Onset Of Systemic Lupus Erythematosus Research Articles

MicroRNA-125b mediates Interferon-γ-induced downregulation of the vitaminD receptor in systemic lupus erythematosus.

The inflammatory factor interferon (IFN)-γ is related to the occurrence and development of systemic lupus erythematosus (SLE). The vitaminD receptor (VDR) has an anti-inflammatory effect and its downregulation is involved in the onset of SLE. Our previous studies have confirmed that the expression of VDR in SLE peripheral blood mononuclear cells (PBMCs) is downregulated, which is negatively correlated with disease activity and inflammation. However, the mechanism underlying VDR downregulation in SLE is unknown. Based on the results of computer simulation analysis, the expression of VDR and four microRNAs (miR-17-3p, miR-34a, miR-346, and miR-125b) in SLE PBMC cells was analyzed under proinflammatory cytokine IFN‑γ treatment, and miR-125b was identified as the target miRNA. The relationship between IFN‑γ, miR-125b, and VDR was further assessed in THP‑1 cells. We showed that IFN‑γ inhibited the expression of VDR and miR-125b. Further study revealed that VDR mRNA was positively correlated with miR-125b in THP‑1 cells after IFN‑γ intervention. After transfection of miR-125b mimic or inhibitor, the expression of VDR in the miR-125b inhibitor group was lower than in the control group and miR-125b mimic group, while expression in the control group was lower than in miR-125b mimic group. Transfection of miR-125b inhibitor into THP‑1 cells could further promote the ability of IFN‑γ to inhibit VDR. The decrease in VDR expression promotes development of inflammation and SLE. These data suggest that miR-125b may mediate inflammatory factor IFN-γ-induced downregulation of VDR in the pathogenesis of SLE.

Number of Attending Physicians and Accumulated Organ Damage in Patients with Systemic Lupus Erythematosus: LUNA Registry Cross-Sectional Study.

Patients with systemic lupus erythematosus (SLE) frequently change attending physicians. The number of changes in attending physicians is related to the accumulated organ damage in patients with diabetes mellitus and inflammatory bowel disease, although similar results are not known for patients with SLE. This study investigated whether the number of attending physicians after the onset of SLE is associated with organ damage. Patients with SLE were enrolled in a multicenter registry of 14 institutions (the Lupus Registry of Nationwide Institutions). Patients with a disease duration of 6months to 10years were included. Exposure was defined as the number of attending physicians. The primary outcome was the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). The secondary outcomes were corticosteroid- and non-corticosteroid-related damage. Multiple logistic regression analysis was used to estimate the association between the number of attending physicians and SDI, adjusting for potential confounders, including age, sex, disease duration, number of hospitalizations due to SLE, disease activity at diagnosis, and emotional health. Of the 702 patients, 86.5% were women (median age 46years, interquartile range 35-58). The disease duration was 7.3years (4.3-11.3), the number of hospitalizations due to SLE was 1 (1-3), the number of attending physicians was 3 (2-4), and SDI was 0 points (0-1). The number of attending physicians was significantly associated with SDI [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.03-1.26]. In the secondary outcome, the number of attending physicians was significantly associated with corticosteroid-related damage (OR 1.22, 95% CI 1.09-1.38). The number of attending physicians was not significantly associated with non-corticosteroid-related damage (OR 1.08, 95% CI 0.99-1.19). This study showed that SDI could increase as the number of attending physicians increases. The impact of changing attending physicians warrants greater attention for SLE and other diseases.

Интерфероны I типа, потребность в глюкокортикостероидах и коморбидность у пациентов с системной красной волчанкой

Background: сomorbidity is one of the factors which considerably reduce life expectancy and affect quality of life of patients with systemic lupus erythematosus (SLE). Interferons (IFNs) are molecules whose changing concentrations may induce the active clinical manifestations of SLE and the increase in risk of comorbidities and their higher severity. The involvement of IFN-α in the development of comorbidities in the adult population of SLE patients may have distinguishing characteristics in cases of childhood-onset SLE and will need further research for better understanding its role. Aim: to assess the relationship between the level of IFN-α and the need for glucocorticosteriods (GCs) and the prevalence of comorbidities in adult SLE patients with different onset ages. Patients and Methods: this non-interventional study included SLE patients (n=71) (SLICC (2012) / EULAR (2019) Criteria) who did not receive genetically engineered biological agents: 43 (60%) patients with SLE onset under the age of 18 years comprised the group of juvenile SLE (jSLE) and 28 (40%) patients with SLE onset at 18 years or older age were included in the group of adult SLE (aSLE). For determining SLE activity during physical examination of patients, the SLEDAI-2K index was used. Serum IFN-α levels were measured by enzyme-linked immunosorbent assay (ELISA). The Charlson comorbidity index (CCI) and the CIRS-G scale were used for assessing comorbidities. Results: in patients with aSLE, serum IFN-α levels were higher and associated with higher GC doses. Also, aSLE patients had higher CCI and CIRS-G scores. As regards comorbid diseases, a statistically significant higher prevalence of peptic (stomach and duodenal) ulcers and menstrual disorders in women was observed. These comorbidities correlated with IFN-α levels. Conclusion: serum IFN-α levels are associated with the use of high GS doses and high CCI and CIRS-G scores, as well as the prevalence of GI diseases and menstrual disorders in women. The anti-interferon therapy seems to be a promising option for reducing "steroid addiction" and related comorbidities. KEYWORDS: systemic lupus erythematosus, interferon, anifrolumab, glucocorticosteroids, comorbidity. FOR CITATION: Aliev D.B., Inamova O.V., Maslyansky A.L. et al. Type I interferon, the need for glucocorticosteroids and comorbidities in patients with systemic lupus erythematosus. Russian Medical Inquiry. 2023;7(3):118–123 (in Russ.). DOI: 10.32364/2587-6821- 2023-7-3-118-123.

Late Onset Systemic Lupus Erythematosus: Different Clinical, Serological Presentations and Damage Compared to Adult Lupus in Egypt

Late Onset Systemic Lupus Erythematosus: Different Clinical, Serological Presentations and Damage Compared to Adult Lupus in Egypt

Presentation of SLE after COVID vaccination in a pediatric patient

BackgroundThe outbreak of severe acute respiratory syndrome coronavirus 2 has had an enormous impact on global health. Vaccination remains one of the most effective interventions for disease prevention. Clinically significant vaccine side effects are uncommon, though autoimmune-mediated disease occurs in a small percentage of vaccine recipients. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that is associated with significant morbidity and mortality. Childhood-onset SLE tends to have more severe disease manifestations than adult-onset SLE. In adults, there are a few reported cases of SLE developing soon after coronavirus disease 2019 (COVID-19) mRNA vaccination.Case presentationA 14-year-old previously healthy male developed laboratory and clinical evidence of SLE, including maculopapular malar rash, arthritis, pleuritic chest pain, and class V (membranous) lupus nephritis, 2 days after his third dose of the Pfizer-BioNTech COVID-19 vaccine. The patient’s symptoms improved after initiation of prednisone and mycophenolate mofetil. We also summarize eleven prior case reports describing SLE after COVID-19 vaccine in adults.ConclusionTo our knowledge, this is the first reported pediatric patient with new onset SLE following COVID-19 mRNA vaccination. While potential mechanistic links exist between COVID-19 vaccination and SLE development, additional studies are necessary to elucidate the exact nature of this relationship.

Unraveling the Link between Interferon-α and Systemic Lupus Erythematosus: From the Molecular Mechanisms to Target Therapies.

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease with a wide range of clinical expressions. The kidney is often affected, usually within 5 years of the onset of SLE, and lupus nephropathy (LN) carries a high risk for increased morbidity. The clinical heterogeneity of the disease is accompanied by complex disturbances affecting the immune system with inflammation and tissue damage due to loss of tolerance to nuclear antigens and the deposition of immune complexes in tissues. Several studies have reported that in human SLE, there is an important role of the Type-I-interferons (INF) system suggested by the upregulation of INF-inducible genes observed in serial gene expression microarray studies. This review aims to describe the transduction pathways of Type-I-interferons, in particular INFα, and its immune-regulatory function in the pathogenesis of SLE and, in particular, in LN. In addition, recent novelties concerning biologic therapy in LN will be discussed.

Clinical Determinants of Childhood Onset Systemic Lupus Erythematosus among Early and Peri-Adolescent Age Groups.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that is associated with significant morbidity and mortality. SLE disproportionately affects women and minorities. Childhood-onset SLE (cSLE) in particular tends to be more aggressive than adult-onset SLE. Despite substantial improvements in the treatment of cSLE, there is significant variability in treatment responses and long-term outcomes. Furthermore, there is a paucity of studies involving cSLE, and in particular, cSLE among different age groups. The aim of this study was to test the hypothesis that an early-onset cSLE cohort would demonstrate unique characteristics with distinctive clinical and laboratory features at disease onset. We specifically investigated whether clinical, epidemiological, or serological factors are differentially associated with early- and late-onset cSLE. This could have direct impact on clinical management with the goal of improving outcomes and quality of life for children with SLE. Our study was conducted at a large tertiary center. We included 213 subjects seen at our pediatric rheumatology clinic aged 4-17 years. Epidemiologic, clinical phenotype, disease severity, serology, treatment, and outcome data were compared between subjects with cSLE onset prior to 10 years of age (early-onset disease, n = 43) and those with cSLE onset greater than 10 years of age (peri-adolescent disease, n = 170). We compared clinical features between early- and peri-adolescent onset cSLE in order to investigate the association between age at disease onset of cSLE and clinical disease expression and outcomes. Of the 213 subjects with cSLE in our study, 43 subjects had early-onset disease (age 2 to ≤9 years) and 170 patients had peri-adolescent onset disease. We found that early-onset cSLE was associated with a higher prevalence of positive anti-dsDNA antibody at cSLE diagnosis, higher anti-dsDNA antibody titer at cSLE diagnosis, rash, and azathioprine use (p < 0.001, p = 0.004, p = 0.011, and p = 0.008, respectively). In contrast, we found that peri-adolescent onset cSLE (≥10 years of age) was associated with worse disease activity (SLEDAI range 0-24) (p < 0.001), higher SLICC at diagnosis (p < 0.001), as well as a higher rate of mycophenolate mofetil and hydroxychloroquine use (p = 0.003 and p < 0.001, respectively). There were no significant differences in the prevalence of neuropsychiatric symptoms or the development of Class IV/Class V lupus nephritis between the early-onset and peri-adolescent groups.

Systemic lupus erythematosus following SARS-CoV-2 vaccination; a review of literature

From March 2020, the coronavirus disease 2019 (COVID-19) pandemic challenged public health and healthcare systems worldwide. Viral infection is one of the environmental factors that has been associated with the development, relapse, or exacerbation of systemic lupus erythematosus (SLE). SLE patients are at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of immune system dysfunction related to their disease as well as immunosuppression medications. So far, the most effective way to reduce SARS-CoV-2 infection-induced hospitalization and death is vaccination. On the other hand, SLE patients present distinct challenges related to the safety and effectiveness of SARS-CoV-2 vaccination. We have reviewed some reports on the onset or flare of SLE post-COVID-19 vaccination. Of note, the mRNA COVID-19 vaccines are associated with increased SLE disease activity, more frequently than the other types of COVID-19 vaccines.

52 Use of corticosteroids in childhood systemic lupus erythematosus: experience from a pediatric rheumatology center

BackgroundChildhood-onset Systemic Lupus Erythematosus (cSLE) is a rare but severe multisystem autoimmune/inflammatory disease that can affect any organ system and cause significant damage, disability and/or death. Corticosteroids are one of the important therapeutic weapons for childhood Systemic Lupus Erythematosus (SLE). Prednisone doses are increased during flare-ups of lupus disease, and then progressively reduced to reach a threshold dose in order to avoid the harmful effects of this treatment in growing children. The oral route is by far the most used over prolonged periods, however corticosteroid boluses are recommended in the treatment of severe acute attacks of the disease.ObjectiveAssess the use of corticosteroids in childhood systemic lupus erythematosus (SLE) and the risk of steroid-related damage.MethodsPatients with childhood -onset SLE (n = 83) treated at paediatric rheumatology centre were followed for 36 months. Information on medication use, disease activity as measured by SLEDAI was collected.ResultsEighty-three (83) patients were studied. Female: male ratio was 1:49. Mean ages at lupus onset and diagnosis were respectively: 10, 12 (±3,88_ and 11, 3 (±3,62) years. Corticosteroids were used in 92% of cases in oral form and on 37% of cases as a bolus of high dose intravenous methylprednisolone. The indication of corticoids bolus was significantly related to severe forms (p = 0,001), high disease activity (p = 0, 00008), and macrophage activation Syndrome (p = 0, 0006). The doses varied between 0.5–1 g/1.73m2. The mean initial disease activity in these patients was 30 ± 10, while that found after taking the treatment was 12.9 ± 15. The decrease was statistically significant (p = 0, 000001). More than half of our patients were on high dose oral corticosteroids (2 mg/kg/d) and only 1/5 of the patients benefited from a dose of (1 mg/kg/day). The use of corticosteroids has been associated with significant side effects, including growth delay (22%), cushingoid obesity (58%), stretch marks (49%), osteoporosis (33%), femoral head osteonecrosis (1%), infections (54%). The association of certain side effects with a high dose of oral corticosteroids (2 mg/kg/day) was significant in this case cushingoid obesity (p = 0, 0003), stretch marks (p = 0.014).ConclusionCorticosteroids are the mainstay of therapy for prompt control of acute disease related inflammation in patients with SLE; they remain the first-line treatment for significant lupus manifestations, especially severe forms and life-threatening situations Higher dosage and longer duration of therapy, which are common in SLE, result in greater risk of adverse effects. Their use wisely is the guarantee of a better response and the reduction of deleterious effect.

44 Pediatric onset systemic lupus erythematosus (p-SLE)

BackgroundPediatric onset Systemic lupus erythematosus (p-SLE) is multisystem autoimmune disease with disease onset before the 18th birthday. It is a highly complex disease with marked heterogeneity between patients, causing anything from mild to life-threatening disease.ObjectiveTo assess thrombomodulin (TM) and D-dimer levels in pediatric systemic lupus erythematosus patients and their correlation to disease activity.MethodsThis study included 40 children diagnosed with systemic lupus erythematosus. They were grouped according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score into group (A) [Mild activity] included 20 children with SLEDAI score less than or equal to 4, group (B) [Moderate-high activity] included 20 children with SLEDAI score >4. Also, 40 apparently healthy children were included as a control group. They were age and sex matched, with the children having SLE.ResultsThe two studied groups had significantly higher TM level than controls, furthermore group B had significantly higher TM level than group A (p< 0.008 in all). The two studied groups had significantly higher frequency of abnormally high TM level than controls, furthermore group B significantly had higher frequency of abnormally high TM level than group A (p< 0.02 in all). SLE children had significantly higher D dimer level than controls, furthermore group B had significantly higher D dimer level than group A (p≤ 0.006 in all). The two studied groups had significantly higher frequency of abnormally high D dimer level than controls, furthermore group B had significantly higher frequency of abnormally high D dimer level than group A (p≤ 0.03 in all). TM had a significant positive correlation with SLEDAI score as r = 0.342 and p = 0.031. D dimer had a significant positive correlation with SLEDAI score as r = 0.42 and p = 0.007.ConclusionThrombomodulin and D dimer are potentially valuable markers of the disease activity and thrombotic tendency in p SLE patients. Thus, regular evaluation may be useful for early detection of thrombotic complications.

47 Systemic lupus erythematosus in Tunisian children: a case series

BackgroundChildhood–onset systemic lupus erythematosus (c-SLE) is the prototype of a multisystemic, inflammatory, heterogeneous autoimmune condition, characterized by simultaneous or sequential organ involvement. Compared with the adult onset form, c-SLE is thought to have a worse prognosis.ObjectivesTo review the epidemiological, and bio-clinical, characteristics of a c-SLE case series.MethodsThe files of patients diagnosed as c-SLE in the pediatrics department of Monastir, Tunisia from January 2004 to March 2022 were reviewed. Mean and standard-deviations were used to express normally-distributed variables, as verified by the Kolmogorov-Smirnov statistical test.ResultsFourteen patients were collected. Female to male ratio was 6:1. Mean ages at lupus onset and diagnosis were 9.9 ± 1.4 years, [5–13.8 years] and 10.75 ± 2.3 years [6–14 years], respectively. Only two children had a family history of autoimmune disease.The initial admission was motivated primarily by skin and musculoskeletal manifestations, in 64.3% and 51.7% of cases, respectively. General signs (fever, asthenia) were observed in 35.7% of cases, hematological and gastrointestinal manifestations in 28.6% of cases each. In 3 cases, upper gastric endoscopy was performed prior to admission, in view of abdominal pain and vomiting.The physical examination noted various anomalies. Malar rash (50%) and discoid lupus (28.6%) were the most frequent cutaneous manifestations, while skin biopsy was performed in three cases, all favorable for lupus. The musculoskeletal manifestations comprised arthralgia (71.4%), arthritis and myositis (14.3% each). Hematological manifestations included thrombocytopenia and leukopenia in 4 cases each, as well as 3 cases of auto-immune hemolytic anaemia and splenomegaly. Renal manifestations were dominated by proteinuria in 7 cases, followed by hematuria in 6 cases, and 2 cases of hypertension (associated with renal failure in one case). The renal biopsy was performed in one case showed a stage-2 lupus nephritis. Pleural effusion was observed in 3 cases, 3 cases of pneumonia, 2 cases of pericarditis, one case of myo-pericarditis and one case of central nervous system (CNS) lupus.Relevant results of the laboratory workup are illustrated in the following table:47 Table 1Laboratory testPerformed (%)Abnormal results (%)Erythrocyte sedimentation rate14 (100%)13 (92%)Antinuclear anti-bodies14 (100%)13 (92%)AntiDNA antibodies7 (50%)5 (71%)AntiSm antibodies8 (57%)5 (62%)Antiphospholipid antibodies8 (57%)5 (62%)Complement11 (78%)9 (81%)The formal diagnosis of SLE was established according to the ACR-1997 criteria in 7 cases (50%), the SLICC-2012 in 4 cases (28.6%) and EULAR/ACR-2019 in 3 cases (21.4%). The c-SLE diagnosis was associated with coeliac disease and Hashimoto thyroiditis in one case each.The therapeutic management was based on corticosteroids in 11 cases, followed by hydroxychloroquine in 3 cases, while cyclophosphamides and immunoglobulin were used for one case each.The outcomes were heterogeneous. Among 11 patients with sufficient follow-up, 6 cases of remission and 2 cases of relapse were noted. Major adverse events were not infrequent: one case each of cardiac tamponade, macrophage activation syndrome and severe CNS lupus were observed, all fatal.ConclusionChildhood–onset systemic lupus is a challenging disease, both to diagnose and to treat. The development of new criteria of higher specificity and sensitivity has greatly helped identify the incomplete types of lupus and allow for early stage diagnosis, and therefore prevent the serious complications of the disease.

85 Systemic lupus erythematosus in Tunisian children: a case series

BackgroundChildhood–onset systemic lupus erythematosus (c-SLE) is the prototype of a multisystem, inflammatory, heterogeneous autoimmune condition, characterized by simultaneous or sequential organ involvement. Compared with the adult-onset form, c-SLE have a worse prognosis.ObjectivesTo review the epidemiological, and bio-clinical, characteristics of a c-SLE case series.MethodsThe files of patients diagnosed as c-SLE in the pediatrics department of Monastir, Tunisia from January 2004 to March 2022 were reviewed. Mean and standard-deviation were used to express normally-distributed variables, as verified by the Kolmogorov-Smirnov statistical test.ResultsFourteen patients were collected. Female to male ratio was 6:1. Mean ages at lupus onset and diagnosis were 9.9 ± 1.4 years, [5–13.8 years] and 10.75 ± 2.3 years [6–14 years], respectively. Only two children had a family history of autoimmune disease.The initial admission was motivated primarily by skin and musculoskeletal manifestations, in 64.3% and 51.7% of cases, respectively. General signs (fever, asthenia) were observed in 35.7% of cases, hematological and gastrointestinal manifestations in 28.6% of cases each. In 3 cases, upper gastric endoscopy was performed prior to admission, in view of abdominal pain and vomiting.The physical examination noted various abnormalities. Malar rash (50%) and discoid lupus (28.6%) were the most frequent cutaneous manifestations, while skin biopsy was performed in three cases, all in keeping with lupus. The musculoskeletal manifestations were arthralgia (71.4%), arthritis and myositis (14.3%). Hematological manifestations included thrombocytopenia and leukopenia in 4 cases, as well as 3 cases of auto-immune hemolytic anaemia and splenomegaly. Renal manifestations were proteinuria in 7, haematuria in 6, and hypertension in 2 (with renal failure in one of the patients). The renal biopsy that was performed in one subject showed a class 2 lupus nephritis. Pleural effusion was observed in 3, pneumonia in 3, pericarditis in 2, myo-pericarditis in 1 and central nervous system (CNS) lupus in 1.Relevant results of the laboratory workup are illustrated in the following table:85 Table 1Laboratory testPerformed (%)Abnormal results (%)Erythrocyte sedimentation rate14 (100%)13 (92%)Antinuclear anti-bodies14 (100%)13 (92%)AntiDNA antibodies7 (50%)5 (71%)AntiSm antibodies8 (57%)5 (62%)Antiphospholipid antibodies8 (57%)5 (62%)Complement11 (78%)9 (81%)The formal diagnosis of SLE was established according to the ACR-1997 criteria in 7 cases (50%), the SLICC-2012 in 4 cases (28.6%) and EULAR/ACR-2019 in 3 cases (21.4%). The c-SLE diagnosis was associated with coeliac disease and Hashimoto thyroiditis in two of the subjects respectively.The therapeutic management was based on corticosteroids in 11 cases, hydroxychloroquine in 3, while cyclophosphamides and immunoglobulin were used for two subjects respectively.The outcomes were heterogeneous. Among 11 patients with sufficient follow-up, 6 cases of remission and 2 cases of relapse were noted. Major adverse events were not infrequent: one case each of cardiac tamponade, macrophage activation syndrome and severe CNS lupus were observed, all fatal.ConclusionChildhood–onset systemic lupus is a challenging disease, both to diagnose and to treat. The development of new criteria of higher specificity and sensitivity has greatly helped identify the incomplete types of lupus and allow for early-stage diagnosis, therefore preventing the serious complications of the disease.

NEW-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS AND STEVEN JOHNSONS SYNDROME WITH SEVERE ARDS HERALDED BY POST-COVID-19 INFECTION MULTISYSTEM INFLAMMATORY SYNDROME IN AN ADULT (MIS-A)

NEW-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS AND STEVEN JOHNSONS SYNDROME WITH SEVERE ARDS HERALDED BY POST-COVID-19 INFECTION MULTISYSTEM INFLAMMATORY SYNDROME IN AN ADULT (MIS-A)

Expression of the miR-9-5p, miR-125b-5p and its target gene NFKB1 and TRAF6 in childhood-onset systemic lupus erythematosus (cSLE)

Childhood- onset systemic lupus erythematosus (cSLE) is a multisystem inflammatory disease that can lead to severe clinical conditions resulting in early comorbidities. Several genetic, environmental, and immunological factors are known to influence the onset of the disease. MiRNAs have been already considered as potential actors involved in the development and activity of the SLE. Thus, understanding the behavior of these regulators can contribute to clarify the inflammatory process affecting SLE patients. Among miRNAs, miR-125b-5p and miR-9-5p targeting NFKB1 and TRAF6 genes can be involved in the etio-pathogenesis of the disease by modulating inflammation. In this study we evaluated miR-9-5p and miR-125b-5p expression and its target genes NFKB1 and TRAF6 in peripheral blood samples (PBMC) from the 35 cSLE patients and 35 healthy controls. MiRNAs and gene target expression have been evaluated by using RT-PCR with specific TaqMan® probes. Both miR-9-5p [Fold Change (FC) = −2.21; p = 0.002] and miR-125b-5p (FC= −3.30; p < 0.0001) and NFKB1 (FC = −1.84; p < 0.001) were downregulated in cSLE patients, while TRAF6 was upregulated (FC = 1.80; p = 0.006) in cSLE patients when compared to controls. A significant correlation was found between miR-125b-5p and its target gene NFKB1 [Spearman (r) = 0.47; p = 0.023]. Our results showed miR-125b-5p and miR-9-5p differential expression in cSLE patients, possibly contributing to better understanding the role of these regulators in cSLE development and disease pathogenesis.

Decreased Jumonji Domain-Containing 3 at the Promoter Downregulates Hematopoietic Progenitor Kinase 1 Expression and Cytoactivity of T Follicular Helper Cells from Systemic Lupus Erythematosus Patients.

T follicular helper (Tfh) cells are overactivated in systemic lupus erythematosus (SLE) patients and contribute to excessive immunity. Hematopoietic progenitor kinase 1 (HPK1), as an inhibitor of T cells, is underexpressed in SLE Tfh cells and consequently induces autoimmunity. However, the reason for downregulation of HPK1 in SLE Tfh cells remains elusive. By combining chromatin immunoprecipitation with quantitative polymerase chain reaction assays, it was found that histone H3 lysine 27 trimethylation (H3K27me3) at the HPK1 promoter in SLE Tfh cells elevated greatly. We also confirmed jumonji domain-containing 3 (JMJD3) binding at the HPK1 promoter in SLE Tfh cells reduced profoundly. Knocking down JMJD3 in normal Tfh cells with siRNA alleviated enrichments of JMJD3, H3K4me3, and mixed-lineage leukemia (MLL) 1 at the HPK1 promoter and increased H3K27me3 number in the region. HPK1 expression was lowered, while Tfh cell proliferation activity, IL-21 and IFNγ secretions in the supernatants of Tfh cells, and IgG1 and IgG3 concentrations in the supernatants of Tfh-B cell cocultures all upregulated markedly. In contrast, elevating JMJD3 amount in SLE Tfh cells by JMJD3-overexpressed plasmid showed opposite effects. The abundances of H3K4me3 and MLL1 at the HPK1 promoter in SLE Tfh cells were greatly attenuated. Our results suggest that deficient JMJD3 binding at the promoter dampens HPK1 expression in SLE Tfh cells, thus making Tfh cells overactive, and ultimately results in onset of SLE.

P13 A case of Kikuchi-Fujimoto disease triggered by an episode of bacterial cellulitis, associated with features of SLE

P13 A case of Kikuchi-Fujimoto disease triggered by an episode of bacterial cellulitis, associated with features of SLE

The effect of air pollution on systemic lupus erythematosus: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from impaired inflammatory responses. Given the role of air pollution on increasing inflammatory mediators, thus, we aimed to systematically review and meta-analyze evidence regarding an association between short-term exposure to air pollution and SLE onset, activity, and hospitalization. Electronic databases including Web of Science, PubMed, Scopus, and Embase were searched for all published articles until July 5, 2021. Newcastle Ottawa Scale (NOS) checklist was used to assess the quality of individual studies. Relevant demographic data and the intended results of the selected studies were extracted, and their adjusted risk ratios (RRs) were pooled using random and fixed effect analysis based on the heterogeneity index. Twelve studies were entered in our systematic review, and finally, six publications were enrolled in meta-analysis. Overall, Meta-analysis showed no significant association between an increase of PM2.5 on the third day and SLEDAI score with pooled adjusted RR of 1.212 (95% CI, 0,853-1.721), p-value = 0.284. However, there was a positive relationship between 6days increase of Particulate matter (PM) 2.5 and the systemic lupus erythematosus disease activity Index (SLEDAI) score (pooled adjusted RR 1.112; 95% CI, 1.005-1.231), p-value = 0.040. There was no significant association between carbon monoxide (CO), nitrogen dioxide (NO2), PM2.5, and PM10 increase in the air and hospitalization of SLE patients with pooled RR of 1.021 (95% CI, 0,986-1.1.057), p-value = 0.249, 1.034 (95% CI, 0.996-1.068); p-value = 0.079, 1.042 (95% CI, 0.994-1.092); p-value = 0.084 and 1.004 (95% CI, 0.996-1.013); p-value = 0.323, respectively. Also, analysis showed a significant relation between ozone (O3) increase and hospitalization with a pooled RR of 1.076 (95% CI, 1.009-1.147); p-value = 0.025. Finally, analysis of SO2 increase and risk of hospitalization demonstrated no significant relationship with the pooled RR of 1.011; (95% CI, 0.962-1.062), p-value = 0.0.671. Our findings prove that PM2.5 was associated with increased SLE risk. We also showed that only O3 was associated with increased hospital admissions of SLE patients.

Depression, anxiety, and sleep quality in childhood onset systemic lupus erythematosus and relationship with brain-derived neurotrophic factor.

The association between brain-derived neurotrophic factor (BDNF) and systemic lupus erythematosus (SLE) is controversial, and no study investigated the clinical associations of BDNF in patients with childhood onset systemic lupus erythematosus (cSLE). In this study, we aimed to investigate the serum levels of BDNF in patients with cSLE and examine whether a relationship of BDNF exists among depression, anxiety, and sleep quality. Thirty patients and age-sex matched healthy controls were included. Depression, anxiety, sleep quality and quality of life were assessed by relevant questionnaires. Disease activity was assessed according to the SLE disease activity index (SLEDAI) and serum BDNF level was measured by the enzyme-linked immunosorbent assay method. Serum BDNF level was significantly lower in cSLE patients than healthy controls (21981 vs 29905 pg/mL, p = 0.001) and significantly decreased level was observed in active cSLE (SLEDAI >0), then those with SLEDAI = 0 (17110 vs 26852 pg/mL, p = 0.005). Although the scores of the depression, anxiety, sleep quality and quality of life questionnaires were strongly correlated with each other, no correlation was observed with serum BDNF levels. In patients with cSLE, serum level of BDNF was significantly decreased compared to healthy controls. Our results suggest that serum BDNF levels were not associated with the presence of anxiety, depression and poor sleep quality and might be dictated by the pathophysiological process of SLE rather than mood disorders.

ПОРАЖЕНИЕ ЖЕЛУДОЧНО-КИШЕЧНОГО ТРАКТА И ГЕПАТОБИЛИАРНОЙ СИСТЕМЫ ПРИ СИСТЕМНОЙ КРАСНОЙ ВОЛЧАНКЕ С ЮВЕНИЛЬНЫМ НАЧАЛОМ

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations that can affect the gastrointestinal tract (GIT). The onset of SLE before adulthood affects the clinical presentation, course, and prognosis. The GIT and the hepatobiliary system involvement in SLE with juvenile onset is regarded as an unfavorable prognosis factor with high probability for development of persistent organ disorders, which is life-threatening in some cases. The article analyzes gastroenterological pathology within SLE in children and adolescents, discusses such lesions as lupus enteritis, exudative enteropathy, intestinal pseudo-obstruction, mesenteric vasculitis, pancreatitis and liver damage on the basis of bibliographical data.

Loss-of-function variants in SAT1 cause X-linked childhood-onset systemic lupus erythematosus

ObjectivesFamilies that contain multiple siblings affected with childhood onset of systemic lupus erythematosus (SLE) likely have strong genetic predispositions. We performed whole exome sequencing (WES) to identify familial rare risk...