Methotrexate and BAFF interaction prevents immunization against TNF inhibitors.

Objectives: TNF inhibitors (TNFi) can induce anti-drug antibodies (ADA) in patients with autoimmune diseases (AID) leading to clinical resistance. We explored a new way of using methotrexate (MTX) to decrease this risk of immunisation.

Methods: We treated BAFF transgenic (BAFFtg) mice, a model of AID in which immunisation against biologic drugs is high, with different TNFi.

TIP, a T-cell factor identified using high-throughput screening increases survival in a graft-versus-host disease model.

A coordinated effort combining bioinformatic tools with high-throughput cell-based screening assays was implemented to identify novel factors involved in T-cell biology. We generated a unique library of cDNAs encoding predicted secreted and transmembrane domain-containing proteins generated by analyzing the Human Genome Sciences cDNA database with a combination of two algorithms that predict signal peptides. Supernatants from mammalian cells transiently transfected with this library were incubated with primary T cells and T-cell lines in several high-throughput assays.