ABSTRACTical practice, but information concerning the prevalence and the clinical and immunological characteristics is not available. It is important to obtain insight into the frequency and severity of the clinical complications of IPH, to clarify whether IPH is a clinically relevant antibody deficiency, and to develop appropriate treatment strategies. In addition, analysis of immunological parameters will enable the comparison of pathophysiological aspects of IPH and CVID.Therefore, we aimed to determine the position of IPH in the spectrum of idiopathic antibody deficiencies through clinical and immunological comparison with CVID. First, we recorded the patients with the clinical phenotypes as established by Chapel et al. 2,7 In addition, we performed flow cytometric immunophenotyping in order to analyze T-cell dependent and independent memory B-cell subset counts 8 and blood B-cell patterns, which are associated with differences in pathophysiological background. 9 Methods PatientsPeripheral blood samples and clinical data were collected for 44 CVID patients and 21 IPH patients. IPH was diagnosed if patients had a reduction of IgG at least 2 SD below the mean for age, an onset of the immunodeficiency after two years of age, exclusion of defined causes of hypogammaglobulinemia and if they did not fulfill the CVID diagnostic criteria with respect to a reduction of two immunoglobulin isotypes and/or a reduced response to vaccination. The group of CVID patients includes the 37 patients who were reported in our original description of the B-cell patterns. 9 In addition, we collected blood from 130 healthy age-matched controls and 26 cord blood samples. This study was approved by the Medical Ethics Committee of the Erasmus MC. Clinical phenotypingClinical data were collected from all IPH and CVID patients to record their clinical phenotypes as previously described by Chapel et al. 2,5 These phenotypes are: 1) no disease-related complications (infections only); 2) autoimmune cytopenias; 3) polyclonal lymphoproliferation (granuloma/LIP/persistent unexplained lympadenopathy); and 4) unexplained persistent enteropathy. In addition, data were collected concerning the frequency and severity of infections and modes of treatment. Pneumococcal polysaccharide vaccination responses were interpreted according to Borgers et al. 10 as an adequate response to half of the measured pneumococcal serotypes. Flow cytometric analysis and assignment of B-cell patternsSix-color flow cytometric immunophenotyping of peripheral blood was performed on a CantoII (BD Biosiences) and data were analyzed using FACS Diva software (BD Biosiences). The following monoclonal antibodies were used: CD19-PerCP-Cy5.5, CD19-PE-Cy7, CD19-APC (all SJ25C1), CD5-APC ( L17F12 ), CD45-PerCP (2D1), CD19-APC (SJ25C1), CD38-PE, CD38-APC and CD38-PE-Cy7 ( HB7), CD27-APC (L128), CD3-PerCP-Cy5.5 (SK7) and CD8-APC-Cy7 (SK1) (all from BD Biosciences), polyclonal IgD-FITC, IgD-PE and IgM-PE (all from Southern Biotechnologies), polyclonal IgG-FITC (Kallestad), IgA-FITC a...