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Concept: Antiphospholipid syndrome


This study aimed to describe the long-term outcome and immunological status of children born to mothers with antiphospholipid syndrome, to determine the factors responsible for childhood abnormalities, and to correlate the child’s immunological profile with their mothers.

Concepts: Child, Childhood, Antiphospholipid syndrome, The Child


GARDASIL (Merck & Co., Inc., Whitehouse Station, NJ, USA) is a quadrivalent human papillomavirus (HPV4) vaccine. An epidemiological study was undertaken to evaluate concerns about the potential for HPV4 vaccination to induce serious autoimmune adverse events (SAAEs). The vaccine adverse event reporting system (VAERS) database was examined for adverse event reports associated with vaccines administered from January 2006 through December 2012 to recipients between 18 and 39 years old with a listed residence in the USA and a specified female gender. It was observed that cases with the SAAE outcomes of gastroenteritis (odds ratio (OR) = 4.6, 95 % confidence interval (CI) = 1.3-18.5), arthritis (OR = 2.5, 95 % CI = 1.4-4.3), systemic lupus erythematosus (OR = 5.3, 95 % CI = 1.5-20.5), vasculitis (OR = 4, 95 % CI = 1.01-16.4), alopecia (OR = 8.3, 95 % CI = 4.5-15.9), or CNS conditions (OR = 1.8, 95 % CI = 1.04-2.9) were significantly more likely than controls to have received HPV4 vaccine (median onset of SAAE symptoms from 6 to 55 days post-HPV4 vaccination). Cases with the outcomes of Guillain-Barre syndrome (OR = 0.75, 95 % CI = 0.42-1.3) or thrombocytopenia (OR = 1.3, 95 % CI = 0.48-3.5) were no more likely than controls to have received HPV4 vaccine. Cases with the general health outcomes of infection (OR = 0.72, 95 % CI = 0.27-1.7), conjunctivitis (OR = 0.88, 95 % CI = 0.29-2.7), or diarrhea (OR = 1.01, 95 % CI = 0.83-1.22) were no more likely than controls to have received HPV4 vaccine. Previous case series of SAAEs and biological plausibility support the observed results. Additional studies should be conducted to further evaluate the potential biological mechanisms involved in HPV4 vaccine-associated SAAEs in animal model systems, and to examine the potential epidemiological relationship between HPV4 vaccine-associated SAAEs in other databases and populations.

Concepts: Immune system, Epidemiology, HPV vaccine, Rheumatoid arthritis, Rheumatology, Systemic lupus erythematosus, Lupus erythematosus, Antiphospholipid syndrome


Systemic lupus erythematosus (SLE) is associated with increased risk of cardiovascular disease because of the premature development of atherosclerotic plaques. It is a complex autoimmune disorder characterized by the production of autoantibodies against self-antigens. These self-antigens include nucleic acids, blood cells, coagulation proteins, and phospholipids that cause disease manifestations in virtually every organ system. Over the last 3 decades, treatment modalities and preventive therapies for SLE patients have substantially improved, producing decreases in mortality from the disease. However, as life expectancy among SLE patients has increased, the incidence of cardiovascular disease has increased as well. Multiple studies suggest that patients with SLE have between a 9-fold and 50-fold increase in risk of developing cardiovascular disease compared with non-SLE patients. It is thought that these increases result from a combination of traditional risk factors, as well as the dysfunctional immune and inflammatory mechanisms in patients with SLE. At this time, there is limited evidence to support specific treatment guidelines for the prevention of cardiovascular disease in SLE patients. The treatment of these patients currently remains to identify and treat the traditional and SLE-related risk factors.

Concepts: Immune system, Cell nucleus, Rheumatoid arthritis, Rheumatology, Systemic lupus erythematosus, Lupus erythematosus, Antiphospholipid syndrome, Malar rash


INTRODUCTION: Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China. METHODS: Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, ADAMTS-13 activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed. RESULTS: In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09+/-4.64 vs. 4.75+/-3.13 g/24h, P=0.007) and serum creatinine (159, 86-215 vs. 81, 68-112 mumol/l, P<0.001), higher scores of total activity indices (AI) (P<0.001), endocapillary hypercellularity (P<0.001), subendothelial hyaline deposits (P=0.003), interstitial inflammation (P=0.005), glomerular leukocyte infiltration (P=0.006), total chronicity indices (CI) (P=0.033), tubular atrophy (P=0.004) and interstitial fibrosis (P=0.018). Patients with renal TMA presented with poorer renal outcome (P=0.005) compared with non-TMA group. Renal TMA (hazard ratio (HR): 2.772, 95% confidence interval: 1.009-7.617, P=0.048) was an independent risk factor for renal outcome in patients with lupus nephritis. The renal outcome was poorer for those with both C4d deposition and decreased serum complement factor H in TMA group (P=0.007). CONCLUSIONS: There were various causes of renal TMA in lupus nephritis. Complement over-activation via both classical and alternative pathways might play an important role in the pathogenesis of renal TMA in lupus nephritis.

Concepts: Immune system, Rheumatology, Systemic lupus erythematosus, Glomerulonephritis, Complement system, Thrombocytopenia, Lupus nephritis, Antiphospholipid syndrome


Triple positivity (positive Lupus Anticoagulant, anticardiolipin and anti β2-glycoptrotein I antibodies) identifies the pathogenic autoantibody (anti Domain I of β2-glycoptroteinI) that is present in patients with definite Antiphospholipid Syndrome (APS). This is supported by the fact that aβ2GPI antibodies obtained by affinity purification in these patients possess LA activity. Moreover, patients and carriers of this profile carry a much higher risk of thrombosis and pregnancy loss than APS patients with positivity for only one of the tests. Thus, very different risk categories exist among patients with APS as well as among carriers of aPL. Clinical studies and interventional trials should first take these high risk subjects into consideration.

Concepts: Immune system, The Canon of Medicine, Avicenna, Warfarin, Autoantibody, Antiphospholipid syndrome, Dilute Russell's viper venom time, Lupus anticoagulant


This study compares the expression levels of tumor necrosis factor ligand superfamily member 4 (TNFSF4) and TNF-R-associated factor 2 (TRAF2) mRNAs in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) against healthy controls. The association of SLE disease activity index (SLEDAI) and clinical features of SLE with altered expression levels of TNFSF4 and TRAF2 mRNAs were also evaluated.

Concepts: Cell nucleus, Rheumatology, Systemic lupus erythematosus, Lupus erythematosus, Glomerulonephritis, Lupus nephritis, Cyclophosphamide, Antiphospholipid syndrome


Catastrophic antiphospholipid syndrome (CAPS) has been associated with several bacterial and viral infections. We presented a case report of a woman who presented to the emergency room, with influenza A virus subtype H1N1 which progressed to CAPS in the course of 17 days. We believe this is the first case that links CAPS with H1N1.

Concepts: Bacteria, Microbiology, Virus, Infection, Influenza, Influenza vaccine, Antiphospholipid syndrome, Influenzavirus A


Antiphospholipid syndrome (APS), as a primary disease or a secondary syndrome in systemic lupus erythematosus (SLE), is characterized by the presence of antiphospholipid antibodies (aPL) and a clinical event. It is likely that both genetic and environmental factors lead to the development of aPL and progression to disease. However, the precise mechanisms are not known. We hypothesize that innate immune activation plays a dual role in APS and SLE, both in the production of aPL (i.e. “initiation” phase) and in the development of a clinical event (i.e. “effector” phase). We have shown that mice immunized with certain phospholipid-binding proteins (e.g. β2-glycoprotein I (β2GPI)), plus a concomitant trigger of innate immunity (e.g. a toll-like receptor 4 (TLR4) ligand), produce a strong β2GPI-reactive T cell response, resulting in high levels of aPL as well as other SLE autoantibodies. We propose that β2GPI, through its interaction with apoptotic cells, permits B cell epitope spread to multiple SLE autoantibodies. Innate immune activation is also implicated in a murine model of aPL-enhanced thrombus formation. This dual role of innate immune activation provides new insight into the mechanisms involved in the initiation of aPL and other SLE-related autoantibodies, as well as the development of aPL-mediated disease.

Concepts: Immune system, Cell nucleus, Innate immune system, Rheumatology, Systemic lupus erythematosus, Lupus erythematosus, Thrombocytopenia, Antiphospholipid syndrome


To investigate whether angiogenic factors are associated with risk of developing preeclampsia in pregnant women with systemic lupus erythematosus (SLE).

Concepts: Rheumatology, Systemic lupus erythematosus, Lupus erythematosus, Proteinuria, Antiphospholipid syndrome, Malar rash


Primary Sjögren’s syndrome is an autoimmune disease affecting the function of exocrine glands. Tumor necrosis factor receptor-1 (TNFR1) is involved in apoptosis through extrinsic pathway initiation. The level of soluble TNFR1 is reported increased in rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren’s syndrome patients. The TNFR1 gene contains a polymorphism that replaced an adenine with a cytosine at the -383 in promoter region position. The TNFR1-383 A˃C polymorphism has been associated with rheumatic diseases. We examined the association between the TNFR1-383 A˃C polymorphism and TNFR1 soluble (sTNFR1) levels and laboratory and clinical characteristics in primary Sjögren’s syndrome patients. Eighty-two patients with primary Sjögren’s syndrome classified using the American-European criteria and 84 healthy subjects were studied. Sjögren’s Syndrome Disease Activity Index (SSDAI) and Sjögren’s Syndrome Disease Damage Index were performed for all patients. Genotypic and allelic frequencies were similar in both groups (P = 0.317 and P = 0.329, respectively). sTNFR1 levels were similar in patients and healthy subjects (P = 0.051). High levels of C-reactive protein (P = 0.045) and rheumatoid factor (P = 0.040) in patients with the A˃C genotype were observed. In these patients, the SSDAI score was higher than in A˃A genotype carriers (P = 0.045). This is the first study that to examine the TNFR1-383 A˃C polymorphism in primary Sjögren’s syndrome patients. Clinical parameters and SSDAI index were associated in A˃C genotype carriers. However, further studies with a larger sample are necessary to verify the association between primary Sjögren’s syndrome and the TNFR1-383 A˃C polymorphism.

Concepts: Gene, Rheumatoid arthritis, Rheumatology, Systemic lupus erythematosus, Lupus erythematosus, Sjögren's syndrome, Arthritis, Antiphospholipid syndrome