Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets

Kidney is a major target organ in both antiphospholipid syndrome(APS)and systemic lupus erythematosus(SLE).The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis(APSN-LN)is intricate and remains largely unrevealed.We proposed in present work,that generation of antiphospholipid antibodies(aPLs),especially those directed towards the oxidized neoepitopes,are largely linked with the redox status along with disease progression.Moreover,we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZW×BXSB F1 mice suffered from APSN-LN.SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties.In current study,we elaborated the therapeutic benefits of SM934 in male NZW×BXSB F1 mice,a murine model develops syndrome resembled human APS associated with SLE,for the first time.SM934 treatment comprehensively impeded autoantibodies production,inflammatory cytokine accumulation and excessive oxidative stress in kidney.Among others,we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets.Collectively,our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.

Association between autoimmune pancreatitis and systemic autoimmune diseases

AIM: To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4). METHODS: The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT). RESULTS: Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sj gren's syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto's thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level. CONCLUSION: The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.

Clinical characteristics of macrophage activation syndrome secondary to systemic lupus erythematosus

Objective To investigate the clinical features of macrophage activation syndrome(MAS)associated with systemic lupus erythematosus(SLE).Methods The clinical data of 15 patients with SLE-induced MAS diagnosed in Peking Union Medical College Hospital from July