Symptoms Of Systemic Lupus Erythematosus Research Articles

Lupus progression deteriorates oogenesis quality in MRL/lpr mice.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of the immune response against self antigens. Numerous reproductive complications, including reduced birth rate and complications for the mother and the fetus during pregnancy, have been observed in women with SLE. In the present study, we aimed to investigate the effect of SLE development on oocyte meiosis in lupus-prone mice. Lupus-prone MRL/lpr mice were used for the experiments: disease-free (4weeks of age) and sick (20weeks of age, virgin and postpartum). The immune response was monitored by flow cytometry, ELISpot, ELISA, and histology. Oocytes were analyzed by fluorescence microscopy based on chromatin, tubulin, and actin structures. The lupus-prone MRL/lpr mice developed age-dependent symptoms of SLE with increased levels of various autoantibodies, proteinuria, and renal infiltrates and a tendency for the immune response to worsen with changes in cell populations and the cytokine profile. The number and quality of oocytes were also affected, and the successful pregnancy rate of MRL/lpr mice was limited to only 60%. Isolated oocytes showed severe structural changes in all studied groups. Systemic alterations in immune homeostasis in SLE affect the quality of developing oocytes, which is evident from a young age. The data obtained is in line with the trend of reduced fertility in lupus-prone MRL/lpr mice. The phenomenon can be explained by changes in the microenvironment of the relevant organs and close connection between ovulation and inflammatory processes.

The first clinical experience with selective DNA plasmasorption using the NucleoCapture Device in the treatment of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology characterized by the overproduction of autoantibodies against various components of the nucleus of the patient's own cells with the development of immunoinflammatory tissue damage. In recent years, more and more data have accumulated on the involvement of neutrophils in the development of the clinical symptoms of SLE, and DNA-containing structures and neutrophil extracellular traps (NETs) playing an important role in this process. Effective neutralization of NETs in SLE can be achieved by removing circulating proteins and molecules associated with NETs from the bloodstream by selective plasma sorption of DNA using the NucleoCapture Device.This article describes the case of a patient who underwent three plasma sorption sessions aiming to suppress the activity of SLE. During the therapy, significant positive dynamics were achieved: the SLEDAI-2K index decreased from 32 to 12 points, the number of leukocytes in the blood normalized, renal function improved, and the immunological activity of the disease decreased.

A Scoping Review of the Positive and Negative Bacteria Associated With the Gut Microbiomes of Systemic Lupus Erythematosus Patients.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems of the body. Recent research on the gut microbiota dysbiosis associated with SLE patients has gained traction and warranted further exploration. It has not been determined whether the change in the gut microbiota is a cause of SLE or a symptom of SLE. However, based on the physiological and pathophysiological role of the bacteria in the gut microbiome, as levels of the bacteria rise or fall, symptomatology in SLE patients could be affected. This review analyzes the recent studies that examined the changes in the gut microbiota of SLE patients and highlights the correlations between gut dysbiosis and the clinical manifestations of SLE. A systematic search strategy was developed by combining the terms "SLE," "systemic lupus erythematosus," and "gut microbiome." Biomedical Reference Collection, CINAHL, Medline ProQuest, and PubMed Central databases were searched by combining the appropriate keywords with "AND." Only full-text, English-language articles were searched. The articles were restricted from 2013 to 2023. Only peer-reviewed controlled studies with both human and animal trials were included in this scoping review. Review articles, non-English articles, editorials, case studies, and duplicate articles from the four databases were excluded. Various species of bacteria were found to be positively or negatively associated with SLE gut microbiomes. Among the bacterial species increased were Clostridium, Lactobacilli, Streptococcus, Enterobacter, and Klebsiella. The bacterial species that decreased were Bifidobacteria, Prevotella, and the Firmicutes/Bacteroidetes ratio. Literature shows that Clostridium is one of several bacteria found in abundance, from pre-disease to the diseased state of SLE. Lachnospiraceae and Ruminococcaceae are both part of the family of butyrate-producing anaerobes that are known for their role in strengthening the skin barrier function and, therefore, may explain the cutaneous manifestations of SLE patients. Studies have also shown that the Firmicutes/Bacteroidetes ratio is significantly depressed, which may lead to appetite changes and weight loss seen in SLE patients. Based on the established role of these bacteria within the gut microbiome, the disruption in the gut ecosystem could explain the symptomatology common in SLE patients. By addressing these changes, our scoping review encourages further research to establish a true causal relationship between the bacterial changes in SLE patients as well as furthering the scope of microbiota changes in other systems and autoimmune diseases.

Evaluation of Type 2 SLE symptoms in patients with a range of lupus nephritis activity.

Type 2 systemic lupus erythematosus (SLE) symptoms, including fatigue, fibromyalgia, and brain fog, contribute to poor health-related quality of life (HRQoL) in patients with lupus. To test the hypothesis that Type 1 (classical inflammatory lupus) activity is associated with Type 2 SLE activity, we characterized the features of Type 2 SLE in patients with a range of lupus nephritis (LN) activity. This was a cross-sectional study of SLE patients [American College of Rheumatology (ACR) 1997 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria] from June 2018 to March 2020. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and the Polysymptomatic Distress Scale. Patients were divided into groups based on their renal status. Active nephritis was defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) lupus nephritis parameter. Differences across groups were analyzed by Fisher's exact test and ANOVA. In this cohort of 244 patients (93% female, mean age 43years, 58% Black), 10% had active nephritis, 35% had historical nephritis, and 55% never had nephritis (non-nephritis). Active nephritis and non-nephritis patients had a similar burden of Type 2 SLE symptoms, despite a difference in Type 1 SLE activity. Patients with active nephritis had higher Type 2 PGA (Physician Global Assessment) scores and reported more Type 2 SLE symptoms than inactive nephritis patients. Patients with inactive nephritis had the lowest Type 2 SLE activity. While Type 2 SLE symptoms are common in SLE, our findings suggest that patients with active nephritis experience significant Type 2 SLE symptoms that may be ameliorated as nephritis improves. We also observed that non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. Therefore, the etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors. Key Points • Patients with active nephritis experienced significant Type 2 symptoms that may be ameliorated as nephritis improves. • Non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. • Because etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors.

Time to diagnosis in systemic lupus erythematosus: Associated factors and its impact on damage accrual and mortality. Data from a multi-ethnic, multinational Latin American lupus cohort.

Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. Of the 1437 included in these analyses, the median time to diagnosis was 6.0months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6months. Patients whose diagnosis took longer than 6months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). In this inception cohort, a maximum time of 24months with a median of 6months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).

The Type 1 & 2 systemic lupus erythematosus model: Perspectives of people living with systemic lupus erythematosus.

In the new Type 1 & 2 model for systemic lupus erythematosus (SLE), Type 1 SLE represents classic inflammatory manifestations, such as arthritis, while Type 2 SLE encompasses symptoms such as pain and fatigue where the relationship to inflammation is less clear. The objective of this study was to interview individuals living with SLE to determine the content and face validity of the Type 1 & 2 SLE model. We conducted a qualitative study using semi-structured interviews with a purposeful sample of participants who met classification criteria for SLE. Participants were asked to describe their experiences with Type 1 & 2 SLE symptoms and treatments, and they indicated if and how their personal experiences aligned with the Type 1 & 2 SLE model. All interviews were audio-recorded and transcribed; applied thematic analysis identified the most frequent and salient themes. We interviewed 42 participants with SLE. Type 2 SLE symptoms, such as pain and fatigue, were very common, with almost all participants experiencing some Type 2 symptoms at some point during their disease course. Participants described Type 1 SLE symptoms as being acute flares and life-threatening and Type 2 SLE symptoms as "everyday lupus" that affected their daily lives and were a dominant part of their SLE disease experience. Most participants stated they want their rheumatologists to discuss Type 2 symptoms during clinical appointments in order to address their full symptom experience. We demonstrated content and face validity of the Type 1 & 2 SLE model with people living with SLE. Participants in our study largely understood the model and felt it accurately reflected their experience living with SLE. Type 2 SLE symptoms are very common in individuals with SLE and impact patients' quality of life. Using the model to address Type 2 SLE symptoms allows the rheumatologist to incorporate the patient's perspective and provide patient-centered care.

An overlapping case of IgG4-related disease and systemic lupus erythematosus treated with belimumab: a case-based review.

IgG4-related disease (IgG4-RD) is a systemic condition in which IgG4+ plasma cell infiltration and fibrosis cause organ swelling and lead to diverse clinical manifestations. Although IgG4-RD typically responds to glucocorticoids (GCs), relapse during tapering occurs and an early GC-sparing approach might therefore be beneficial. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiple symptoms that is also treated with GCs as a first-line therapy. Recently, belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor, was approved, but reports of use for IgG4-RD are scarce. Here, we present a rare case of IgG4-RD complicated with SLE which was successfully treated with belimumab. A 67-year-old man was diagnosed with IgG4-RD based on a high serum IgG4 level and histopathological findings. Furthermore, he had pericardial effusion on echocardiography, and laboratory tests revealed thrombocytopenia, autoimmune hemolysis, positive anti-nuclear antibodies, positive anti-DNA antibodies, and hypocomplementemia. These data led to an SLE diagnosis. Treatment was started with prednisolone at 40mg/day, plus hydroxychloroquine, which initially improved both the SLE and IgG4-RD symptoms. During the GC tapering, belimumab was added and clinical symptoms resolved completely. Our case and the literature review summarize reported rare overlapping cases of IgG4-RD and SLE and suggest that belimumab is a promising candidate for the treatment of IgG4-RD.

Locus coeruleus tyrosine hydroxylase positive neurons mediated the peripheral and central therapeutic effects of transcutaneous auricular vagus nerve stimulation (taVNS) in MRL/lpr mice

ObjectiveThis study aims to investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on the development of systemic lupus erythematosus (SLE) in MRL/lpr mice. MethodsMRL/lpr mice were treated with taVNS for ten weeks. Locus coeruleus (LC) tyrosine hydroxylase positive (TH+) neurons were selectively lesioned by stereotactic injection of 6-hydroxydopamine (6-OHDA) or selectively activated by chemogenetic methods. Sympathetic denervation was conducted by intraperitoneal injection of 6-OHDA. ResultsTaVNS activated the TH + neurons in LC. TaVNS produced central therapeutic effects by reducing the number of hippocampal microglia, and increasing the number of surviving LC TH+ neurons in MRL/lpr mice. TaVNS also retarded the development of lymphadenectasis and splenomegaly, decreased the proportion of double-negative T (DNT) cells, and alleviated nephritis in MRL/lpr mice. The lesion of LC TH+ neurons eliminated both these central and peripheral therapeutic effects of taVNS, while chemogenetic activation of LC TH+ neurons mimicked most central and peripheral protective effects of taVNS in MRL/lpr mice. Furthermore, taVNS regulated the autonomic nervous system in MRL/lpr mice. ConclusionThis study provides direct evidence that taVNS can retard the development of peripheral and central symptoms of SLE, which is mediated by the LC TH+ neurons.

Transcriptomic Features of systemic lupus erythematosus Patients in Flare and Changes during Acute In-Hospital Treatment.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies. RNA-sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analyzed and scored to elucidate the transcriptomic changes during treatment. Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts, and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts. In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.

Recommendations for Improving Systemic Lupus Erythematosus Care From Black Adults

Racial inequities in incidence, morbidity, and mortality are a defining feature of systemic lupus erythematosus (SLE). Health care systems are integral to addressing these inequities. However, qualitative evidence that highlights Black SLE care experiences is limited. To identify opportunities for improving SLE care based on the experiences and perspectives of Black adults with SLE. In this qualitative study, an interpretive description approach was used and data were analyzed using inductive thematic analysis. Semistructured interviews with Black adults in Michigan who were diagnosed with SLE were conducted. Interviews occurred from November 2, 2021, to July 19, 2022, and data analysis occurred from May 6, 2022, to April 12, 2023. Deidentified transcripts from the interviews were analyzed to develop themes that focused on opportunities to improve quality of care and symptom management. The participants included 30 Black adults with SLE (97% women; mean age, 41 years; range, 18-65 years). Four main themes were identified: (1) awareness of SLE signs and symptoms before diagnosis (participants emphasized delays in diagnosis and how knowledge concerning SLE could be limited in their families and communities); (2) patient-clinician interactions (participants faced discrimination in health care settings and talked about the value of coordinated and supportive health care teams); (3) medication adherence and health effects (participants experienced a range of adverse effects from medications that treat SLE and described how monitoring medication use and efficacy could inform tailored care approaches); and (4) comprehensive care plans after diagnosis (participants reported persistent pain and other symptoms despite treatment). In the context of disease management, participants emphasized the importance of behavioral change and the negative impact of social risk factors. The findings of this qualitative study suggest how limited information about SLE, experiences of racism, treatment regimens, and social risk factors may affect Black people with SLE. Future research should further engage and include Black communities within the context of treatment and intervention development to reduce racial inequities.

Irradiation Attenuates Systemic Lupus Erythematosus-Like Morbidity in NZBWF1 Mice: Focusing on CD180-Negative Cells.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can induce systemic inflammation. Ultraviolet-A and X-ray irradiation have been reported to have therapeutic effects in patients with SLE. We previously demonstrated that CD180-negative cells, these are radiosensitive, contribute to the development of SLE-like morbidity in NZBWF1 mice. In this study, the effects of irradiation on SLE-like morbidity manifestations in NZBWF1 mice and on CD180-negative cells were investigated. Whole-body irradiation, excluding the head, attenuated SLE-like morbidity in vivo, as indicated by the prevention of the renal lesion development, inhibition of anti-dsDNA antibody production, reduction of urinary protein levels, and prolongation of the lifespan. Irradiation also reduced the proportion of CD180-negative cells in the spleen. Although other immune cells or molecules may be triggered because of the whole-body irradiation treatment, previous research, and the current results suggest a strong relationship between the radiation-induced decrease in CD180-negative cells and the amelioration of SLE-like morbidities. Clinical trials assessing CD180-negative cells as a therapeutic target for SLE have been hampered by the lack of validated cell markers; nonetheless, the present findings suggest that radiotherapy may be a new therapeutic strategy for managing SLE symptoms.

Haloperidol's Cytogenetic Effect on T Lymphocytes of Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients: An In Vitro Study.

Investigating haloperidol's cytogenetic behavior in cultured human T lymphocytes of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Four haloperidol solutions were added in cultures of peripheral blood lymphocytes of healthy individuals, SLE, and RA patients. After 72 hours of incubation, the cultured lymphocytes were plated on glass slides, and stained with the fluorescence plus Giemsa method, and sister chromatid exchanges (SCEs), proliferation rate index (PRI), and mitotic index (MI) were measured with the optical microscope. Result analysis revealed: (a) a statistically significant (p=0.001) dose-dependent increase of SCEs in SLE patients compared to healthy individuals; (b) a statistically significant (p=0.001) dose-dependent decrease of SCEs in RA patients for haloperidol concentrations 5, 10μg/mL; (c) a statistically significant (p=0.001) dose-dependent increase of SCEs in RA patients for haloperidol concentrations 20, 100μg/mL; and (d) a statistically significant (p=0.001) dose-dependent reduction of PRI and MI in both patient groups compared to healthy individuals. Furthermore, a correlation was observed between (a) SCE and PRI index variations, (b) MI and SCE index variations, and (c) PRI and MI index variations. Haloperidol affects T lymphocytes from SLE and RA patients by modifying DNA replication procedures, DNA damage response, and ferroptosis. Considering the wide use of haloperidol in neuropsychiatric symptoms of SLE and RA patients, further studies with more immune cell subsets are needed to evaluate its effects on human genetic material.

Akkermansia muciniphila and Lactobacillus plantarum ameliorate systemic lupus erythematosus by possibly regulating immune response and remodeling gut microbiota.

Systemic lupus erythematosus (SLE), characterized by persistent inflammation, is a complex autoimmune disorder that affects all organs, challenging clinical treatment. Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Modulating the gut microbiome is proposed as a promising approach for fine-running parts of the immune system, relieving systematic inflammation in multiple diseases. This study demonstrated that the administration of Akkermansia muciniphila and Lactobacillus plantarum contributed to an anti-inflammatory environment by decreasing IL-6 and IL-17 and increasing IL-10 levels in the circulation. The treatment of A. muciniphila and L. plantarum restored the intestinal barrier integrity to a different extent. In addition, both strains reduced the deposit of IgG in the kidney and improved renal function significantly. Further studies revealed distinct remodeling roles of A. muciniphila and L. plantarum administration on the gut microbiome. This work demonstrated essential mechanisms of how A. muciniphila and L. plantarum remodel gut microbiota and regulate the immune responses in the SLE mice model. IMPORTANCE Several pieces of research have demonstrated that certain probiotic strains contribute to regulating excessive inflammation and restoring tolerances in the SLE animal model. More animal trials combined with clinical studies are urgently needed to further elucidate the mechanisms for the effect of specific probiotic bacteria in preventing SLE symptoms and developing novel therapeutic targets. In this study, we explored the role of A. muciniphila and L. plantarum in ameliorating the SLE disease activity. Both A. muciniphila and L. plantarum treatment relieved the systemic inflammation and improved renal function in the SLE mouse model. We demonstrated that A. muciniphila and L. plantarum contributed to an anti-inflammatory environment by regulating cytokine levels in the circulation, restoring the intestinal barrier integrity, and remodeling the gut microbiome, however, to a different extent.

The Prevalence of Dry Eye Syndrome in Systemic Lupus Erythematosus Patients in Saudi Arabia

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a chronic multi-systemic autoimmune connective tissue disorder that is known to have variable manifestations with a remitting/relapsing course depending on the affected system. SLE can affect all the major organs in the human body including the heart, brain, and kidneys. Although the eye is not a primary target of autoimmune insult in SLE patients, one third of patients can present with significant ocular manifestations as it can affect any part of the ocular system. Furthermore, ocular involvement could be the first presenting symptom of SLE and may mirror the systemic disease activity. The worldwide prevalence of SLE varies, however, based on a study conducted in 2002 in central Saudi Arabia, the prevalence of SLE was estimated to be 19.28 per 100,000.
 
 STUDY AIM: To identify the prevalence of dry eye syndrome in Systemic Lupus Erythematosus diagnosed patients in Riyadh.
 
 METHODS: A cross sectional study that involved a total of 135 patients from Rheumatology outpatient clinic setting at King Khalid University Hospital in Riyadh, Kingdom of Saudi Arabia. Data was collected via McMonnies questionnaire, which is used as a screening tool for dry eye syndrome. Data analysis included descriptive statistics computed for continuous variables, including means, standard deviation (SD), minimum and maximum values, as well as 95% confidence interval (CI). Percentages and 95% CI were used for categorical variables.
 
 RESULTS: Out of 135 SLE patients, females were 87.4% ±2.9 (95%CI: 80.6–92.1.3), while males were 12.6% ±2.9 (95%CI: 7.9–19.4), Among the 118 female patients, 56% (n=66) lied between the age of 25-45 years. Most common symptom in 45.9% (95%CI: 37.6–54.5) of our patients was Dryness of Eyes. The predominant age group of our cohort was that of 25–45 years (57%) Among our cohort, 50.4% (95%CI: 41.9–58.8) patients suffered from Dry eye syndrome, with 12.6% males and 87.4% females.
 
 CONCLUSION: A high prevalence of dry eye syndrome was found in our study with a percentage of 50.4%, also a female predominance was found in patients having dry eye syndrome.

Complex relationships between inflammatory manifestations/type 1 and type 2 symptoms in systemic lupus erythematosus: A narrative literature review.

Recent studies have highlighted that systemic lupus erythematosus (SLE) is characterized by different types of symptoms: type 1 symptoms related to inflammation and disease activity and type 2 symptoms such as fatigue, anxiety-depression, and pain. Our aim was to investigate the relation between type 1 and type 2 symptoms, and their impact on health-related quality of life (HRQoL) in SLE. A literature review was conducted about disease activity/type1 and type 2 symptoms. Articles in English published after 2000 were located on Medline via Pubmed. The articles chosen evaluated at least one type 2 symptom or HRQoL using a validated scale in adult patients. Overall, 182 articles were analyzed and 115 were retained including 21 randomized, controlled trials and corresponding to 36 831 patients. We found that in SLE, inflammatory activity/type 1 symptoms were mostly uncorrelated with type 2 symptoms and/or HRQoL. Several studies even showing an inverse relationship. No or weak correlation was observed in 85, 3% (92, 6%), 76, 7% (74, 4%) and 37, 5% (73, 1%) of studies (patients) for fatigue, anxiety-depression, and pain, respectively. For HRQoL, no or weak correlation was observed in 77, 5% of studies (88% of patients). Type 2 symptoms are poorly correlated with inflammatory activity/type 1 symptoms in SLE. Possible explanations and implications for clinical care and therapeutic evaluation are discussed.

An early-onset SLE patient with a novel paternal inherited BACH2 mutation.

BACH2-related immunodeficiency and autoimmunity (BRIDA) is an inborn error of immunity, newly reported in 2017, presenting with symptoms of immunoglobulin deficiency and ongoing colitis. Studies using a mouse model have demonstrated that BACH2 deficiency predisposes individuals to systemic lupus erythematosus (SLE); however, no BACH2 deficiency has been reported in SLE patients. Here we describe a patient with BRIDA presenting with early-onset SLE, juvenile dermatomyositis, and IgA deficiency. Whole exome sequencing analysis of the patient and her parents revealed a novel heterozygous point mutation in BACH2, c.G1727T, resulting in substitution of a highly conserved arginine with leucine (R576L), which is predicted to be deleterious, in the patient and her father. Reduced BACH2 expression and deficient transcriptional repression of the BACH2 target, BLIMP1, were detected in PBMCs or lymphoblastoid cell lines of our patient. Notably, extreme reduction of memory B cells was detected in the patient's father, although he had no obvious symptoms. SLE symptoms and recurrent fever were relieved by treatment with prednisone combined with tofacitinib. Thus, we present the second report of BRIDA and demonstrate that BACH2 may be a monogenic cause of SLE.

Bipolar Disorder with Psychosis Featured in Patient with Systemic Lupus Erythematosus

Abstracts Introductions: Bipolar disorder (BD) is a mental disorder that imposes unusual shifts in mood, energy, activity levels, and the ability to carry out day-to-day tasks, characterized by biphasic mood episodes of mania or hypomania and depression. More than half of all individuals diagnosed with BD experience psychosis features in their lifetime. The cause of BD is not entirely known, study claims that BD may occur due to or associated with autoimmune diseases. Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with various physical manifestations, including neuropsychiatric features. Case: This case report will discuss a 22-year-old female with BD admitted to the emergency room due to solid psychosis features. The patient was diagnosed with SLE 3 years ago but never controlled prior to the disease history. The psychiatrist’s treatment in the emergency room was an extra injection of haloperidol 5 mg IM and diazepam 10 mg IM, continued with oral medication clozapine 25 mg two times a day and additional therapies such as cognitive behavioral therapy (CBT) and family therapy. The treatment from the internist was symptomatic medication due to the acute SLE symptoms, followed by autoimmune medicines such as steroids and hydroxychloroquine. Conclusions: BD may be associated with SLE. Psychosis features generally occur in BD, usually in the manic period. Treatment should be done for both psychiatric and internal medicine problems. As the SLE symptom was controlled, the BD symptom improved.

Olanzapine’s Cytogenetic Effect on T Lymphocytes in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients: In Vitro Study

This study will investigate olanzapine's cytogenetic behavior in cultured human T lymphocytes in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Three olanzapine solutions were added in cultures of peripheral blood lymphocytes of healthy individuals, SLE, and RA patients. After 72 hours of incubation, the cultured lymphocytes were plated on glass slides and stained with the fluorescence plus Giemsa method. Sister chromatid exchanges (SCEs), proliferation rate index (PRI), and mitotic index (MI) were measured with the optical microscope. There was a statistically significant (p=0.001) dose-dependent increase of SCEs in SLE and RA patients compared to healthy individuals and a statistically significant (p=0.001) reduction of PRI and MI in the highest concentration in the SLE group. Moreover, Spearman's rank correlation coefficient was applied to calculate the correlation between SCEs, PRI, and MI. Negative significant correlations were noticed for both patient groups concerning SCEs-PRI alterations and SCEs-MI alterations. Conversely, positive correlations were noticed for both patient groups for PRI-MI alterations. Conclusions: Olanzapine affects T lymphocytes from SLE and RA patients by modifying DNA replication procedures and DNA damage response. Considering the use of olanzapine in neuropsychiatric symptoms of SLE, further in vivo studies are necessary to evaluate its effect on human DNA.

A rare simultaneous presentation of combined occlusion and optic neuritis in a lupus erythematosus patient with anti-phospholipid antibody syndrome.

A known case of Systemic Lupus Erythematosus (SLE) developed sudden loss of vision (no light perception) with relative afferent pupillary defect in her right eye (RE) and fundus examination revealed cherry red spot over tomato splash background with tortuous and dilated veins suggestive of combined central retinal arterial and vein occlusion. Left eye (LE) had 6/6 vision but posterior segment revealed a hyperemic disc. Fundus fluorescein angiography (FFA) revealed delayed arm to retina time and increased arterial to vein transit time in RE. LE showed pooling of dye around optic disc suggestive of SLE related Optic neuritis. Patient was re-evaluated and she tested positive for Lupus anticoagulant. Patient was diagnosed to have anti-phospholipid antibody syndrome (APS) occurring secondary to SLE. She was started on intra venous steroids, anti-coagulants and disease progression in left eye was controlled. We report a rare simultaneous presentation of complete combined occlusion of central retinal artery and vein (CCRAVO) in RE and Optic neuritis in LE which has not been reported in literature so far. Ocular involvement may precede other systemic symptoms in SLE, so ophthalmologist should know about this rare simultaneous presentation. Ocular activity can correlate with systemic disease activity and starting early effective treatment can prevent other systemic lesion and can be life saving.

IoT‐based systemic lupus erythematosus prediction model using hybrid genetic algorithm integrated with ANN

AbstractInternet of things (IoT) is commonly employed to detect different kinds of diseases in the health sector. Systemic lupus erythematosus (SLE) is an autoimmune illness that occurs when the body's immune system attacks its own connective tissues and organs. Because of the complicated interconnections between illness trigger exposure levels across time, humans have trouble predicting SLE symptom severity levels. An effective automated machine learning model that intakes IoT data was created to forecast SLE symptoms to solve this issue. IoT has several advantages in the healthcare industry, including interoperability, information exchange, machine‐to‐machine networking, and data transmission. An SLE symptom‐predicting machine learning model was designed by integrating the hybrid marine predator algorithm and atom search optimization with an artificial neural network. The network is trained by the Gene Expression Omnibus dataset as input, and the patients' data are used as input to predict symptoms. The experimental results demonstrate that the proposed model's accuracy is higher than state‐of‐the‐art prediction models at approximately 99.70%.