T-cell homing receptor expression in IgA nephropathy

Background. IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA (pIgA). In IgAN, mucosal pIgA production is reduced while systemic production is increased, making the latter the likely source of mesangial pIgA, and suggesting a displacement of pIgA-producing cells from mucosal to systemic sites. Upon activation, lymphocytes migrate through the circulation up-regulating homing receptors (HR) which direct their return to appropriate effector locations. We investigated the HR expression of T-cell subsets in IgAN, healthy adults and membranous nephropathy (MN). Methods. Peripheral blood cells were labelled for CD3, CD4 and CD8, and for L-selectin (naive cells), integrin alpha(4)beta(1) (systemically homing cells) and integrin alpha(4)beta(7) (mucosally homing cells) and analysed by flow immunocytometry. Results. In IgAN, CD3T cells displayed reduced L-selectin and increased alpha(4)beta(1) hi expression, with no difference in alpha(4)beta(7). No abnormality of T-cell HR expression was found in MN. Both IgAN and healthy adults maintained their patterns of T-cell HR expression when studied again at a later time point, and the changes in IgAN were entirely accounted for by the CD4T-cell subset with CD8 HR expression being normal. Conclusions. The consistently reduced L-selectin expression by CD4T cells indicates increased activation of this subset in IgAN. These activated cells express alpha(4)beta(1) rather than alpha(4)beta(7), and therefore home to systemic effector sites. CD4T cells regulate antibody production, including IgA. As pIgA is overproduced in systemic sites in IgAN, we hypothesize that these activated systemic homing CD4T cells may direct the aberrant systemic pIgA production observed in IgAN.