Summary Polymorphisms in the transcription factor interferon (IFN) regulatory factor 5 (IRF5) have been identified that show strong association with increased risk of developing the autoimmune disease systemic lupus erythematosus (SLE). A potential pathologic role for IRF5 in SLE development is supported by the fact that increased IRF5 mRNA and protein abundance are observed in primary blood cells of SLE patients that correlate with increased risk of developing the disease. Here, we demonstrate that IRF5 is required for pristane-induced SLE via its ability to control multiple facets of autoimmunity. We show that IRF5 has a distinct influence on pathological hypergammaglobulinemia and provide evidence for its role in regulating IgG1 class switching and antigen specificity. Examination of in vivo cytokine expression (and autoantibody production) identified an imbalance in Irf5−/− mice favoring Th2 polarization. In addition, we provide clear evidence that loss of Irf5 significantly weakens the in vivo type I IFN signature critical for disease pathogenesis in this model of murine lupus. Together, these findings demonstrate the global effect that IRF5 has on autoimmunity and provides significant new insight into how overexpression of IRF5 in blood cells of SLE patients may contribute to disease pathogenesis.

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Systemic lupus erythematosus (SLE) is known for marked heterogeneity of clinical manifestations and pathogenesis with the potential of affecting virtually every organ system. Neuropsychiatric manifestations of systemic lupus erythematosus are difficult to recognize and treat as they remain one of the least understood complications of this disease. Our case describes a 42-year-old female who presented to the emergency department with proximal weakness of the left lower extremity, magnetic resonance imaging (MRI) of the brain revealed a small infarct in the medial left temporal lobe. Workup was remarkable for elevated inflammatory markers. The patient was discharged on appropriate medical therapy however returned to the emergency department one month later after a witnessed focal seizure. Neuroimaging was consistent with cerebral vasculitis and autoimmune workup revealed a diagnosis of SLE. Our case highlights the importance of recognizing that neuropsychiatric manifestations of SLE often occur in absence of other systemic manifestations and can be the initial presentation of SLE. Maintaining a high clinical suspicion for Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) could afford the ability to halt disease progression in the earliest of phases and thus improve quality of life through early administration of appropriate pharmacotherapy.

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Purple urine bag syndrome has been identified since 1978 with higher prevalence among those individuals who reside in nursing homes and those with a long-term indwelling Foley catheter. In addition to prolonged catheterization and institutionalization, the female gender, alkaline urine, and chronic constipation are other predisposing factors. Purple urine bag syndrome is also associated with bacterial urinary tract infections that produce enzymes, sulphatase and phosphatase involved in the breakdown of tryptophan. The final metabolites include indigo, which has a blue hue, and indirubin with a red hue, which when mixed, produce a purple color. Treatment includes antibiotics for the associated urinary tract infection as well as exchange of the Foley catheter and appropriate catheter care using proper sterile technique. However, there are no set guidelines instructing how aggressively to treat. The patient is a 60-year-old male who presented to the hospital for clogged chronic Foley catheter who developed purple urine bag syndrome.

Polymorphisms in the transcription factor interferon (IFN) regulatory factor 5 (IRF5) have been identified that show strong association with increased risk of developing the autoimmune disease systemic lupus erythematosus (SLE). A potential pathologic role for IRF5 in SLE development is supported by the fact that increased IRF5 mRNA and protein abundance are observed in primary blood cells of SLE patients that correlate with increased risk of developing the disease. Here, we demonstrate in clean littermates that IRF5 is required for pristane-induced lupus via its ability to control multiple facets of autoimmunity. We show that IRF5 has a distinct influence on pathological hypergammaglobulinemia and provide evidence for its role in regulating IgG1 class switching and antigen specificity. Examination of in vivo cytokine expression (and autoantibody production) identified an imbalance in Irf5-/- mice favoring Th2 polarization. In addition, we provide clear evidence that loss of Irf5 significantly weakens the in vivo type I IFN signature that is critical for disease pathogenesis in this model of murine lupus. Together, these findings demonstrate the global effect that IRF5 has on autoimmunity and provides significant new insight into how overexpression of IRF5 in blood cells of SLE patients may contribute to disease pathogenesis.

Introduction: Unroofed coronary sinus-atrial septal defect (CS-ASD) is a very rare anomaly that may be easily missed by transthoracic echocardiography. Case: A 59 year old woman presented with chronic and progressively worsening dyspnea. TTE demonstrated preserved ejection fraction, right ventricular and atrial dilation, and elevated pulmonary artery pressures. Color doppler demonstrated a persistent diastolic flow at the interatrial septum immediately above the plane of the tricuspid valve, suspicious for atrial septal defect (Fig. 1). Such aberrant flow was not observed on multiple prior TTEs. Decision-Making: Given the uncertain nature of the abnormal color flow seen, further imaging was pursued with a gated Cardiac CT with contrast. CT imaging demonstrated a dilated coronary sinus with a communication between the roof of the terminal coronary sinus and the left atrium, consistent with an unroofed coronary sinus-atrial septal defect (CS-ASD) (Fig. 2). There was no evidence of a persistent left superior vena cava. Cardiac MRI demonstrated a significant right to left shunt with a Qp/Qs of 1.53 using phase contrast imaging. Discussion: CS-ASD is a very rare cardiac anomaly and is the most uncommon type of ASD (<1%), often associated with a persistent left superior vena cava. Given the posterior nature of the defect, it is often missed on TTE. In our case, suspicion was raised by a small abnormal color jet of flow coming from the interatrial septum. Cardiac CT is an excellent diagnostic modality for CS-ASD given its excellent visuospatial capabilities and ability to evaluate pulmonary veins. Cardiac MRI may serve as a helpful adjunct in quantification of shunt flow.

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