Major histocompatability complex class II (MHCII) molecules are an essential component of the mammalian adaptive immune response. The expression of MHCII genes is regulated by a cell-specific multiprotein complex, termed the MHCII enhanceosome. The heterotrimeric RFX complex is the key DNA-binding component of the MHCII enhanceosome. The RFX complex is comprised of three proteins, RFXB, RFXAP, and RFX5, all of which are required for DNA binding and activation of MHCII gene expression. Static light scattering and chemical cross-linking of the three RFX proteins show that RFXB and RFXAP are monomers and that RFX5 dimerizes through two separate domains. One of these domains, the oligomerization domain, promotes formation of a dimer of dimers of RFX5. In addition, we show that the RFX complex forms a 2:1:1 complex of RFX5.RFXAP.RFXB, which can associate with a further dimer of RFX5 to form a 4:1:1 complex through the oligomerization domain of RFX5. On the basis of these studies, we propose DNA-binding models for the interaction between the RFX complex and the MHCII promoter including a DNA looping model. We also provide direct evidence that the RFX5(L66A) point mutation prevents dimerization of the RFX complexes and propose a model for how this results in a loss of MHCII gene expression.

Content available: Audio Recording

No abstract

Introduction: We present a case series of patients with de novo autoimmune hepatitis following COVID vaccination. Case Description/Methods: A 68-year-old female with a past medical history of GERD and diverticulitis presents with the sudden onset of dark urine three days after receiving the second Moderna COVID vaccine. This is followed by right upper quadrant pain, jaundice, nausea, vomiting, and acholic stools. She denies any other associated symptoms. She endorses a family history of rheumatoid arthritis but denies any family history of liver disease/cancer. The patient is admitted and is found to have AST: 1,650, ALT: 1,604, alkaline phosphatase: 225, and total bilirubin: 4.1. Labs include positive IgG: 2,160 and positive ANA. Liver biopsy reveals intense lymphocytic, plasmacellular, eosinophilic, and neutrophilic hepatitis with bridging necrosis. Trichrome stain shows portal/periportal fibrosis. These findings are consistent with autoimmune hepatitis, and she is subsequently started on mycophenolate mofetil (MMF) and prednisone with improvement in her liver enzymes and symptoms. A 43-year-old female with a past medical history of keratoconus presents to the clinic with painless jaundice for one week. She endorses feeling fatigued as well for the past three months after receiving her second Moderna COVID vaccine. She denies any other associated symptoms. She endorses occasional alcohol use and denies any family history of liver disease/cancer or autoimmune disease. Her home medications include oral contraceptives and ibuprofen. Laboratory evaluation is remarkable for AST: 579, ALT: 800, alkaline phosphatase: 130, and total bilirubin: 6.7. MRI/MRCP is unremarkable for biliary obstruction or cirrhosis. She is found to have anti-smooth muscle antibody titers of 1:160 and IgG of 1,629. Liver biopsy reveals lymphoplasmacytic infiltrate with eosinophils, interface hepatitis, triaditis, necroinflammation with necrosis, and periportal septate fibrosis. The patient is diagnosed with autoimmune hepatitis and is started on MMF and prednisone with clinical improvement. Discussion: These cases demonstrate that COVID vaccination may play a role in inciting de novo autoimmune hepatitis in some patients. This can be a challenging situation for many clinicians to navigate, as COVID remains a significant threat to patients' health. Patients with autoimmune risk factors may benefit from closer laboratory evaluation and monitoring for any symptoms surrounding COVID vaccination.

Introduction: Weil's disease (Leptospirosis) is a relatively common worldwide zoonotic infection due to Leptospira spp. However, leptospirosis is underreported due to its low incidence in the United States and its variable presentation. Furthermore, leptospirosis-induced acute hepatic injury is extremely rare. The purpose of this case report to enlighten urban practitioners to consider testing for leptospirosis in patients with acute liver injury. We are reporting a rare case of leptospirosis induced acute liver injury. Case Description/Methods: A 38 year-old-male with no past medical history presented with 6-day history of fever, abdominal pain, N/V, fatigue and myalgia. On presentation patient was vitally stable, physical exam, ill appearing man with icterus sclera, mild tenderness in RUQ abdomen.