001). The baseline value of serum magnesium was 0.819mmol/L, with values of 0.799mmol/L in the infection group and 0.854mmol/L in the noninfection group (p = .000). The following clinical variables were significantly different between the two groups (p < .05): age, duration, hospitalization stay, fever, serositis, and SLE Disease Activity Index 2000 (SLEDAI 2K). The laboratory parameters, including hemoglobin, white blood cell count, albumin level, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, and complement C3 were also significantly different between the two groups (p < .05). The mortality was 4.4% (21/476), with 20 cases occurring in the infection group. Logistic regression analysis showed that hypomagnesemia was associated with an increased risk of infection (p = .001) and poor prognosis (p = .015). Hypermagnesemia was rare in new-onset SLE patients. Hypomagnesemia was common and was associated with an increased risk of infection in new-onset SLE patients.

Two clusters of systemic lupus erythematosus patients with muscle involvement in a Chinese cohort.

This study aimed to depict the clinical features, including myositis specific or associated antibody (MSA/MAA) profile of systemic lupus erythematosus (SLE) patients with muscle involvement in a Chinese cohort. We retrospectively studied a cohort of 1696 SLE inpatients and screened for concurrent myositis features from January 2013 to June 2021. Propensity score matching was applied to enroll controls without myositis features from our cohort. Demographic, clinical and laboratory variables were collected. MSA/MAA panels containing 16 autoantibodies (TIF1-γ, MDA5, NXP2, Mi-2α/β, SAE1, Jo-1, PL-7, PL-12, EJ, OJ, SRP, HMGCR, cN-1A, PM-Scl75/100, Ku and Ro52) were tested by line-blotting assay. Binary logistic regression and K-means clustering were applied. Forty-one of 1696 (2.42%) SLE patients in our SLE inpatient cohort showed features of myositis. Binary logistic regression revealed that new-onset SLE (odds ratio [OR]=4.77, 95% CI=1.10-20.57), interstitial lung disease (ILD) (OR=10.07, 95% CI=1.65-61.51), positive anti-U1RNP antibody (OR=4.38, 95% CI=1.08-17.75), and Raynaud's phenomenon (OR=7.94, 95% CI=1.41-44.69) were associated with muscle involvement. Except for anti-Ro52 (50%), anti-Ku antibody (38.2%) was the next frequently detected MSA/MAA in the panel, followed by anti-NXP2 antibody (11.8%). It was noteworthy that multiple MSA/MAAs (≥2, excluding anti-Ro52) coexisted in 9 patients. Patients with myositis features were clustered into 2 subgroups. Cluster 1 was characterized by anti-Ku or anti-Ro52 with high SLE Disease Activity Index, whereas cluster 2 presented with anti-U1RNP, Raynaud's phenomenon and pulmonary arterial hypertension resembling mixed connective tissue disease. In our Chinese SLE inpatient cohort, muscle involvement was infrequent. Nevertheless, distinct features in these SLE patients deserve further study.

New-onset systemic lupus erythematosus following BNT162b2 mRNA COVID-19 vaccine: a case series and literature review.

Emerging data evaluated the possible link between the Coronavirus 19 (COVID-19) vaccine and acute flares of rheumatic autoimmune diseases. However, the association between the COVID-19 vaccine and the development of de-novo rheumatic autoimmune diseases remained unclear. We report the first case series of three male patients who developed new-onset systemic lupus erythematosus following receiving Pfizer BNT162b2 mRNA vaccination. The clinical characteristics share some similarities with drug-induced lupus. More patients with SLE following COVID-19 may be diagnosed in the future. Additional studies will provide more significant insights into the possible immunogenic influence of the COVID-19 vaccine.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00296-022-05203-3.

Systemic lupus erythematosus manifestation following COVID-19 infection: A coincidental or causal relation

Several intricate interactions of environmental and genetic factors can lead to autoimmune conditions in susceptible hosts. Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease which can be triggered or exacerbated by infection or infectious reactions. The causal link between infections and autoimmunity has been established through clinical studies. Though several viral infections have been associated with SLE, yet the impact of COVID-19 on SLE onset and flares has not been well established. We report a young female who developed new-onset SLE shortly after having COVID-19 infection. Her clinical and lab parameters were highly suggestive of SLE and she responded to standard medical therapy. We also briefly discuss the pathogenetic mechanisms of autoimmunity in cases of viral infections.

The in vitro effects of vitamin 1, 25(OH) 2 D3 on expression of cytokines: In new-onset systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a variety of factors in the immune system. Awareness of the role of cytokines in SLE has led to new clinical perspectives in its pathogenesis; therefore, the aim of this study was to investigate the effect of vitamin 1, 25(OH) 2 D3 (D3) on the expression of IL-2, IL-4, IL-5, IL-10, and IFN-γ cytokines in patients with lupus. A total of 65 new-onset SLE patients were enrolled in the study. After peripheral blood mononuclear cell isolation, the lymphocytes of each patient were divided into two groups, one treated with a concentration of 50μmol vitamin D3 (test) and the other untreated with vitamin D3 (control), were cultured. After 24hours, the cultured cells were collected and the expressions of IL-2, IL-4, IL-5, IL-10, and IFN-γ genes were analyzed by RT-qPCR. It was observed that vitamin D3 reduced expression of IFN-γ, IL-4, IL-5, and IL-10 genes by 73, 50, 37, and 29%, respectively, and increased IL-2 gene expression by 31% (p ≤ 0.05). With different patterns of cytokine changes in patients with lupus in different studies, it seems that the pattern of cytokine changes is largely dependent on the phase of the disease and with this study it can be concluded that vitamin D3 administration at the time of diagnosis and in the early stages and before starting treatment have different effects from its administration in the acute stage of the disease, which requires further studies to prove. It seems that in patients with systemic lupus erythematosus, vitamin D should be administered taking into account the phase of the disease.

P237 New-onset systemic lupus erythematosus following COVID-19 vaccination: a report of two cases

Abstract Background/Aims There is a growing number of reports of new-onset autoimmune disease or complications of underlying autoimmune disorders following COVID-19 infection and vaccination. Methods We describe two cases of systemic lupus erythematosus (SLE) that developed de novo in two female patients shortly after receiving their COVID-19 vaccinations. Results The first case is a 29-year-old female with no prior medical history. One week following her COVID-19 Pfizer/BioNTech vaccination, she developed widespread pruritus, fatigue, myalgia, arthralgia, fever and night sweats. Blood tests showed pancytopenia and she was referred for an urgent haematology opinion due to lymphoma. Positron Emission Tomography/computed tomography (PET/CT) demonstrated widespread lymphadenopathy. Bone and lymph node biopsy showed reactive changes only. Her symptoms progressed with polyarticular inflammatory arthritis, oral ulceration, Raynaud’s, pleuritic chest pain, palmar purpuric rash, and a widespread tender urticarial rash. Further investigations showed low complement C3/C4, anti-double stranded DNA antibody titre (dsDNA) &amp;gt;200 IU/mL, positive Anti-Ro antibody, positive Anti-La antibody, weakly positive anti-RNP antibody and an Anti-C1q antibody &amp;gt;400 units/ml with a urine protein/creatinine ratio (PCR) of 39 mg/mmol. A diagnosis of SLE with urticarial vasculitis was made and she commenced Hydroxychloroquine in addition to weaning prednisolone (60mg). A skin biopsy confirmed lupus vasculitis. Despite high dose prednisolone, urine PCR increased over 2 weeks from 39 to 84 mg/mmol. Renal biopsy demonstrated class 3 lupus nephritis. She was pulsed with 500mg IV methyl prednisolone over 3 days and commenced mycophenolate 1g BD. Within weeks she was in clinical remission. The second case is a 70-year-old female with a past medical history of diverticulosis, uterine fibroids and small hand joint osteoarthritis. She presented with a sudden onset, 6-week history of bilateral symmetrical small and large joint synovitis that developed 8 days following the first dose of the COVID-19 Oxford-AstraZeneca vaccine. Her investigations showed reduced lymphocyte counts (0.9 109/L), raised CRP 26 mg/L and ESR 32 mm/hr. Antinuclear antibodies were weakly positive with a homogenous pattern. DsDNA titre was raised at 175 IU/mL and C4 reduced at 0.14 g/L. There was no proteinuria or any evidence of major internal organ involvement. She was started on a short reducing course of oral prednisolone given the severity of her presenting clinical features. Her symptoms improved, with no recurrence on stopping steroids but she has continued elevation in DsDNA; a conservative management approach is being adopted. Conclusion Both cases met the EULAR/ACR and SLICC classification criteria for SLE. There was a clear temporal association between the onset of SLE symptoms and COVID-19 vaccination. Our cases raise the possible association/causation of SLE following COVID-19 vaccination. Potential mechanisms include immune responses elicited by the COVID-19 vaccination, triggering autoimmunity in genetically predisposed individuals. Further research and data from registries are required. Disclosure J. Beynon: None. M. Alsharkawy: None. L. Sammut: None. J. Ledingham: None.

New-onset Systemic Lupus Erythematosus presenting with Macrophage Activation Syndrome and Diffuse Alveolar Hemorrhage: a case-based review

Macrophage activation syndrome is a form of secondary hemophagocytic lymphohistiocytosis in the setting of autoimmune diseases. It’s a rare, hyperinflammatory complication requiring prompt institution of therapy to prevent organ dysfunction and death. We report a young female presenting with macrophage activation syndrome with multiorgan failure and diffuse alveolar hemorrhage in the setting of inaugural systemic lupus erythematosus. The patient was successfully treated with steroids, plasma exchange and cyclophosphamide.

Systemic lupus erythematosus and antiphospholipid syndrome after COVID-19 vaccination. A case report.

IntroductionCOVID-19 vaccines have some adverse effects, mostly mild. However, by presenting an immunological challenge to the individual, they could infrequently trigger immune-mediated diseases.Case reportWe report the case of a 42-year-old woman, with no previous medical history, who received the first dose of vaccine against COVID-19 and developed inflammatory arthralgias, associated with sudden onset dyspnea and hypoxemia. Pulmonary thromboembolism was documented and the diagnosis of systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS) was suspected. Autoantibodies were measured confirming this suspicion. After a few days, she presented a massive pericardial effusion with cardiac tamponade that required surgical management. She received treatment with hydroxychloroquine, corticosteroids and anticoagulation with improvement of all symptoms.DiscussionThere is controversy regarding the potential of COVID-19 vaccines to induce autoimmunity. Studies addressing the safety of using these vaccines have reported the occurrence of mild local and systemic reactions, most frequently in young adults. So far there are few reports of patients who have developed autoimmune or autoinflammatory diseases after getting vaccinated with any of the COVID-19 vaccines. To the best of our knowledge, to date this is one of the first cases of new-onset SLE and secondary APS after COVID-19 vaccination.

MicroRNA-30a Targets Notch1 to Alleviate Podocyte Injury in Lupus Nephritis

ABSTRACT The microRNA miR-30a has been reported to mitigate podocyte damage and resist injurious factors in lupus nephritis (LN), but the precise molecular mechanisms underlying these effects remain elusive. We hypothesized that miR-30a can ameliorate podocyte injury by downregulating the Notch1 signaling pathway and investigated the role of miR-30a in the pathogenesis of podocyte-treated with Immunoglobulin G from patients with LN (IgG-LN). The study enrolled 30 patients from new-onset systemic lupus erythematosus and 28 healthy individuals, then evaluated the levels of their serum miR-30a using RT-qPCR. Additionally, MPC5 cells were transfected with NICD-vector to overexpress Notch1, then with miR-30a mimics or inhibitors to determine miR-30a effects on Notch1. Analysis of function and regulatory mechanisms were performed with RT-qPCR, Western blotting, and CCK8 assays. Furthermore, we verified the candidate sequence targeted by miR-30a using a luciferase reporter gene assay. We observed a significant decrease in the serum miR-30a levels in patients with LN. Also, in IgG-LN-treated podocytes, miR-30a decreased and Notch1 expression was elevated. Bioinformatic analysis and transfection experiments revealed that Notch1 is a direct target of miR-30a. Further supporting this finding, miR-30a upregulation appeared to alleviate IgG-LN-treated podocyte injury, and Notch1 overexpression reversed this effect. To conclude, miR-30a can ameliorate podocyte injury via suppression of the Notch1 signaling pathway.

Effect of sera from lupus patients on the glomerular endothelial fibrinolysis system.

Dysregulation of the coagulation fibrinolysis system in resident glomerular cells is associated with the pathogenesis of lupus nephritis. However, the role of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) in resident glomerular cells remains undetermined. We examined the expression of PAI-1 and tPA mRNA in cultured normal human glomerular endothelial cells (GECs) treated with serum from patients with systemic lupus erythematosus (SLE) using quantitative reverse transcription polymerase chain reactions. We determined the relationship between PAI-1/tPA mRNA expression and several clinical/laboratory parameters. Serum from 16 patients (nine patients with new-onset SLE and seven patients with stable SLE) was used in the study. Plasminogen activator inhibitor-1 and tPA mRNA expression was significantly higher in GECs treated with serum of patients with new-onset SLE than other groups. The PAI-1 and tPA mRNA levels were also significantly correlated in GECs treated with serum from patients with SLE. Interestingly, both PAI-1 and tPA mRNA levels in GECs were inversely correlated with serum C4 level and positively correlated with SLE disease activity. These results suggest that serum from patients with SLE may activate the fibrinolysis system in glomerulus, which may be involved in the pathogenesis of lupus nephritis.

A case of new-onset SLE during pregnancy an initial manifestation with all diagnostic criteria: The challenges of diagnosis and managing a complex disease in a low resource setting

Systemic lupus erythematosus (SLE) is a complex chronic multiorgan autoimmune disease. When newly diagnosed during pregnancy or puerperium, it is known as new-onset SLE during pregnancy. Delayed or missed diagnosis of newonset SLE during pregnancy may occur due to similar clinical manifestation of SLE with normal physiological changes of pregnancy and lupus nephritis with preeclampsia. New-onset SLE during pregnancy has major organ involvement with poor maternal and foetal outcomes. Management options are limited due to teratogenic side effects of drugs in pregnancy. This is further compounded in a low resource setting with lack of health seeking behaviours and inadequate access to timely care. Multidisciplinary management with close medical, obstetric, neonatal monitoring, patient education and improved access to care is essential for better outcomes. Our aim is to report a 19 year old primigravida with new onset SLE in pregnancy and multiorgan involvement fulfilling all criteria for diagnosis of SLE at the first presentation.

First Diagnosis of Systemic Lupus Erythematosus in Hospitalized Patients: Clinical Phenotypes and Pitfalls for the Non-Specialist

BackgroundPrompt recognition of systemic lupus erythematosus (SLE) in hospitalized patients presenting with severe disease is essential to initiate treatment. We sought to characterize the phenotype of hospitalized patients with new-onset SLE and estimate potential diagnostic delays. MethodsAn observational study of 855 patients (“Attikon” SLE cohort). Clinical phenotype was categorized according to the leading manifestation that led to hospitalization. Disease features, time to diagnosis, classification criteria, and the SLE Risk Probability Index (SLERPI) were recorded for each patient. ResultsThere were 191 patients (22.3% of the total cohort) hospitalized due to manifestations eventually attributed to SLE. Main causes of admission were neuropsychiatric syndromes (21.4%), cytopenias (17.8%), nephritis (17.2%), and thrombotic events (16.2%). Although 79.5% of patients were diagnosed within 3 months from hospitalization, in 39 patients diagnosis was delayed, particularly in those with hematological manifestations. At hospitalization, a SLERPI >7 (indicating high probability for SLE) was found in 87.4% of patients. Patients missed by the SLERPI had fever, thrombotic or neuropsychiatric manifestations not included in the algorithm. Lowering the SLERPI threshold to 5 in patients with fever or thrombotic events increased the diagnostic rate from 88.8% to 97.9% in this subgroup, while inclusion of all neuropsychiatric events yielded no additional diagnostic value. ConclusionOne in five patients with new-onset SLE manifest disease presentations required hospitalization. Although early diagnosis was achieved in the majority of cases, in approximately 20%, diagnosis was delayed. A lower SLERPI cut-off (≥5) in patients with fever or thrombosis could enhance early diagnosis.