Systemic Lupus Erythematosus Flare Research Articles

Recurrent Mycobacterium tuberculosis infection in systemic lupus erythematosus patient: case report and review

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterised by an underlying immunodeficiency state, worsened by the use of immunosuppressive drugs in its treatment. Hence patients with SLE are at increased risk of opportunistic infections, one of which is tuberculosis. Tuberculosis (TB) is one of the most common infectious diseases globally, with Indonesia having the second highest prevalence in the world. Further research towards better management of these two disease entities is thus required. We report a patient with SLE flare and recurrent tuberculosis infection.

Bacteremia in Systemic Lupus Erythematosus in Patients from a Spanish Registry: Risk Factors, Clinical and Microbiological Characteristics, and Outcomes.

To describe the incidence of bacteremia in a large multicentric cohort of patients with systemic lupus erythematosus (SLE) and their clinical characteristics and to identify risk factors. All bacteremic episodes from the Spanish RELESSER registry were included. Clinical and laboratory characteristics concerning bacteremia and SLE status, as well as comorbidities at the time of infection, were retrospectively collected. A comparison with sex- and age-matched SLE controls without bacteremia was made. A logistic regression was conducted. The study included 114 episodes of bacteremia in 83 patients. The incidence rate was 2.7/1000 patient-years. At the time of bacteremia, the median age was 40.5 (range: 8-90) years, and 88.6% of patients were female. The Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index was 4 [interquartile range (IQR) 8]; 41% had an SLE flare (66% severe); Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was 3 (IQR 4). A comorbidity was recorded in 64% of cases. At the time of bacteremia, 88.6% received corticosteroids (68.6% > 10 mg/day) and 57% immunosuppressors. Gram-negative bacilli, most frequently Escherichia coli (29.8%), caused 52.6% of the episodes. The bacteremia-related mortality was 14% and bacteremia was recurrent in 27.2% of cases. A dose-response relationship was found between corticosteroids and bacteremia risk. In the multivariate analysis, these factors were associated with bacteremia: elevated creatinine (OR 1.31, 95% CI 1.01-1.70; p = 0.045), diabetes (OR 6.01, 95% CI 2.26-15.95; p < 0.001), cancer (OR 5.32, 95% CI 2.23-12.70; p < 0.001), immunosuppressors (OR 6.35, 95% CI 3.42-11.77; p < 0.001), and damage (OR 1.65, 95% CI 1.31-2.09; p < 0.001). Bacteremia occurred mostly in patients with active SLE and was frequently associated with severe flares and corticosteroid use. Recurrence and mortality were high. Immunosuppressors, comorbidities, and disease-related damage were associated with bacteremia.

Safety and tolerability of sifalimumab, an anti-interferon-α monoclonal antibody, in Japanese patients with systemic lupus erythematosus: A multicenter, phase 2, open-label study

Objectives: To evaluate the safety of sifalimumab in Japanese patients with systemic lupus erythematosus (SLE).Methods: This phase 2, open-label study consisted of a 52-week initial stage (Stage I) and a long-term extension (Stage II). In Stage I, sequential cohorts of patients received ascending doses of sifalimumab (intravenous [IV] 1.0, 3.0, and 10.0 mg/kg or subcutaneous 100 mg every 2 weeks; IV 600 and 1200 mg every 6 weeks). In Stage II, patients enrolled before June 2012 received the same dose of sifalimumab as during Stage I for up to 157 weeks or sifalimumab 600 mg IV every 4 weeks if they enrolled later. The safety of sifalimumab was assessed by adverse events (AEs).Results: Thirty patients enrolled in Stage I and 21 patients entered Stage II. The majority of patients experienced AEs (96.7% in Stage I and 100% in Stage II); most were mild or moderate in severity. Serious AEs occurred in 30.0% and 57.1% of patients in Stage I and II, respectively; most were instances of SLE flares. The proportion of patients in Stage I and II who had AEs leading to discontinuation was 10.0% and 28.6%, respectively.Conclusion: Sifalimumab was well tolerated in Japanese patients with SLE.Trial registration: ClinicalTrials.gov identifier: NCT01031836.

Manifestation and management of pregnancy with systemic lupus erythematosus and/or preeclampsia

Systemic lupus erythematosus (SLE) is a rheumatic illness that often affects pregnancy outcome of young women of reproductive age. Preeclampsia is a common gestational complication. SLE flare during pregnancy and preeclampsia share common clinical features, such as hypertension, proteinuria, and thrombocytopenia, making differentiation between these two conditions difficultly. The signs and symptoms of new-onset SLE during pregnancy or postpartum may mimic those of preeclampsia, while SLE associated arthritis/arthralgia, alopecia, and ulceration were less commonly found comparing with those non-pregnant patients. SLE is a risk factor for preeclampsia and both affect maternal and fetal outcomes. Changes in angiogenic factors precede the onset of preeclampsia in SLE pregnancies. Low-dose aspirin may decrease the risk for preeclampsia in pregnant women with SLE. Pregnant women should be treated for SLE flare rather than for preeclampsia for the better of the mother and baby when it is difficult to differentiate between these two conditions. Key words: Pre-eclampsia; Pregnancy complications; Lupus erythematosus, systemic; Diagnosis, differential

Extrafollicular responses in humans and SLE.

Chronic autoimmune diseases, and in particular Systemic Lupus Erythematosus (SLE), are endowed with a long-standing autoreactive B-cell compartment that is presumed to reactivate periodically leading to the generation of new bursts of pathogenic antibody-secreting cells (ASC). Moreover, pathogenic autoantibodies are typically characterized by a high load of somatic hypermutation and in some cases are highly stable even in the context of prolonged B-cell depletion. Long-lived, highly mutated antibodies are typically generated through T-cell-dependent germinal center (GC) reactions. Accordingly, an important role for GC reactions in the generation of pathogenic autoreactivity has been postulated in SLE. Nevertheless, pathogenic autoantibodies and autoimmune disease can be generated through B-cell extrafollicular (EF) reactions in multiple mouse models and human SLE flares are characterized by the expansion of naive-derived activated effector B cells of extrafollicular phenotype. In this review, we will discuss the properties of the EF B-cell pathway, its relationship to other effector B-cell populations, its role in autoimmune diseases, and its contribution to human SLE. Furthermore, we discuss the relationship of EF B cells with Age-Associated B cells (ABCs), a TLR-7-driven B-cell population that mediates murine autoimmune and antiviral responses.

Nicotinamide alleviates kidney injury and pregnancy outcomes in lupus-prone MRL/lpr mice treated with lipopolysaccharide

Systemic lupus erythematosus (SLE) increases the risk of preterm birth and preeclampsia (PE). The flares of SLE during pregnancy or after delivery are also problematic. We have previously demonstrated that nicotinamide (NAM), a non-teratogenic amide of vitamin B3, reduces inflammation and oxidative stress and improves PE-like phenotype and pregnancy outcomes in the mouse models of PE. The present study aimed to establish a model to investigate the pregnancy outcomes and flares of SLE in pregnant mice with SLE and to examine whether NAM is beneficial to pregnant mice with SLE. We used pregnant and non-pregnant lupus-prone MRL/lpr mice treated with or without a Toll-like receptor (TLR) ligand lipopolysaccharide (LPS) because TLR4 signaling reportedly exacerbates SLE and pregnancy; MRL/+ mice were used as controls. Blood pressure (BP) and urinary albumin excretion were increased only in the pregnant MRL/lpr-LPS mice. LPS together with pregnancy exacerbated glomerulonephritis, and the most severe inflammation was observed in the kidneys of the pregnant MRL/lpr-LPS mice. The shortening of pregnancy periods, increase in fetal demise percentage, and reduction in fetal weight were observed only in the pregnant MRL/lpr-LPS mice. NAM improved BP and kidney injury, prolonged pregnancy periods, and improved fetal growth in the pregnant MRL/lpr-LPS mice. The results suggest that SLE patients are prone to develop poor pregnancy outcome, and likely develop severe nephropathy and kidney inflammation. NAM may be a novel therapeutic option that improves kidney injury and pregnancy outcomes, thereby benefiting pregnant patients with SLE.

A case of Lemierre syndrome combined with a suspected systemic lupus erythematosus flare

Lemierre syndrome develops in healthy young patients as a result of bacteremia after oral cavity infection. It causes thrombophlebitis in the internal jugular vein. Infection can easily occur during immunosuppressive treatment in patients with systemic lupus erythematosus and become severe. We present a case of Lemierre syndrome in a patient with systemic lupus erythematosus. A 56-year-old woman presented with fever, left lower toothache, and skin symptoms from the left neck to the anterior chest. Clinical presentation and laboratory investigations revealed Lemierre syndrome. The inflammation and thrombus disappeared with antibiotic and anticoagulant therapies. However, transient hypocomplementemia and elevated antinuclear antibody levels were observed during treatment; therefore, a concomitant systemic lupus erythematosus flare was considered. In systemic lupus erythematosus patients with Lemierre syndrome, complement and antinuclear antibody levels are modified, so other indicators should be precisely evaluated, such as levels of urinary protein, sediment, serum creatinine and anti-dsDNA antibody, and systemic lupus erythematosus disease activity index.

Utility of neutrophil CD64 and serum TREM-1 in distinguishing bacterial infection from disease flare in SLE and ANCA-associated vasculitis.

Bacterial and opportunistic infections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis owing to treatment with immunosuppressants. Commonly used laboratory tests are unreliable in differentiating infection from active disease patients. Fc receptor (FcγR1 or CD64) expression on neutrophils and soluble TREM-1 (triggering receptor expressed on monocytes) are potential biomarkers of bacterial infections. Our aim was to measure the clinical usefulness of quantitative CD64 measurement on neutrophils and soluble TREM-1 measurements in differentiating bacterial infection from active disease in patients with SLE and ANCA vasculitis. Patients with bacterial infection (n = 25), active disease (n = 51), and healthy controls (n = 20) were included. Neutrophil CD64 expression using flow cytometry and sTREM-1 and procalcitonin levels by ELISA were studied. The percentage of neutrophils with CD64 expression and their mean fluorescence intensity in patients with infection (68.8 (56.9-86.5)%, 1037 (229-1828)) were significantly (p < 0.05) higher as compared to those without infection (7.7 (2.6-13.1)%, 456 (20-968)) and controls (7.05 (1.4-9.5)%, 99.5 (54.7-140.7)). The sensitivity and specificity of CD64 expression on neutrophils to diagnose bacterial infection (using a cutoff value of 30%) was 85% and 84%, respectively, whereas the sensitivity and specificity of procalcitonin was 75% and 85%, respectively. There was no significant difference in soluble TREM-1 levels between the two groups. Quantitative measurement of CD64 on neutrophils can distinguish between systemic infection and the flare of autoimmune diseases.

Reprint of "The interaction between environmental triggers and epigenetics in autoimmunity"

Systemic lupus erythematosus flares when genetically predisposed people encounter environmental agents that cause oxidative stress, such as infections and sunlight. How these modify the immune system to initiate flares is unclear. Drug induced lupus models demonstrate that CD4+ T cells epigenetically altered with DNA methylation inhibitors cause lupus in animal models, and similar T cells are found in patients with active lupus. How infections and sun exposure inhibit T cell DNA methylation is unclear. DNA methylation patterns are replicated each time a cell divides in a process that requires DNA methyltransferase one (Dnmt1), which is upregulated as cells enter mitosis, as well as the methyl donor S-adenosylmethionine, created from dietary sources. Reactive oxygen species that inhibit Dnmt1 upregulation, and a diet poor in methyl donors, combine to cause lupus in animal models. Similar changes are found in patients with active lupus, indicating a mechanism contributing to lupus flares.

139. Disease flares during pregnancy and postpartum in patients with systemic lupus erythematosus

Introduction Prior studies found conflicting results about whether lupus is likely to flare during or after pregnancy. Understanding the effect pregnancy has on disease activity is clinically significant for the patient. Objective Using a large cohort of pregnant and non-pregnant women with lupus, we measured the effect of pregnancy on disease flares in systemic lupus erythematosus and estimated modification by hydroxychloroquine (HCQ) use. Methods Data were prospectively collected in the Hopkins Lupus Cohort 1987–2015. Women aged 14–45 years with >1 measurement of disease activity were included. The time-varying exposures were classified as pregnancy, postpartum, or non-pregnant/non-postpartum periods. Two postpartum times periods were analyzed: 3 months and 12 months. Flares were defined as change in Physician Global Assessment (PGA) ⩾1 from previous visit. A stratified Cox model estimated hazard ratios with bootstrap 95% CIs. Results There were 1349 patients, including 398 pregnancies in 304 patients. There was an increased rate of flare during pregnancy (HR: 1.59; 95% CI: 1.27, 1.96), however this effect was modified by HCQ use, with the HR of flares in pregnancy compared to non-pregnant/non-postpartum periods estimated to be 1.83 (95% CI: 1.34, 2.45) for patients with no HCQ use and 1.26 (95% CI: 0.88, 1.69) for patients with HCQ use. The risk of flare was similarly elevated among non-HCQ users in the 3-months postpartum (HR: 1.63; 95% CI: 1.04, 2.39), but not among women taking HCQ (HR: 1.25; 95% CI: 0.71, 1.87). There was no increased risk of flare during the 12-month postpartum period, with no modification by HCQ. Discussion Our study supports and extends previous findings that the incidence of flare is increased during pregnancy and within the 3-months postpartum. Continuing HCQ, however, appeared to mitigate the risk of flare during and after pregnancy. No increased rate of flare was observed during a 12-month postpartum period.

SLE and Serum Complement: Causative, Concomitant or Coincidental?

Background Systemic Lupus Erythematosus (SLE) is an incurable autoimmune disorder with complement activation playing a key role in the pathogenesis of immune-mediated tissue injury. While quantifying complement to monitor SLE disease activity has been the standard of care since the 1950s, decreased complement levels are not consistently associated with flares. Objective We seek to clarify the SLE phenotype in which complement deficiency is causative, concomitant, or coincidental. Methods A PUBMED literature review was conducted using key words 'complement,' 'SLE,' and 'SLE flares' in English-only journals from 1972-2017. Relevant clinical studies and review articles were found that examined the measurement of complement levels in SLE, and more specifically, interpretation of low serum complement levels regardless of disease activity. Conclusion Complement activation plays a key role in the pathophysiology of SLE and it is recommended to continue monitoring serum levels of C3 and C4 to assess for disease activity. However, it is important to note that decreased serum complement is not consistently associated with disease flares.It is clinically important to find novel ways to assess disease activity in SLE. Reduced serum levels of cell-bound complement activation products may more accurately reflect disease activity than conventional serum C3 and C4 monitoring.

UnMASking the diagnosis: Acute severe necrotizing pancreatitis in the setting of systemic lupus erythematosus complicated by macrophage activation syndrome

Systemic lupus erythematosus (SLE) is a common rheumatologic condition with known GI involvement. Acute pancreatitis (AP) is a rare GI complication of SLE and is typically associated with increased disease activity. Macrophage activation syndrome (MAS) is an unusual, hyper-inflammatory response to a rheumatologic stimulus characterized by hyperferritinemia, pancytopenia, thermal dysregulation and multi-organ dysfunction. MAS, more commonly seen in children, has been reported to complicate both adult onset SLE and AP. We present a case of necrotizing AP secondary to an SLE flare complicated by MAS in an adult patient successfully treated with anakinra.

Intracranial hypertension, nephritis and serositis complicating unexpected pregnancy in a lupus patient

Background: Systemic lupus erythematosus (SLE) flare in pregnancy is challenging. The simultaneous occurrence of intracranial hypertension (IH) is unusual and raises the possibility of being a presentation of neuropsychiatric SLE. Aim of the work: We here discuss the presentation and management of a complicated case of lupus associated with IH, lupus nephritis (LN) and serositis in unplanned pregnancy. Case presentation: A 26-year old SLE patient presented 10 weeks pregnant with marked pleural effusion, hypertension, grade V papilledema, impaired renal functions, proteinuria (2.2 g/24 h), high anti-double stranded deoxyribonucleic acid and consumed complement (C3). Renal biopsy revealed LN (class IV and V). MRI brain demonstrated features consistent with IH and perimetry revealed early optic nerve affection. Ultrasound-guided pleurocentesis and relieving lumbar puncture were performed. Pulse methylprednisolone and cyclosporine A (CsA) (2 mg/kg/day) were provided. Acetazolamide was added to manage the IH and meticulous control of BP was achieved. In 2 weeks renal functions, proteinuria and papilloedema improved. The patient gave birth via vaginal delivery at full term to a normal healthy boy. On follow-up after delivery, proteinuria ranged from 100 to 300 mg/24 h with normal renal functions and fundus. The patient was maintained on CsA, hydroxychloroquine and tapering doses of steroids with no relapses. Conclusion: Pregnant SLE cases presenting with IH, LN and serositis are challenging concerning the management of SLE activity. IH may be a sign of lupus activity and its resolution coincides with the control of the flare. Lower dose CsA is potentially effective in treating LN in pregnancy with no reported side effects.

Systemic lupus erythematosus flare up as acute spinal subarachnoid hemorrhage with bilateral lower limb paralysis.

Subarachnoid hemorrhage (SAH) is an uncommon complication of systemic lupus erythematosus (SLE). Solitary association of fatal spinal SAH as a complication of SLE, has not been encountered much in literature although coexisting acute cerebral and spinal SAH have been associated with SLE. We present a 39-year old female with initial diagnosis of SLE eight years ago who suddenly developed a productive cough, acute abdomen and paralysis of the lower limbs. Magnetic resonance imaging of the spine revealed thoracic spinal SAH with varying degrees of thoracic spinal cord compression. The hemorrhage was total evacuated via surgery. She regained normal function of her lower limbers after the operation with no further neurological complications. One of the rare but fatal complications of SLE is solitary spinal SAH without cranial involvement. The best and most appropriate management of this kind of presentation is surgical decompression of the hematoma with total hemostasis. The cause of hemorrhage should be identified intra-operatively and treated appropriately.

Management and outcomes of pregnancy with or without lupus nephritis: a systematic review and meta-analysis.

BackgroundAlthough it is well established that systemic lupus erythematosus (SLE) negatively affects pregnancy outcomes, there is insufficient evidence on the effect of lupus nephritis (LN) on antenatal management and pregnancy outcomes. We performed a systematic review and meta-analysis to determine the association of LN with management and pregnancy outcomes in SLE patients.MethodsEmbase, Medline, Cochrane, and ClinicalTrials.gov were carefully searched for relevant English and Chinese language studies. A total of 2,987 articles were reviewed. Data were extracted that compared management and pregnancy outcomes in SLE pregnant women with LN vs without LN. Risk of bias was assessed by a modified version of the Newcastle-Ottawa Scale and the STROBE checklist. Combined odds ratios (OR) and 95% confidence intervals (CI) were obtained and sensitivity analysis was performed using RevMan 5.3 software.ResultsSixteen studies, including 1,760 pregnant patients with SLE, were included. Gestational hypertension (OR=5.65, 95% CI=2.94–10.84), preeclampsia (OR=2.84, 95% CI=1.87–4.30), SLE flare (OR=2.66, 95% CI=1.51–4.70), renal flare (OR=15.18, 95% CI=5.89–39.14), proteinuria (OR=8.86, 95% CI=4.75–16.52), and hypocomplementemia (OR=2.86, 95% CI=1.68–4.87) were significantly affected in pregnant women with LN. Anti-Sjögren’s syndrome-related antigen A/Ro autoantibodies were negatively associated with pregnant women with LN (OR=0.57, 95% CI=0.33–0.98). Pregnant women with LN presented a significant decrease in live births (OR=0.62, 95% CI=0.49–0.80) and a significant increase in preterm births (OR=1.92, 95% CI=1.49–2.49) and fetal growth restriction (OR=1.43, 95% CI=1.08–1.91). Regarding antenatal management, steroids (OR=2.48, 95% CI=1.59–3.87) and immunosuppressant treatment (OR=6.77, 95% CI=3.30–13.89) were more frequently used in women with LN.ConclusionThis review identified a significant association between the aforementioned outcomes and SLE pregnant patients with LN. In patients with SLE, LN increased the risks for adverse pregnancy outcomes and the use of medication. Therefore, special treatment and close monitoring should be allocated to pregnant women with LN.

Long-term immunogenicity of a quadrivalent human papillomavirus vaccine in systemic lupus erythematosus

ObjectivesTo evaluate the 5-year immunogenicity of a quadrivalent human papillomavirus (HPV) vaccine (GARDASIL) in patients with systemic lupus erythematosus (SLE). MethodsFemale SLE patients and controls, aged 18–35 years, who received GARDASIL in 2011 and sero-converted 12 months post-vaccination were followed for persistence of immunogenicity. Antibody measurement to HPV serotypes 6, 11, 16, 18 was repeated at 5 years. The rate of sero-reversion was compared between patients and controls, and factors associated with sero-reversion of the anti-HPV antibodies were studied. Results50 SLE patients and 50 controls were vaccinated with GARDASIL. Among subjects who sero-converted at 1 year and consented for this study, antibodies to HPV serotypes 6, 11, 16 and 18 at 5 years were persistent in 24/27 (89%), 26/31 (84%), 32/34 (94%) and 24/25 (96%) of the SLE patients; and 32/33 (97%), 32/33 (97%), 32/32 (100%) and 23/24 (96%) of the controls, respectively. Antibody titers to HPV-6 and 16 were significantly lower in patients than controls. Seven (21%) SLE patients had sero-reversion of ≥1 anti-HPV antibodies. Sero-reverted patients experienced significantly more SLE flares, particularly renal, and had received significantly higher cumulative doses of prednisolone, mycophenolate mofetil and tacrolimus than those with persistent immunogenicity. The cumulative doses of prednisolone correlated inversely and significantly with the anti-HPV 6, 11, and 16 titers at 5 years. ConclusionsImmunogenicity of the quadrivalent HPV vaccine was retained in a high proportion of SLE patients at 5 year. Patients with more SLE renal flares and had received more immunosuppression were more likely to have sero-reversion of the anti-HPV antibodies.Clinical trial registration number: US ClinicalTrials.gov (NCT00911521 & NCT02477254).

Severe infections in systemic lupus erythematosus: disease pattern and predictors of infection-related mortality

Infection is a major cause of morbidity and mortality among patients with systemic lupus erythematosus (SLE). To describe the pattern of serious infections in patients with SLE and to identify the predictors of infection-related mortality among SLE patients with serious infections, we prospectively studied all SLE patients who were hospitalized with infections in Sarawak General Hospital during 2011-2015. Demographic data, clinical features, and outcomes were collected. Cox regression analysis was carried out to determine the independent predictors of infection-related mortality. There were a total of 125 patients with 187 episodes of serious infections. Our patients were of multiethnic origins with female predominance (89.6%). Their mean age was 33.4 ± 14.2years. The patients had a mean disease duration of 66.8 ± 74.0months. The most common site of infection was pulmonary (37.9%), followed by septicemia (22.5%). Gram-negative organisms (38.2%) were the predominant isolates within the cohort. There were 21 deaths (11.2%) during the study period. Independent predictors of infection-related mortality among our cohort of SLE patients were flare of SLE (HR 3.98, CI 1.30-12.21) and the presence of bacteremia (HR 2.54, CI 0.98-6.59). Hydroxychloroquine was protective of mortality from serious infections (HR 9.26, CI 3.40-25.64). Pneumonia and Gram-negative organisms were the predominant pattern of infection in our SLE cohort. The presence of flare of SLE and bacteremia were independent prognostic predictors of infection-related mortality, whereas hydroxychloroquine was protective of infection-related mortality among SLE patients with serious infections.

The interaction between environmental triggers and epigenetics in autoimmunity

Systemic lupus erythematosus flares when genetically predisposed people encounter environmental agents that cause oxidative stress, such as infections and sunlight. How these modify the immune system to initiate flares is unclear. Drug induced lupus models demonstrate that CD4+ T cells epigenetically altered with DNA methylation inhibitors cause lupus in animal models, and similar T cells are found in patients with active lupus. How infections and sun exposure inhibit T cell DNA methylation is unclear. DNA methylation patterns are replicated each time a cell divides in a process that requires DNA methyltransferase one (Dnmt1), which is upregulated as cells enter mitosis, as well as the methyl donor S-adenosylmethionine, created from dietary sources. Reactive oxygen species that inhibit Dnmt1 upregulation, and a diet poor in methyl donors, combine to cause lupus in animal models. Similar changes are found in patients with active lupus, indicating a mechanism contributing to lupus flares.

Computational Modeling of the Impact of Inflammation on Renal Hemodynamic Function

Systemic lupus erythematosus (SLE) is a chronic multi‐system autoimmune disease characterized by inflammation and alternating periods of flares and remission. Hypertension is a common comorbidity observed in SLE affecting up to 74% of this patient population. Lupus nephritis (LN) is a common manifestation of SLE but whether flare and remission impacts renal hemodynamic function or contributes to hypertension remains unclear. Mathematical modeling is an experimental approach that can provide valuable insight for predicting pathophysiological mechanisms. We hypothesize that developing a mathematical model of SLE flares will provide predictive mechanistic insight into renal hemodynamic changes that drive subsequent hypertension via inflammatory pathways. This study utilizes physiological simulation to test whether episodes of inflammation impair renal hemodynamic function and increase long‐term blood pressure. A previously described model of LN and renal inflammation by Budu‐Grajdeanu et al. (PMID: 20478032) was modified and incorporated into HumMod, a large integrative model of human physiology. To model SLE flares and remission, moderate or high inflammatory insults were given for 28 days followed by remission for 28 days for a total of 12 months. Glomerular filtration rate decreased during inflammatory episodes, and returned towards normal as inflammation subsided; however, it trended downward throughout the year (Figure 1). The number of sclerotic and non‐functional nephrons increased over the course of the simulation. Blood pressure was unchanged in both cases (Figure 2). These results suggest repeated inflammatory insults can impact renal hemodynamics and renal injury and may have the potential to eventually increase blood pressure. Longer simulations and further validation are needed to accurately model the chronic damage and loss of nephrons during SLE flares and remission and the impact of inflammatory mediators on renal hemodynamics, tubular function, and long‐term blood pressure control.Support or Funding InformationVA Merit Award (BX002604‐01A2)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Critical Review on Obstetric Follow-up of Women Affected by Systemic Lupus Erythematosus.

To review the existing recommendations on the prenatal care of women with systemic lupus erythematosus (SLE), based on currently available scientific evidence. An integrative review was performed by two independent researchers, based on the literature available in the MEDLINE (via PubMed), EMBASE and The Cochrane Library databases, using the medical subject headings (MeSH) terms "systemic lupus erythematosus" AND "high-risk pregnancy" OR "prenatal care." Studies published in English between 2007 and 2017 were included; experimental studies and case reports were excluded. In cases of disagreement regarding the inclusion of studies, a third senior researcher was consulted. Forty titles were initially identified; four duplicates were excluded. After reading the abstracts, 7 were further excluded and 29 were selected for a full-text evaluation. Systemic lupus erythematosus flares, preeclampsia, gestation loss, preterm birth, fetal growth restriction and neonatal lupus syndromes (mainly congenital heart-block) were the major complications described. The multidisciplinary team should adopt a specific monitoring, with particular therapeutic protocols. There are safe and effective drug options that should be prescribed for a good control of SLE activity. Pregnant women with SLE present an increased risk for maternal complications, pregnancy loss and other adverse outcomes. The disease activity may worsen and, thereby, increase the risk of other maternal-fetal complications. Thus, maintaining an adequate control of disease activity and treating flares quickly should be a central goal during prenatal care.