Up-regulation of interleukin-4 and CD23/Fc epsilon RII in minimal change nephrotic syndrome

Although the pathogenesis of childhood minimal change nephrotic syndrome (M CNS) has not been clearly defined, the current hypothesis favors an involve ment of T cell dysfunction. The symptom onset and the relapse of MCNS are f requently associated with allergy and increased IgE levels in sera. Since a T cell-derived cytokine interleukin-4 (IL-4) plays a key role in the regul ation of IgE production and allergic response, we investigated the role of IL-4 in the pathophysiology of MCNS. Using fluorescence-activated cell scan ning we observed a significantly higher expression of CD23, the type II IgE receptor (Fc epsilon RII), on fresh B cells from active MCNS patients (n=2 2) compared with age-matched healthy normal controls (n=12). The upregulati on of CD23 correlates with greater IL-4 activity in the culture supernatant of MCNS peripheral blood lymphocytes (PBLs) than normal PBLs stimulated by mitogens, as assessed by the CD23-inducing effect of the PBL supernatant o n tonsillar B cells. Furthermore, Northern blot and reverse transcription-b ased polymerase chain reaction analysis have revealed significantly elevate d levels of IL-4 mRNAs both in mitogen-stimulated and unstimulated MCNS PBL s, compared with healthy normals or disease controls with other renal disor ders. Together these results strongly suggest that the upregulation of IL-4 in T cells may be part of the T cell dysfunction involved in MCNS.