Plasma Epstein Barr viral load in adult-onset Hodgkin lymphoma in South India

Objective/background: Epstein Barr Virus (EBV) DNA load is increasingly being used as a noninvasive biomarker for detecting EBV association in lymphomas. Since there is a need of data from India, we undertook to prospectively evaluate plasma EBV DNA load as a marker of EBV association in newly diagnosed adult-onset Hodgkin lymphoma (HL). Methods: EBV DNA was quantified using real-time polymerase chain reaction. In a subset of patients, an assay was validated qualitatively with EBV latent membrane protein-1 (LMP1) immunohistochemistry (IHC). Wherever possible, follow-up plasma samples post three cycles of chemotherapy were obtained. Results: Over a period of 10 months, 33 newly diagnosed adult-onset HL were enrolled in the study. Pretherapy plasma EBV DNA was detectable in ∼49% (16/33) patients (viral loads range, 1.0–51.2 × 103 copies/mL) and undetectable in 30 voluntary blood donors. LMP1 IHC was positive in 56% of cases tested (14/25). Sensitivity and specificity of plasma EBV DNA with respect to LMP1 IHC were 86% and 100%, respectively. Of the eight patients in whom follow-up plasma was available, in five EBV baseline-positive patients EBV load reverted to negative postchemotherapy and corroborated with clinical remission. Conclusion: Plasma EBV DNA load estimation may be useful in detecting EBV-association and possibly monitoring the response to therapy in EBV-related HL especially in our country where EBV association of HL is higher than in developed nations. Keywords: Epstein–Barr Virus, Hodgkin lymphoma, LMP1 immunohistochemistry, Real-time PCR, Viral loa

Interaction of α-catulin with dystrobrevin contributes to integrity of dystrophin complex in muscle

The dystrophin complex is a multimolecular membrane-associated protein complex whose defects underlie many forms of muscular dystrophy. The dystrophin complex is postulated to function as a structural element that stabilizes the cell membrane by linking the contractile apparatus to the extracellular matrix. Abetter understanding of how this complex is organized and localized will improve our knowledge of the pathogenic mechanisms of diseases that involve the dystrophin complex. In a Caenorhabditis elegans genetic study, we demonstrate that CTN-1/alpha-catulin, a cytoskeletal protein, physically interacts with DYB-1/alpha-dystrobrevin (a component of the dystrophin complex) and that this interaction is critical for the localization of the dystrophin complex near dense bodies, structures analogous to mammalian costameres. We further show that in mouse alpha-catulin is localized at the sarcolemma and neuromuscular junctions and interacts with alpha-dystrobrevin and that the level of alpha-catulin is reduced in alpha-dystrobrevin- deficient mouse muscle. Intriguingly, in the skeletal muscle of mdx mice lacking dystrophin, we discover that the expression of alpha-catulin is increased, suggesting a compensatory role of alpha-catulin in dystrophic muscle. Together, our study demonstrates that the interaction between alpha-catulin and alpha-dystrobrevin is evolutionarily conserved in C. elegans and mammalian muscles and strongly suggests that this interaction contributes to the integrity of the dystrophin complex