Lupus

To evaluate factors associated with COVID-19 severity outcomes in patients with systemic lupus erythematosus (SLE).

This was a cross-sectional analysis of baseline data of a prospective, multi-stage cohort study—“The ReumaCoV Brazil”—designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. SLE adult patients with COVID-19 were compared with those without COVID-19. SLE activity was evaluated by the patient global assessment (PGA) and SLE Disease Activity Index 2000 (SLEDAI-2K).

604 SLE patients were included, 317 (52.4%) with COVID-19 and 287 (47.6%) in the control group. SLE COVID-19 patients reported a lower frequency of social isolation and worked more frequently as health professionals. There was no difference in the mean SLEDAI-2K score between groups in the post–COVID-19 period (5.8 [8.6] vs. 4.5 [8.0]; p = 0.190). However, infected patients reported increased SLE activity according to the Patient Global Assessment (PGA) during this period (2.9 [2.9] vs. 2.3 [2.6]; p = 0.031. Arterial hypertension (OR 2.48 [CI 95% 1.04–5.91], p = 0.041), cyclophosphamide (OR 14.32 [CI 95% 2.12–96.77], p = 0.006), dyspnea (OR: 7.10 [CI 95% 3.10–16.23], p < 0.001) and discontinuation of SLE treatment medication during infection (5.38 [CI 95% 1.97–15.48], p = 0.002), were independently associated with a higher chance of hospitalization related to COVID-19. Patients who received telemedicine support presented a 67% lower chance of hospitalization (OR 0.33 [CI 95% 0.12–0.88], p = 0.02).

Hypertension and cyclophosphamide were associated with a severe outcome, and telemedicine can be a useful tool for SLE patients with COVID-19.

Biomarkers of disease activity in lupus nephritis (LN) are in demand. This is because they may be useful in patients who are unable to undergo invasive kidney biopsy, as predictors of renal function, and for early detection of LN recurrence. The focus is on the measurement of urinary chemokines and cytokines, especially in urinary biomarkers, which are non-invasive and simple. In our previous report, we reported that kidney injury molecule-1 (KIM-1) is expressed in injured tubules and that the number of tubular-KIM-expressing positive cells correlates with renal pathology findings and also with urinary (u)-KIM-1 levels. However, there have been no reports examining the effect of u-KIM-1 levels on response to therapy, correlation with renal pathology, and usefulness as a predictor of renal function.

U-KIM-1 levels were measured by ELISA in 61 SLE patients. In 38 active LN who underwent renal biopsy, we also examined whether u-KIM-1 levels affected LN disease activity, renal histological findings, and predictors of renal function.

In SLE patients, proteinuria and u-KIM-1 levels were elevated in active LN compared to inactive LN. U-KIM-1 and proteinuria decreased with intensified treatment. U-KIM-1 levels also correlated with the percentage of glomerular crescent formation in renal pathology. In addition, patients with higher baseline u-KIM-1 levels had significantly higher eGFR and lower LN disease activity at 12 months after treatment intensification.

These data suggest that u-KIM-1 levels correlate with LN disease activity and renal histopathology findings and may be used as a predictor of treatment response.

We aimed to investigate the rate of non-adherence to antimalarials and glucocorticoids (GCs) and to analyze their potential relationships with sociodemographic characteristics, disease activity and accumulate damage in a cohort of Systemic lupus erythematosus (SLE) patients.

A cross-sectional study was conducted among 670 patients. The Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) and the Lupus Damage Index Questionnaire (LDIQ) were used to assess disease activity and accumulated damage.

The prevalence of non-adherence to antimalarials and GCs were 10.67% and 39.61%. 86.9% of participants indicated that the reason for stopping therapy was the presence of side effects. SLE patients with non-adherence to antimalarials and GCs had significantly higher scores in disease severity (SLAQ) compared to adherence patients (5.03 (2.12) vs 4.39 (2.61); p = .004 and (4.75 (2.29) vs 4.05 (2.78); p ≤ .001).

Adherence to the treatment indicated in SLE differs from drug to drug. Findings highlight the importance of developing interventions to support adherence and improve outcomes among patients.

The study aimed to explore the effect of serum uric acid (SUA) level on the progression of kidney function in systemic lupus erythematosus (SLE) patients

A total of 123 biopsy-proven lupus nephritis (LN) patients were included in this retrospective observational study. Cox proportional hazard regression analyses as well as restricted cubic spline analyses were performed to identify predictors of renal outcome in LN patients. We also performed a systematic review and meta-analysis for SUA and overall kidney outcomes in SLE patients.

Based on the laboratory tests at renal biopsy, 72 (58.5%) of the 123 patients had hyperuricemia. The median (IQR) follow-up duration was 3.67 years (1.79–6.63 years), and a total of 110 (89.4%) patients experienced progression of LN. Increased serum uric acid level, whether analyzed as continuous or categorical variable, was associated with higher risk of LN progression in Cox proportional hazard regression model (hazard ratio [HR]: 1.003, 95% confidence interval [CI]: 1.001–1.005; HR: 1.780, 95% CI: 1.201–2.639, respectively). This relationship maintained in women (HR: 1.947, 95% CI: 1.234–3.074) but not men (HR: 2.189, 95% CI: 0.802–5.977). The meta-analysis showed a similar result that both continuous and categorical SUA were positively associated with the risk of kidney function progression in LN (weighted mean difference [WMD]: 1.73, 95% CI: 0.97–2.49; odds ratio [OR]: 1.55, 95% CI: 1.20–2.01, respectively).

Our study found overall and especially in women that higher SUA in LN patients were associated with increased risk of renal progression. Meta-analysis yielded consistent results. Future studies are required to establish if uric acid can be used as a biomarker for risk assessment and/or as a novel therapeutic target in SLE.

To investigate the efficacy and safety of telitacicept treatment in a Chinese SLE cohort, with real-life settings.

All patients with SLE who were receiving telitacicept treatment at least 4 weeks were included, and were followed up. Patients received subcutaneous injection of telitacicept weekly based on the standard treatment. SLE responder index-4 (SRI-4) was assessed before the first administration and at least 4 weeks after the first administration. Disease flares during the follow-up period were defined as an increase in disease activity and the number or dose of immunosuppressive drugs.

After 4–45 weeks’ administration of telitacicept, 80% (n = 16) reached SRI-4 response. The prednisolone dosage declined from a mean of 30.25 mg/d (95% CI 21.99–38.51) before treatment to 13.25 mg/d (95% CI 9.92–16.58) after treatment. The proportion of patients without receiving an immunosuppressive drug increased from 15% to 43% at the endpoint. 19 cases showed various reduction of IgM after treatment (p < 0.05) and C3 and C4 showed either stable or an upward trend. The 24 h urinary protein median value of the 14 cases (baseline 24 h urinary protein >0.5 g/d) showed significant reduction, and 7 of them turned negative. Adverse events were mild to moderate and controllable.

Telitacicept is a potential treatment option for patients with SLE, especially in lupus nephritis, with significantly increased SRI-4 response rate and reduced the glucocorticoid and immunosuppressive drugs.

Lupus nephritis (LN) is a major issue that adds a burden on patients with systemic lupus erythematosus (SLE). Immunoglobulin-binding protein 1 (IGBP1) is identified as a phosphoprotein that has been recently reported to be linked to the B-cell receptor complex and regulates differentiation, proliferation, apoptosis, and tolerance of B cells. Its diagnostic and/or prognostic role in LN has been highlighted only recently.

This study aims to evaluate the relation between serum IGBP1 and SLE disease activity and/or renal activity and to investigate the validity of IGBP1 as a biomarker for LN.

96 participants were enrolled and divided into three groups: nephritis, nonnephritis, and control groups. The patients with SLE were diagnosed according to the Systemic Lupus International Collaborating Clinics classification (SLICC) criteria. The serum IGBP1 level was assayed using an enzyme-linked immunosorbent assay (ELISA). Assessments were conducted using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k) and renal biopsy for LN patients.

The nephritis and nonnephritis groups had higher IGBP1 levels than the controls; the nephritis group had the highest serum IGBP1 levels (p < .001). Significant correlations were found between IGBP1 levels and proteinuria (r = 0.568, p = .001) and renal SLEDAI (r = 0.475, p = .006) in the nephritis group; on the other hand, the correlation of serum IGBP1 levels with SLEDAI-2K was non-significant for both groups (nephritis and nonnephritis groups). The IGBP1 levels were significantly different among histopathologic classes (p < .001), with class V showing the highest level. Moreover, it showed a significant positive correlation with the pathologic activity index. Compared with renal SLEDAI for identifying active renal affection in patients with SLE, the serum IGBP1 level with a cut-off value of 547.45 ng/mL is a valid biomarker for detecting active nephritis with 93.8% sensitivity and 96.9% specificity.

The serum IGBP1 levels were high in patients with LN and were positively correlated with the pathologic activity index. The serum IGBP1 level of 547.45 ng/mL is a valid biomarker for detecting active nephritis. Thus, we recommend that clinicians monitor the serum IGBP1 level of patients with SLE to detect LN.

Cardiac involvement is one of the most frequent manifestations of Systemic Lupus Erythematosus (SLE). Transthoracic echocardiogram (TTE) may be valuable for the early detection of cardiac abnormalities in SLE. Few studies analyze both TTE findings in SLE and the risk factors that predispose to different cardiac manifestations in a long follow-up cohort. We aimed to investigate cardiac involvement’s prevalence, risk factors, and outcomes in a Spanish Lupus Clinic.

Spanish single-center prospective study of cardiac involvement in SLE. Two hundred and one patients met the 2019 EULAR/ACR classification criteria, performed TTE, and were eligible for the study.

Cardiac involvement was present in 43.8%. Patients with older age, hypertension, hyperlipidemia, higher body mass index, peripheral arterial disease, thrombosis, and major cardiovascular events had significantly more cardiac involvement. Neurological, hematological, and serosal involvement (pleuritis and/or pericarditis) were clinical risk factors for abnormal TTE. The combination of the four clinical variables (dyspnea, chest pain, cough, and/or syncope) was present in 40.9% of the patients with abnormal TTE in the follow-up and was superior to each of the manifestations separately. Troponin I (TnI) ≥ 0.2 ng/mL and NTproBNP ≥ 300 pg/mL were excellent biomarkers with a good correlation with cardiac abnormalities. Anti-B2GP1 was the only autoantibody associated with cardiac involvement in our cohort. Presenting cardiac involvement was correlated with higher SLICC Damage Index and increased mortality risk in the 2-year follow-up period.

Cardiac involvement in SLE is diverse, heterogeneous, and highly prevalent. Presenting a pathological TTE was associated with greater damage accrual and greater mortality. Based on our results, we consider that echocardiographic screening of patients with SLE is essential, especially those symptomatic and/or with risk factors, to diagnose and treat cardiac involvement earlier.

To analyze the characteristics of peripheral blood lymphocyte subsets in systemic lupus erythematosus (SLE) patients with infection and non-infection group. Explore the risk factors of infection in SLE patients and establish a risk matrix model to predict the occurrence of co-infection.

total of 333 SLE patients without infection, 163 patients suffering from infection, and 132 healthy controls (HCs) were recruited. General clinical data and disease activity indicators were collected. The levels of total T, B, CD4⁺T, CD8⁺T, NK, Th1, Th2, Th17, and Treg cells in peripheral blood of HCs, SLE patients (including infected and non-infected group) were analyzed by flow cytometry. The risk assessment model was constructed, and the receiver operating characteristic curve was drawn. 39 SLE patients with infection and 20 patients without infection were randomly selected to evaluate the predictive power of the regression model.

The levels of T, B, CD4⁺T, CD8⁺T, and NK cells in the infected patients were significantly decreased when compared with that of both non-infected patients and HCs (p < .05). The non-infected patients had a higher level of Th17 than that of HCs (p < . 05), but the absolute numbers of Th17 in infected patients was the lowest among the three groups (p < .001). The number of Treg cells in SLE patients was significantly lower than that of HCs (p < .01), and the infected patients had the fewest Treg cells among all these groups (p < . 05). A risk assessment model for SLE with infection was established, p = 1/(1⁻e^−y), Y = 1.763-0.004 × Absolute number of CD4 ⁺ T cells-0.005 × Absolute number of NK cells −0.005 × Platelet count(×10¹²/L) + 1.033 × Absolute number of lymphocytes (×10⁹/L) + 0.023 × C-reactive protein (mg/dL), whose predictive sensitivity is 77.5%, and specificity is 78.3%.

The new risk assessment model exhibits good predictive ability to assess co-infection risk in SLE patients. T cells, NK cells, and CD4 ⁺ T cells along with other parameters help in differentiating Lupus with infection from Lupus alone.

Despite an important increase in lifespan over the last decades, patients with systemic lupus erythematosus (SLE) still have to face a high morbi-mortality, particularly related to cardiovascular diseases, infections and cancers. Such events are more commonly found during old age in the general population, raising the hypothesis of an acceleration of the aging process in SLE patients. In this pilot study, we wanted to test the hypothesis that SLE would be associated with an accelerated biological aging measured by the epigenetic clocks models.

We applied DNA methylation-based biomarkers of age in publicly available datasets of SLE patients. For every SLE patient and control included in the dataset, we calculated their epigenetic age and a measure of epigenetic age acceleration, according to Horvath’s epigenetic clock model.

We included in our analysis two distinct DNA methylation datasets of 30 subjects (among which 15 with SLE) and 55 subjects (among which 30 with SLE), respectively. In both datasets, there was a statistically significant correlation between chronological age and epigenetic age. We did not observe any statistically significant difference in the measure of epigenetic age acceleration between SLE patients and controls.

We did not observe any evidence of an accelerated biological aging in SLE patients, according to Horvath’s epigenetic clock model.

Alexithymia is considered as a reduced capacity to be aware of, to clearly recognize, and to define one’s feelings with a limited fantasy and a concrete, externally oriented cognitive style. Some studies have stated that alexithymia is more common in systemic lupus erythematosus patients (SLE) than in general population but there is a paucity of studies in such context.

To study the prevalence of alexithymia in a sample of SLE patients looking for associated epidemiological and clinical findings and its relationship to quality of life.

Cross-sectional study in 93 SLE patients collecting clinical, epidemiological, and serological data, data on quality of life by 12 item short health survey (SF-12), and alexithymia by Toronto scale (TAS-26). Disease’s cumulative damage was measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage index.

In this sample (90.3% females and median age of 46 years), 55.9% had alexithymia; 22/92 (23.9%) did not and 19/93 (20.4%) had inconclusive results. Alexithymia presence had a positive association with age (p = 0.01) and a negative association with presence of glomerulonephritis (25% vs 59%; p = 0.005) and glucocorticoid use (19.2% vs 59.0%; p = 0.0007). A negative correlation of TAS-26 was observed with mental domain of (r = −0.46; p < 0.0001) and physical domain (r = −0.32; p = 0.004) of SF-12, but not with cumulative damage index.

We found a high prevalence of alexithymia in this sample of SLE patients that negatively associated with quality of life, but not with cumulative damage index.

Systemic lupus erythematosus (SLE) is an autoimmune disease based on the pathology of small-vessel inflammation, which can affect multiple organs. Diffuse alveolar hemorrhage (DAH) is a rare and severe complication of SLE with high mortality, most commonly seen in young women. It often appears along with clinical manifestations of sudden dyspnea, hemoptysis, and rapid onset of hypoxemia, which develops into respiratory failure and even multiple organs damage.

The case of a 28-year-old female who was diagnosed with SLE complicated with DAH is presented here. The patient, who experienced recurring DAH, responded poorly to the common therapy of high-dose glucocorticoid plus cyclophosphamide and plasma exchange. After the treatment was adjusted to a multi-target regimen of glucocorticoid, tacrolimus, mycophenolate mofetil, and belimumab, the symptoms began to improve.

The multi-target regimen may be a new treatment strategy of SLE complicated with DAH.

Systemic lupus erythematosus (SLE) predominantly occurs in women of child-bearing age. Selecting drugs for pregnant SLE patients has always been a difficult choice. Although there have been several reports of safety of belimumab in SLE patients during pregnancy, the data are far from sufficient.

We report on 4 cases of belimumab exposure in pregnant SLE patients. We also summarized 6 case reports and case series which were previously published. Further, we compared the different outcomes among SLE patients and their babies who continued with belimumab during pregnancy with those who discontinued belimumab in early pregnancy.

Two cases discontinued belimumab in the early pregnancy, while the other two received belimumab until the late pregnancy. All the four women tolerated belimumab. Newborns have all developed normally and continue without complications during 1 year of follow-up.

In this small case series, we found that belimumab was well tolerated in pregnant SLE patients. There were no safety signals for the mothers or their babies.

The severity of lupus nephritis (LN) varies between different ethnicities. However, there are limited data regarding disease severity for LN in patients from the Arabian Gulf region; moreover, there are no treatment guidelines developed specifically for this population. The objective of this review was to characterise the incidence of LN, current treatment practices, the severity of LN, and the pathophysiology and biomarkers associated with LN in the Arabian Gulf region.

A literature search using EMBASE was conducted in October, 2021 to identify publications reporting on the incidence, treatment practices, severity, pathophysiology or biomarkers associated with LN, from countries in the Arabian Gulf region (including Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates). Additional relevant publications were provided by collaborators. A manual review of the publications was conducted to determine their relevance and data on the outcomes of interest were extracted.

Of 3705 publications, 54 publications were identified as relevant. LN is one of the most commonly diagnosed renal diseases within the Arabian Gulf and approximately 10%–36% of all renal biopsies are for LN. Treatment patterns within the region appear to vary and generally follow treatment guidelines recommended by the Asia Pacific League of Associations for Rheumatology (APLAR), the European Alliance of Associations for Rheumatology (EULAR) and Kidney Disease Improving Global Outcomes (KDIGO). The majority of patients receive cyclophosphamide for induction therapy, whilst others receive mycophenolate mofetil. Most studies showed that the most frequently diagnosed class of LN within the Arabian Gulf region was Class IV (up to 63% of patients with LN). Sustained or increased levels of serum creatinine and proteinuria; and depressed levels of complement C3/C4 were commonly seen among patients with LN from the Arabian Gulf region.

This review identified that LN may manifest more severely among patients from the Arabian Gulf region than in other populations, such as Caucasian populations. A greater understanding of LN and the treatment practices within the region, as well as the development of more specific treatment guidelines for this population may help improve outcomes for patients with LN in the Arabian Gulf region.