Lack of T cells in Act1-deficient mice results in elevated IgM-specific autoantibodies but reduced lupus-like disease

Act1 is a negative regulator of B‐cell activation factor of the TNF family (BAFF) and CD40L‐induced signaling. BALB/C mice lacking Act1 develop systemic autoimmunity resembling systemic lupus erythematosus (SLE) and Sjögren's syndrome (SjS). SLE and SjS are characterized by anti‐nuclear IgG autoantibody (ANA‐IgG) production and inflammation of peripheral tissues. As autoantibody production can occur in a T‐cell dependent or T‐cell independent manner, we investigated the role of T‐cell help during Act1‐mediated autoimmunity. Act1‐deficiency was bred onto C57Bl/6 (B6.Act1^?/?) mice and B6.TCRβ^?/?TCRδ^?/?Act1^?/? (TKO) mice were generated. While TCRβ/δ‐sufficient B6.Act1^?/? mice developed splenomegaly and lymphadenopathy, hypergammaglobulinemia, elevated levels of ANA‐IgG, and kidney pathology, TKO mice failed to develop any such signs of disease. Neither B6.Act1^?/? nor TKO mice developed SjS‐like disease, suggesting that epigenetic interactions on the BALB/C background are responsible for this phenotype in BALB/C.Act1^?/? mice. Interestingly, BAFF‐driven transitional B‐cell abnormalities, previously reported in BALB/C.Act1^?/? mice, were intact in B6.Act1^?/? mice and largely independent of T cells. In conclusion, T cells are necessary for the development of SLE‐like disease in B6.Act1^?/? mice, but not BAFF‐driven transitional B‐cell differentiation.     

A 5-year study of the performance of the Verigene Gram-positive blood culture panel in a pediatric hospital

High accuracy of direct from positive blood culture molecular panels is imperative, particularly for the detection of resistance determinants as it allows for antimicrobial optimization prior to conventional susceptibility testing. In this study, we provide extensive data since implementation of the Verigene Gram-positive blood culture panel (BC-GP) in 2013. Within 5 years, 1636 blood culture bottles positive for a Gram-positive organism were tested on the BC-GP panel. The BC-GP panel identified 1520 Gram-positive organisms in 1636 (92.9%) blood cultures tested. For positive blood cultures, we observed 96.4% (806/834) concordance to the species level. Compared with conventional antimicrobial susceptibility testing, the positive percent agreement (PPA) of methicillin-resistant SA (MRSA) (50) and methicillin-resistant SE (MRSE) (365) was 100%. The mecA gene was detected in two methicillin-susceptible Staphylococcus aureus (MSSA) and one methicillin-susceptible S. epidermidis (MSSE) with a negative percent agreement (NPA) of 99.1% (221/223) and 99.2% (120/121), respectively. The PPA and NPA for vancomycin-resistant Enterococcus faecium (VRE) was 100%. The BC-GP panel demonstrated excellent performance and clinicians can confidently de-escalate antimicrobial therapy in the absence of mecA and vanA/B gene.