The "antibodyome": or, how to find antibodies?

The importance of alloantibodies in acute and chronic allograft rejection has been highlighted over the past few decades. Besides human leukocyte antigen (HLA) antibodies, representing the most important group of antibodies in renal transplantation, non-HLA antigens such as MHC class I polypeptide-related sequence A (MICA) antibodies have also been implicated in renal allograft outcome. However, the identification of alloantibodies and autoantibodies and their antigens is technically difficult. Recently, Li and colleagues have performed an integrative genomic analysis of serological responses to non-HLA antigens in 18 pediatric renal transplant patients to identify new types of antibodies and their tissue specificity by cross-mapping kidney compartment-specific gene probes to protein targets on a protein array (1). Several non-HLA targets were detected against kidney compartment-specific antigens with the highest signal recognition for the renal pelvis. On the one hand, this integrative approach may provide a powerful and cost-efficient tool to detect autoantibodies involved in autoimmune diseases to investigate their specificity, relevance and pathogenetic role. On the other hand, the clinical relevance of these autoantibodies remains to be shown, and it should be explained how mainly intracellular proteins can provide relevant antigens.