Onset Of Systemic Lupus Erythematosus Research Articles

New-onset acute psychosis as a manifestation of lupus cerebritis following concomitant COVID-19 infection and vaccination: a rare case report

BackgroundRare cases of COVID-19 infection- and vaccine-triggered autoimmune diseases have been separately reported in the literature. In this paper, we report the first and unique case of new onset acute psychosis as a manifestation of lupus cerebritis following concomitant COVID-19 infection and vaccination in a previously healthy 26-year-old Tunisian female.Case presentationA 26-years old female with a family history of a mother diagnosed with schizophrenia, and no personal medical or psychiatric history, was diagnosed with mild COVID-19 infection four days after receiving the second dose of Pfizer-BioNTech COVID-19 vaccine. One month after receiving the vaccine, she presented to the psychiatric emergency department with acute psychomotor agitation, incoherent speech and total insomnia evolving for five days. She was firstly diagnosed with a brief psychotic disorder according to the DSM-5, and was prescribed risperidone (2 mg/day). On the seventh day of admission, she reported the onset of severe asthenia with dysphagia. Physical examination found fever, tachycardia, and multiple mouth ulcers. Neurological evaluation revealed a dysarthria with left hemiparesis. On laboratory tests, she had severe acute kidney failure, proteinuria, high CRP values, and pancytopenia. Immune tests identified the presence of antinuclear antibodies. Brain magnetic resonance imaging (MRI) revealed hyperintense signals in the left fronto-parietal lobes and the cerebellum. The patient was diagnosed with systemic lupus erythematosus (SLE) and put on anti-SLE drugs and antipsychotics, with a favorable evolution.ConclusionsThe chronological relationship between COVID-19 infection, vaccination and the first lupus cerebritis manifestations is highly suggestive, albeit with no certainty, of the potential causal link. We suggest that precautionary measures should be taken to decrease the risk of SLE onset or exacerbation after COVID-19 vaccination, including a systematic COVID-19 testing before vaccination in individuals with specific predisposition.

Higher Genetic Risk Loads Confer More Diverse Manifestations and Higher Risk of Lupus Nephritis in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using clinical and serological manifestations in SLE patients. We genotyped a total of 1,655 Korean patients with SLE (n=1,243 as a discovery set and n=412 as a replication set) using a customized genome-wide single-nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well-validated non-HLA SNPs and HLA haplotypes of SLE-risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration. Childhood-onset SLE (<16 years) conferred the highest genetic risk compared with adult-onset (16-50 years) or late-onset (>50 years) SLE (P = 6.8 × 10-6 ). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (β=0.143, P = 1.8 × 10-6 ). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio [HR] 1.74, P = 2.2 × 10-8 ) and anti-Sm antibody production (HR 1.85, P = 2.8 × 10-5 ). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10-5 ) and class V (HR 2.79, P = 1.0 × 10-3 ), but especially lupus nephritis class V in anti-Sm-positive SLE (area under the curve 0.68, P = 1.8 × 10-4 ). Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti-Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients.

Avascular necrosis in systemic lupus erythematosus patients: Analysis of the demographics, clinical manifestations, management and outcomes

Avascular necrosis (AVN) is a rare complication of systemic lupus erythematosus (SLE) that may develop from the disease or its treatment. To present the clinical characteristics, management and outcomes of SLE patients with AVN. The SLE patients with AVN on X-ray or magnetic resonance imaging (MRI) following up at Fatima Memorial Hospital College of Medicine and Dentistry Shadman, Lahore, Pakistan were studied. Detailed medical history, clinical examination, laboratory investigations, treatment details and outcomes were recorded. Out of 230 SLE patients, 20 (8.6%) had AVN; 80% females, F:M 4:1 with a mean age at onset of SLE 19.8 ± 6.5 years, and mean duration till occurrence of AVN 3.9 ± 2.3 years. AVN developed within 4 years of onset in 80% of patients. Mucocutaneous symptoms were the most common presentation (95%) and 65% had positive antiphospholipid antibodies. Until AVN development, all patients received a mean of 3.5 ± 0.7 g pulse steroid and a mean cumulative oral steroid dose of 18.6 ± 6.2 g. AVN was in the hip joint in 95% of cases, 80% were bilateral. AVN was grade II in 45% patients, grade III in 25% (n = 5), I in 20% (n = 4) and grade IV in 10% (n = 2). Grade I and II had preserved joint function and didn't need any surgery compared to stage III and IV. In SLE patients, AVN is a relatively early complication occurring within 4 years of illness in patients with a young age at onset, and have a better outcome when detected at earlier stages.

Risk factors for avascular necrosis in patients with systemic lupus erythematosus: a multi-center cohort study of Chinese SLE Treatment and Research Group (CSTAR) Registry XXII

BackgroundAvascular necrosis is a common organ damage in SLE patients, which can influence patients’ life quality. Conflicting results exist in risk factors of AVN in SLE patients. The aim of this study was to illustrate risk factors predicting the occurrence of avascular necrosis (AVN), also known as osteonecrosis, in systemic lupus erythematosus (SLE) patients in Chinese SLE Treatment and Research Group (CSTAR), a multi-center cohort of Chinese SLE patients.MethodsSLE patients in CSTAR without existing AVN at registration were included. At least two follow-ups and an observation period of no less than 2 years for AVN event were required. Univariate and multivariate Cox regression analyses were used to evaluate risk factors for AVN in SLE patients. Coefficient B was transformed to risk score for the development of a risk stratification model.ResultsOne hundred six (2.59%) of 4091 SLE patients were diagnosed AVN during follow-ups of no less than 2 years. Multi-variate Cox regression analysis suggested that SLE onset age ≤ 30 (HR 1.616, p 0.023), arthritis (HR 1.642, p 0.018), existing organ damage (SDI ≥ 1) at registration (HR 2.610, p < 0.001), positive anti-RNP (HR 1.709, p 0.006), and high glucocorticoid maximum daily dose at registration (HR 1.747, p 0.02) were independent risk factors. A risk stratification system was developed according to the risk factors, and patients were divided into high risk (3–6) and low risk (0–2). The AUC of 0.692 indicated moderate discrimination. The calibration curve in internal validation was drawn.ConclusionPatients with SLE onset age ≤ 30, arthritis, existing organ damage (SDI ≥ 1) at registration, positive anti-RNP, and high glucocorticoid maximum daily dose at registration are at high risk for AVN and require attention.

The dynamic relationship of gut microbiota with sex hormones in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease. The sex hormones estrogen and testosterone may have an influence on the production of antibodies. In addition, the gut microbiota also shows an effect on the onset and progression of SLE. Hence, the molecular interplay between sex hormones in terms of gender difference, gut microbiota and SLE is being clarified day after day. The aim of this review is to investigate the dynamic relationship of the gut microbiota with sex hormones in systemic lupus erythematosus taking into account the bacterial strains shown to be affected, effects of antibiotics and other factors that affect the gut microbiome, which itself strongly affects the pathogenesis of SLE.

Risk factors for the femoral head aseptic necrosis development in patients with systemic lupus erythematosus

Objective: to identify risk factors for the development of the femoral head aseptic necrosis (FHAN) and osteoarthritis (OA) of the hip joint (HJ) in patients with systemic lupus erythematosus (SLE) according to a retrospective analysis.Material and methods.The retrospective study included data from the case histories of 103 patients with SLE who underwent total hip arthroplasty (HA) (unilateral in 82 patients, bilateral in 21). The total follow-up period ranged from 2 years to 21 years. Among the patients included in thestudy, the majority were women (86.4%), the ratio of women and men was 7:1. At the time of surgery, the average age of women was 36.3±13.25 years, men – 36.2±9.57 years, duration of the disease – 168.0±132.5 months. SLE activity was assessed using the SLEDAI-2K scale. All patients were taking glucocorticoids (GC). The average duration of GC treatment was 89.0±87.2 months. 71.8% of patients received immunosuppressive therapy: hydroxychloroquine – 55.3%, azathioprine – 10.7%, methotrexate – 5.8%. The functional status of hip joint was determined using the Harris scale; by the time of surgery, the average score was 45.6±13.1 points. Pain intensity was assessed using a visual analogue scale and reached an average of 70.1±16.0 mm.Results and discussion. In 58.5% of patients with SLE, the indication for HA was FHAN (Group 1) and in 41.6% – OA of HJ (Group 2). At the time of HA, the duration of the disease was longer and the age was higher in group 2 than in group 1 (p&lt;0.05). An analysis of individual clinical manifestations of SLE that preceded the development of HJ pathology revealed that arthritis and the presence of an antinuclear factor, ANF, were associated with the development of FHAN (p=0.022 and p=0.04, respectively). At the onset of the disease, patients of the 1st group, compared with patients of the 2nd group, more often had lesions of the skin, kidneys and serositis (22.9 and 20.5%; 14.5 and 11.7%; 68.7 and 64.7 %, respectively), but they were less likely to have mucous membranes and the central nervous system (CNS) involvement (14.5 and 23.5%; 10.4 and 17.6%, respectively). However, these differences did not reach statistical significance. Almost all of these disease manifestations, with the exception of the mucous membranes and the CNS lesions, were more often observed in patients with the development of FHAN, which indicates a higher activity of the disease at the onset of SLE. At the time of HA, we did not find any relationship between SLE activity and FHAN formation and hip OA. Patients of the 1st and 2nd groups in the same number of cases had mild (56.2 and 58.8%, respectively) and moderate (35.4 and 32.4%, respectively) activity according to SLEDAI-2K. No activity (SLEDAI-2K – 0 points) was also observed in patients of both groups with the same frequency (8.3 and 8.8% of cases, respectively). Associations of cumulative and daily doses of GC with the development of FHAN and OA of HJ were not revealed. In the 1st group, the average daily dose of GC was slightly higher, and the cumulative dose was less than in the 2nd group (8.59±4.75 and 7.79±5.39 mg; 20.0±11.9 and 23.8±19.2 g, respectively), but these differences were not significant (p&gt;0.05).Conclusion. In SLE patients, the incidence of FHAN and HJ OA was comparable. At the time of HA, SLE patients with HJ OA were older and had a longer duration of the disease than patients with FHAN. The risk factors for FHAN were arthritis and ANF positivity at the onset of SLE.

Elevated Antibody Titers to Epstein-Barr Virus and Cytomegalovirus in Patients with Drug-Induced Lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease, which has been associated with Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection. Drug-induced lupus (DIL) is a lupus-like disease caused by the intake of therapeutic drugs, which has been estimated to cause approximately 10-15% of lupus-like cases. Although SLE and DIL share common clinical symptoms, there are some fundamental differences between DIL and SLE onset. Moreover, it remains to be examined whether environmental factors, such as EBV and CMV infections, may contribute to the development of DIL. This study focused on examining the possible association between DIL and EBV and CMV infections, by examining IgG titers to EBV and CMV antigens in serum samples by enzyme-linked immunosorbent assays. Antibody titers to EBV early antigen-diffuse and CMV pp52 were found to be significantly elevated in both SLE and DIL patients compared to healthy controls, although no correlation was found for antibodies to the two virus antigens in the respective disease groups. Moreover, total IgG titers were reduced in SLE and DIL serum samples, which may reflect a general lymphocytopenia, which commonly is associated with SLE. The current findings support that EBV and CMV infections may contribute to the development of DIL and that onset of both diseases are related.

Significance of the weighted complement domain of the EULAR/ACR classification criteria in juvenile onset systemic lupus erythematosus.

We aimed to compare the clinical and laboratory characteristics of patients with SLE according to the weighted complement status of the EULAR/ACR criteria and investigate whether different weighting of the complement status at disease onset is associated with outcomes. Patients diagnosed with juvenile onset SLE who fulfilled the 2019 EULAR/ACR classification criteria were retrospectively analyzed. Among 43 patients included, hypocomplementemia was observed in 37 (86%), mostly with a low level of both complement C3 (C3) and complement C4 (C4) (53.5%). In patients with low levels of both C3 and C4, more common cutaneous (65.2% vs 28.6%, p: 0.045), musculoskeletal involvement (78.3% vs 42.9%, p: 0.039), autoimmune hemolytic anemia (52.2% vs 14.3%, p: 0.035), positive anti-dsDNA (65.2% vs 21.4%, p: 0.017) and anti-Sm antibodies (60.9% vs 21.4%, p: 0.04) were observed. In addition these patients had higher scores from the 2019 EULAR/ACR classification criteria (26 vs 15.5, p: < 0.0001). Remission and flare rates, and SLE associated damage were not differed according to the complement status in patients with hypocomplementemia. Observation of more frequent clinical and serological activity with higher total scores from the EULAR/ACR classification criteria supported the higher scoring of patients with low C3 and C4 in the weighted criteria. However, since significant number of patients did not exhibit low complement C4, and the frequency of kidney involvement did not differ according to the weighted complement status, complement C3 might be suggested as a more important diagnostic tool in patients with juvenile onset SLE. Also, weighted complement status at onset did not seem to affect the disease outcomes.

Systemic lupus erythematosus with diffuse alveolar hemorrhage.

Systemic lupus erythematosus with diffuse alveolar hemorrhage.

Severe and life-threatening onset of systemic lupus erythematosus

Severe and life-threatening onset of systemic lupus erythematosus

Vitamin D Status and SLE Disease Activity among Dubai Hospital Lupus Patients

Background: Vitamin D deficiency is common worldwide, but is particularly prevalent in the Middle Eastern region, where cultural and religious factors influence its incidence further. As patients with Systemic Lupus Erythematosus (SLE) avoid sun exposure and use medications that could potentially result in vitamin D deficiency, this problem becomes more apparent. Unfortunately, there are no data available on the prevalence of vitamin D deficiency among patients with SLE in our local area. Objective: To assess the prevalence of vitamin D deficiency among patients with a new onset of systemic lupus erythematosus in Dubai, and to determine whether low vitamin D levels are correlated with disease activity. Methodology and Data Collection: a retrospective cohort study of patients with new onset of Systemic Lupus Erythematosus, being diagnosed in less than 1 year and were followed up at Dubai Hospital (UAE) from January 2009 till December 2012. Demographic and clinical data were collected as well as 25(OH) D3 levels. The incidence of vitamin D insufficiency was calculated as a ratio between the numbers of patients with 25(OH) D levels below the specified cut-off values (30ng/ml and 10ng/ml, respectively). SLE was diagnosed according to the American college of rheumatology (ACR SLE) classification criteria of 1997. Patients with drug-induced SLE and vitamin D deficiency were excluded. Results: a total number of 150 patients were included. 87% (n=131) were females and 13% (n=19) were males. The mean vitamin D level at the baseline was 21.6+/- 47 (mean +/- SD), increased to 27.8+/- 16 at 1 year, while the SLEDAI has improved from 8.3+/-5 (mean +/- SD) to 2.4 +/- 2.9 at 1 year respectively. The changes in vitamin D level as well as the SLEDAI were statistically significant with a P value &lt;0.001. Spearman correlation test showed a statistically significant inverse correlation between vitamin D level versus SLEDAI % from baseline to 1-year later. Conclusion: This study showed a direct inverse relationship between lupus activity and a low level of vitamin D. Furthermore, the SLE disease activity score got better with the improvement in vitamin D level, measured at baseline, and after 12 months period.

Mendelian randomization analysis suggests no associations of herpes simplex virus infections with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) characterized by immune dysfunction is possibly more vulnerable to herpes simplex virus (HSV) infection. The infection has been intensively considered a common onset and exacerbation of SLE. This study is aimed at elucidating the causal association between SLE and HSV. A bidirectional two-sample Mendelian Randomization (TSMR) analysis was systematically conducted to explore the causal effect of SLE and HSV on each other. The causality was estimated by inverse variance weighted (IVW), MR-Egger and weighted median methods based on the summary-level genome-wide association studies (GWAS) data from a publicly available database. Genetically proxied HSV infection exhibited no causal association with SLE in the forward MR analysis using IVW method (odds ratio [OR] = 0.987; 95% confidence interval [CI]: 0.891-1.093; p = 0.798), nor did HSV-1 IgG (OR = 1.241; 95% CI: 0.874-1.762; p = 0.227) and HSV-2 IgG (OR = 0.934; 95% CI: 0.821-1.062; p = 0.297). Similar null results with HSV infection (OR = 1.021; 95% CI: 0.986-1.057; p = 0.245), HSV-1 IgG (OR = 1.003; 95% CI: 0.982-1.024; p = 0.788) and HSV-2 IgG (OR = 1.034; 95% CI: 0.991-1.080; p = 0.121) were observed in the reverse MR where SLE served as the exposure. Our study demonstrated no causal association between the genetically predicted HSV and SLE.

Association of Ultraviolet B Radiation and Risk of Systemic Lupus Erythematosus Among Women in the Nurses' Health Studies.

Ultraviolet (UV) radiation exposure is associated with photosensitivity, rashes, and flares in systemic lupus erythematosus (SLE). However, it is not known whether UV exposure increases risk of developing SLE. We examined UV exposure and SLE risk in a large prospective cohort. The Nurses' Health Study (NHS) enrolled 121,700 US female nurses in 1976; in 1989, 116,429 nurses were enrolled in NHS II. Biennial questionnaires collected lifestyle and medical data. Self-reported incident SLE by American College of Rheumatology classification criteria was confirmed by medical record review. Ambient UV exposure was estimated by linking geocoded residential addresses with a spatiotemporal UV exposure model. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) across tertiles of time-varying cumulative average UV. We examined SLE risk overall and stratified by anti-Ro/La antibodies and by cutaneous manifestations from 1976 through 2014 (NHS)/2015 (NHS II), adjusting for confounders. With 6,054,665 person-years of exposure, we identified 297 incident SLE cases; the mean ± SD age at diagnosis was 49.8 ± 10.6 years. At diagnosis, 16.8% of women had +anti-Ro/La, and 80% had either +anti-Ro/La or ≥1 cutaneous manifestation. Compared with the lowest UV exposure tertile, risk of overall SLE was increased, but not significantly (HR 1.28 [95%CI 0.96-1.70]). Women in the highest tertile had increased risk of malar rash (HR 1.62 [95% CI 1.04-2.52]). Cumulative UV exposure was not associated with SLE risk. Higher UV exposure, however, was associated with increased risk of malar rash at presentation. UV exposure may trigger SLE onset with malar rash among susceptible women.

Association of Antiphospholipid Antibodies with Clinical Manifestations in Children with Systemic Lupus Erythematosus.

The aim of the study is to evaluate the effect of the presence of antiphospholipid antibodies on the clinical and laboratory manifestations, disease activity and outcomes of the disease in patients with childhood-onset systemic lupus erythematosus (cSLE). We conducted a 10-year cross-sectional study with a retrospective analysis of clinical and laboratory parameters and outcome of the disease (kidney, nervous system involvement, thrombosis). For the purpose of the study, patients were divided into cohort groups based on the presence of antiphospholipid antibodies (aPLA), named the aPLA positive group, or their absence, named the aPLA negative group. Values of aPLA were defined in reference laboratories. The disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, whereas tissue damage degree was measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage Index (SLICC/ACR DI; SDI; DI). Research in our center showed that patients with cSLE often had hematological, cutaneous, and non-thrombotic neurological manifestations. Antiphospholipid antibodies may be present transiently or permanently. A significant change in the titer value was observed in the IgG isotype of aCLA. The presence of higher values of IgM β2GP1 at the beginning indicates that higher disease activity can be expected. Higher disease activity correlates with greater tissue damage. Additionally, it has been shown that aPLA positive patients have two and a half times higher risk of tissue damage than aPLA negative ones. Our study shows that the presence of antiphospholipid antibodies in patients with childhood onset systemic lupus erythematosus may indicate a higher risk of tissue damage, but since it is a rare disease in childhood, prospective and multicenter studies are necessary to assess the importance of the presence of these antibodies.

Pristane cadmium chloride nanoemulsion accelerates the onset of systemic lupus erythematosus in a C57BL/6 mouse model.

To accelerate the onset of systemic lupus erythematosus in C57BL/6 mice by injecting cadmium chloride nanoemulsion and shorten the traditional modeling time. Pristane cadmium chloride nanoemulsion was prepared, and 66 C57BL/6 mice were randomly divided into four groups. The pristane group was intraperitoneally injected with 0.6mL of pristane blank nanoemulsion, the model group was injected with 0.6mL of pristane cadmium chloride nanoemulsion, the Cadmium chloride control group was injected with 0.6mL of cadmium chloride nanoemulsion, and the control group was injected with the same amount of 0.9% sodium chloride solution. Urine protein content, anti-dsDNA antibody content, Th1 cell/Th2 cell ratio, and kidney staining were detected in each group. The model group began to develop disease in the 4th week, the anti-dsDNA antibody level reached 566.71 ± 1.44ng/L, and the proteinuria reached 245.38 ± 30.54ng/mL. The model group showed an onset at least 5 weeks earlier than that in the pristane group. There was no significant difference in anti-dsDNA antibody content between Cadmium chloride control group and blank group. At the 12th week, the Th1/Th2 cell ratio in the model group significantly decreased, and the pathological changes in the kidneys were consistent with the typical manifestations of lupus in mouse models. These results suggest that cadmium chloride promotes earlier onset of pristane-induced systemic lupus erythematosus in a C57BL/6 mouse model.

Methyl Donor Micronutrients: A Potential Dietary Epigenetic Target in Systemic Lupus Erythematosus Patients.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by an aberrant immune response and persistent inflammation. Its pathogenesis remains unknown; however, a complex interaction between environmental, genetic, and epigenetic factors has been suggested to cause disease onset. Several studies have demonstrated that epigenetic alterations, such as DNA hypomethylation, miRNA overexpression, and altered histone acetylation, may contribute to SLE onset and the disease's clinical manifestations. Epigenetic changes, especially methylation patterns, are modifiable and susceptible to environmental factors such as diet. It is well known that methyl donor nutrients, such as folate, methionine, choline, and some B vitamins, play a relevant role in DNA methylation by participating as methyl donors or coenzymes in one-carbon metabolism. Based on this knowledge, this critical literature review aimed to integrate the evidence in animal models and humans regarding the role of nutrients in epigenetic homeostasis and their impact on immune system regulation to suggest a potential epigenetic diet that could serve as adjuvant therapy in SLE.

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