Neutrophil proteases degrade autoepitopes of NET-associated proteins

Neutrophils can form neutrophil extracellular traps (NETs) to capture microbes and facilitate their clearance. NETs consist of decondensed chromatin decorated with anti-microbial proteins. Here, we describe the effect of neutrophil proteases on the protein content of NETs. We show that the neutrophil serine proteases degrade several neutrophil proteins associated with NETs. Interestingly, the anti-bacterial proteins associated with NETs, such as myeloperoxidase, calgranulin B and neutrophil elastase (NE), seem to be less susceptible to proteolytic degradation than other NET proteins, such as actin and MNDA. NETs have been proposed to play a role in autoimmune reactions. Our data demonstrate that a large number of the autoepitopes of NET proteins that are recognized by autoantibodies produced by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients are also removed by the proteases. In conclusion, neutrophil serine proteases have a major impact on the NET proteome and the proteolytic changes of NET-associated proteins may counteract autoimmune reactions to NET components.     

Clinical and subclinical cardiovascular disease in female SLE patients: Interplay between body mass index and bone mineral density

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.

Differences in SLE disease activity between patients of Caucasian and South‐East Asian/Chinese background in an Australian hospital

Aim: We performed a semiprospective and retrospective review of all admissions to a single institution of systemic lupus erythematosus (SLE) patients, admitted due to active disease. The aim was to describe differences in disease activity as a cause of hospital admissions between patients originating from South‐East Asia/China (SAC) and Caucasians. Method: There were 210 patients admitted for active disease, with a total of 567 admissions for active SLE over a 16‐year period. Allowing for patients who had left our database, there was a total of 3415 patient years of observation. Results: Patients from SAC with a flare requiring admission presented earlier in their disease course and with more active disease than did Caucasians (median SLE Disease Activity Index 13 vs. 8, P= 0.002). They had longer inpatient stays (7 vs. 5 days P = 0.03). There was a trend to higher rates of re‐presentation to hospital for flare (59% in SAC patients vs. 41% in Caucasians, P = 0.09) with more subsequent admissions (3 vs. 2 P = 0.06) despite a shorter period of observation. Conclusions: South‐East Asian/Chinese were more likely to be diagnosed with class III/IV glomerulonephritis and require cyclophosphamide both at presentation and subsequent admissions. More patients from SAC were readmitted to hospital for severe central nervous system disease after their first hospital admission. In this population, lupus patients had more severe flares and more frequently required admission for these than Caucasians.     

Immune therapy of lupus: what is on the horizon?

Systemic lupus erythematosus (SLE) is a complex disease whichhas posed a continuing challenge to scientists and cliniciansof diverse areas of specialization. It serves as a model forthe study of the mechanisms of autoimmunity—providingan important basis for the development of novel targeted therapiesin lupus and related conditions. The pathophysiology of SLE stems from the abnormal clearanceof apoptotic cells and/or endothelial activation. Material fromdying cells such as apoptotic blebs that are not efficientlyremoved may act as antigenic stimuli and lead to the developmentof autoantibodies with consequent formation of immune complexesand an inflammatory response in a variety of organ systems [1].This     

Pediatric lupus versus adult lupus role of the laboratory

Systemic lupus erythematosus (SLE) is the archetypical immunologic disease. Approximately 20% of patients present in the first two decades of life. This article highlights some of the differences between pediatric and adult onset lupus.Children are defined as different from adults on the basis of age. Lupus presents with different gender ratios based on hormonal or pubertal status with more significant skewing toward female patients in the childbearing years. Female patients in the childbearing years appear to have a higher relative risk for mortality. Despite this, children have greater disease severity at onset based on the number of patients who present with significant organ inflammation, the amount of corticosteroids required and the abnormalities in lupus serologies including autoantibodies and low complements. Children present frequently with congenital and acquired complement defects. Children have an increased risk of infections that can be confused with lupus. They have a higher risk of serious pneumococcal infection and may have less protection from vaccinations received at the time of disease onset.The clinical immunology laboratory is critical in the diagnosis and treatment of pediatric SLE. The rapid analysis and transfer of laboratory results can be life saving for the child with suspected new onset lupus. The laboratory is also helpful in determining disease activity through analysis of immunologic trends over time in pediatric lupus patients. This is especially important in the noncompliant adolescent patient who has a correlation between disease activity and lupus serologic tests. Finally, the clinical immunology laboratory is an important tool for better understanding of the immunologic phenomena associated with lupus and of disease pathophysiology.     

Bullous systemic lupus erythematosus with antiphospholipid syndrome

We report the case of a 44-year-old male with a 10-year history of manifestations of the rare form of bullous systemic lupus erythematosus (SLE) with coexisting antiphospholipid syndrome (APS) that remained undiagnosed until thrombotic-embolic episodes appeared and high titres of anticardiolipin (ACL) antibodies were detected. The patient fulfilled the criteria for SLE and the atypical cutaneous manifestations together with histopathological changes and a favourable response to sulphones were the grounds for the diagnosis of the bullous variety of SLE. Treatment with prednisolone, acenocoumarol and dapsone resulted in marked clinical improvement, reduction in antinuclear antibodies (ANAs) and normalization of ACL antibody titres.