Upadacitinib as Novel Treatment for Rheumatoid Arthritis with T-Cell Granular Lymphocytic Leukemia: A Case Report and Narrative Review

T-cell large granular lymphocyte (T-LGL) leukemia is a rare and indolent clonal disorder of LGLs, associated with rheumatoid arthritis and neutropenia. The authors present a case of a 62-year-old male with rheumatoid arthritis (RA) who was diagnosed with T-LGL leukemia, with predominant neutropenia, and a poor response to conventional treatment. Subsequently, tofacitinib (a Janus Kinase 1 and 3 inhibitor, [JAK1/3 inhibitor]) resulted in improvement of the patient’s RA symptoms and temporary improvement of the neutropenia. Ultimately, upadacitinib (a specific JAK1 inhibitor) resulted in further improvement of the neutropenia and control of his RA. To the best of our knowledge, this is the first case report of coexisting RA and LGL leukemia that was treated with upadacitinib and showed clinical improvement.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Membrane (M) and Spike (S) Proteins Antagonize Host Type I Interferon Response

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide and has infected more than 250 million people. A typical feature of COVID-19 is the lack of type I interferon (IFN-I)-mediated antiviral immunity in patients. However, the detailed molecular mechanisms by which SARS-CoV-2 evades the IFN-I-mediated antiviral response remain elusive. Here, we performed a comprehensive screening and identified a set of SARS-CoV-2 proteins that antagonize the IFN-I response. Subsequently, we characterized the mechanisms of two viral proteins antagonize IFN-I production and downstream signaling. SARS-CoV-2 membrane protein binds to importin karyopherin subunit alpha-6 (KPNA6) to inhibit interferon regulatory factor 3(IRF3) nuclear translocation. Further, the spike protein interacts with signal transducer and activator of transcription 1 (STAT1) to block its association with Janus kinase 1 (JAK1). This study increases our understanding of SARS-CoV-2 pathogenesis and suggests novel therapeutic targets for the treatment of COVID-19.