Generation of recombinant hyperimmune globulins from diverse B-cell repertoires

Plasma-derived polyclonal antibody therapeutics, such as intravenous immunoglobulin, have multiple drawbacks, including low potency, impurities, insufficient supply and batch-to-batch variation. Here we describe a microfluidics and molecular genomics strategy for capturing diverse mammalian antibody repertoires to create recombinant multivalent hyperimmune globulins. Our method generates of diverse mixtures of thousands of recombinant antibodies, enriched for specificity and activity against therapeutic targets. Each hyperimmune globulin product comprised thousands to tens of thousands of antibodies derived from convalescent or vaccinated human donors or from immunized mice. Using this approach, we generated hyperimmune globulins with potent neutralizing activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in under 3 months, Fc-engineered hyperimmune globulins specific for Zika virus that lacked antibody-dependent enhancement of disease, and hyperimmune globulins specific for lung pathogens present in patients with primary immune deficiency. To address the limitations of rabbit-derived anti-thymocyte globulin, we generated a recombinant human version and demonstrated its efficacy in mice against graft-versus-host disease

Cerebral salt wasting syndrome: Review

Abstract Hyponatremia is the most frequent electrolyte disorder in critically neurological patients. Cerebral salt wasting syndrome (CSW) is defined as a renal loss of sodium during intracranial disease leading to hyponatremia and a decrease in extracellular fluid volume. The pathogenesis of this disorder is still not completely understood. Sympathetic responses as well as some natriuretic factors play a role in this syndrome. Distinction between SIADH and CSW might be difficult. The essential point is the volemic state. It is necessary to rule out other intermediate causes. Treatment requires volume replacement and maintenance of a positive salt balance. Mineral corticoids may be useful in complicated cases