title: Increased serum IgM, immunodeficiency, and autoimmunity: A clinical series.
abstract: BACKGROUND
  Primary immunodeficiencies (PIDs) are generally characterized by recurrent infections; however they may be complicated by other clinical disorders such as allergy, autoimmunity, and lymphoproliferation. In particular, autoimmunity may be the first manifestation of the disease in patients with low serum immunoglobulins (Ig) levels. Here we describe a group of patients that share features of immunodeficiency and autoimmunity.
  
  
  METHODS
  All patients went through a complete T and B cell subset characterization and a B cell function analysis in the peripheral blood by flow-cytometry. B cell proliferation and plasma cell differentiation was measured, in vitro, after CpG stimulation for 7 days as previously described. Semi-quantitative PCR analysis for AID and UNG expression as well as serum levels of BAFF were carried out in order to better define the diagnosis.
  
  
  RESULTS
  Immunological and molecular analysis did not lead to the identification of known molecular defect typical of Hyper IgM syndrome. A comparative study of the peripheral blood B cell subsets between patients and healthy donors showed that in patients with autoimmune manifestations all circulating B cells expressed high amounts of surface IgM.
  
  
  CONCLUSIONS
  These results suggest that the increased IgM expression on circulating B cells, reflecting B cell activation, might identify a clinical condition characterized by hyper IgM serum levels of unknown molecular defects, associated with susceptibility to infections and autoimmunity.
authors.affiliation: "Sapienza" University of Rome, II School of Medicine, S. Andrea University Hospital, Chair and Division of Allergy, Clinical Immunology and Rheumatology, Rome, Italy pyke@inwind.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Picchianti Diamanti
authors.affiliation: Immunology Unit, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: M Manuela
authors.initials: MM
authors.lastname: Rosado
authors.affiliation: Immunology Unit, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Scarsella
authors.affiliation: Immunology Unit, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Rome, Italy Liver Research Unit, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ceccarelli
authors.affiliation: "Sapienza" University of Rome, II School of Medicine, S. Andrea University Hospital, Chair and Division of Allergy, Clinical Immunology and Rheumatology, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Laganà
authors.affiliation: "Sapienza" University of Rome, II School of Medicine, S. Andrea University Hospital, Chair and Division of Allergy, Clinical Immunology and Rheumatology, Rome, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: D'Amelio
authors.affiliation: Immunology Unit, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Rome, Italy Diagnostic Immunology Unit, Department of Laboratories, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Carsetti
mesh_terms: D000328:Adult; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology; D004406:Dysgammaglobulinemia / Q000276:immunology*; D005260:Female; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged
keywords: B cell subsets; IVIG and isotype switching; autoimmunity; common variable immunodeficiency (CVID); hyper-IgM syndrome