Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology that affects multiple tissues and organs [1]. The main immunological alterations observed in these patients are the loss of tolerance to self-antigens with polyclonal activation of B lymphocytes, production of different auto-antibodies, and an altered function of T cells [2-4]. In addition, several abnormalities of B lymphocytes, including an increased Ca2+ influx, and a decreased fraction of na？ve B cells with enhanced levels of circulating plasmablasts have been described [5,6]. Furthermore, B lymphocytes from SLE patients show an increased synthesis of certain cytokines (for example, IL-10), and have an important role as antigen presenting cells, inducing the activation of CD4+ auto-reactive T cells, which in turn allow the activation and differentiation of B cells, and the production of high affinity auto-antibodies [5,7]. Thus, it is very likely that the hyperactivity of B cells and auto-antibody production in SLE depend on the interactions of self antigens with B cell surface immunoglobulin receptors, and the cognate interaction of these cells with helper T lymphocytes. Several subsets of CD4+ cells with immuno-regulatory activity have been described, including T regulatory (TREG) lymphocytes, and type-1 T regulatory (Tr1) cells [8,9]. TREG lymphocytes are characterized by the expression of CD4 and by high levels of the α chain of IL-2 receptor (CD25) as well as by their lack of responsiveness to antigenic stimulation [8,10]. These CD4+CD25bright CTLA-4+ cells arise from thymus as natural regulatory cells and exert their activity by cell-to-cell contact as well as by inducing the differentiation of CD4+CD25- lymphocytes into regulatory cells [6,10,11]. On the other hand, Tr1 lymphocytes express CD4 and synthesize IL-10 [9]. These regulatory cells are antigen specific lymphocytes derived from conventional CD4+CD25- naive precursors upon exposure to antigen and IL-10 [9,12]. Addition