Understanding and measuring human B‐cell tolerance and its breakdown in autoimmune disease

The maintenance of immunological tolerance of B lymphocytes is a complex and critical process that must be implemented as to avoid the detrimental development of autoreactivity and possible autoimmunity. Murine models have been invaluable to elucidate many of the key components in B‐cell tolerance; however, translation to human homeostatic and pathogenic immune states can be difficult to assess. Functional autoreactive, flow cytometric, and single‐cell cloning assays have proven to be critical in deciphering breaks in B‐cell tolerance within autoimmunity; however, newer approaches to assess human B‐cell tolerance may prove to be vital in the further exploration of underlying tolerance defects. In this review, we supply a comprehensive overview of human immune tolerance checkpoints with associated mechanisms of enforcement, and highlight current and future methodologies which are likely to benefit future studies into the mechanisms that become defective in human autoimmune conditions.     

The genetics,structure and function of the M1 aminopeptidase oxytocinase subfamily and their therapeutic potential in immune-mediated disease

The oxytocinase subfamily of M1 aminopeptidases plays an important role in processing and trimming of peptides for presentation on major histocompatibility (MHC) Class I molecules. Several large-scale genomic studies have identified association of members of this family of enzymes, most notably ERAP1 and ERAP2, with immune-mediated diseases including ankylosing spondylitis, psoriasis and birdshot chorioretinopathy. Much is now known about the genetics of these enzymes and how genetic variants alter their function, but how these variants contribute to disease remains largely unresolved. Here we discuss what is known about their structure and function and highlight some of the knowledge gaps that affect development of drugs targeting these enzymes.     

Tryptophan-kynurenine profile in pediatric autoimmune hepatitis

Immunologic Research - The impairment of regulatory T cells (Tregs) is a characteristic feature of autoimmune hepatitis (AIH), and the degradation of tryptophan (Trp) to kynurenine (Kyn), by gamma...