Plasma interferon-alpha protein levels during pregnancy are associated with lower birth weight in systemic lupus erythematosus.

Objectives: Adverse pregnancy outcomes are more common in women with systemic lupus erythematosus (SLE) compared with healthy women, but we lack prognostic biomarkers. Plasma interferon alpha (IFNα) protein levels are elevated in a subgroup of pregnant women with SLE, but whether this is associated with pregnancy outcomes is unknown. We investigated the relationship between IFNα, adverse pregnancy outcomes and the presence of autoantibodies in SLE pregnancy.

Regional European genetic ancestry predicts type I interferon level and risk of severe viral infection.

Background: Viral infection outcomes vary widely between individuals, ranging from mild symptoms to severe organ failure and death, and it is clear that host genetic factors play a role in this variability. Type I interferon (IFN) is a critical anti-viral cytokine, and we have previously noted differences in type I IFN levels between world populations.

Methods: In this study, we investigate the interrelationship between regional European genetic ancestry, type I IFN levels and severe viral infection outcomes.

Low CD4 + T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy.

Background: Lymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are affected by pregnancy and if they relate to autoantibody profiles and/or IFNα protein in SLE pregnancy.

Methods: Repeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC).

Urinary aberrations in systemic lupus erythematosus not always indicative of lupus nephritis: a cross-sectional cohort study.

Introduction: Kidney biopsy is the reference tool for diagnosing and guiding treatment strategies in inflammatory renal diseases, such as lupus nephritis (LN). We investigated the histopathological findings in first-time kidney biopsies from a large cohort of SLE patients. We focused on the occurrence and type of histopathological findings other than LN, and fulfillment of renal criteria in established SLE classification systems were analyzed.

Occurrence and localization of FOXP3 + cells in kidney biopsies in lupus nephritis and ANCA-associated vasculitis.

The study aims to increase the understanding regarding the role of regulatory T cells (Tregs) in lupus nephritis (LN) and ANCA-associated vasculitis (AAV) by comparing their localization in renal tissue and changes following immunosuppressive therapy. Kidney biopsies from 12 patients with LN and 7 patients with AAV were examined. Kidney biopsies had been performed both at active disease and following immunosuppressive treatment.

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

Background: An 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.

Interleukin (IL) 16: a candidate urinary biomarker for proliferative lupus nephritis.

Objective: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). The pathogenesis is incompletely understood and diagnostic biomarkers are scarce. We investigated interleukin (IL) 16 as a potential biomarker for LN in a well-characterised cohort of patients with SLE.

Anti-phosphatidylserine/prothrombin antibodies and thrombosis associate positively with HLA-DRB1*13 and negatively with HLA-DRB1*03 in SLE.

Objectives: Emerging evidence demonstrates that aPS-PT associate with thrombotic events. Genetic predisposition, including HLA-DRB1 alleles, is known to contribute to the occurrence of conventional aPL [anti-β2glycoprotein-I (anti-β2GPI) and aCL]. We investigated associations between aPS-PT and HLA-DRB1* alleles and thrombosis in SLE.

Four Systemic Lupus Erythematosus Subgroups, Defined by Autoantibodies Status, Differ Regarding HLA-DRB1 Genotype Associations and Immunological and Clinical Manifestations.

Objective: The heterogeneity of systemic lupus erythematosus (SLE) constitutes clinical and therapeutical challenges. We therefore studied whether unrecognized disease subgroups can be identified by using autoantibody profiling together with HLA-DRB1 alleles and immunological and clinical data.

Methods: An unsupervised cluster analysis was performed based on detection of 13 SLE-associated autoantibodies (double-stranded DNA, nucleosomes, ribosomal P, ribonucleoprotein [RNP] 68, RNPA, Smith [Sm], Sm/RNP, Sjögren's syndrome antigen A [SSA]/Ro52, SSA/Ro60, Sjögren's syndrome antigen B [SSB]/La, cardiolipin [CL]-Immunoglobulin G [IgG], CL-Immunoglobulin M [IgM], and β glycoprotein I [β GPI]-IgG) in 911 patients with SLE from two cohorts.

Myocardial infarctions, subtypes and coronary atherosclerosis in SLE: a case-control study.

Objective: Patients with SLE have increased risk of myocardial infarction (MI). Few studies have investigated the characteristics of SLE-related MIs. We compared characteristics of and risk factors for MI between SLE patients with MI (MI-SLE), MI patients without SLE (MI-non-SLE) and SLE patients without MI (non-MI-SLE) to understand underlying mechanisms.

Associations with thrombosis are stronger for antiphosphatidylserine/prothrombin antibodies than for the Sydney criteria antiphospholipid antibody tests in SLE.

Objectives: Antiphosphatidylserine/prothrombin complex antibodies (aPS/PT) are risk factors for thrombosis, yet further validation of their clinical relevance in different ethnic groups is required. We investigated the performance of aPS/PT of IgA/G/M isotypes among Sudanese and Swedish systemic lupus erythematosus (SLE) patients.

Methods: Consecutive SLE patients/matched controls from Sudan (n = 91/102) and Sweden (n = 332/163) were included.

Activated low-density granulocytes in peripheral and intervillous blood and neutrophil inflammation in placentas from SLE pregnancies.

Objective: Women with SLE face an increased risk of adverse pregnancy outcomes compared with healthy women, but the underlying immunological mechanisms are unknown. Given the recognised association of neutrophil activation with SLE pathogenesis, we examined whether there is increased neutrophil activation and inflammation in blood and placenta in SLE relative to healthy pregnancy.

Methods: At delivery, peripheral blood, maternal-derived intervillous blood and placentas were collected from 12 SLE and 10 healthy control pregnancies.

Resorption of immune deposits in membranous lupus nephritis following rituximab vs conventional immunosuppressive treatment.

Objectives: Studies on repeat renal biopsies in membranous LN (MLN) are limited, and evaluation of treatment response is mainly based on proteinuria. EM of renal biopsies from rituximab (RTX)-treated MLN patients has revealed resorption of sub-epithelial ICs. Whether resorption phenomena are useful for treatment evaluation, or differs between treatment regimens is not known.

Plasma C4d Correlates With C4d Deposition in Kidneys and With Treatment Response in Lupus Nephritis Patients.

Objective: To examine whether C4d plasma levels correlate with treatment response and C4d kidney deposition in systemic lupus erythematosus (SLE) with lupus nephritis (LN).

Methods: C4d plasma levels were analyzed by a unique assay specifically detecting C4d arising from complement activation and C4 plasma levels were quantified with competitive ELISA. SLE patients with LN (71) and active SLE patients without LN (22) plus 145 controls were included.

Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus.

We investigated whether belimumab treatment impacts on levels of autoantibodies and cytokines of interest in systemic lupus erythematosus (SLE). Longitudinally collected serum samples from 78 belimumab-treated Swedish SLE patients were analysed. Serum cytokine levels were determined using Luminex xMAP technology, and nuclear antigen autoantibody specificities using addressable laser bead immunoassay.

Increased levels of anti-dsDNA antibodies in immune complexes before treatment with belimumab associate with clinical response in patients with systemic lupus erythematosus.

Introduction: Immune complexes are of importance in systemic lupus erythematosus pathogenesis, and autoantibodies are believed to participate in immune complex formation. Quantification of autoantibody levels in circulating IC might be of prognostic value.

Methods: A C1q-binding-eluting technique was applied to purify immune complexes from 55 belimumab-treated systemic lupus erythematosus patients during a 24-month follow-up.

ALCAM and VCAM-1 as urine biomarkers of activity and long-term renal outcome in systemic lupus erythematosus.

Objectives: We investigated the cell adhesion molecules (CAMs) Vascular CAM 1 (VCAM-1) and Activated Leucocyte CAM (ALCAM) as urinary biomarkers in SLE patients with and without renal involvement.

Methods: Female SLE patients (n = 111) and non-SLE population-based controls (n = 99) were enrolled. We measured renal activity using the renal domain of the BILAG index and urine (U) and plasma (P) concentrations of soluble (s)VCAM 1 and U-sALCAM using ELISA.

Sjögren Syndrome in Systemic Lupus Erythematosus: A Subset Characterized by a Systemic Inflammatory State.

Objective: An often-neglected subset of patients with systemic lupus erythematosus (SLE) is those with secondary Sjögren syndrome (SLE-sSS). Further, primary SS overlaps and can be difficult to delineate from SLE. To shed light on the SLE-sSS subset, we investigated a large and well-characterized SLE cohort, comparing patients with SLE-sSS and SLE patients without SS (SLE-nonsSS) and controls.

High levels of circulating interferons type I, type II and type III associate with distinct clinical features of active systemic lupus erythematosus.

Background And Aim: Interferons (IFNs) are considered to be key molecules in the pathogenesis of systemic lupus erythematosus (SLE). We measured levels of type I, II and III IFNs in a large cohort of patients with systemic lupus erythematosus (SLE) and controls and explored associations among high levels of different IFN types and distinct SLE features.

Methods: Four hundred ninety-seven well-characterized SLE patients and 322 population controls were included.

Serum Axl predicts histology-based response to induction therapy and long-term renal outcome in lupus nephritis.

Axl is a receptor tyrosine kinase with important functions in immune regulation. We investigated serum levels of soluble (s)Axl in lupus nephritis (LN) in association with renal disease activity, tissue damage and treatment response. We surveyed 52 patients with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III/IV LN and 20 healthy controls.

Glomerular membrane attack complex is not a reliable marker of ongoing C5 activation in lupus nephritis.

Complement plays an important role in the pathogenesis of lupus nephritis (LN). With the emergence of therapeutic complement inhibition, there is a need to identify patients in whom complement-driven inflammation is a major cause of kidney injury in LN. Clinical and histopathological data were obtained retrospectively from 57 biopsies with class III, IV, and V LN.

B cell alterations during BAFF inhibition with belimumab in SLE.

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, which exhibits multiple B cell abnormalities including expanded populations of memory B cells and elevated levels of autoantibodies. Belimumab is a monoclonal antibody targeting the B cell cytokine BAFF (a.k.

The Impact of Belimumab and Rituximab on Health-Related Quality of Life in Patients With Systemic Lupus Erythematosus.

Objective: Accumulating evidence supports an impaired health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). We investigated the effects of 2 biologic treatments on HRQoL of patients with SLE.

Methods: Patients with SLE from the Karolinska University Hospital treated with belimumab (n = 34) or rituximab (n = 35) were included; normative values derived from Swedish population-based controls matched for age and sex were used for the purpose of comparisons.

Smoking reduces the efficacy of belimumab in mucocutaneous lupus.

Objectives: Recently, we demonstrated a negative impact of smoking on belimumab efficacy in patients with systemic lupus erythematosus (SLE). Here, we particularly investigated clinical effects of belimumab and a potential impact of smoking in mucocutaneous and articular SLE.

Methods: We surveyed 62 SLE patients treated between 2011 and 2017.