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Abstract 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. Methods Repeated 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. Results Women 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. Conclusion Our 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.

Objective: In patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients. Methods: First, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models. Results: The epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p < 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q. Conclusion: In this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE. [ABSTRACT FROM AUTHOR]

ObjectiveIn patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients.MethodsFirst, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models.ResultsThe epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p < 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q.ConclusionIn this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.

The article discusses research which investigated safety and effectiveness of rituximab in anti-synthetase antibody positive and negative patients with idiopathic inflammatory myopathy (IIM). Topics explored include the clinical characteristics and prevalence of IIM, the selection and evaluation of patients from the Swedish Rheumatology Quality Register, and brief details about the rituximab dosage administered and patient outcomes observed.

Objective: To describe the clinical and serological features of a prospectively followed cohort of early diagnosed systemic lupus erythematosus (SLE) patients during a one-year follow-up period. Methods: SLE patients with disease duration less than 12 months were consecutively enrolled in a multicentre, prospective study. At study entry and then every 6 months, a large panel of data was recorded. Results: Of 260 patients enrolled, 185 had at least 12 months of follow-up; of these, 84.3% were female, 92.4% were Caucasians. Mean diagnostic delay was about 20 months; higher values of European Consensus Lupus Activity Measurement (ECLAM) and of organs/systems involved were both associated with shorter diagnostic delay. Clinical and serological parameters improved after study entry. However, patients' quality of life deteriorated and cardiovascular risk factors significantly increased. About one-third of patients with active disease at study entry went into remission (ECLAM=0). Negative predictors for remission were: oral ulcers, arthritis, low C4, anti-SSB (Ro) antibodies and therapy with mycophenolate. There was a widespread use of glucocorticoids both at baseline and during follow-up. Conclusion: Clinical symptoms and serological parameters improve during the first period after diagnosis. However, patients' quality of life deteriorates. The widespread use of glucocorticoids is probably the reason for the early significant increase of some cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Antinuclear antibodies (ANAs) are useful for the diagnosis of ANA-associated systemic rheumatic disease (AASRD). The objective of this study was the evaluation of an immunoassay that detects antibodies to a mixture of 17 antigens as an alternative to indirect immunofluorescence (IIF). Methods: Nine thousand eight hundred and fifty-six consecutive patients tested for ANAs were tested by IIF and EliA connective tissue disease screen (Thermo-Fisher). Medical records were reviewed for 2475 patients, including all patients that tested positive/equivocal by either test and a selection of 500 patients that tested negative. Results: Concordance between IIF and EliA was 83.1%. AASRD was found in 12.8% of IIF-positive patients, 30.2% of EliA-positive patients and 0.4%, 46.6%, 5.8% and 3.0% of patients that tested, respectively, double negative, double positive, single positive for EliA and single positive for IIF. The association with AASRD increased with increasing antibody level. IIF and EliA were positive in, respectively, 90.4% and 69.9% of systemic lupus erythematosus (n=83), 100% and 84.1% of systemic sclerosis (n=63), 86.7% and 93.3% of Sjögren's syndrome (n=45), 88.2% and 52.9% of polymyositis/dermatomyositis (n=17), and in all cases of mixed connective tissue disease (n=8). The specificity was projected to be 94%–96% for EliA and 86% for IIF. When all AASRDs were taken together, the areas under the curve of receiver operator curves were similar between IIF and EliA. Conclusions: The positive predictive value for AASRD was higher for EliA than for IIF, but, depending on the disease, EliA might fail to detect antibodies that are detected by IIF. Combining immunoassay with IIF adds value. [ABSTRACT FROM AUTHOR]

Objectives Rheumatoid arthritis (RA) patients show low serum levels of the Ag dipeptidyl peptidase IV (DPP-IV/CD26), both soluble CD26 (sCD26) concentration and its DPP-IV activity. The aim of this study was to test if anti-DPP-IV/CD26 Abs (Anti-CD26) cleared sCD26. Design & methods Serum Anti-CD26 and Total titers (as comparison) of isotypes IgA, IgM and IgG as well as sCD26 concentration and DPP-IV activity were measured in a cohort of RA patients undergoing different biological and non-biological therapies (n = 105) and controls (n = 50). Results Anti-CD26 levels were increased approximately two-fold for each isotype in RA, were not related to the sCD26 clearance, showed several correlations with disease activity parameters, were significantly higher in smokers and they were not ACPA. Anti-CD26 Igs showed high diagnostic power (82% sensitivity and 96% specificity) and their levels differed amongst the different groups of patients stratified by the type of therapy. Conclusions As DPP-IV/CD26 is associated to factors triggering RA in the lung and periodontal tissue, these results suggest that Anti-CD26 isotypes may participate in pathogenesis and may be useful as biomarkers for earlier diagnosis and/or precision medicine. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is often characterized by the presence of rheumatoid factor, anti-citrullinated protein antibodies, and bone erosions. Current therapies can compromise immunity, leading to risk of infection. The interleukin-20 receptor (IL-20R) axis comprising IL-19, IL-20, and IL-24 and their shared receptors activates tissue homeostasis processes but not the immune system. Consequently, modulation of the IL-20R axis may not lead to immunosuppression, making it an interesting drug target. We evaluated the role of the IL-20R axis in RA and associations between plasma cytokine levels and clinical disease., Methods: Plasma IL-19, IL-20, and IL-24 levels were measured in early RA patients during a treat-to-target strategy by enzyme-linked immunosorbent assays. The IL-20R1 and IL-22R1 levels in paired peripheral blood mononuclear cells and synovial fluid mononuclear cells from a different cohort of RA patients were evaluated by flow cytometry and confocal microscopy. Monocytes/macrophages were stimulated with heat-aggregated human immunoglobulin immune complexes and immune complexes containing citrullinated fibrinogen, and osteoclasts were incubated with IL-19, IL-20, and IL-24., Results: The plasma concentrations of IL-20 and IL-24 (but not IL-19) were increased in early RA patients compared with healthy controls (both P < 0.002) and decreased after 6 months of treatment (both P < 0.0001). The expression of IL-22R1 (but not IL-20R1) was increased on monocytes from RA synovial fluid compared with monocytes from both RA and healthy control peripheral blood. The plasma concentrations of IL-20 and IL-24 were increased in rheumatoid factor and anti-citrullinated protein antibody positive compared with negative early RA patients (all P < 0.0001). Immune complexes stimulated the production of the IL-20R cytokines by monocytes/macrophages. Increased baseline plasma concentrations of IL-20 and IL-24 were associated with Sharp-van der Heijde score progression after 24 months (Spearman's rho = 0.19 and 0.26, both P < 0.05) in the early RA patients. The IL-22R1 was expressed by osteoclast precursors and in multinucleated osteoclasts. IL-20 and IL-24 increased the secretion of monocyte chemoattractant protein 1 by these cells., Conclusions: This study suggests that IL-20 and IL-24 link RA-associated autoantibodies with radiographic progression via the IL-22R1. Modulation of this axis holds promise as feasible anti-erosive treatment modalities in seropositive RA.