Modulation of adaptive immune response following intravenous immunoglobulin therapy in common variable immunodeficiency.

C ommon variable immune deficiency (CVID) is the most frequent symptomatic primary immune deficiency in adults with a prevalence of approximately 1 in 25,000 in the general population [1]. Indeed patients frequently become symptomatic later in life; however, their clinical history may reveal features of the disease dating back to early childhood. The disorder is characterized by recurrent and/or severe infections and may be associated with autoimmunity and increased risk of lymphoid malignancies. CVID probably represents a heterogeneous group of disorders culminating in late-onset antibody failure. The genetic basis of CVID has been identified in only a minority of patients; it is likely that in the majority of patients the disease may have a polygenic origin [2]. Since the cause of CVID is unknown and the clinical features variable, there is no universally accepted definition of the disorder and several diagnostic criteria have been proposed [3]. The diagnostic criteria of the ESID (European Society of Immunodeficiencies)/PAGID (Pan American Group for Immune Deficiency) comprise three aspects: (i) hypogammaglobulinemia with immunoglobulin G (IgG) levels 2 standard deviations below the mean value, (ii) impaired vaccine responses or absent isohemagglutinins, and (iii) exclusion of other causes of hypogammaglobulinemia. The typical defect in CVID is the failure of B lymphocytes to differentiate into switched memory B cells and plasma cells [4]. Several abnormalities of T cells have also been described in CVID, including oligoclonal expansion of CD8+T cells and decreased numbers of CD4+T cells [5]. Moreover, T lymphocytes show an impaired secretion of several soluble mediators. The current standard of care for patients with CVID is lifelong replacement with intravenous immunoglobulin preparations (IVIg) that reduce the frequency of infections and the progression of complications, including suppurative lung disease. IVIg use is increasing rapidly, given its efficacy also in patients with autoimmune and inflammatory disorders. IVIg therapeutic effect seems to be related not only to antibody replacement but also to active modulation of immune responses [6]. Such immunomodulatory effects have been hypothetized but never proven. The aim of our study was to address this issue by using a gene expression approach.