Lupus

There is limited knowledge on the relative impact of lupus nephritis (LN) on morbidity and mortality in population-based systemic lupus erythematous (SLE) cohorts. Here, the primary aim was to compare mortality rates between patients with and without LN in a population-based SLE cohort.

The study cohort included all SLE patients resident in the city of Oslo during 1999–2008. Follow-up time was median 14 (0–15) years. Presence of LN was defined according to the 1987 American College of Rheumatology classification criteria for SLE. LN class was determined by renal biopsy. Data on kidney function, including presence of end-stage renal disease (ESRD), were obtained from patient charts. Standardized mortality ratios (SMRs) were estimated by comparing deaths in the SLE cohort with age- and gender-matched population controls.

We found that 98/325 SLE patients (30%) developed LN, 92% of whom had occurrence within the first five years from disease onset. Incidence rate of ESRD was 2.3 per 1000 patient-years. A total of 56 deaths occurred during the study period, corresponding to an overall SMR in the SLE cohort of 2.1 (95% confidence interval (CI) 1.2–3.4). Estimated SMR for LN patients was 3.8 (95% CI 2.1–6.2), and for SLE patients without LN it was 1.7 (95% CI 0.9–2.7).

In this population-based SLE cohort, we found that LN was associated with increased morbidity and mortality, whereas SLE patients who did not develop LN had good overall prognoses regarding survival.

We investigated the effect of hydroxychloroquine (HCQ) on S100A8 and S100A9 serum levels in systemic lupus erythematosus (SLE) patients with low disease activity receiving immunosuppressants.

SELENA-SLEDAI, Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum levels of complement factors, anti-dsDNA antibodies, and white blood cell, lymphocyte, and platelet counts were used to evaluate disease activity, cutaneous disease activity, and immunological activity, respectively. Serum S100A8 and S100A9 were measured at HCQ administration and after 3 or 6 months using ELISA.

S100A8 and S100A9 serum levels were elevated at baseline and the magnitude of decrease from baseline at 3 and 6 months after HCQ administration was greater in patients with renal involvement than in those without (baseline: S100A8, p = 0.034; S100A9, p = 0.0084; decrease: S100A8, p = 0.049; S100A9, p = 0.023). S100 modulation was observed in patients with (n = 17; S100A8, p = 0.0011; S100A9, p = 0.0002) and without renal involvement (n = 20; S100A8, p = 0.0056; S100A9, p = 0.0012), and was more apparent in patients with improved CLASI activity scores (improved: S100A8, p = 0.013; S100A9, p = 0.0032; unimproved: S100A8, p = 0.055; S100A9, p = 0.055). No associations were observed for immunological biomarkers.

HCQ may improve organ involvement in SLE by modulating S100 protein levels, especially in patients with renal or skin involvement.

The aim of this study was to assess whether lupus is associated with poorer outcomes after primary total hip arthroplasty (THA).

We used the 1998–2014 US National Inpatient Sample data. Multivariable-adjusted separate logistic regression models assessed the association of lupus with post-operative complications (implant infection, transfusion, THA revision and mortality) and health care utilization outcomes (total hospital charges, discharge to an inpatient facility and length of hospital stay >3 days) post-THA, adjusting for demographics, underlying diagnosis, comorbidity, insurance payer and hospital characteristics, using odds ratios (OR) and 95% confidence intervals (CI).

Among 4,116,485 primary THA hospitalizations, 22,557 (0.5%) were in patients with lupus. Patients with lupus were younger and more likely to be female, African-American or Hispanic, living in the South, or to have Medicaid insurance, and had higher comorbidity or lower income. In multivariable-adjusted analyses, the presence of lupus was associated with significantly higher risk of implant infection, transfusion, discharge to an inpatient facility and higher hospital charges above the median, with respective ORs of 1.95 (95% CI, 1.28, 2.97), 1.34 (95% CI, 1.25, 1.43), 1.21 (95% CI, 1.01, 1.44) and 1.38 (95% CI, 1.30, 1.47). Lupus was not significantly associated with the risk of revision, mortality or hospital stay >3 days; the ORs were 1.10 (95% CI, 0.68, 1.78), 0.95 (95% CI, 0.61, 1.47) and 1.06 (95% CI, 0.99, 1.13), respectively.

Lupus was associated with a higher risk of implant infection, transfusion, discharge to an inpatient facility and higher hospital charges post-primary THA. Insight into modifiable factors associated with these outcomes may improve outcomes in patients with lupus undergoing THA.

The objective of this study was to observe the expression features of erythroblast macrophage protein (EMP) between the tissues of MRL/lpr mice, a mouse model of systemic lupus erythematosus (SLE), and control mice.

We examined the serum ANA in both mice groups through indirect immunofluorescence (IIF). Expression features of EMP in bone marrow, liver, renal, spleen, brain, and lung tissues of the MRL/lpr mice and control mice groups were followed using quantitative real-time polymerase chain reaction (Q-PCR). Meanwhile, the expression of EMP was located through immunohistochemical (IHC) studies and the expressive cell identified through double immunofluorescent labeling.

IIF showed that lupus mice have strong positive fluorescence, but no significant fluorescence was observed in control mice. Q-PCR detection revealed that EMP was expressed in the marrow, liver, renal, spleen, lung, and brain tissues of lupus mice. The highest levels were observed in the bone marrow, but there was no statistical difference between these tissues. EMP mRNA expression in the liver (t = 2.747, p = 0.01) and bone marrow (t = 3.853, p = 0.008) of lupus mice was significantly higher than in the control mice. However, no differences in EMP mRNA expression were observed in the renal, spleen, lung, and brain tissues between the lupus and control mice (p > 0.05). In addition, the IHC results showed that EMP protein is ubiquitously expressed in all of the tissues of the lupus and control mice. The positive expression rate in the bone marrow and liver tissues of the lupus mice was higher than in the control mice, but without an obvious difference in the other tissues. The double IF staining method shows that EMP protein was expressed in macrophages in the tissues of the lupus mice and the control mice.

Our data showed that EMP is ubiquitously expressed in macrophages at all of the tissues of the lupus and control mice. However, the expression of EMP in bone marrow and liver tissues of lupus mice was higher than in the control mice, which indicates that EMP may be important in the development of SLE.

Cognitive impairment is a common neuropsychiatric manifestation of systemic lupus erythematosus (SLE). However, it is not routinely assessed for despite its high prevalence and significant disease burden.

This study aimed to determine the prevalence of mild cognitive impairment (MCI) using the Montreal Cognitive Assessment (MoCA) and its associated factors among patients diagnosed with SLE in Malaysia.

A total of 200 SLE patients were recruited prospectively from the outpatient clinics of two tertiary hospitals in Malaysia. Standardized clinical interview was utilized to obtain information on socio-demographic characteristics. All patients were then assessed using the MoCA questionnaire for presence of cognitive impairment; the Patient Health Questionnaire 9 (PHQ-9) for presence of depressive symptoms; and the Wong–Baker Faces Pain Scale (WBFPS) for severity of pain. The evaluation of disease activity and severity were performed by the treating rheumatologists and nephrologists using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics Damage Index (SLICC DI).

The prevalence of MCI was 35%. The significant associated factors from the bivariate analysis were male gender (p = 0.04), educational level (p = 0.00), WBFPS score (p = 0.035) and anticardiolipin IgM (p = 0.01). Further analysis using logistic regression model found that male gender (OR = 7.43, 95% confidence interval 1.06–52.06, p = 0.04), lower educational level (OR = 4.4, 95% confidence interval 1.47–13.21, p = 0.01) and presence of anticardiolipin IgM (OR = 6.81, 95% confidence interval 1.45–32.01, p = 0.031) were associated with impaired MoCA scores. Also, increasing pain scores increased the risk of patients being affected by cognitive impairment.

Over one-third of patients with SLE in our cohort were found to have MCI. Risk factors included male gender, lower educational level, higher pain score and presence of anticardiolipin IgM. Physicians are encouraged to perform routine screening to detect cognitive dysfunction in patients with SLE in their clinical practice as part of a more comprehensive management.

Hydroxychloroquine (HCQ) is a key therapy in systemic lupus erythematosus (SLE). Medication non-adherence is reported in up to 80% of lupus patients and results in increased morbidity, mortality, and health care utilization. HCQ levels are a sensitive and reliable method to assess medication adherence. Our study evaluated the role of HCQ level measurement in routine clinical care and its association with disease activity in a predominantly Hispanic population.

SLE patients from the Columbia University Lupus cohort treated with HCQ for ≥ 6 months and reporting medication adherence were included. HCQ levels were measured by whole blood high performance liquid chromatography. Non-adherence was defined as an HCQ level <500 ng/ml. The association between HCQ levels and disease activity measured by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was evaluated.

One hundred and eight patients were enrolled; the median age was 38 years, 91% were female, and 63% were Hispanic. The median SLEDAI-2K was 4.3 (0–20). Forty-one percent of patients had an HCQ level <500 ng/ml consistent with non-adherence, of which 19% had undetectable levels. A higher SLEDAI-2K score was associated with low HCQ levels (p = 0.003). This association remained significant after adjusting for depression (p = 0.0007).

HCQ levels < 500 ng/ml were associated with higher disease activity and accounted for 32% of the SLEDAI-2K variability. HCQ blood measurement is a simple and reliable method to evaluate medication adherence in SLE. Reasons for non-adherence (levels < 500 ng/ml) should be further explored and addressed.

Depressive and anxiety symptoms are common in children and youth and may impact outcomes for individuals with childhood-onset systemic lupus erythematosus. Research into the prevalence of depressive and anxiety symptoms and childhood-onset systemic lupus erythematosus comorbidity has reported conflicting results.

To synthesize current knowledge regarding the prevalence of depressive and anxiety symptoms in childhood-onset systemic lupus erythematosus.

Studies were identified through a comprehensive search of MEDLINE, EMBASE, PsychINFO, LILACS and Web of Science (from database inception to July 2018) using MESH headings and keywords for ‘lupus erythematosus’, and ‘depression’ or ‘anxiety’. Included studies measured depressive and/or anxiety symptoms prospectively among children and youth aged 8 to 21 years with a diagnosis of childhood-onset systemic lupus erythematosus. Neuropsychiatric systemic lupus erythematosus was included. Studies without use of validated screening tools for major depressive disorder or anxiety disorders were excluded, as were studies where diagnosis was by retrospective analysis of patient charts. Data were extracted by two independent coders and where discrepancies occurred, agreement was reached by consensus.

In total, 70 studies met the criteria for full text review and of these, 14 were included in the final analysis. The majority (70%) of studies were of cross-sectional design, with sample sizes ranging from 20 to 100 (mean = 48) participants. The mean age of participants was 15.9 years and participants were predominantly female. Prevalence rates for depressive symptoms ranged from 6.7% to 59%. Anxiety symptom prevalence was 34% to 37%. All studies employed self-report instruments to assess depressive and anxiety symptoms; none of the studies utilized a semi-structured diagnostic interview to make psychiatric diagnoses. Significant heterogeneity precluded meta-analysis of the data.

Depressive and anxiety symptoms may be common comorbidities of childhood-onset systemic lupus erythematosus; however, current research is limited by a paucity of studies, small sample sizes and an inability to confirm psychiatric diagnoses. Future research addressing these limitations is needed.

This study aims to inhibit antiphospholipid syndrome (APS) serum derived IgA anti-beta-2-glycoprotein I (aβ2GPI) binding using Domain I (DI).

Serum from 13 APS patients was tested for IgA aβ2GPI and Anti-Domain I. Whole IgA was purified by peptide M affinity chromatography from positive serum samples. Serum was tested for IgA aβ2GPI binding in the presence and absence of either DI or of two biochemically modified variants containing either 20 kDa of poly(ethylene glycol) (PEG) or 40 kDa of PEG.

Significant inhibition with DI was possible with average inhibition of 23% (N = 13). Further inhibitions using 20 kDa PEG-DI and 40 kDa PEG-DI variants showed significant inhibition (p = 0.0001) with both the 40 kDa PEG-DI and 20 kDa PEG-DI variants showing increased inhibition compared with DI alone (p = 0.0001 and p = 0.001, n = 10).

Inhibition of IgA aβ2GPI by DI is possible and can be enhanced by biochemical modification in a subset of patients.

Systemic lupus erythematosus (SLE) is a chronic, multisystemic, immune-mediated disorder associated with a substantial hospitalization risk. As a comparatively rare disease, there is a sparsity of research examining the burden of hospital admission in the contemporary era. We aim to describe national trends in hospitalization rates in England between 1998 and 2015 for SLE, using rheumatoid arthritis (RA) and general population rates as comparison cohorts for benchmarking.

Hospital admission rates, emergency and day-case admission rates, length of stay and bed days used were calculated using finished consultant episodes from Hospital Episode Statistics data. Cochran-Armitage tests and linear regression quantified the significance and magnitude of change over time.

SLE admissions increased from 8.97 to 9.04 per 100,000 (p < 0.001) between 1998 and 2015. By comparison, RA admissions rose from 71.0 to 171.6 per 100,000 (p < 0.001) and all-cause admissions rose from 24,500 to 34,500 per 100,000 (p < 0.001). Emergency admissions decreased both for SLE (2.6 to 1.2 per 100,000) and RA (12.8 to 4.4 per 100,000) despite all-cause emergency admissions increasing from 9400 to 10,300 per 100,000. SLE and RA day cases increased, whilst median length of stay decreased. Despite increasing admissions, total bed days for SLE and RA fell by 60% and 90%, respectively.

Whilst all-cause emergency admissions rose in the general population, those for SLE fell. Length of stay and bed days reduced and day cases increased, probably reflecting changing therapeutic strategies. This potentially large reduction in resource utilization warrants consideration when assessing the impact of new therapies.