Moesin: A novel receptor on NK lymphocytes binds to TOMM40 on K562 leukemia cells initiating cytolysis.

Natural killer lymphocytes (NK cells) are the first line of defense (innate immunity) against viral infections and leukemia since they do not require activation to deliver a lethal hit to infected/aberrant cells. In contrast, T lymphocytes require stimulation by a foreign/neo - antigen, which may take days before they are active against the pathogen (adaptive immunity). A number of receptors on activated NK cells that kill the prototypical leukemia target cell line, K562, have been identified. To date, the receptor(s) by which freshly isolated unstimulated NK cells (naïve, nNK) kill K562 has not been fully elucidated. We provide peptide sequence and immune-blot data from ligand pull down experiments that moesin, a protein that typically links the inner leaf of the plasma membrane to the cytoskeleton, additionally, in NK cells, localizes to the cell surface where it may bind to its ligand, TOMM40 (aka Haymaker, HYMKR), on leukemia cells thereby initiating their destruction. Flow cytometry experiments with a mouse monoclonal antibody (Mab) to a moesin peptide (554 to 565) were performed. Moesin was detected on the surface of CD3-, CD16+nNK cells but was not detected on the surface of freshly isolated unstimulated CD3+, CD16- T cells or CD19+, CD16- B cells from healthy subjects. Moesin, is therefore another marker that distinguishes unstimulated CD3-, CD16+ NK cells from other non-activated lymphocytes. The anti -moesin peptide Mab was highly effective (>95% inhibition) in blocking target cell cytolysis by CD16+ lymphocytes demonstrating that moesin-HYMKR interaction appears to be necessary for most of the observed cell death of K562 caused by unstimulated NK cells.

BK virus encephalopathy and sclerosing vasculopathy in a patient with hypohidrotic ectodermal dysplasia and immunodeficiency.

Human BK polyomavirus (BKV) is reactivated under conditions of immunosuppression leading most commonly to nephropathy or cystitis; its tropism for the brain is rare and poorly understood. We present a unique case of BKV-associated encephalopathy in a man with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) due to IKK-gamma (NEMO) mutation, who developed progressive neurological symptoms. Brain biopsy demonstrated polyomavirus infection of gray and white matter, with predominant involvement of cortex and distinct neuronal tropism, in addition to limited demyelination and oligodendroglial inclusions. Immunohistochemistry demonstrated polyoma T-antigen in neurons and glia, but expression of VP1 capsid protein only in glia. PCR analysis on both brain biopsy tissue and cerebrospinal fluid detected high levels of BKV DNA. Sequencing studies further identified novel BKV variant and disclosed unique rearrangements in the noncoding control region of the viral DNA (BKVN NCCR). Neuropathological analysis also demonstrated an unusual form of obliterative fibrosing vasculopathy in the subcortical white matter with abnormal lysosomal accumulations, possibly related to the patient's underlying ectodermal dysplasia. Our report provides the first neuropathological description of HED-ID due to NEMO mutation, and expands the diversity of neurological presentations of BKV infection in brain, underscoring the importance of its consideration in immunodeficient patients with unexplained encephalopathy. We also document novel BKVN NCCR rearrangements that may be associated with the unique neuronal tropism in this patient.

Clinical performance of Roche Cobas 4800 HPV Test.

Evaluation of the Cobas 4800 test demonstrated that Cobas had a low rate of cross-reactivity with low-risk human papillomavirus (lrHPV), a 3.74% disconcordance rate between prealiquots and postaliquots, and failure rates of 4.57% and 1.16%, respectively, after vortexing and swirling. This study demonstrated that the Cobas test has good sensitivity, accuracy, and reproducibility for detecting 14 high-risk HPV (hrHPV) genotypes.