This is the first study to find ubiquitinated proteins in NETs, and evidence for adaptive immune responses directed towards ubiquitinated NET proteins in SLE. The distinct differences in ubiquitin species profile in NETs compared with healthy controls may contribute to dampened anti-inflammatory responses observed in SLE. These results also support a role for extracellular ubiquitin in inflammation in SLE.

Formation of autoantibodies to carbamylated proteins (anti-CarP) is considered detrimental in the prognosis of erosive rheumatoid arthritis (RA). The source of carbamylated antigens and the mechanisms by which anti-CarP antibodies promote bone erosion in RA remain unknown. Here, we find that neutrophil extracellular traps (NETs) externalize carbamylated proteins and that RA subjects develop autoantibodies against carbamylated NET (cNET) antigens that, in turn, correlate with levels of anti-CarP. Transgenic mice expressing the human RA shared epitope (HLADRB1* 04:01) immunized with cNETs develop antibodies to citrullinated and carbamylated proteins. Furthermore, anti–carbamylated histone antibodies correlate with radiographic bone erosion in RA subjects. Moreover, anti–carbamylated histone–immunoglobulin G immune complexes promote osteoclast differentiation and potentiate osteoclast-mediated matrix resorption. These results demonstrate that carbamylated proteins present in NETs enhance pathogenic immune responses and bone destruction, which may explain the association between anti-CarP and erosive arthritis in RA.

This is the largest reported series of patients with SLE and PRES. We were able to corroborate the known risk factors for of PRES, and found two previously undescribed factors (lymphopenia and dyslipidemia), which suggests that endothelial dysfunction is a key element in PRES pathogenesis in lupus patients.

No abstract

Systemic lupus erythematosus (SLE) is a multi-organic autoimmune disease with a wide variety of clinical manifestations. However, hepatic dysfunction is not included in the diagnostic criteria for the disease and has not been recognized properly. The spectrum of hepatic involvement described in these patients ranges from abnormalities in liver function tests (LFTs) to fulminant hepatic failure. Usually, abnormalities in LFTs are only mild and transient, have a hepatocellular pattern and are not related to SLE but rather are mostly drug related. The most frequent finding on liver biopsy is steatosis (non-alcoholic fatty liver disease). Patients do not frequently progress to advanced chronic liver disease, and their outcome is favourable. Those who develop cirrhosis have traditional risk factors, such as other non-SLE-related conditions. In this work, we aim to review hepatic manifestations in patients with SLE, as well as the diagnostic and therapeutic approaches used for different liver diseases in these patients.