RESUMEN
Hereditary hemorrhagic telangiectasia (HHT) is a risk of infection, such as by brain abscess associated with pulmonary arteriovenous malformations. However, association between HHT and recurrent erysipelas is not well described. HHT can cause vessel malformations in organs, leading to various serious outcomes. Prophylactic treatment is effective, but many people with HHT are undiagnosed. HHT is not described as a risk factor for soft tissue infection, but may increase the risk of serious infections requiring hospitalization. Our 72-year-old female patient was admitted for recurrent erysipelas. Pulmonary nodules indicated pulmonary arteriovenous fistula on chest computed tomography. By recognizing this combination, although seemingly unrelated problems, we could diagnose HHT and the patient could receive adequate treatment to prevent life-threatening events. The recurrent erysipelas was likely associated with HHT. Recurrent erysipelas is an important presentation which may facilitate early diagnosis of HHT.
RESUMEN
The chromatin protein positive coactivator 4 (PC4) has multiple functions, including chromatin compaction. However, its role in immune cells is largely unknown. We show that PC4 orchestrates chromatin structure and gene expression in mature B cells. B-cell-specific PC4-deficient mice show impaired production of antibody upon antigen stimulation. The PC4 complex purified from B cells contains the transcription factors (TFs) IKAROS and IRF4. IKAROS protein is reduced in PC4-deficient mature B cells, resulting in de-repression of their target genes in part by diminished interactions with gene-silencing components. Upon activation, the amount of IRF4 protein is not increased in PC4-deficient B cells, resulting in reduction of plasma cells. Importantly, IRF4 reciprocally induces PC4 expression via a super-enhancer. PC4 knockdown in human B cell lymphoma and myeloma cells reduces IKAROS protein as an anticancer drug, lenalidomide. Our findings establish PC4 as a chromatin regulator of B cells and a possible therapeutic target adjoining IKAROS in B cell malignancies.