Male Systemic Lupus Erythematosus Research Articles

Worse cardiovascular and renal outcome in male SLE patients

Systemic lupus erythematosus (SLE) in males is rare and poorly understood. Thus, still little is known about sex differences in SLE. We set out to identify sex differences regarding clinical manifestations as well as renal and cardiovascular outcomes of SLE. We analyzed patient data from the Swiss SLE Cohort Study. Cumulative clinical manifestations according to the updated American College of Rheumatology criteria were recorded at inclusion. Cardiovascular events were recorded within Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-SDI). Renal failure was defined as eGFR < 15 ml/min/1.73 m2, initiation of renal replacement therapy or doubling of serum creatinine which were all assessed yearly or documented as end stage renal disease in SLICC-SDI. Risk differences were calculated using logistic regression and cox regression models. We analyzed 93 men and 529 women with a median follow up time of 2 years. Males were significantly older at diagnosis (44.4 versus 33.1 years, p < 0.001) and had less often arthritis (57% versus 74%, p = 0.001) and dermatological disorders (61% versus 76%, p < 0.01). In multivariate analysis female sex remained a significantly associated with arthritis and dermatological disorders. In multivariate analysis men had a significantly higher hazard ratio of 2.3 for renal failure (95% confidence interval (95%-CI) 1.1–5.2, p < 0.04). Total SLICC-SDI Score was comparable. Men had significantly more coronary artery disease (CAD) (17% versus 4%, p < 0.001) and myocardial infarction (10% versus 2%, p < 0.01). In multivariate analysis, male sex remained a significant risk factor for CAD (odds ratio (OR) 5.6, 95%-CI 2.3–13.7, p < 0.001) and myocardial infarction (OR 8.3, 95%-CI 2.1–32.6, p = 0.002). This first sex study in a western European population demonstrates significant sex differences in SLE. Male sex is a risk factor for cardiovascular events and renal failure in SLE. Potential etiological pathomechanisms such as hormonal or X-chromosomal factors remain to be further investigated.

Utility of renal resistive index measurement in juvenile systemic lupus erythematosus: a cross-sectional single-center study.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with a complex etiopathogenesis. Renal involvement is the most common and devastating complication of the disease. Renal resistive index (RRI) was suggested as a noninvasive biomarker for lupus nephritis in previous studies. This is the first study to investigate the role of RRI measurement in juvenile SLE patients. This cross-sectional study included 25 juvenile SLE patients and 25 healthy controls. Demographic and clinical features were recruited from the medical files of the patients. RRI measurements were performed with color Doppler ultrasonography from intrarenal arteries when Doppler angles were 30-60 in right and left kidneys. Of 25 (19 female, 6 male) SLE patients, nineteen (76%) patients had urinary abnormalities during follow-up, and renal biopsy was performed in 14 patients, of which 9 (64.3%) had class 2 and 5 (35.7%) had class 4 lupus nephritis. RRI was found significantly higher in SLE group than healthy controls. RRI did not differ between SLE patients, grouped according to the presence of renal involvement and class IV lupus nephritis. RRI did not correlate with serum creatinine, GFR, spot urine protein/creatinine, and albumin/creatinine ratio. Although RRI was found significantly higher in juvenile SLE, it is not affected by GFR, proteinuria level, or the renal biopsy results, even the presence of proliferative nephritis. The underlying pathogenetic mechanisms of increased RRI in SLE should be clarified in further studies. Key Points • Renal resistive index (RRI) is a parameter derived from renal Doppler ultrasound imaging and shows the intrarenal arterial resistance. • This study reveals that RRI is increased in juvenile systemic lupus erythematosus. • RRI was previously related with renal involvement, particularly class 4 lupus nephritis in adults. However, RRI was not affected by the presence or degree of renal involvement in juvenile SLE patients in our study.

Gender Disparities in Hospitalization Outcomes and Healthcare Utilization Among Patients with Systemic Lupus Erythematosus in the United States.

Background Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by various clinical manifestations. Despite efforts to improve outcomes, mortality rates remain high, and certain disparities, including gender, may influence prognosis and mortality rates in SLE. This study aims to examine the gender disparities in outcomes of SLE hospitalizations in the US. Methods We conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) database between 2016 and 2020. The NIS database is the largest publicly available all-payer database for inpatient care in the United States, representing approximately 20% of all hospitalizations nationwide. We selected every other year during the study period and included hospitalizations of adult patients (≥18 years old) with a primary or secondary diagnosis of SLEusing International Classification of Diseases, Tenth Revision (ICD-10) codes. The control population consisted of all adult hospitalizations. Multivariate logistic regression was used to estimate the strength of the association between gender and primary and secondary outcomes. The regression models were adjusted for various factors, including age, race, median household income based on patients' zip codes, Charlson comorbidity index score, insurance status, hospital location, region, bed size, and teaching status. To ensure comparability across the years, revised trend weights were applied as the healthcare cost and use project website recommends. Stata version 17 (StataCorp LLC, TX, USA) was used for the statistical analyses, and a two-sided P-value of less than 0.05 was considered statistically significant. Results Among the 42,875 SLE hospitalizations analyzed, women accounted for a significantly higher proportion (86.4%) compared to men (13.6%). The age distribution varied, with the majority of female admissions falling within the 30- to 60-year age range, while most male admissions fell within the 15- to 30-year age category. Racial composition showed a slightly higher percentage of White Americans in the male cohort compared to the female cohort. Notably, more Black females were admitted for SLE compared to Black males. Male SLE patients had a higher burden of comorbidities and were more likely to have Medicare and private insurance, while a higher percentage of women were uninsured. The mortality rate during the index hospitalization was slightly higher for men (1.3%) compared to women (1.1%), but after adjusting for various factors, there was no statistically significant gender disparity in the likelihood of mortality (adjusted odds ratio (aOR): 1.027; 95% confidence interval (CI): 0.570-1.852; P=0.929). Men had longer hospital stays and incurred higher average hospital costs compared to women (mean length of stay (LOS): seven days vs. six days; $79,751 ± $5,954 vs. $70,405 ± $1,618 respectively). Female SLE hospitalizations were associated with a higher likelihood of delirium, psychosis, and seizures while showing lower odds of hematological and renal diseases compared to men. Conclusion While women constitute the majority of SLE hospitalizations, men with SLE tend to have a higher burden of comorbidities and are more likely to have Medicare and private insurance. Additionally, men had longer hospital stays and incurred higher average hospital costs. However, there was no significant gender disparity in the likelihood of mortality after accounting for various factors.

Small Vessel Vasculitis, an Uncommon Presentation of Systemic Lupus Erythematosus: A Case Report

Introduction: Systemic lupus erythematosus (SLE) has diverse clinical manifestations. Vasculitis is one of the clinical manifestations found in SLE. Vasculitis is present in different clinical forms, with purpura lesions seeming to be uncommon. Case Presentation: We report a case of a 20-year-old male SLE patient who developed purpura on his extremities. Histologically, the lesions were suggestive of leukocytoclastic vasculitis.

SPECTRUM OF CLINICAL MANIFESTATIONS, AUTOANTIBODIES AND LEVELS OF INFLAMMATORY MARKERS IN MEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Relevance. The proportion of men among patients with systemic lupus erythematosus (SLE) is only 4-22%, but possible differences in the context of the clinical course and prognosis of the disease in this group of patients require more detailed study.&#x0D; Objective: to assess the spectrum of clinical manifestations, autoantibodies and the level of inflammatory markers in men with SLE.&#x0D; Materials and methods. 371 patients with SLE were examined, including 321 women (86.5%) and 50 men (13.5%). Clinical data, SLEDAI index and SLICC/DI damage, levels of inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) and spectrum of specific autoantibodies (antibodies to dsDNA, Sm, Ro/SSA, La/SSB, RNP, antiphospholipid antibodies) were evaluated.&#x0D; Results. Alopecia (18.0% vs 33.0%; p=0.036) and arthralgia (22.0% vs 40.0%; p=0.016) were significantly less common in men with SLE. In contrast, nephritis with nephrotic syndrome was more than three times more common in male SLE patients (14.3%) than in women (4.1%; p=0.032). There was also a difference in the frequency of serositis: men were significantly more likely to have pleurisy (36.7%) than women (21.6%; p=0.044). Nervous system involvement was less common in men (12.0% vs 29.6%; p=0.007), as well as Raynaud's syndrome (16.0% vs 29.8%; p=0.05) and Sjogren's syndrome (0% vs 8.0%, p=0.023) compared with women. However, trophic ulcers were three times more common in men with SLE (14.3% vs 3.5%; p=0.019). Involvement of the mononuclear phagocyte system, heart, lungs, constitutional symptoms, antiphospholipid syndrome, hematological manifestations did not differ significantly between the representatives of both sexes. There were also no gender differences in SLEDAI indices and SLICC damage, erythrocyte sedimentation rate, C-reactive protein, C3, C4 complement levels. Antibodies to Ro/SSA were significantly less common in male SLE patients than in women (23.1% and 58.5%, respectively, p=0.033).&#x0D; Conclusions. Men with SLE are less likely to have alopecia, arthralgia, Raynaud's syndrome, nervous system involvement and Sjogren's syndrome than women. However, males with SLE are more likely to have kidney disease with nephrotic syndrome, pleuritis and trophic ulcers. Presence of anti-Ro/SSA antibodies in men with SLE is less common than in women.

Risk factors for mortality in systemic lupus erythematosus patients: Analysis of adult and pediatric cohorts in Taiwan.

Overall survival of systemic lupus erythematosus (SLE) patients significantly increased in recent decades, however, the relative risk of mortality is still high. Long-term survival outcome of pediatric SLE remains unclear. This study aims to explore the long-term survival rate and its predictors in patients with systemic lupus erythematosus (SLE). A retrospective, hospital-based cohort study was performed between 2004 and 2018 in a tertiary referral medical center in Taiwan. Data on comorbidities, medications, and causes of admission were collected for risk factor analysis using time-dependent multivariate Cox proportional hazards models. A total of 2392 adults and 115 pediatric SLE patients were enrolled (female, n = 2157 and 95, respectively). The 10-year survival rates were 93.2%, 90.2%, 98.9%, and 100% in adult women, adult men, girls, and boys with SLE, respectively. The overall mortality rate was 2.09 case/100 patient-years (PY) for male SLE and 1.39 case/100 PY for female SLE patients. Male SLE patients did not have a statistically significantly higher mortality rate than female SLE patients in each age stratification. Infectious disease (n = 119), heart failure (n = 21), and cerebrovascular accident (n = 14) were the leading causes of death in adult SLE patients. Advanced age (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.03-1.05), treatment with mean dosage of systemic glucocorticoid equivalent to >10 mg/d of prednisolone (HR: 1.71, 95% CI: 1.14-2.57), comorbidities with malignancy (HR: 1.94, 95% CI: 1.22-3.09), chronic kidney disease (HR: 1.86, 95% CI: 1.25-2.77), hypertension (HR: 1.42, 95% CI: 1.01-1.98), and admission due to bacterial pneumonia (HR: 1.92, 95% CI: 1.12-3.31) and sepsis (HR: 2.78, 95% CI: 1.51-5.13) were independent risk factors for mortality in SLE patients. SLE patients with advanced age, malignancy, chronic kidney disease, hypertension, treated with a higher average dosage of glucocorticoids, and admission due to bacterial pneumonia and sepsis have an increased risk of mortality.

Sex differences in systemic lupus erythematosus (SLE): an inception cohort of the Chinese SLE Treatment and Research Group (CSTAR) registry XVII.

The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort. Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex. In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P < 0.001), fever (male vs. female: 18.0% vs. 14.6%, P = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P = 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P < 0.001), and treatment with cyclophosphamide (CYC) (P < 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P < 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P = 0.026), high serum creatinine (P < 0.001), higher end-stage renal failure rates (P = 0.002), musculoskeletal damage (P = 0.023), cardiovascular impairment (P = 0.009), and CYC use (P = 0.001); while leukopenia (P = 0.017), arthritis (P = 0.014), and mycophenolate usage (P = 0.013) rates were lower. Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.

Sex-based comparison of CD4+ T cell DNA methylation in lupus reveals proinflammatory epigenetic changes in men

Systemic lupus erythematosus (SLE) is more common in women than men, but the disease is more severe when it affects men. Lupus CD4+ T cells demonstrate dysregulated DNA methylation patterns. The purpose of this study was to investigate genome-wide CD4+ T cell differential DNA methylation between men (n = 12) and women (n = 10) with SLE. DNA methylation was evaluated using the Infinium MethylationEPIC array, and differences between male versus female SLE patients were calculated with probe-wise linear regressions with adjustment for age and disease activity. We identified 198 hypomethylated and 108 hypermethylated CpG sites in CD4+ T cells isolated from male compared to female SLE patients, annotated to 201 and 102 genes, respectively. A great proportion of these genes were related to apoptosis and immune functions. Among differentially methylated genes, CASP10, which is involved in the extrinsic apoptotic pathway, and multiple genes involved in T cell function and differentiation such as ELAVL1, UHRF1, and SMAD2, were hypomethylated in men compared to women with SLE. Importantly, network analysis of differentially methylated genes revealed a pattern consistent with increased activation of ROCK, PP2A, PI3K, and ERK1/ERK2 in men compared to women with SLE. These data provide epigenetic evidence suggesting activation of key T cell pathways in men compared to women with SLE and shed new light into possible mechanisms underlying increased SLE disease severity in men.

Lack of Association Between Sex Hormones, MDSCs, LDGs and pDCs in Males and Females With Systemic Lupus Erythematosus.

Plasmacytoid dendritic cells (pDCs) and low-density granulocytes (LDGs) are interferon-alpha producing cells that create a pro-inflammatory response in Systemic Lupus Erythematosus (SLE) leading to auto antibody production and organ damage. Both pDCs and LDGs have been shown to be dysfunctional in patients with active SLE. Myeloid-derived suppressor cells (MDSCs) have the capacity to control T and B cell activation and differentiation, and have recently been identified as cells of interest in SLE as well. While not fully understood, previous studies have suggested that pDCs are regulated in part by both X chromosome inactivation and estradiol. Whether sex chromosomes or sex hormones regulate MDSCs and LDGs remain to be determined. We aimed to explore the relative role of sex and sex hormones on pDC, MDSC and LDG frequency and function in SLE patients. We recruited patients with SLE as defined by ACR or SLICC classification criteria and healthy controls in conjunction with the Cleveland Clinic Lupus Cohort and Clinical Research Unit. We analyzed serum sex hormone levels by ELISA, and frequencies of pDCs, MDSCs, and LDGs among PBMCs and serum cytokine levels by flow cytometry. PBMCs were further analyzed for expression of genes involved in or induced by toll-like receptor (TLR)7 or TLR9 stimulation. In all SLE patients, the serum estradiol/testosterone ratio and levels of granulocytic MDSCs and LDGs were increased, while levels of pDCs were decreased. Furthermore, pDCs from active SLE patients expressed lower levels of TLR7 and TLR9 and showed diminished production of TLR9-induced IFNα and TNFα as compared to healthy controls. LDGs from healthy controls and SLE patients expressed very low levels of TLR7 and TLR9 and largely failed to respond to TLR9 stimulation. Thus, regardless of sex and sex-hormone levels, frequencies of pDCs, MDSCs and LDGs, TLR7 and TLR9 expression, and TLR9-driven cytokine production were similarly altered in male and female SLE patients.

Renal TLR7 expression is associated with renal injury in female mouse model of systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disorder associated with exaggerated immune activation, autoantibody production, and immune complex formation. SLE patients are predominantly women of reproductive age that often present with end organ damage, specifically in the kidneys, and hypertension. This detrimental sequelae is likely due to deposition of the immune complexes and the resulting inflammation, but the exact mechanisms are unknown. It is known however that immune complexes activate toll like receptors (TLRs) on immune cells and TLR7 particularly is known to promote the development and acceleration of the pathogenesis of SLE. Therefore, we hypothesized that renal TLR7 drives the renal injury and hypertension in female SLE mice.MethodsDouble‐stranded DNA (dsDNA) autoantibodies, a hallmark of SLE, and albuminuria, a marker of renal injury, were monitored at 30 and 35 weeks of age in female and male SLE (NZBWF1) and control (NZW) mice. Glomerular filtration rate (GFR) was measured by sinistrin clearance and renal TLR7 and tumor necrosis factor (TNF)‐α expression were measured via Western blot to assess renal function and renal inflammation at the end of 35 weeks. Mean arterial pressure was also measured in conscious mice at 35 weeks of age using indwelling arterial catheters.ResultsAt 30 weeks, female SLE mice had elevated plasma dsDNA autoantibodies compared to female controls (4.6e5 ± 1.3e5 vs 8.9e4 ± 3.3e4; n=3‐5; all p&lt;0.05), male SLE mice (6.3e4 ± 2.7e4 U/mL), and male controls (4.8e4 ± 9.3e3). At 30 weeks, 32% (7 out of 22) of female SLE mice had albuminuria versus 5% (1 out of 22) of female controls, 5% (1 out of 20) of male SLE, and no male controls. At 35 weeks, 63% (10 out of 16) of female SLE mice had albuminuria versus 5% (1 out of 22) of female controls, 5% (1 out of 19) of male SLE, and no male controls. GFR was lower in female SLE mice compared to males at this same time point (865 ± 77 vs. 1066 ±60 μL/min/100 g body weight; p=0.029). Female SLE mice expressed a significantly higher renal cortical expression of TLR7 (3.9e5 ± 8.0e4 intensity units) than both female control (7.5e4 ± 2.6e3 intensity units; p &lt; 0.001) and male SLE mice (7.0e4 ± 1.5e4 intensity units; p &lt; 0.001). Renal cortical expression of TNF‐α, a downstream effector of TLR7, was increased in female SLE mice (1.3e6 ± 3.7e5 intensity units) when compared to both female control mice (1.2e5 ± 3.4e4 intensity units; p &lt; 0.001) and male SLE mice (5.1e5 ± 1.6e5 intensity units; p &lt; 0.001). Both female and male SLE mice were hypertensive at 35 weeks: blood pressure was higher in female SLE than female controls (152 ± 5 vs. 126 ± 3 mmHg; n=6‐8; p=0.003) and in male SLE compared to male controls (152 ± 4 vs. 136 ± 4 mmHg; n=6‐11; p=0.041).ConclusionThese data indicate that increased expression of renal TLR7 and TNF‐α is associated with renal injury and hypertension in female SLE mice. In addition, these data suggest a potential sex difference in the pathogenesis of SLE in males. Therapeutic strategies targeting the TLR7 molecular pathway should be further investigated in both female and male lupus nephritis.

Systemic lupus erythematosus in a male patient in lower Assam

Systemic lupus erythematosus (SLE) is one of the numerous diseases called “the great imitators” because it frequently resembles or is misdiagnosed as other illnesses. SLE is a chronic autoimmune inflammatory disorder that affects multiple systems and has a wide range of symptoms. The female to male ratio varies between 7 and 15 to 1. A number of observations point to an estrogen impact as the cause of this variance. Because sex hormonal impacts are likely to be modest in youngsters, the female to male ratio is 3:1. Renal involvement and seizures are more common in male SLE patients than photophobia and cutaneous symptoms. Males likewise appear to have a more devastating consequence. As a result, we feel that male lupus patients are uncommon, the illness’s symptoms are life-threatening, and that early discovery of the disease will result in a better outcome for these patients. Here, we report the case of SLE with an unusual presentation in a 44-year-old man from lower Assam to emphasize the importance of a high index of suspicion in such patients.

LАТЕ ONSET OF SLE IN MALES: A MISDIAGNOSED DISEASE

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of antibodies to components of the cell nucleus in association with a diverse array of clinical manifestations. When the immune system attacks its own tissues, it causes widespread inflammation and tissue damage in affected organs. It can affect the joints, skin, brain, lungs, kidneys, and blood vessels. The primary pathological findings in patients with SLE are those of inflammation, vasculitis, immune complex deposition, and vasculopathy. Late-onset SLE represents a specific subgroup of SLE and is often initially missed leading to a significant delay in diagnosis.&nbsp; Elderly patients frequently present to hospital with nonspecific symptoms such as fatigue, recurrent fever of an unknown cause, weight loss, serositis (pleural and/or pericardial effusions), and acute kidney injury. We are describing a case of late onset SLE in a male patient that has been previously only syptomaticaly treated for the complications of the disease itself, whilst it took a longer period for physicians to think of SLE and make further investigations about it, because of the age and sex of the patient.&nbsp; Keywords: systemic lupus erythematosus, male, late onset, pleural effusion, myocadritits. &nbsp;

Identification of IFI44L as a new candidate molecular marker for systemic lupus erythematosus.

We screened the type I interferon signal pathway factor involved in the pathogenesis of systemic lupus erythematosus (SLE) by whole-genome sequencing in SLE patients and initially analyse their potential functions. Use high-throughput sequencing technology to sequence mRNAs on peripheral blood mononuclear cells from SLE patients and healthy controls,and screen out differentially expressed genes related to the type I interferon (IFN) pathway. Quantitative reverse transcription PCR (RT-qPCR) was utilised to verify the expression of the IFI44L gene in SLE patients and healthy controls, and the correlation between its expression level and clinical test indicators of SLE patients were analysed. The receiver operating characteristic (ROC) analyses were conducted to explore the value of IFI44L for SLE diagnosis. Cell counting kit-8 assay and flow cytometry were used to detect the effects of IFI44L on cell proliferation, apoptosis, and cell cycle. A total of 122 genes were significantly up-regulated and 34 genes were significantly down-regulated in the SLE group compared with the healthy control group in this research. The significantly up-regulated IFI44L in SLE patients was verified by RT-qPCR (p<0.01), furthermore, male SLE patients were significantly higher than that in female SLE patients (p<0.05). Moreover, ROC analyses proved IFI44L may have diagnostic value for SLE. Meanwhile, IFI44L expression level was significantly correlated with platelets, mean platelet volume, red blood cell distribution width to platelet ratio, complement component 3, and C-reactive protein (p<0.05). In addition, under the action of high interferon, IFI44L can resist the proapoptotic effect of IFN-α and improve the proliferation activity of cells. IFI44L may play an important role in SLE pathology through abnormal regulation of the type I interferon signalling pathway.

The impact of sex on susceptibility to systemic lupus erythematosus and rheumatoid arthritis; a bioinformatics point of view

The unknown etiology of systemic autoimmune diseases, such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA), with a remarkable predominance of female, have prompted many researchers for unveiling the precise molecular mechanisms involved in this gender bias. In fact, depending on hormones and transcribed genes from sex chromosomes, at least, the initial mechanisms involved in pathogenesis might differ largely. With the aim of elucidating the above mechanisms, we have tried to specify the differentially expressed genes (DEGs) extracted from microarray libraries from both female and male SLE and RA patients. Subsequently, the androgen and estrogen receptor elements (ARE and ERE) among differentially expressed transcription factors (TFs) and the DEGs located on X or Y chromosomes have been determined. Moreover, the pathways regarding the common DEGs in both sexes are enriched. Our data revealed several ARE and ERE-containing genes (LCN2, LTF, RPL31, RPL9, RPS17, RPS24, RPS27L, S100A8, ABCA1, HIST1H2BD, ISG15, MAFB, GNLY, EVL, and HDC) to be associated with the related autoimmune disease and sex. Also, two DEGs (KDM5D and RPS4Y1) in SLE patients were determined to be on Y chromosome with one had been proved to be associated with autoantigens in SLE. Altogether, our data showed a number of plausible pathways in both autoimmune conditions together with the relevance of several sex-related genes in the mentioned diseases pathogenesis.

MO314ANA POSITIVITY IN IGA NEPHROPATHY: IS SYSTEMIC LUPUS ERYTHEMATOSUS COMING UP?

Abstract Background and Aim. IgA nephropathy (IgAN) is the most common chronic primary glomerulonephritis leading to progressive renal failure in 1/3 of patients. Although it is a limited non-systemic renal disease, many systemic diseases, such as Systemic Lupus Erythematosus (SLE), are sporadically associated with mesangial IgA deposits. We investigate frequency and meaning of ANA positivity in IgAN. Methods. All biopsy-proven IgAN patients followed in our Unit with ANA positivity were selected. Data are compared by non parametric test (Wilcoxon signed-rank test). Results. 15/68 (22%) IgAN patients resulted ANA+ during a 9-year median follow-up. 10 were females and five were male. Mean age was low. Renal function was normal in 9/15. 24 h Proteinuria was non nephrotic in 15/16. In 10 patients there was low C3. Patient characteristics are summarized in Table 1. At follow-up, renal function did not change significantly (p=NS), however mean 24h-Uprot reduced (p=0.075) Table 2. One male developed SLE, one female a lupus-like Mixed Connective Tissue Disease. Conclusions. Our data suggest that 1) in 22% of IgAN patients ANA positivity could be detected; 2) ANA+ IgAN patients are mostly women with normal renal function and non nephrotic proteinuria; 3) after a median 9-year follow-up, ANA+ IgAN patients, on therapy, presented a stable renal function and a reduced proteinuria; 4) ANA+ IgAN patients could develop SLE. More clinical observations and studies are needed for supporting the hypothesis that IgAN+ANA positivity could be part of a new clinical entity of SLE patients.

METABOLIC AND STRUCTURAL MUSCULAR CHANGES DRIVEN BY CHRONIC DISEASE-LIKE IFN-G EXPOSURE

Abstract Cardiovascular myopathies and fatigue have been associated with chronic inflammatory responses and activated cell-mediated immunity. We report aberrant cardiovascular activity in the form of reduced ejection fraction in vivo in male mice with persistent low-level expression of IFN-g (ARE mice). ARE mice have a replacement with random nucleotides in the 3 prime UTR of the IFN-g gene that serves to remove a regulatory element (AU Rich) that is integral at controlling the stability of IFN-g mRNA. ARE mice had increased cellular and mineral, infiltrates into heart tissue and mitochondria linked metabolic changes that were concomitantly observed following a stress-exacerbated decrease in heart function, with or without exposure to IFN-a. Our data also demonstrates an increase in glucose expenditure and increased general fatigue of ARE mice as well as structural and ultrastructural changes in the heart in male mice. We also observe a decrease in the transcripts and a reversible decrease in function of aerobic respiratory components in the muscle of male mice exposed to IFN-g. Notably, we observe a decrease in X chromosome linked pyruvate dehydrogenase, a key component in pyruvate facilitated entry to the TCA cycle, and other downstream mitochondrial genes. Furthermore, the in vivo data revealed an increase in factors associated with fatigue, such as lactic acid production and changes in expression of genes associated with an increase inanaerobic respiration in cardiac musculature. These results indicate that the chronic expression of IFN-g results in a model for male biased heart failure understress in an autoimmune environment, like the idiopathic cardiomyopathy found in male Systemic Lupus Erythematosus patients.

The Analysis of Clinical Features of Systemic Lupus Erythematosus (SLE) in Children

Objective: Observe the clinical characteristics of children with SLE, namely, to observe the symptoms and laboratory examinations, such as blood routine, blood lipid, immunoglobulin, complement, autoantibodies, serum 25 (OH) D and other indicators, and to explore the clinical characteristics, the difference and the significance of vitamin D supplements between male and female SLE patients in children respectively. Methods: We enrolled 64 cases of SLE patients in children who were admitted into the department of pediatrics and rheumatology of the third affiliated hospital of sun yat-sen university in guangzhou from May 1, 2011 to February 1, 2019, They were analyzed retrospectively, adopting ?² test for statistical analysis. Results: 64 cases of SLE in children, which included 10 cases of male and 54 cases of female. Clinical manifestations: facial skin rash in 48 patients (75%), fever in 38 cases (59.4%), arthritis in 28 cases (43.8%), oral ulcer in 18 cases (28.1%), serositis in13 cases (20.3%), and the sun allergy in 9 cases (14.1%), the damage of central nervous system in 7 cases (10.9%) . Laboratory examination: 30 cases of leukopenia (46.9%), anemia in 30 cases (46.9%), thrombocytopenia in 12 cases (18.8%), hematuria in 18 cases (28.1%), proteinuria in 33 cases (51.2%), 6 patients with renal impairment (9.4%), antinuclear antibody positive in 63 cases (98.4%), anti-double-stranded DNA (dsDNA) antibody positive in 48 cases (75%), anti SSA antibody positive in 44 cases (68.7%), SSB antibody positive in 33 cases (51.6%), Sm antibody positive in 40 cases (62.5%), nucleosome antibody positive in 28 cases (43.8%) .Among these children, male SLE patients were higher than female children with SLE in the damage of kidney, Sm antibodies and resisting nucleosome antibody positive rates (?²= 4.451, 8.336, 6.803, P&lt;0.05), the female children with SLE was higher than male SLE Children in the anti-SSB antibody positive rate (?²=4.945, P &lt; 0.05). In 64 cases of SLE children, which included 52 cases were lower than the normal level of serum 25 (OH) D measurements, 12 cases were in the normal lower limit of serum 25 (OH) D measurements, at the same time, the female SLE. Patients was higher than male children with SLE in the reduce rate of serum 25 (OH) D (?²= 8.351, P &lt; 0.05). Conclusion: Male SLE patients which appeared damage of kidney easier than female patients , the proteinuria was the most common in the damage of kidney. Resistance to Sm antibodies which was the risk factor of renal injury with higher incidence in male children with SLE; Anti nucleosome antibody which was the risk factor for the disease activity in male children with SLE were higher than female children with SLE. It was estimated that the risk of Sjogren's syndrome appeared in female with SLE were higher than that in male SLE children. In this retrospective study, the serum 25 (OH) D levels were significantly lower in children with SLE, and vitamin D supplementation was required.

Contributions of the lupus register of the Spanish Society of Rheumatology (RELESSER) to the knowledge of systemic lupus erythematosus in Spain

The lupus register of the Spanish Society of Rheumatology (RELESSER) is a multicentre register of patients with systemic lupus erythematosus (SLE) under follow-up by Spanish Rheumatology Services. It contains data on a total of 4024 patients with SLE. So far, 14 studies have been published from the transversal phase of RELESSER. Here we report the more relevant contributions of those studies, according to the authors’ perspective, concerning cumulative clinical characteristics, level of activity, treatments, refractory disease, damage and mortality. We also review the main results of the analysis regarding incomplete SLE, lupus nephritis, respiratory manifestations, cardiovascular disease, serious infection, malignancies, fibromyalgia, SLE in males, SLE in Hispanics and juvenile-onset SLE, comparing the main characteristics of each subgroup to the global cohort. RELESSER has become one of the most important clinical SLE registers around the world, with a high yield in terms of knowledge generation about the disease in Spain, also useful for the entire scientific community.

Korelasi antara kadar serum trigliserida dan nilai carotid intima media thickness pada pasien dengan lupus eritematosus sistemik

Background: Early atherosclerosis and its complications are currently the main problems causing morbidity and mortality in systemic lupus erythematosus (SLE). Early detection and diagnosis of atherosclerosis is performed using ultrasound (USG) B-mode by measuring the mean carotid intima media thickness (CIMT). One of the risk factors of atherogenesis that are still controversy and have not been studied are triglycerides.&#x0D; Objective: This study aimed to determine the correlation between serum triglyceride levels and CIMT mean values in patients with SLE at Sanglah Hospital.&#x0D; Method: Design of the study was an analytic cross sectional study. The inclusion criteria in this study were 12-year-old or better male and female SLE patients, willing to participate in the study by signing informed consent. The exclusion criteria in this study were patients with other autoimmune diseases, diabetes, obesity, end-stage chronic kidney disease, hypertension, malignancy, smokers. Serum triglyceride levels were tested from blood samples and CIMT mean values were measured with B-mode ultrasound.&#x0D; Results: From 54 samples, data characteristics were all females, median of age 31.5 (15-57) years, disease duration 44.5 ± 5.408 months, body mass index 20.48 ± 0.541 kg / m2, serum triglyceride 168.46 ± 17.49 mg / dL and mean CIMT 0,475 (0.28-0.84) mm. Those data were analyzed with Spearman correlation, between serum triglyceride level and mean value of CIMT were r= 0,391 and p= 0,003.&#x0D; Conclusion: Conclusion of this study was that there was a moderate mean correlation between serum triglyceride levels and CIMT mean values ??in patients with SLE in Sanglah Hospital.

Fibrosis, Thrombosis, and Dacrocytosis: An Unusual Case of Male Systemic Lupus Erythematosus

Fibrosis, Thrombosis, and Dacrocytosis: An Unusual Case of Male Systemic Lupus Erythematosus