Challenging the Standard Immunogenicity Assessment Approach: 1-Tiered ADA Testing Strategy in Clinical Trials.

The ADA testing strategy for protein therapeutics was established almost two decades ago when assay methodologies were rudimentary, and serious immunogenicity-related safety issues had recently been observed with some biotherapeutics. The current testing paradigm employs multiple tiers and stringent cut points to minimize false negatives, reflecting a conservative stance towards ADA analysis. The development of highly sensitive ADA assay platforms and technologies such as humanized or fully human monoclonal antibody (mAb) drugs has put the traditional, resource-intensive 3-tiered testing approach under scrutiny.

Synergistic sequence contributions bias glycation outcomes.

The methylglyoxal-derived hydroimidazolone isomer, MGH-1, is an abundant advanced glycation end-product (AGE) associated with disease and age-related disorders. As AGE formation occurs spontaneously and without an enzyme, it remains unknown why certain sites on distinct proteins become modified with specific AGEs. Here, we use a combinatorial peptide library to determine the chemical features that favor MGH-1.

Inflammation, metabolic dysregulation, and pulmonary function among obese urban adolescents with asthma.

Rationale: Insulin resistance and low high-density lipoprotein (HDL) are associated with pulmonary morbidity, including asthma, but the underlying mechanisms are not well elucidated.

Objectives: To investigate whether systemic inflammation underlies the association of metabolic abnormalities with pulmonary function among urban adolescents.

Methods: Th-cell responses and monocyte subsets, and their association with serum homeostatic model assessment of insulin resistance (HOMA-IR) and HDL, and pulmonary function were quantified in 168 adolescents, including 42 obese subjects with asthma, 42 normal-weight subjects with asthma, 40 obese subjects without asthma, and 44 healthy control subjects.