Manifestations Of Systemic Lupus Erythematosus Research Articles

Peripheral Blood Mononuclear Cells and Serum Cytokines in Patients with Lupus Nephritis after COVID-19.

Systemic lupus erythematosus (SLE) patients have an increased risk of infections and infection-related mortality. Therefore, during the global SARS-CoV-2 pandemic, SLE patients were particularly vulnerable to SARS-CoV-2 infections. Also, compared to other patients, SLE patients seem to develop more severe manifestations of coronavirus disease 2019 (COVID-19), with higher rates of hospitalization, invasive ventilation requirements, or death. This study evaluated the immune parameters after SARS-CoV-2 infection in SLE patients. We analyzed subpopulations of peripheral blood cells collected from patients with renal manifestation of SLE (lupus nephritis, LN). LN patients were divided into two subgroups: those unexposed to SARS-CoV-2 (LN CoV-2(-)) and those who had confirmed COVID-19 (LN-CoV-2(+)) six months earlier. We analyzed basic subpopulations of T cells, B cells, monocytes, dendritic cells (DCs), and serum cytokines using flow cytometry. All collected data were compared to a healthy control group without SARS-CoV-2 infection in medical history. LN patients were characterized by a decreased percentage of helper T (Th) cells and an increased percentage of cytotoxic T (Tc) cells regardless of SARS-CoV-2 infection. LN CoV-2(+) patients had a higher percentage of regulatory T cells (Tregs) and plasmablasts (PBs) and a lower percentage of non-switched memory (NSM) B cells compared to LN CoV-2(-) patients or healthy controls (HC CoV-2(-)). LN patients had a higher percentage of total monocytes compared with HC CoV-2(-). LN CoV-2(+) patients had a higher percentage of classical and intermediate monocytes than LN CoV-2(-) patients and HC CoV-2(-). LN CoV-2(+) patients had higher serum IL-6 levels than HC CoV-2(-), while LN CoV-2(-) patients had higher levels of serum IL-10. LN patients are characterized by disturbances in the blood's basic immunological parameters. However, SARS-CoV-2 infection influences B-cell and monocyte compartments.

The phenotype of systemic lupus erythematosus as a factor in rational therapy choosing

Systemic lupus erythematosus (SLE) is characterized by a variety of clinical manifestations, which are defined as separate phenotypes of the disease. Despite the universality of immunopathological reactions, which are based on the formation of anti-nuclear antibodies and antibodies to native DNA, the spectrum and severity of immunological disorders in individual phenotypes are different. The role of type I interferons (IFN) in the SLE pathogenesis has now been proven. Hypersecretion of IFN-α and IFN-β leads to the production of antibodies against the components of the cell nucleus through activation of the native and adaptive immunity system. The current treatment strategy provides for achieving remission or low activity with immunosuppressants, including selective ones, such as biological agents. According to the updated international recommendations, anifrolumab, monoclonal antibodies against type I IFN, which has demonstrated high efficacy in the treatment of SLE with skin-mucous and joint lesions., can be used for the treatment of SLE along with rituximab and belimumab. The article presents our own clinical observation on the analysis of the effecacy and safety of anifrolumab in the treatment of a young patient with high-activity SLE and pronounced skin manifestations. It was shown that after the first injections of the drug, there was a rapid dynamics of skin and joint syndrome, the activity of SLE decreased from maximum to minimum according to the SELENA-SLEDAI index. The results obtained confirm the rationale of including anifrolumab in the treatment regimen in cases of insufficient previous therapy.

The immunology of systemic lupus erythematosus.

Understanding the pathogenesis and clinical manifestations of systemic lupus erythematosus (SLE) has been a great challenge. Reductionist approaches to understand the nature of the disease have identified many pathogenetic contributors that parallel clinical heterogeneity. This Review outlines the immunological control of SLE and looks to experimental tools and approaches that are improving our understanding of the complex contribution of interacting genetics, environment, sex and immunoregulatory factors and their interface with processes inherent to tissue parenchymal cells. Efforts to advance precision medicine in the care of patients with SLE along with treatment strategies to correct the immune system hold hope and are also examined.

Concomitant sickle cell disease and systemic lupus erythematosus: A single-center case series.

Sickle cell disease (SCD) and systemic lupus erythematosus (SLE) are two uncommon disorders each characterized by multisystemic manifestations. Individuals with SCD exhibit abnormalities in the complement pathway, which may predispose patients to develop autoimmune disorders such as SLE. As many manifestations of SLE mimic those of SCD, diagnosis and therapeutic management of SLE in a patient with known SCD may be delayed. In this study, we describe our institutional experience of diagnosing and managing concomitant SCD and SLE. We offer insights into the complex interplay between these conditions to enhance early recognition and effective management of concurrent SCD and SLE.

Tremor as a Neuropsychiatric Manifestation of Systemic Lupus Erythematosus: A Case Report and Review of Related Literature

Tremor as a Neuropsychiatric Manifestation of Systemic Lupus Erythematosus: A Case Report and Review of Related Literature

Lupus nephritis and thrombotic microangiopathy: A review

Lupus nephritis (LN) is one of the most common organ-specific manifestations of systemic lupus erythematosus (SLE). Various clinical signs of LN develop in at least 50% of patients with SLE. In addition to LN, the spectrum of renal lesions associated with SLE also includes vascular pathology. One of the variants of renal microvascular injury is thrombotic microangiopathy (TMA), the mechanisms of which are diverse. The review focuses on the main forms of TMA, including antiphospholipid syndrome and nephropathy associated with antiphospholipid syndrome, TMA caused by complement system regulation disorders and deficiency of ADAMTS13. In most cases, these forms of TMA are combined with LN. However, they may also exist as a single form of kidney damage. This article discusses the TMA pathogenesis, the impact on kidney prognosis, and treatment options.

Interleukin-17 as a biomarker for lupus nephritis: correlation with disease activity indices and histopathological classification

BackgroundLupus nephritis (LN) is one of the devastating manifestations of systemic lupus erythematosus (SLE). It is a leading cause of death in SLE patients. Interleukin 17(IL-17) is involved in the development of several autoimmune diseases. It causes inflammation and organ damage by exaggerating the immune response and augmenting antibody production by B cells. We assessed the role of IL-17A in LN and its relation to other markers of disease activity and different histopathological classes.ResultsWe evaluated serum IL-17A in forty LN patients and thirty SLE patients without LN (non-LN). We found that LN patients had a significantly higher IL-17A level in comparison to non-LN. In the LN group, IL-17A was positively correlated with the systemic lupus erythematosus disease activity index (SLEDAI), protein/creatinine (P/C) ratio, 24-hour urinary proteins, anti-nucleosome, and anti-dsDNA antibodies and negatively correlated with C3 and C4. IL-17A was higher in class III and IV compared to class II and V LN. ROC curve analysis of IL-17A revealed 75% sensitivity and 76.7% specificity for LN, and the AUC was 0.791.ConclusionLupus nephritis patients have a higher serum level of IL-17A than those without LN, which is more pronounced in patients with class-III and IV LN. Moreover, IL-17A has good sensitivity and specificity for LN and correlates with the disease activity indices; hence, it may be a prognostic marker for LN in SLE patients.

Genetic polymorphisms in genes involved in the type I interferon system (STAT4 and IRF5): association with Asian SLE patients.

Systemic lupus erythematosus (SLE) is a common autoimmune disease with a polymorphic clinical presentation involving multisystem damages with significant differences in prevalence and disease severity among different ethnic groups. Although genetic, hormonal, and environmental factors have been demonstrated to contribute a lot to SLE, the pathogenesis of SLE is still unknown. Numerous evidence revealed that gene variants within the type I interferons (IFN) signaling pathway performed the great genetic associations with autoimmune diseases including SLE. To date, through genome-wide association studies (GWAS), genetic association studies showed that more than 100 susceptibility genes have been linked to the pathogenesis of SLE, among which TYK2, STAT1, STAT4, and IRF5 are important molecules directly connected to the type I interferon signaling system. The review summarized the genetic associations and the detailed risk loci of STAT4 and IRF5 with Asian SLE patients, explored the genotype distributions associated with the main clinical manifestations of SLE, and sorted out the potential reasons for the differences in susceptibility in Asia and Europe. Moreover, the therapies targeting STAT4 and IRF5 were also evaluated in order to propose more personalized and targeted treatment plans in SLE.

Study of Serum Complement 3 Split Product iC3b /C3 Ratio in a Cohort of Systemic Lupus Erythematosus Patients

Abstract Background Systemic lupus erythematosus (SLE) is a chronic autoimmune systemic disease that causes widespread multi organ inflammation. The exact cause of SLE remains unclear; however, genetic, hormonal, and environmental factors contribute to the development of the disease. Aim of the Work The aim of this study is to measure the ratio of complement split product iC3b to C3 and its relation to disease activity and lupus nephritis in a cohort of SLE patients. Patients and Methods This study is a Cross sectional case control study conducted in internal medicine and Rheumatology unit, Ain Shams university hospital and Rheumatology unit, Maadi military hospital. Our study included. Results The present study shows that female were (76%) in active group of SLE patients and (60%) in inactive group while male were (24%) and (40%) respectively. with no significant difference. The mean of Disease Duration was (5.66 ± 1.97) with a range from 3 and 10 years in active group of SLE patients and (5.08 ± 1.54) with a range from 3 and 9 years in inactive group. with no significant difference. Regarding clinical manifestations of SLE the present study shows that active group of SLE patients had statistically highly significant increase in incidence of lupus nephritis, arthritis, serositis, oral ulcers, malar rash (p < 0.001) with significant increase in incidence of alopecia and neurological manifestations (p < 0.05). The current study shows that active group of SLE patients had statistically significantly higher mean ESR, anti-DNA titre, 24hr urinary proteins, serum creatinine, serum urea, and GFR levels (p = 0.000) than inactive group, Also active group had significant leucopenia, anemia (p = 0.000, 0.005 respectively) and C3 was significantly more consumed than inactive group (p < 0.05) Conclusion The ratio of complement split product iC3b to C3 concentrations correlates with the extent of SLE disease activity more than C3 alone. Furthermore, the iC3b:C3 ratio may discriminate between patients with lupus nephritis and patients without lupus nephritis. Detection of SLE disease activity and lupus nephritis by iC3b/C3 ratio help to make a proper decision in management to induce remission.

A Rare Case of Concurrent Lupus Mastitis and Sarcoidosis in a 62-Year-Old Female.

Systemic lupus erythematosus (SLE) and sarcoidosis are two of the most well-recognized, chronically diagnosed conditions in the United States, with a plethora of known multisystem manifestations. With regard to breast pathology, lupus mastitis is a relatively uncommon manifestation of SLE, commonly involving both the mammary gland and subcutaneous soft tissues of the breast. Sarcoidosis in the breast is a similarly, exceedingly rare manifestation of this multi-system disorder, classically presenting with non-caseating granulomas. Both present with non-specific mammographic and sonographic features. We present a 62-year-old female with known diagnosis of discoid lupus and Graves' disease who presented initially with an abnormal screening mammogram, ultimately undergoing mammographic work-up and subsequent biopsy demonstrating lupus mastitis, including vasculitis, panniculitis, and fibrosis with chronic inflammation. The patient was also found to have small non-caseating granulomas, some in a perivascular distribution, classically seen in sarcoidosis. Given the rarity of both manifestations, our case explores the coexistence of these autoimmune processes and this atypical presentation.

Update on lupus nephritis

In addition to the butterfly rash, lupus nephritis is the most specific manifestation of systemic lupus erythematosus (SLE). The perspective on this organ manifestation has fundamentally changed as well as the manifestation of SLE itself 40 years after the first multicenter clinical study on lupus nephritis. Even if there is a faint glimpse of hope of a cure, there is still the fight against the problem of nonresponders and also the progressive loss of organ function. This update gives an overview of the current importance of lupus nephritis in the context of the whole SLE disease, of the special features and on the options provided by the new diagnostic and therapeutic developments.

Atypical Presentations of Pediatric-acquired Thrombotic Thrombocytopenic Purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) in children is a rare, severe thrombotic microangiopathy. This condition is characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia due to reduced activity of the von Willebrand factor-cleaving protease ADAMTS13. A retrospective case series evaluating data collected from the medical files of 4 children diagnosed with iTTP. The presented case series depicts a variety of iTTP presentations: 1 case of primary iTTP, 1 case induced by Shiga toxin, 1 associated with RAS-associated autoimmune leukoproliferative disease (RALD), and 1 initial manifestation of systemic lupus erythematosus (SLE). Notably, 2 patients recovered without undergoing plasma exchange. Early ADAMTS13 testing in children with unexplained hemolysis or thrombocytopenia is crucial. The diverse underlying causes, including infections and autoimmune disorders, underscore the complexity of iTTP in the pediatric population. These cases highlight the necessity for personalized treatment approaches that consider each patient's unique clinical situation and potential alternatives or modifications to conventional therapeutic regimens.

Symmetric leukoencephalopathy associated with systemic lupus erythematosus: A systematic review of a distinctive neurorheumatologic syndrome

BackgroundA symmetric leukoencephalopathy can occur in the context of systemic lupus erythematosus (SLE), often as a first manifestation of underlying rheumatologic disease. Recognition of this distinctive syndrome can prompt investigation for SLE when undiagnosed, or prompt treatment initiation when the diagnosis is already known. Earlier recognition of this syndrome could lead to more effective treatment of the disease. MethodsClinical, laboratory, and radiographic features of three patients were described from an academic medical center in the United States with treatment dates between 2015 and 2022. A systematic review of literature from 1991 to 2023 yielded data for an additional 23 patients. ResultsTwenty-six total patients with symmetric leukoencephalopathy were included in this study. The median age of the patients was 37 years (range 10–69), 22 patients (85 %) were female, and 4 (15 %) were male. Fourteen of 26 patients (54 %) had this as the first clinical manifestation of SLE. Contrast enhancement was present on MRI brain in 3/26 (88 %) patients. Twenty patients (77 %) were treated with pulse-dose steroids, and all but one patient received some immunomodulatory therapy. Seven patients (27 %) progressed to death. No meaningful predictive differences were found between patients who survived and those who did not. ConclusionsIn this case series and literature review patients developed symmetric leukoencephalopathy in systemic lupus erythematosus most often as the first clinical manifestation of SLE. Clinicians should consider this syndrome in any patient with acute onset of symmetric leukoencephalopathy on brain magnetic resonance imaging.

Lupus Enteritis: A Rare Presentation of Lupus Flare

Abstract Among the various manifestations of systemic lupus erythematosus, lupus enteritis is an uncommon entity. A 14-year-old female, suffering from lupus, presented with abdominal pain, nausea, vomiting, and weight loss. A large hard palate ulcer, high erythrocyte sedimentation rate, and low complement levels led us to suspect lupus enteritis, which was subsequently confirmed by imaging and treated promptly. Accurate history, astute clinical examination, and contrast-enhanced computed tomography scan of the abdomen contribute invaluably to the diagnosis of this rare condition and distinction from its various mimics.

Analysis of Albumin to Globulin Ratio as A Prognostic Predictor in Lupus Nephritis Patients

Lupus Nephritis (LN) is a manifestation of Systemic Lupus Erythematosus (SLE), which targets the kidney. Based on histopathology, the World Health Organization divides the disease into five classes: normal pattern, mesangial, focal, diffuse proliferative, and membranous. Albumin to Globulin Ratio (AGR) compares serum albumin with serum globulin levels. Low AGR value is associated with poor prognosis of diseases such as cancer, liver cirrhosis, and other chronic inflammatory diseases such as LN. This study aimed to analyze the AGR value as a prognostic predictor in LN patients based on disease classes with a retrospective descriptive cross-sectional approach. Total subjects were 109, which consisted of class 1 (n=15), class 2 (n=37), class 3 (n=9), class 4 (n=21), and class 5 LN (n=27). Data of disease classes, serum albumin, and serum globulin/total protein levels were collected. SPSS version 25, Mann-Whitney, Kruskal-Wallis, Chi-Square, and Spearman's correlation test were used for statistical analysis. The ROC curve determined the cut-off. Test results were significant if p <0.05. The lowest mean AGR value (0.79) was found in class 4 LN (p<0.05). The optimal cut-off AGR was 1.10 to categorize mild-moderate and severe degrees. AGR prognostic value: sensitivity=95.8%; specificity=78.8%; Positive Prediction Value (PPV)=78.0%; Negative Prediction Value (NPV)=96.0%, accuracy = 86.2%. There was a negative strong correlation between the AGR value and LN class with a correlation coefficient R of -0.777 (p<0.001). AGR marker has a good sensitivity and specificity as a predictor of LN progression.

Neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review.

Neuropsychiatric systemic lupus erythematosus (NPSLE) refers to the neurological and psychiatric manifestations of systemic lupus erythematosus (SLE), which remainpoorly understood yet often have a profound effect on the lives of afflicted patients. The aim of this study is to synthesize the available information on the pathogenesis, diagnostics, management, and prognosis of this disease. Our hope is to increase awareness and call for further investigations that may optimize NPSLE patient outcomes and quality of life.We performed a literature review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, resulting in 11 studies of inclusion. Within each study, we extracted data on epidemiologic factors, diagnostics, therapeutic modalities, and prognosis for each neuropsychiatric condition.The most widely discussed neuropsychiatric manifestations of SLE based on the American College of Rheumatology (ACR) classifications included status epilepticus (SE) and seizures, transverse myelitis (TM), and cognitive dysfunction. SE and TM had a prevalence of 1-2%, while cognitive dysfunction was nearly 38%. Diagnostics varied depending on symptom presentation but often included brain magnetic resonance imaging (MRI) and antibody testing. Treatment for NPSLE is still widely understudied, but concurrent treatment with immunosuppressants and anti-inflammatories for symptom control and more targeted immunotherapies based on the specific condition is often effective. Prognosis is highly symptom dependent, ranging from a 12.5% one-year mortality in SE and seizure patients to near resolution of symptoms in certain presentations including idiopathic intracranial hypertension and cerebellar ataxia.Further studies are needed to better understand the pathophysiology, diagnostics, and effective therapeutic measures for NPSLE. The severity of these manifestations and generally poor prognosis highlightthe need for more research to accurately diagnose and treat this disease. While there is still little data available, this literature review serves to provide updated context on this condition.

A nomogram to predict the risk of proliferative lupus nephritis in patients with systemic lupus erythematosus involving the kidneys

Proliferative lupus nephritis (PLN) is a serious organ-threatening manifestation of systemic lupus erythematosus (SLE) that is associated with high mortality and renal failure. Here, we analyzed data from 1287 SLE patients with renal manifestations, including 780 of which were confirmed as proliferative or non-proliferative LN patients by renal biopsy, divided into a training cohort (547 patients) and a validation cohort (233 patients). By applying a least absolute shrinkage and selection operator (LASSO) regression approach combined with multivariate logistic regression analysis to build a nomogram for prediction of PLN that was then assessed by receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves (DCA) in both the training and validation cohorts. The area under the ROC curve (AUC) of the model in the training cohort was 0.921 (95% confidence interval (CI): 0.895–0.946), the AUC of internal validation in the training cohort was 0.909 and the AUC of external validation was 0.848 (95% CI: 0.796–0.900). The nomogram showed good performance as evaluated using calibration and DCA curves. Taken together, our results indicate that our nomogram that comprises 12 significantly relevant variables could be clinically valuable to prognosticate on the risk of PLN in SLE, so as to improve patient prognoses.

Recurrent Achilles Tendon Rupture in Multiple Sites as a Primary Manifestation of Systemic Lupus Erythematosus in a 32-Year-Old Patient: A Case Report

Recurrent Achilles Tendon Rupture in Multiple Sites as a Primary Manifestation of Systemic Lupus Erythematosus in a 32-Year-Old Patient: A Case Report

#2139 Non-lupus full house nephropathy: a debatable entity

Abstract Background and Aims The presence of a full house (FH) pattern at immunofluorescence on kidney biopsy in a patient without clinical and laboratory features of systemic lupus erythematosus (SLE) has led to the descriptive term non-lupus full house nephropathy (NLFHN). This systematic review and meta-analysis focus on NLFHN nomenclature, clinical findings and outcomes. Method In a reiterative process, all identified terms for NLFHN and other MeSH terms were searched in PubMed. Out of 344 results, 57 records published between 1982 and 2022 were included in the analysis. Clinical data of single patients from different reports were collected and analysed. Results Out of the 57 records, 61% were case reports. NLFHN was addressed with 17 different names; the same name used by different authors could refer to different entities. We identified 148 patients: 75 (51%) were males; median age 35 (23-58) years. Serum creatinine and proteinuria at onset were 1.4 (0.8-2.5)mg/dL and 5.7 (2.7-8.8)g/day. Overall, about half of patients achieved complete response. A causative agent was identified in 51 (44%) patients, predominantly infections(41%). Secondary NLFHN was mostly non-relapsing with worse kidney function at onset compared to idiopathic NLFHN (P = 0.001). Among the 57 (50%) patients with idiopathic NLFHN, complete response was comparable between patients treated with immunosuppression and supportive therapy; however, proteinuria and creatinine at onset were higher in patients treated with immunosuppression (P = 0.089 and P = 0.066). The remaining 7 (6%) patients developed SLE after a median follow-up of 5.0 (1.9-9.0) years. Conclusion The place of NLFHN among glomerular diseases is still uncertain, due to the lack of high-quality evidence and consensus on nomenclature. NLFHN can be evaluated as initial manifestation of SLE, isolated manifestation of SLE or a new disease unrelated to SLE. Data support the classification of SLE and NLFHN as distinct clinical entities, with comparable outcome. However, RCTs are needed to drive strong conclusions on treatments and outcomes.

#1833 Analysis of clinical and laboratory manifestations in different classes of lupus nephritis—a Serbian single center experience

Abstract Background and Aims Lupus nephritis represents one of the most serious manifestations of systemic lupus erythematosus. The gold standard for determining the class of lupus nephritis is percutaneous kidney biopsy and the histopathological analysis of the biopsy specimen. The aim of this study was to analyze the clinical and laboratory characteristics of different histopathological classes of lupus nephritis (LN) at the time of the systemic lupus diagnosis and onset of symptoms. Method This retrospective cross-sectional study included a total of 54 subjects who were hospitalized at the Clinic for Nephrology and Clinical Immunology of the University Clinical Center of Vojvodina from 2017 to 2022 and underwent percutaneous kidney biopsy. Available clinical and laboratory data, as well as the histopathological findings of kidney biopsies, were analyzed. Based on the histopathological classification, patients were divided into four groups (Class II, III, IV, and V), and the clinical and laboratory characteristics were analyzed for all subjects. Due to a low number of patients, no analysis of Class I and Class VI was made. Results The most prevalent class among the subjects was Class IV, in which the lowest values of the C3 complement component were recorded. Subjects in this LN class had higher blood pressure values, a higher frequency of clinical manifestations such as arthralgia, and joint swelling. Class IV LN was also associated with elevated anti-dsDNA antibody values with a significant statistical significance (p = 0.004), lower red blood cell parameters, and higher levels of nitrogenous substances compared to other classes. The lowest values of total serum proteins and albumins, as well as the highest values of total cholesterol, LDL cholesterol, and triglycerides, were observed in the group of subjects with Class V LN; C-reactive protein had the highest average values in Class III and IV, which showed a statistical significance (p = 0.007). The lowest values of total serum calcium and iron were in Class III, and 24-hour proteinuria was most pronounced in Class V (p = 0.001), whereas microscopic hematuria was most present in Class II LN (p = 0.03). Conclusion Patients with lupus nephritis exhibit different clinical and laboratory manifestations based on histopathological classification and the time of diagnosis. The results of this study suggest their potential use in diagnosis, assessment of histopathological classification, and the development of a targeted and personalized therapeutic approach. These parameters will be used to develop machine learning models which might help in further evaluation and treatment.