Anti-ELANE polyclonal antibody

Loss of tolerance to nuclear antigens and multisystem tissue destruction is a hallmark of systemic lupus erythematosus (SLE). Although the source of autoantigen in lupus remains elusive, a compelling hypothetical source is dead cell debris that drives autoimmune activation. Prior reports suggest that neutrophil extracellular traps (NETs) and their associated death pathway, NETosis, are sources of autoantigen in SLE. However, others and we have shown that inhibition of NETs by targeting the NADPH oxidase complex and peptidylarginine deiminase 4 (PADI4) did not ameliorate disease in spontaneous murine models of SLE. Furthermore, myeloperoxidase and PADI4 deletion did not inhibit induced lupus. Since NET formation may occur independently of any one mediator, to address this controversy, we genetically deleted an additional important mediator of NETs and neutrophil effector function, neutrophil elastase (ELANE), in the MRL.Fas(lpr) model of SLE. ELANE deficiency, and by extension ELANE-dependent NETs, had no effect on SLE nephritis, dermatitis, antiself response, or immune composition in MRL.Fas(lpr) mice. Taken together with prior data from our group and others, these data further challenge the paradigm that NETs and neutrophils are pathogenic in SLE.

Objectives: Severe congenital neutropenia (SCN) is a primary immunodeficiency disease characterized by the early onset of recurrent infections and persistent severe neutropenia, with or without genetic defect. We aimed to study the different clinical features and hematological and bone marrow characteristics of patients with SCN and the non-congenital form of severe neutropenia (SN) with unknown etiology. Methods: Thirty-nine Chinese children with severe neutropenia for longer than 6months unrelated to virus infection or autoimmune diseases were enrolled in the study to analyse the clinical, laboratory, and molecular characteristics. They were followed clinically to observe their remission status. Results: Seven patients were found to have SCN mutations, including ELANE and G6PC3. Among 26 patients with close follow-up, one died for an unknown reason, and 10 resolved spontaneously with a median neutropenia duration of 14.5 months; these patients were designated as having recovered SN. The demographic characteristics of both groups were similar, with a median infection rate of 5 times/year. SCN patients had more frequent infection than recovered SN patients (4 times/year, P = 0.039). The median absolute neutrophil count (ANC) was 0.40 x 10(9)/L in SCN patients, which was significantly higher than 0.2 x 10(9)/L in SN with unknown etiology and 0.21 x 10(9)/L in recovered SN patients (P = 0.021, P = 0.017). The median monocyte count was 1.60 x 10(9)/L in SCN patients, which was also significantly higher than 0.57 x 10(9)/L in SN of unknown etiology and 0.55 x 10(9)/L in recovered SN patients (P = 0.018, P = 0.001). Bone marrow examinations demonstrated myeloid maturation arrest at the myelocyte-metamyelocyte stage in SCN patients and normal findings in SN with unknown etiology and recovered SN patients. Conclusions: Patients with severe neutropenia due to gene mutations demonstrate more serious symptoms than patients with unknown etiology. Patients with relatively higher ANC and monocyte counts are more likely to have known gene mutations. Future studies should focus on more detailed laboratory investigation, prolonged follow-up and advanced molecular biology tools to facilitate accurate diagnosis and effective treatment.