Systemic Lupus Erythematosus Women Research Articles

A Comparison of Obstetric Outcomes in Antiphospholipid Syndrome Among Pregnant Women With Systemic Lupus Erythematosus.

Objective The aim of this study was to evaluate the maternal and perinatal outcomes in systemic lupus erythematosus (SLE) women with antiphospholipid syndrome (APS). Methods This retrospective case-control study was conducted among pregnant women with SLE with and without APS. Group A included SLE patients with APS, whereas group B included pregnant SLE women without APS. Data were expressed as mean ± standard deviation (SD). Frequency and percentage were computed for categorical data. The chi-square test was used to analyze the difference between categorical data. Results Out of 125 cases of SLE, APS was found in 72 (57.6%) women. Almost 95.8% of patients were on treatment (aspirin and enoxaparin) in group A. Preterm delivery (31.89±7.36 versus 34.46±4.97; p=0.021) and termination of pregnancy (18.1% [13/72] versus 5.7% [3/53]; p=0.04) were statistically significant in group A. Among these terminations, second-trimester intrauterine deathis found to be more in group A (SLE with APS)(16.7% [12/72]) as compared to group B(SLE without APS)(5.7% [3/53])with a p-value of 0.05. Perinatal outcomes including NICU admissions (39% [23/59] versus 24% [12/50]; p=0.071) and neonatal death (12.3% [7/57]; p=0.015) were also found to be statistically significant between the two groups. Conclusion APS with SLE is associated with adverse pregnancy outcomes such as preterm birth, termination of pregnancy due to second-trimester fetal loss, more NICU admission, and neonatal deaths when compared to the control group. Hence, pregnancies with APS with SLE require vigilant monitoring and frequent follow-ups to ensure a positive pregnancy outcome.

Pregnancies in patients with systemic lupus erythematosus during 2000–2018 in Finland: a case–control study

ObjectivesThe aim was to investigate, how pregnancies proceed in patients with systemic lupus erythematosus (SLE) compared to their individually matched population controls.Material and methodsAdult incident SLE patients were identified from the register of new special reimbursement decisions for SLE drugs in 2000–2014. For each patient, 1–3 randomly selected controls from the Population Register Centre were matched. Data regarding pregnancies were obtained from the Finnish Medical Birth Register, Care Register and Register of Congenital Malformations until 2018. The study utilized data from the Drug Purchase Register and educational information from Statistic Finland.ResultsA total of 163 deliveries for 103 mothers with SLE and 580 deliveries for 371 population controls were identified. The duration of pregnancies in SLE women was significantly shorter compared to controls (38.9 versus 39.6 weeks). There were more urgent Caesarean Sections. (15% versus 9%) and need for care at neonatal intensive care unit (NICU) (21% versus 11%) among deliveries in SLE mothers. No statistical difference was observed between SLE and control groups in the occurrence of preeclampsia or major congenital malformations. Gestational age was 2.5 weeks shorter when the mother experienced pre-eclampsia. Hydroxychloroquine was purchased by 30% of SLE mothers during pregnancy.ConclusionThe course of pregnancies in Finnish SLE patients seems to be quite moderate compared to controls, and no new safety issues were detected. The low utilization of hydroxychloroquine indicates that the benefits of the drug to pregnancy and disease course are not optimally recognized by specialists treating SLE mothers.

Association of the polymorphisms rs179008 (TLR7), rs2004640 (IRF5), rs1800795 (IL-6) and rs2280788 (CCL5) with systemic lupus erythematosus in women of Mayan ethnicity from Yucatan

Introduction: IFN-α is the main cytokine in SLE, and single nucleotide polymorphisms (SNP) in different genes could induce it. Aim: To determine the association of rs2004640 (IRF5), rs179008 (TLR7), rs1800795 (IL-6) and rs2280788 (CCL5) with SLE in Mexican women with Mayan ethnicity. Methods: DNA and RNA were isolated from the peripheral blood of 110 patients and 200 healthy control subjects. SNP genotyping and gene expression analysis of IRF5, TLR7, IL-6 and IFN-α were determined by real-time PCR and analyzed with SNP Stat, Stata 10.1 and Graph Pad Prism v5. Results: rs2004640, rs179008, and rs1800795 in both groups were according to Hardy-Weinberg equilibrium. Risk alleles rs179008T and rs2004640T frequencies were higher in controls (p = 0.015 and p = 0.028, respectively), whereas rs179008A frequency was higher in patients (p = 0.015). Allelic combination AGT frequency was higher in patients (p = 0.001). IL-6 rs1800795C > G and CCL5 rs2280788G > C frequencies did not show significant differences (p > 0.05), being rs2280788G (CCL5) monomorphic in controls. SLE patients showed higher TLR7, IRF5, IL6, and IFN-α mRNA levels. IRF5 expression was higher in SLE patients homozygous for rs2004640T (IRF5). Conclusion: This work showed the contribution of TLR7 and IRF5 in SLE pathogenesis in Mayan females from Yucatan.

Financial Hardship and Sleep Quality Among Black American Women With and Without Systemic Lupus Erythematosus.

To compare dimensions of financial hardship and self-reported sleep quality among Black women with versus without systemic lupus erythematosus (SLE). Participants were 402 Black women (50% with validated diagnosis of SLE) living in Georgia between 2017 and 2020. Black women with SLE were recruited from a population-based cohort established in Atlanta, and Black women without SLE were recruited to be of comparable age and from the same geographic areas as SLE women. Financial hardship was measured using three different scales: financial adjustments, financial setbacks, and financial strain. Sleep was assessed continuously using the Pittsburgh Sleep Quality Index (PSQI) scale. Each dimension of financial hardship was analyzed separately in SLE-stratified multivariable linear regression models and adjusted by sociodemographic and health status factors. Dimensions of financial hardship were similarly distributed across the two groups. Sleep quality was worse in Black women with, versus without, SLE (p < .001). Among Black women with SLE, financial adjustment was positively associated with a 0.40-unit increase in poor sleep quality (95% CI = 0.12-0.67, p = .005). When accounting for cognitive depressive symptoms, financial setbacks and strain were somewhat attenuated for Black women with SLE. Overall, no associations between financial hardships and sleep quality were observed for the women without SLE. Black women with SLE who experience financial hardships may be more at risk for poor sleep quality than Black women without SLE. Economic interventions targeting this population may help improve their overall health and quality of life.

Fragility fractures in lupus patients: Associated factors and comparison of four fracture risk assessment tools.

Osteoporosis (OP) and fragility fractures (FF) are common comorbidities in patients with systemic lupus erythematosus (SLE). This study aimed to (1) assess the prevalence of these conditions in a cohort of SLE patients (2) evaluate the risk factors associated with FF, and (3) compare the accuracy of four different FF risk assessment algorithms to determine which performs better in this specific rheumatologic population. We conducted a cross-sectional study with SLE women who underwent bone mineral density assessment by dual-energy X-ray absorptiometry (DEXA) within 3months of their last visit. Conventional radiology methods were used to evaluate the presence of FF. The 10-year risk of osteoporotic fractures was estimated using four tools: DeFRA, FRAX (adjusted for GC dosage), GARVAN, and QFracture. The comparison of these computational tools was analyzed by the area under the receiver operating characteristic (ROC) curves. We analyzed 86 SLE patients with a median age of 56years (IQR 12.1) and a median age at diagnosis of 34years (IQR 17.2). The median T-score values at the femoral neck and lumbar spine were -1.6 (IQR 0.9) and -1.7 (IQR 1.1), respectively. Of the patients, 33 (38.4%) had OP, with 13 patients (15.1%) experiencing FF. Univariate analysis showed that the presence of FF was associated with thrombocytopenia (p = .01), hemolytic anemia (p = .0001), and the intake of cyclosporine A (p = .002), cyclophosphamide (p = .006), and rituximab (p = .001). The median 10-year risk of major FF for the four calculation tools were as follows: DeFRA 9.85 (IQR 8.6); FRAX GC 8.8 (IQR11.7); GARVAN 12 (IQR 8.2); QFracture 4.1 (IQR 5.8). We observed a significant correlation among all instruments evaluated (p < .0001); in particular, the best correlation was recorded between the FRAX GC and the DeFRA (r = 0.85). DeFRA was the best tool for this population with an AUC of 0.94 (p < .0001, CI 0.88-1). OP is a common comorbidity in SLE patients, even in younger patients. FF appears to be more frequent in patients with hematologic involvement. The comparison of the four algorithms shows that DeFRA is the most accurate tool and should be applied to SLE patients.

Breastfeeding in women with systemic lupus erythematosus: results from a Norwegian quality register

BackgroundKnowledge on breastfeeding among women with systemic lupus erythematosus (SLE) is sparse. We wanted to identify the frequency of breastfeeding in SLE, and to compare breastfeeding women with SLE to non-breastfeeding women to examine possible differences in disease characteristics and self-reported health data between the groups.MethodsProspective data on women with SLE from RevNatus, a consent-based Norwegian nationwide quality register was used for this study. Data were collected during January 2016 to September 2021. We used data registered at inclusion when planning pregnancy or in 1st trimester, and 6 weeks, 6 and 12 months after delivery. Breastfeeding and non-breastfeeding patients were compared according to demographic, serological and obstetric data as well as disease activity, medication, self-reported pain, and fatigue.ResultsA total of 114 pregnancies in 101 SLE women were included in the analysis. A majority of the women (78%) breastfed six weeks postpartum. Six and 12 months after delivery, breastfeeding rates were 54% and 30% respectively. Six weeks postpartum, non-breastfeeding women showed higher prevalence of emergency caesarean delivery (p = 0.038), preeclampsia (p = 0.056) and lower educational level (p = 0.046) compared to breastfeeding women. 12 months after delivery, we observed a higher frequency of multiparity among breastfeeding women (p = 0.017) compared to non-breastfeeding. Overall, we found low disease activity in both groups at all registrations in the follow-up, and disease activity did not differ between the groups. More than 70% of both breastfeeding and non-breastfeeding women used hydroxychloroquine (HCQ).ConclusionsBreastfeeding rate in women with SLE was high six weeks postpartum. Multiparous women breastfed longer than primiparas. Disease activity, use of HCQ, and self-reported health data were comparable between the groups. Our data indicate that health professionals should encourage women with SLE to breastfeed.

Metabolomic Profile of Insulin Resistance Women with Systemic Lupus Erythematosus.

The aims of this study were in systemic lupus erythematosus (SLE) patients: 1) to compare the metabolomic profile of insulin resistance (IR) with controls and 2) to correlate the metabolomic profile with other IR surrogates and SLE disease variables and vitamin levels. In this cross-sectional study, serum samples were collected from women with SLE (n=64) and gender- and age-matched controls (n=71), which were not diabetic. Serum metabolomic profiling was performed using UPLC-MS-MS (Quantse score). HOMA and QUICKI were carried out. Serum 25(OH)D concentrations were measured by chemiluminescent immunoassay. In women with SLE, the metabolomic Quantose score significantly correlated with HOMA-IR, HOMA2-IR, and QUICKI. Although concentrations of IR metabolites were not different between SLE patients and controls, fasting plasma insulin levels were higher and insulin sensitivity lower in SLE women. Interestingly, the Quantose IR score was significantly correlated with complement C3 levels (r=0.7; p=0.001). 25 (OH)D did not correlate with any metabolite or the Quantose IR index. Quantose IR may be a useful tool for IR assessment. There was a possible correlation between the metabolomic profile and complement C3 levels. The implementation of this metabolic strategy may help develop biochemical insight into metabolic disorders in SLE.

Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus

BackgroundAn increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined whether low-density granulocytes (LDG) and granulocyte activation increase during pregnancy, and related the results to IFNα protein levels, autoantibody profile, and gestational age at birth.MethodsRepeated blood samples were collected during pregnancy in trimesters one, two, and three from 69 women with SLE and 27 healthy pregnant women (HC). Nineteen of the SLE women were also sampled late postpartum. LDG proportions and granulocyte activation (CD62L shedding) were measured by flow cytometry. Plasma IFNα protein concentrations were quantified by single molecule array (Simoa) immune assay. Clinical data were obtained from medical records.ResultsWomen with SLE had higher LDG proportions and increased IFNα protein levels compared to HC throughout pregnancy, but neither LDG fractions nor IFNα levels differed during pregnancy compared to postpartum in SLE. Granulocyte activation status was higher in SLE relative to HC pregnancies, and it was increased during pregnancy compared to after pregnancy in SLE. Higher LDG proportions in SLE were associated with antiphospholipid positivity but not to IFNα protein levels. Finally, higher LDG proportions in trimester three correlated independently with lower gestational age at birth in SLE.ConclusionOur results suggest that SLE pregnancy results in increased peripheral granulocyte priming, and that higher LDG proportions late in pregnancy are related to shorter pregnancy duration but not to IFNα blood levels in SLE.

Studying Pregnancy Outcome Risk in Patients with Systemic Lupus Erythematosus Based on Cluster Analysis

Background. Pregnancy in systemic lupus erythematosus (SLE) patients is a challenge due to the potential maternal and fetal complications. Therefore, a multidisciplinary assessment of disease risk before and during pregnancy is essential to improve pregnancy outcomes. Objectives. Our purpose was to (i) define clusters of patients with similar history and laboratory features and determine the associative maternal and perinatal outcomes and (ii) evaluate the risk spectrum of maternal and perinatal outcomes of pregnancy in SLE patients, represented by our established risk-assessment chart. Methods. Medical records of 119 patients in China were analyzed retrospectively. Significant variables with p &lt; 0.05 were selected. The self-organizing map was used for clustering the data based on historical background and laboratory features. Results. Clustering was conducted using 21 maternal and perinatal features. Five clusters were recognized, and their prominent maternal manifestations were as follows: cluster 1 (including 27.73% of all patients): preeclampsia and lupus nephritis; cluster 2 (22.69%): oligohydramnios, uterus scar, and femoral head necrosis; cluster 3 (13.45%): upper respiratory tract infection; cluster 4 (15.97%): premature membrane rupture; and cluster 5 (20.17%): no problem. Conclusion. Pregnancy outcomes in SLE women fell into three categories, namely high risk, moderate risk, and low risk. Present manifestations, besides the medical records, are a potential assessment means for better management of pregnant SLE patients.

Breastfeeding Initiation, Duration, and Associated Factors in Mothers with Systemic Lupus Erythematosus.

<b><i>Objective:</i></b> To study breastfeeding initiation, duration, and associated factors in patients with systemic lupus erythematosus (SLE), a cross-sectional study comparing with SLE and non-SLE mothers was conducted. <b><i>Methods:</i></b> Thirty patients with SLE who had pregnancy outcomes from September 2018 to December 2020 and 120 non-SLE patients (excluding mothers with other immune system diseases) were included in the study. Data on sociodemographic, obstetric, and SLE clinical information were collected. Breastfeeding initiation, breastfeeding duration, and reasons for not initiating breastfeeding were investigated via telephone. <b><i>Results:</i></b> The rate in breastfeeding of SLE group was significantly lower than non-SLE group (36.7% versus 86.7%, respectively, <i>p</i> &lt; 0.001; odds ratio 0.059; 95% confidence interval 0.015-0.241). Non-SLE mothers had a longer duration of breastfeeding than mothers with SLE (log-rank <i>p</i> = 0.001). Fearing of the adverse effects of drugs on babies is the main reason (68.4%) for not initiating breastfeeding in SLE group. Infants with high weight and Apgar scores, primipara women, and having a college degree were significantly associated with breastfeeding among patients with SLE. <b><i>Conclusion:</i></b> SLE women showed a lower breastfeeding rate and shorter breastfeeding duration. Postpartum medications are safe for lactation in most patients with SLE. Targeted intervention programs that enhance breastfeeding consultations are required for this group.

Low serum lipocalin-2 in pregnant women with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) pregnancies are considered high-risk due to risk of disease flare and pregnancy complications. A more in-depth understanding of the immunological alterations in SLE patients during pregnancy and identification of predictive biomarkers may help to achieve stable disease and to avoid pregnancy complications. Lipocalin-2 (LCN2) has been implicated as a potential biomarker for rheumatic diseases and preeclampsia, but remains unexplored in SLE pregnancies. We measured LCN2 levels in serum samples from SLE pregnancies (n=25) at seven different time points. Samples were taken preconception, in each trimester, at 6 weeks, 6 months and 12 months postpartum. Serum LCN2 levels were compared to samples from rheumatoid arthritis (RA) (n=27) and healthy (n=18) pregnancies at each time point using t-test, and for all time points using a linear mixed effects model. In addition, we investigated the association between LCN2 levels and disease activity, CRP, kidney function, BMI, treatment regimen and adverse pregnancy outcome for SLE and RA patients. We found significantly lower serum LCN2 levels throughout pregnancy in SLE patients with quiescent disease compared to RA and healthy pregnancies. We did not find an association between serum LCN2 and disease activity or adverse pregnancy outcome in SLE pregnancies. In a population of SLE women with low disease activity we have not found evidence that serum LCN2 levels predict disease activity or adverse pregnancy outcomes. Further studies are needed to elucidate a possible biological role of low LCN2 levels in SLE pregnancies.

Effects of perinatal disease activity on offspring's growth in patients with systemic lupus erythematosus

IntroductionTo systematically analyze the associations of perinatal disease activity with adverse outcomes of Chinese patients with systemic lupus erythematosus (SLE) and their offspring.Material and methodsData of prenatal SLE patients and healthy pregnant woman admitted to our hospital during October 2001 to January 2018 were retrospectively collected, and the status of SLE offspring was followed-up in March 2020. Disease activity was evaluated by SLE disease activity index 2000 (SLEDAI-2k), and those with scores &gt; 6 were defined as having active disease.ResultsTotally 198 deliveries of 194 SLE patients and 199 deliveries of healthy women were documented. Maternal and fetal adverse outcomes occurred in 74 (37.4%) and 90 (45.5%) deliveries of SLE patients respectively, which was significantly higher than those of healthy subjects. Among SLE patients, the active group had higher rates of gestational hypertension (p&lt;0.001), preeclampsia/eclampsia (p&lt;0.001), low birth weight (p&lt;0.001), premature birth (p&lt;0.001) and fetal growth restriction (FGR) (p&lt;0.01) than inactive group. Multivariate logistic analysis revealed that perinatal renal activity was associated with gestational hypertension (OR 4.43, p&lt;0.001), preeclampsia/ eclampsia (OR 9.14, p&lt;0.001), low birth weight (OR 2.24, p&lt;0.05) and premature birth (OR 4.20, p&lt;0.001). Compared with the general population, SLE offspring had relatively high rates of eczema (50/142 35.2%) and congenital heart disease (6/142 4.2%), which were irrelevant to perinatal disease activity, but related to specific antibodies.ConclusionsFor perinatal SLE women, renal activity is associated with a variety of adverse pregnancy outcomes. However, maternal perinatal disease activity does not seem to affect the growth of their offspring.

Preparing for Pregnancy in Women with Systemic Lupus Erythematosus-A Multidisciplinary Approach.

Highlights What are the main findings? Unified, practical approach for preconception counselling of SLE women. What is the implication of the main finding? What can be learned by the rheumatologist: the need for early referral for preconception counselling, risk stratification including from obstetrical point of view (preeclampsia (PE), anaesthetic evaluation), in vitro fertilisation, allowed medication during pregnancy (SLE-specific or non-specific), the need to evaluate for other autoimmune conditions includ-ing for thyroid disease.What can be learned by the obstetrician: how to assess activity and damage in SLE including scoring, autoantibody evaluation, and allowed vaccination from the SLE point of view. Pregnancy is one of the most challenging processes the human body is exposed to: the healthy mother can carry to term a genetically different new-born, while her immune system adapts to tolerate this new status and avoids rejection. In autoimmune disorders, motherhood is even more challenging, with additional medical counselling, mother care, and foetus development checks being necessary. While the aspects of supplementary mother care and pregnancy progress tracking are associated with well-established medical procedures and protocols, counselling, be it pre- or post-conception, is still underestimated and scarcely applied. Indeed, over the past decades, medical counselling for this particular population has changed significantly, but from a healthcare’s provider point of view, more is required to ensure a smooth, controllable pregnancy evolution. One of the most frequent autoimmune diseases affecting young females during their fertile years is Systemic Lupus Erythematosus (SLE). Like other heterogenous diseases, it exposes the mother to severe, organ-threatening complications and unpredictable evolution. Both the disease and its treatment can significantly affect the mother’s willingness to engage in a potentially risky pregnancy, as well as the likeliness to carry it to term without any impairments. A good collaboration between the patient’s rheumatologist and obstetrician is therefore mandatory in order to: (a) allow the mother to make an informed decision on pursuing with the pregnancy; (b) ensure a perfect synchronization between pregnancy terms and treatment; and (c) avoid or minimize potential complications. The best approach to achieve these outcomes is pregnancy planning. Moreover, knowing one desired prerequisite for a successful pregnancy evolution in SLE mothers is a stable, inactive, quiescent disease for at least six months prior to conception, planning becomes more than a recommended procedure. One particular aspect that requires attention before conception is the treatment scheme applied before delivery as autoantibodies can influence significantly the course of pregnancy. In this view, future SLE mothers should ideally benefit from preconception counselling within their agreed care pathway. A multidisciplinary team including at least the rheumatologist and obstetrician should be employed throughout the pregnancy, to decide on the appropriate timing of conception and compatible medication with respect to disease activity, as well as to monitor organ involvement and foetus development progress.

Increased risk of being diagnosed with endometriosis in patients with Systemic lupus erythematosus: a population-based cohort study in Taiwan

Epidemiological study shows inconsistent results in the association between endometriosis and Systemic lupus erythematosus (SLE). We conducted a nationwide retrospective cohort study and analyzed data from the Taiwan Longitudinal Health Insurance Research Database 2000 (n = 958,349) over a 13-year follow-up period (2000–2013). After matching 1930 SLE women with 7720 non-SLE women in a 1:4 ratio by age, we used Cox proportional hazard regression to calculate the adjusted hazard ratio (aHR) for endometriosis diagnosed after SLE. We also used a diagnosis of endometriosis with previous gynecologic surgery codes as secondary outcomes and performed sensitivity analyses using a landmark analysis. After adjustment for age, urbanization, income, length of hospital stay, and comorbidities in the age-matched group, women with SLE had a higher risk of endometriosis than women without SLE (aHR 1.32, 95% CI 1.02–1.70). When we defined endometriosis as patients with an ICD-9 endometriosis code after undergoing gynecologic surgery, the increased risk of endometriosis in patients with SLE was not significant. Our findings suggest that the risk of endometriosis was significantly elevated in the cohort of women with SLE compared with the age-matched general cohort of women. The burden of endometriosis in SLE patients requires special attention.

Staphylococcus aureus peptidoglycan (PGN) induces pathogenic autoantibody production via autoreactive B cell receptor clonal selection, implications in systemic lupus erythematosus

ObjectivesThere is an intricate interplay between the microbiome and the immune response impacting development of normal immunity and autoimmunity. However, we do not fully understand how the microbiome affects production of natural-like and pathogenic autoantibodies. Peptidoglycan (PGN) is a component of the bacterial cell wall which is highly antigenic. PGNs from different bacteria can differ in their immune regulatory activities. MethodsC57BL/6 and MRL/lpr mice were intraperitoneally injected with saline or PGN from Staphylococcus aureus or Bacillus subtilis. Spleen anti-double-stranded DNA (dsDNA) IgG + B cells were sorted for B-cell receptor sequencing. Serum autoantibody levels and kidney damage were analyzed. Further, the association between plasma S. aureus translocation and systemic lupus erythematosus (SLE) pathogenesis was assessed in women. ResultsAdministration of B. subtilis PGN induced natural-like anti-dsDNA autoantibodies (e.g., IgM, short lived IgG response, and no tissue damage), whereas S. aureus PGN induced pathogenic anti-dsDNA autoantibodies (e.g., prolonged IgG production, low IgM, autoantibody-mediated kidney damage) in C57BL/6 and/or MRL/lpr mice. However, serum total IgG did not differ. S. aureus PGN induced antibodies with reduced clonality and greater hypermutation of IGHV3-74 in splenic anti-dsDNA IgG + B cells from C57BL/6 mice. Further, S. aureus PGN promoted IgG class switch recombination via toll-like receptor 2. Plasma S. aureus DNA levels were increased in women with SLE versus control women and correlated with levels of lupus-related autoantibodies and renal involvement. ConclusionsS. aureus PGN induces pathogenic autoantibody production, whereas B. subtilis PGN drives production of natural nonpathogenic autoantibodies.

OP0002 LOW COMPLEMENT LEVELS IN THE FIRST TRIMESTER PREDICT DISEASE FLARE IN SLE PREGNANCY: A NETWORK META-ANALYSIS ON 532 PATIENTS.

BackgroundThe complement system is a key-player in the pathogenesis of systemic lupus erythematosus (SLE); its decreases correlate with disease activity and precedes flare. Since synthesis of complement proteins increase during gestational course, it is debated whether complement levels exert a prognostic role in pregnant women with SLE.ObjectivesWe performed a network meta-analysis to assess the prognostic role of complement in pregnant SLE women, to evaluate the possible role of complement fluctuations during pregnancies.MethodsData from available prospective studies (Jan 2002-Dec 2020) investigating pregnancies in at least 50 SLE patients, excluding miscarriages before 12 weeks, were pooled together. After a systematic literature search, corresponding authors of 19 retrieved studies meeting inclusion criteria were invited to contribute with additional data, including complement levels [6 months before pregnancy, at conception, 1st trimester (T1), 2nd trimester (T2), 3rd trimester (T3) and 3 months after delivery].ResultsA total of 532 SLE women from four eligible studies were included in the analysis [1-4]. Lupus Nephritis (LN) was diagnosed in 237 patients (44.5%) and Antiphospholipid Syndrome in 68 (12.8%). A total of 170 patients (32%) experienced a flare during pregnancy, defined as need of new Immunosuppressants or increase of prednisone &gt; 9 mg/day.Patients with LN had significantly lower mean levels of complement (C3 at conception; C3 at T1; C3 after 3 months of delivery; C4 at all timepoints except for C4 at T3). SLE patients who experienced flares during pregnancy had significantly lower mean levels of complement (all timepoints for both C3 and C4). Table 1 shows the mean C3 and C4 levels in different timepoints according to diagnosis and flare during pregnancy. The lowest levels of complement were observed in patients with a concomitant diagnosis of LN and presence of flare, particularly during the T1 (Figure 1). Nevertheless, both in LN and flare groups the lowest levels of C3 and C4 were documented at T1.Table 1.Complement levels at the different timepoints according to diagnosis or presence of flare (bold results are statistically significant)Patients with LN(237)Patientswithout LN (295)Patients with Flare (170)Patients without Flare (362)Patients with LN and Flare (73)Patients with LN and without Flare (164)C3 6 months before pregnancy (mean ±SD)90.7±18.694.1±25.285.6±19.195.6±23.375 ±17.999.1±12.5C3 conception (mean ±SD)96.1±13.991.1±1395.3±19.591.8±9.197 ±21.695.6±7.1C3 1sttrimester (mean ±SD)84.6±32.298.4±14.178.3±22.8100.5±20.756.8 ±19.997.2±28.7C3 2ndtrimester (mean ±SD)108.5±21108.3±12.294.16±13.4115.7±12.387.5 ±10.9118.6±16.8C3 3rdtrimester (mean ±SD)105.5±15.7108.2±19.198.97±18.6111.4±1698.1 ±12.6109.1±15.8C3 3 months after delivery (mean ±SD)93.4±12103.1±15.492.4±15.7102.6±13.490.5 ±10.894.8±12.3C4 6 months before pregnancy (mean ±SD)15.7±5.514.1±2.811.8±3.916.5±3.310.5±3.418.4±4.2C4 conception (mean ±SD)15.4±4.113.9±2.813.3±3.215.7±3.411±1.317.8±3C4 1sttrimester (mean ±SD)15±7.816.3±2.812.5±5.917.5±4.29.3±7.617.9±6.2C4 2ndtrimester (mean ±SD)17.7±4.718.7±4.215.5±4.319.8±3.713.6±4.119.6±3.5C4 3rdtrimester (mean ±SD)17.8±4.417.5±5.115.7±5.818.6±415.8±4.818.8±3.9C4 3 months after delivery (mean ±SD)16.2±4.319.8±6.914.9±3.920±6.413.3±3.117.6±4Figure 1.Complement Levels during time in patients with Lupus Nephritis and presence, or absence, of flare.ConclusionIn this prospective large cohort of SLE patients low C3/C4 levels, particularly in T1, were associated with a higher frequency of flare. Lowering levels of complement, especially in T1, even within normal range might alert the treating clinicians in predicting disease course and consequently avoid flares, especially in LN.

AB0497 IMMUNOLOGICAL DISEASE ACTIVITY PARAMETERS AT CONCEPTION ARE RISK FACTORS FOR PRETERM BIRTH AND LOW BIRTH WEIGHT IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

BackgroundWomen with systemic lupus erythematosus (SLE) are known to have more difficulty in achieving a successful pregnancy than healthy women. They have a higher risk for adverse pregnancy outcomes (APOs) including preterm birth (PB), low birth weight (LBW). (1,2). Many reports revealed that these APOs are related to uncontrolled high disease activity (3,4). Therefore, it is important for SLE women who hope to conceive to control disease activity strictly. However, it is not clear to what extent disease activity should be strictly controlled, including serum parameters such as complement levels and anti-dsDNA antibodies.ObjectivesThe purpose of this study was to determine whether disease activity parameters at conception could be a risk factor for PB or LBW among APOs in patients with SLE.MethodsDisease activity parameters including SLEDAI score, LLDAS achievement rate, serum complement levels (C3, C4, CH50), and anti-dsDNA antibody titer were retrospectively collected from medical records. We then collected information related to each APOs (PB and LBW), and analyzed the association with disease activity parameters.ResultsThe subjects were 60 pregnancies of 45 patients. As for a comprehensive disease activity index at conception, SLEDAI score or the rate of LLDAS achievement became risk factors for PB (both of p&lt;0.01, Table 1), and SLEDAI score was also a risk factor for LBW (P=0.04, Table 1). Analysis of immunological disease activity parameters showed that low C3 or high titer of anti-dsDNA antibody were risk factors for PB (P=0.03 and 0.01, respectively, Table 1). In the logistic regression analysis of PB, the cut-off levels of C3 and anti-dsDNA antibody were 62 mg/dl and 5.4 IU/ml, respectively (Figure 1 [1]-A, [1]-D). The risk of PB was significantly higher in the cases with low serum C3 and high anti-dsDNA antibody titer at conception (P=0.02).Similarly, low C3 or CH50 were risk factors for LBW (P=0.02 and 0.03, respectively, Table 1). Logistic regression analysis for LBW showed the cut-off level of C3 as 87 mg/dl, and CH50 as 41.8 IU/ml (Figure 1 [2]-A, [2]-C). Cases with low C3 and low CH50 were at higher risk for LBW (P=0.03).Table 1.Association between disease activity parameters and PB or LBWPreterm birth (PB)Low birth weight (LBW)PB (+)(n = 14)PB (-)(n = 46)P valueLBW (+)(n = 23)LBW (-)(n = 37)P value Achievement of LLDAS, n (%)##5 (41.7)30 (71.4)0.0912 (63.2)23 (65.7)1.00 Achievement of LLDAS without a glucocorticoid dose, n (%)##5 (41.7)37 (88.1)&lt; 0.01*13 (68.4)29 (82.9)0.31 SLEDAI score#3.5±2.91.1±1.3&lt;0.01*2.3±2.11.3±2.00.04* C3, mg/dl#77.3±19.094.7±21.20.03*80.5±16.396.7±22.70.02* C4, mg/dl#16.1±9.019.2±6.30.1617.6±6.319.1±7.40.56 CH50, IU/ml#37.3±10.641.1±8.50.1736.5±6.642.2±9.70.03* Anti-dsDNA antibody, IU/ml#32.5±68.55.5±11.10.01*20.7±55.87.0±12.20.34(Values are presented as mean ± standard deviation or number (%). #Wilcoxon rank sum test; ##Fisher’s exact test; *P &lt; 0.05.)Figure 1.Logistic regression analysis of cut-off value of PB and LBW for C3, C4, CH50 and anti-dsDNA antibody.(ROC curves based on logistic regression analysis of cut-off levels for disease activity parameters, including C3, C4, CH50, and anti-dsDNA antibody titer. [1] showed ROC curves for PB, and [2] showed those for LBW.)ConclusionWe revealed that disease activity parameters of SLE at coception are strongly associated with negative pregnancy outcomes; PB and LBW. These include low serum C3 and CH50 levels and high anti-dsDNA antibody titers. In particular, low serum complement is a risk factor for both PB and LBW. Therefore, it is important to strictly control these disease activity parameters at conception in women with SLE.

Long non-coding RNA Xist contribution in systemic lupus erythematosus and rheumatoid arthritis

Growing evidence points towards the role of the long non-coding (lnc)-RNA Xist expressed in female cells as a predominant key actor for the sex bias observed in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Indeed, in female cells, lnc-Xist controls transcription directly by spreading across the inactivated X chromosome (Xi) and indirectly by sequestring miRNAs as a sponge. The inactivation process at Xi is altered in lymphocytes from SLE women and associated with important variations in ribonucleoproteins (RNP) associated with lnc-Xist. In fibroblast-like synoviocytes (FLS) and osteoclasts from RA women, proinflammatory and proliferative pathways are upregulated due to the sequestration effect exerted by lnc-Xist overexpression on miRNAs. The key role played by lnc-Xist in SLE and RA is further supported by it's knock down that recapitulates the SLE B cell extrafollicular profile and controls RA associated FLS proinflammatory cytokine production and proliferation.

Association of High Calcitriol Serum Levels and Its Hydroxylation Efficiency Ratio with Disease Risk in SLE Patients with Vitamin D Deficiency.

Vitamin D (calcidiol) deficiency in systemic lupus erythematosus (SLE) is more frequent than in healthy subjects (HS); it is associated with clinical activity and damage in SLE. Although calcidiol is considered the best indicator of the vitamin D serum status, its deficiency could not reflect its hydroxylation efficiency ratio and calcitriol serum status. This study was aimed at assessing the association of calcidiol and calcitriol serum levels and its hydroxylation efficiency ratio with the risk to clinical and renal disease activities in SLE patients. A cross-sectional study was conducted in 308 SLE and HS women; calcidiol and calcitriol serum levels were evaluated by immunoassays. SLE patients showed lower calcidiol serum levels vs. HS (21.2 vs. 24.2 ng/mL; p < 0.001). Active SLE patients presented higher calcidiol/calcitriol ratio scores vs. inactive SLE patients (2.78 vs. 1.92 pg/ng; p = 0.02), and SLE patients with renal disease activity showed a pattern of calcidiol-deficient levels (19.5 vs. 25.3 ng/mL; p < 0.04) with higher calcitriol levels (47 pg/mL vs. 41.5 pg/mL; p = 0.02) and calcidiol/calcitriol ratio scores (2.13 vs. 1.54 pg/ng; p < 0.02) compared to SLE patients without renal disease activity. Calcidiol levels were negatively correlated with calcitriol levels (r = −0.26; p = 0.001) and urine proteins (mg/dL) (r = −0.39; p < 0.01). Regarding calcitriol levels, it was positively correlated with the blood lymphocyte count (r = 0.30; p < 0.001) and negatively correlated with the glomerular filtration rate (r = −0.28; p = 0.001). Moreover, the calcitriol/calcidiol ratio was positively correlated with urine proteins (r = 0.38; p < 0.01). The calcidiol deficiency (OR = 2.27; 95% CI = 1.15-4.49; p < 0.01), high calcitriol levels (T3rd, OR = 4.19, 95% CI = 2.23-7.90; p < 0.001), and a high calcitriol/calcidiol ratio score (T3rd, OR = 5.93, 95% CI: 3.08-11.5; p < 0.001) were associated with the risk for SLE. In conclusion, a pattern of calcidiol deficiency with high calcitriol serum levels and a high vitamin D hydroxylation efficiency ratio was associated with disease risk in SLE patients.

Remission or low disease activity at pregnancy onset are linked to improved foetal outcomes in women with systemic lupus erythematosus: results from a prospective observational study.

Systemic lupus erythematosus (SLE) patients show variably increased risk for pregnancy complications. We analysed pregnancy outcomes (foetal and maternal), patterns of disease activity and use of medications in a contemporary Caucasian SLE population. Prospective observational study, involving hospital units and private rheumatologists in Greece, of incident pregnancies (period 2015-2018) in women with SLE. Clinical and obstetrical monitoring was performed at regular intervals up to 9 months post-partum. Regression and mixed model analyses were used to determine predictors for adverse foetal outcomes and flares. We monitored 82 pregnancies in 64 SLE patients. Foetal loss, prematurity and small for gestational age neonate occurred at 15.8%, 34.1% and 8.5%, respectively; 53.7% of pregnancies were complicated with at least one adverse outcome. Patients with antiphospholipid antibodies (aPL) had increased risk (odds ratio [OR] 5.67, p=0.015), whereas those at low disease activity at pregnancy onset were protected (OR 0.20, p=0.024) against foetal complications. Persistent activity and glucocorticoid intake during pregnancy also predicted poor foetal outcomes. SLE patients experienced an average 1.08 mild/moderate and 0.27 severe flares. The latter occurred more frequently post-partum, in patients with alopecia (OR 8.92, p=0.003), hypocomplementaemia (OR 10.34, p=0.038) and nephritis (OR 7.32, p=0.052). Lupusactivity post-labour was paralleled by decreased use of hydroxychloroquine, glucocorticoids and azathioprine. In SLE women, foetal complications are common especially in the presence of aPL and increased activity, which corroborates the importance of pregnancy planning and tight disease control at pregnancy onset. Flares, mostly mild or moderate, can occur both during and after pregnancy.