Indeed, in CVID PPVlow patients and in some CVID patients, Forssman antigen was the only investigated TACA for which higher-intensity signals were detected. a common feature of primary antibody deficiencies (PADs), despite the pathogenetic heterogeneity of these disorders, involving monogenetic, polygenetic, and still-unexplained defects.1,2 These disorders are associated with a plethora of clinical sequelae, including severe and recurrent infections, microbial dysbiosis, autoimmunity, allergy, granulomatous disease, and malignancy.1,3,4 The surface of all living cells is glycosylated, and the composition varies between cell type,5 individuals, and species.6 The prominent exposure of carbohydrate structures (glycans) on the surface of cells or Ciclopirox bacterial capsules renders them accessible to antibodies, which facilitates the detection and elimination of pathogens or aberrant cells, as well as leads to adverse reactions in transfusion/transplantation procedures (blood groups antigens) or to the acute rejection of xenografts (eg, Gal structures). Because of the altered expression of biosynthetic enzymes, such as Ciclopirox glycosyltransferases or glycosidases, the glycome of cells is often changed under pathological conditions, including cancer.7 Although tumor-associated carbohydrates (TACAs) are exploited as diagnostic markers,8 there is also evidence for naturally occurring antibodies to TACAs in healthy individuals.9 Insufficient responses to glycan-based Ciclopirox vaccines or low titers of isohemagglutinins, antibodies to polysaccharide blood group antigens, are characteristic and diagnostic features of common variable immunodeficiency (CVID), the most frequent symptomatic antibody deficiency diagnosed in adulthood.10,11 Patients with specific antibody deficiency (SPAD) exhibit poor responses to structural or capsular polysaccharides of bacteria (eg, Vi vaccine14) or the measurement of preexisting antibody titers (eg, isohemagglutinins) relies on a restricted number of glycan epitopes, thus providing only a narrow perspective of the actual degree of the Rabbit Polyclonal to JunD (phospho-Ser255) immunodeficiency. Further disadvantages of diagnostic vaccination include diagnostic delay, interlaboratory variation, serotype-specific responses, age differences in antibody responses, or the challenging interpretation of preimmunization vs postimmunization specific antibody levels in patients not receiving IgG replacement therapy.10,11,15-18 The broader assessment of glycan-specific antibodies in patients may better reflect the immune defect and also facilitate treatment decisions, such as regarding life-long IgG-replacement therapy. Glycan array technology allows the high-throughput analysis of specific antibody responses to carbohydrate antigens.19-21 In a previous study using glycan array version 5.1 of The Consortium for Functional Glycomics (CFG) to decipher the IgG repertoire of healthy individuals, we found that classes of glycans were recognized with different intensity, depending on the terminal carbohydrate moiety.9 Here, we used glycan array technology to investigate the IgG antibody Ciclopirox repertoire of PAD patients in terms of clinically relevant carbohydrate epitopes, including microbial glycans, self-antigens, xenoantigens, and TACAs. Materials and methods Study design This nonrandomized study was designed to investigate the human IgG anti-carbohydrate repertoire, in healthy and disease conditions, using glycan array technology combined with a computational system level approach. To this end, sera or purified IgG samples from healthy individuals or patients, as well as control antibodies, were screened on microarrays by the CFG or the US National Center for Functional Glycomics (NCFG). Patient samples Human blood was collected from healthy donors (HDs) or patients upon informed and written consent, in accordance with the Declaration of Helsinki. All experimental protocols were approved by the local institutional and/or licensing committees (KEK-BE: 148/10 and KEK No. 224/01). Therapeutic-naive patients followed at the University Hospital of Bern from January 2005 to December 2011 were retrospectively identified. Additional sera from therapeutic-naive patients without IgG-replacement therapy were provided by B.G. CVID was defined in accordance with the criteria of the Pan-American Group for Immunodeficiency and the European Society for Immunodeficiency.22 Inclusion criteria for IgGSD were a normal total IgG concentration with a significant decrease (>2 standard deviations below the mean for the age) in the serum concentrations of 1 1 IgG subclasses23 and recurrent episodes of infection. Symptomatic hypogammaglobulinemia (HGG) was defined as decreased total IgG concentration but not fulfilling the criteria for CVID with respect.