title: Should mild hypogammaglobulinemia be managed as severe hypogammaglobulinemia? A study of 389 patients with secondary hypogammaglobulinemia.
abstract: BACKGROUND
  Although secondary hypogammaglobulinemia is more frequent than primary hypogammaglobulinemia, its etiology and management are poorly described, particularly for mild hypogammaglobulinemia.
  
  
  METHODS
  This retrospective observational study included all adult patients with a gammaglobulin level <6.4g/L on serum electrophoresis identified at Dijon teaching hospital between April and September 2012. Clinico-biological features, etiologies and infectious complications were collected at inclusion and compared between group 1 (gammaglobulin <5g/L, severe hypogammaglobulinemia), and group 2 (gammaglobulin <6.4 and ≥5g/L, mild hypogammaglobulinemia).
  
  
  RESULTS
  Among the 4011 serum electrophoreses, 570 samples from 389 patients had gammaglobulin levels below 6.4g/L: 156 (40%) in group 1 and 233 (60%) in group 2. Mean age±SD was 67 (15) years, and sex ratio was 1.04 (M/F) with no difference between the two groups. An etiology was identified in 79% and 58% of patients in groups 1 and 2, respectively (p<0.0001). The main etiologies were similar in both groups and included malignant hemopathy treated with cytostatic agents (n=129, 33%), smoldering or newly-diagnosed hemopathy without treatment (n=49, 13%) and immunosuppressive treatment (n=91, 23%). The incidence of hypogammaglobulinemia-related infections was 22/100/year, with no significant difference between the two groups (p=0.17). Vaccination coverage against pneumococcus was 33%, and higher in group 1 (46% vs. 24%; p<0.0001). When no cause was known at inclusion, an etiology was discovered in 22/130 patients (17%), 11 in each group.
  
  
  CONCLUSIONS
  Though mild hypogammaglobulinemia does not meet the classical criteria for hypogammaglobulinemia (<5g/L), the etiology and infectious risk are similar. It therefore requires investigation and vaccination.
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, 21079 Dijon, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Blot
authors.affiliation: Laboratory of Immunology, Dijon University Hospital, 21079 Dijon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Boyer
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, 21079 Dijon, France; Faculty of Medicine, University of Burgundy, Dijon, France; INSERM, UMR1098, University of Franche-Comté, 25030 Besançon, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Samson
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, 21079 Dijon, France; Faculty of Medicine, University of Burgundy, Dijon, France; INSERM, UMR1098, University of Franche-Comté, 25030 Besançon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Audia
authors.affiliation: Faculty of Medicine, University of Burgundy, Dijon, France; Department of Internal Medicine and Systemic Diseases, Dijon University Hospital, 21079 Dijon, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Devilliers
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, 21079 Dijon, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Leguy
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, 21079 Dijon, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Berthier
authors.affiliation: Faculty of Medicine, University of Burgundy, Dijon, France; Department of Internal Medicine and Systemic Diseases, Dijon University Hospital, 21079 Dijon, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Besancenot
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, 21079 Dijon, France; Faculty of Medicine, University of Burgundy, Dijon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lorcerie
authors.affiliation: Laboratory of Immunology, Dijon University Hospital, 21079 Dijon, France; Faculty of Medicine, University of Burgundy, Dijon, France.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lakomy
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, 21079 Dijon, France; Faculty of Medicine, University of Burgundy, Dijon, France; INSERM, UMR1098, University of Franche-Comté, 25030 Besançon, France. Electronic address: Bernard.bonnotte@chu-dijon.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
mesh_terms: D000361:Agammaglobulinemia / Q000150:complications / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D000368:Aged; D004586:Electrophoresis; D005260:Female; D006801:Humans; D007239:Infections / Q000209:etiology / Q000276:immunology; D008297:Male; D022242:Pneumococcal Vaccines / Q000627:therapeutic use; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D022242:Pneumococcal Vaccines
keywords: Etiology; Hypogammaglobulinemia; Infection; Vaccination