Primary membranous nephropathy (MN) is an autoimmune disease caused by autoantibody binding to podocytes in human glomeruli. The disease leads to end-stage renal disease in about 30% of patients, even after treatment with immunosuppressive therapies. The discovery of serum autoantibodies against the Phospholipase A 2 Receptor 1 (PLA 2 R1) in 70% of patients with MN has resulted in substantial improvements of diagnosis, disease classification, treatment and prognosis. However, due do the lack of a rodent animal model, it has not been formally proven that human PLA 2 R1-antibodies induce disease. With the aim to define the role of human PLA 2 R1-antibodies in MN pathogenesis, we studied the impact of human PLA 2 R1-antibodies in minipigs. Methods: For passive transfer experiments, minipigs received plasma or purified total IgG from patients with PLA 2 R1-associated MN or from healthy controls. Further, active immunization was performed using human recombinant PLA 2 R1 protein. The presence of PLA 2 R1antibodies and development of proteinuria were monitored in the serum and urine of minipigs. Kidney samples were analyzed using immunohistochemistry, immunofluorescence and electron microscopy. Results: PLA 2 R1 is expressed on the podocytes on the minipig in a pattern identical to that in human kidneys. Human PLA 2 R1-antibodies bind to the minipig PLA 2 R1 both in vitro and in vivo. The passive transfer experiments using plasma or purified IgG from patients with PLA 2 R1-associated MN to minipigs resulted in development of all functional and morphologic characteristics of human MN in minipigs. Human PLA 2 R1-antibodies were detectable in the blood of the minipigs and could be eluted from the glomeruli of the minipigs. Importantly, the eluted human PLA 2 R1-antibodies were of the IgG4 subclass. Transfer of healthy human plasma of total IgG did not lead to any histomorphological changes resembling MN. The active immunization of minipigs with the human PLA 2 R1 protein led to generation of anti-PLA 2 R1 antibodies, which also resulted in the induction of all characteristics of human MN in the kidneys of the minipigs. Conclusions: By applying a translational approach from humans to minipigs we demonstrated that human PLA 2 R1-antibodies are pathogenetic and induce MN. In addition, we created a humanized model of autoimmune PLA 2 R1-induced MN by active immunization of minipigs with PLA 2 R1.

A 62-year-old man was admitted to the emergency department with hypotension and altered consciousness. On physical examination, he had hyperpigmentation of the skin and mucous membranes. Admission tests revealed hypoglycemia, hyponatremia, and hyperkalemia. Fluid resuscitation was initiated with no improvement in blood pressure. Because adrenal crisis was suspected, blood samples for cortisol and adrenocorticotropic hormone were collected before commencing hydrocortisone, after which blood pressure improved and electrolyte disturbances disappeared. The tests revealed decreased serum cortisol and an increase in adrenocorticotropic hormone. A magnetic resonance imaging scan of the abdomen revealed evidence of bilateral adrenal hemorrhage. Positive antiphospholipid antibodies were detected during the investigations. This case underscores the importance of prompt evaluation of clinical signs and symptoms that may indicate adrenal crisis.

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BackgroundThe term aspergillosis from a clinical point of view includes allergic bronchopulmonary aspergillosis, invasive forms of the airway, cutaneous and extrapulmonary aspergillosis and finally chronic non-invasive or semi-invasive pulmonary forms. All of them produced by different species of Aspergillus. In addition, the presentation of aspergillosis together with tuberculosis are rare in scientific literature. We report a case of Chronic pulmonary aspergillosis and tuberculosis in a 72-year-old man Case presentation The patient is a 72-year-old man who was admitted with a 2-year history of constitutional syndrome, dry cough and moderate exertion dyspnea. Chest X-ray showed a rounded mass in the upper lobe of the left lung surrounded by radiolucent areas that suggest cavitations. Computed tomography with chest contrast revealed "tree in bud" pattern in the upper right and middle lobe and lesions of a cystic appearance with the presence of multiple masses with a density of soft tissues. Bronchioalveolar lavage analyses demonstrate Aspergillus fumigatusConclusionsChronic cavity aspergillosis is an uncommon form characterized by cavitation, fibrosis and pleural thickening seen in immunocompetent or mildly immunocompromised patients with chronic respiratory diseases, especially TB.