title: Surface Plasmon Resonance Analysis Shows an IgG-Isotype-Specific Defect in ABO Blood Group Antibody Formation in Patients with Common Variable Immunodeficiency.
abstract: BACKGROUND
  Common variable immunodeficiency (CVID) is the most common clinically severe primary immunodeficiency and comprises a heterogeneous group of patients with recurrent severe bacterial infections due to the failure to produce IgG antibodies after exposure to infectious agents and immunization. Diagnostic recommendations for antibody failure include assessment of isoagglutinins. We have readdressed this four decades old but still accepted recommendation with up to date methodology.
  
  
  METHODS
  Anti-A/B IgM- and IgG-antibodies were measured by Diamed-ID Micro Typing, surface plasmon resonance (SPR) using the Biacore(®) device and flow cytometry.
  
  
  RESULTS
  When Diamed-ID Micro Typing was used, CVID patients (n = 34) showed IgG- and IgM-isoagglutinins that were comparable to healthy volunteers (n = 28), while all XLA patients (n = 8) had none. Anti-A/B IgM-antibodies were present in more than 2/3 of the CVID patients and showed binding kinetics comparable to anti-A/B IgM-antibodies from healthy individuals. A correlation could be found in CVID patients between levels of anti-A/B IgM-antibodies and levels of serum IgM and PnP-IgM-antibodies. In contrast in CVID patients as a group ABO antibodies were significantly decreased when assessed by SPR, which correlated with levels of switched memory, non-switched memory and naïve B cells, but all CVID patients had low/undetectable anti-A/B IgG-antibodies.
  
  
  CONCLUSIONS
  These results indicate that conventional isoagglutinin assessment and assessment of anti-A/B IgM antibodies are not suited for the diagnosis of impaired antibody production in CVID. Examination of anti-A/B IgG antibodies by SPR provides a useful method for the diagnosis of IgG antibody failure in all CVID patients studied, thus indicating an important additional rationale to start immunoglobulin replacement therapy early in these patients, before post-infectious sequelae develop.
authors.affiliation: Department of Transfusion Medicine, Medical University of Vienna , Vienna , Austria ; Center of Biomedical Technology, Danube University Krems , Krems an der Donau , Austria.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fischer
authors.affiliation: Department of Transfusion Medicine, Medical University of Vienna , Vienna , Austria.
authors.forename: Wendelin
authors.initials: W
authors.lastname: Wolfram
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna , Vienna , Austria.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna , Vienna , Austria.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna , Vienna , Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Wahrmann
authors.affiliation: Immunology Outpatient Clinic , Vienna , Austria.
authors.forename: Martha M
authors.initials: MM
authors.lastname: Eibl
authors.affiliation: Immunology Outpatient Clinic , Vienna , Austria.
authors.forename: Hermann M
authors.initials: HM
authors.lastname: Wolf
keywords: B cell subsets; anti-ABO antibodies; blood groups; common variable immunodeficiency; isoagglutinins; natural antibodies; pneumococcal polysaccharide