When the Cure Becomes the Problem: A Case Report of Immune Reconstitution Inflammatory Syndrome Associated With Varicella Encephalitis.

Immune reconstitution inflammatory syndrome (IRIS) describes a constellation of inflammatory symptoms that develop following the initiation of antiretroviral therapy (ART) in patients with advanced human immunodeficiency virus (HIV). Here, we present a case of a 39-year-old male-to-female transgender patient with advanced HIV who was started on ART during a hospitalization for acute encephalopathy due to a combination of methicillin-resistant Staphylococcus aureus (MRSA) meningitis and varicella encephalitis. After adequate treatment of these infections and five weeks after initiation of ART, she developed inflammatory symptoms of malaise, fever, and tachycardia, as well as laboratory findings of leukocytosis consistent with an inflammatory process. Infectious workup did not reveal any evidence of a new infection, and no other undiagnosed inflammatory processes were discovered to explain these symptoms. A diagnosis of IRIS was suspected, possibly induced by a prior varicella infection. Diagnosis of IRIS can be difficult due to heterogeneous symptoms, differing etiologies, variable patient presentations, and the lack of universal diagnostic criteria. As instances of IRIS are not uncommon in patients with a low CD4 count who start on ART, there should be a high index of suspicion when patients present with inflammatory symptoms after initiation of ART. With increased recognition of the disease and improved standardization of diagnostic criteria, more could be understood about the underlying disease process which may allow for better targeted therapies and individualized treatments for patients who develop the immune reconstitution inflammatory syndrome.

Cogan's Syndrome: Clinical Presentations and Update on Treatment.

PURPOSE OF REVIEW: Cogan's syndrome (CS) is a rare systemic vasculitis that can severely affect vision and hearing, which may also have significant systemic effects. Early recognition of this autoimmune disorder and intervention can minimize disabling and irreversible damage. RECENT FINDINGS: This article will review the varying clinical presentations of CS and emerging information of systemic disease associated with CS. We will also review recently published promising treatment outcomes using immune modulating medications. As our framework for recognizing the markers of CS and the associated systemic disorders expands, more effective guidelines and treatment options may emerge.

Dominant-negative effect of truncated mannose 6-phosphate/insulin-like growth factor II receptor species in cancer.

Oligomerization of the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) is important for optimal ligand binding and internalization. M6P/IGF2R is a tumor suppressor gene that exhibits loss of heterozygosity and is mutated in several cancers. We tested the potential dominant-negative effects of two cancer-associated mutations that truncate M6P/IGF2R in ectodomain repeats 9 and 14. Our hypothesis was that co-expression of the truncated receptors with the wild-type/endogenous full-length M6P/IGF2R would interfere with M6P/IGF2R function by heterodimer interference. Immunoprecipitation confirmed formation of heterodimeric complexes between full-length M6P/IGF2Rs and the truncated receptors, termed Rep9F and Rep14F. Remarkably, increasing expression of either Rep9F or Rep14F provoked decreased levels of full-length M6P/IGF2Rs in both cell lysates and plasma membranes, indicating a dominant-negative effect on receptor availability. Loss of full-length M6P/IGF2R was not due to increased proteasomal or lysosomal degradation, but instead arose from increased proteolytic cleavage of cell-surface M6P/IGF2Rs, resulting in ectodomain release, by a mechanism that was inhibited by metal ion chelators. These data suggest that M6P/IGF2R truncation mutants may contribute to the cancer phenotype by decreasing the availability of full-length M6P/IGF2Rs to perform tumor-suppressive functions such as binding/internalization of receptor ligands such as insulin-like growth factor II.