Complement-Mediated Thrombotic Microangiopathy in a Patient With Antiphospholipid Syndrome and Anti-glomerular Basement Membrane Antibodies.

Thrombotic microangiopathy (TMA) is a range of diseases characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ injury. Complement-mediated TMA is a rare, life-threatening subtype of TMA that occurs due to the uncontrolled activation of the alternative complement pathway in the absence of normal regulation, often resulting from deficiencies of various regulatory proteins. Anti-glomerular basement membrane (anti-GBM) disease, previously known as Goodpasture syndrome, is a life-threatening form of vasculitis in which immunoglobulin G autoantibodies bind to the alpha-3 chain of type IV collagen in alveolar and glomerular basement membranes. We present the case of a patient with a history of antiphospholipid syndrome who was diagnosed with complement-mediated TMA during hospital admission for elevated anti-GBM antibody titers discovered during an outpatient evaluation for elevated creatinine levels. Upon admission, treatment was started for presumed anti-GBM disease, including high-dose intravenous methylprednisolone injections and multiple plasmapheresis sessions. However, renal biopsy results showed no evidence of anti-GBM disease, but rather evidence of TMA. Subsequent laboratory studies revealed decreased complement levels, suggestive of a diagnosis of complement-mediated TMA. The patient was started on rituximab and eculizumab infusions, and she was discharged in stable condition after a 15-day hospitalization with outpatient appointments scheduled for genetic testing and further infusions. This case illustrates the importance of recognizing the key clinical and diagnostic features of complement-mediated TMA to promptly initiate appropriate therapy.

Genera of Inocybaceae: New skin for the old ceremony.

A six-gene phylogeny of the Inocybaceae is presented to address classification of major clades within the family. Seven genera are recognized that establish a global overview of phylogenetic relationships in the Inocybaceae. Two genera-Nothocybe and Pseudosperma-are described as new. Two subgenera of Inocybe-subg. Inosperma and subg. Mallocybe-are elevated to generic rank. These four new genera, together with the previously described Auritella, Tubariomyces, and now Inocybe sensu stricto, constitute the Inocybaceae, an ectomycorrhizal lineage of Agaricales that associates with at least 23 plant families worldwide. Pseudosperma, Nothocybe, and Inocybe are recovered as a strongly supported inclusive clade within the family. The genus Nothocybe, represented by a single species from tropical India, is strongly supported as the sister lineage to Inocybe, a hyperdiverse genus containing hundreds of species and global distribution. Two additional inclusive clades, including Inosperma, Tubariomyces, Auritella, and Mallocybe, and a nested grouping of Auritella, Mallocybe, and Tubariomyces, are recovered but with marginal statistical support. Overall, the six-gene data set provides a more robust phylogenetic estimate of relationships within the family than do single-gene and single-gene-region estimates. In addition, Africa, India, and Australia are characterized by the most genera in the family, with South America containing the fewest number of genera. A total of 180 names are recombined or proposed as new in Inosperma, Mallocybe, and Pseudosperma. A key to genera of Inocybaceae is provided.