title: Value of reflex testing based on hypogammaglobulinemia as demonstrated in serum protein electrophoresis.
abstract: OBJECTIVE
  Hypo-gammaglobulinemia (hypoGG) in serum protein electrophoresis (SPE) reflects, variably, reduced serum immunoglobulin (Ig) concentrations, which may be caused by hematological neoplasms, among other causes. HypoGG in the absence of a discernible M-spike (MC) has been the basis of reflexive testing e.g., by immunofixation electrophoresis (IFE). However, the utility of this practice has not been fully evaluated. Thus, we aimed to (1) determine the predictive power of hypoGG for reduced Ig levels, (2) compare the IFE positive rates and sensitivity between hypoGG and non-hypoGG patients, and (3) examine the M-protein isotype distributions.
  
  
  METHODS
  We retrospectively analyzed 3974 matched SPE and IFE results at the Sunnybrook Health Sciences Centre from January 2010 to June 2013. SPE and IFE were performed on the Sebia Capillarys™ 2 and Hydrasys™ systems respectively.
  
  
  RESULTS
  2723/3974 (68.5%) patients were SPE negative, 246/2723 (9%) had hypoGG and 192 (7.1%) were IFE positive. HypoGG predicted 93.1% cases with at least one Ig reduction. Among SPE-negative patients, the IFE positive rate and sensitivity in hypoGG were 12.2% and 15.6% respectively, compared to 6.4% and 77.1% in normo-GG. Proportion of non-IgG isotypes in both groups were comparable but fewer MC were detected in hypoGG.
  
  
  CONCLUSIONS
  Both the 7% false negative rate of SPE and the poor sensitivity (16%) of reflex testing based on hypoGG should be taken into consideration when devising a screening strategy based on SPE.
authors.affiliation: Department of Clinical Pathology, Sunnybrook Health Sciences Centre, Ontario; Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. Electronic address: pc.chan@sunnybrook.ca.
authors.forename: Pak Cheung
authors.initials: PC
authors.lastname: Chan
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
authors.forename: Jialun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000361:Agammaglobulinemia / Q000097:blood* / Q000175:diagnosis*; D001797:Blood Protein Electrophoresis / Q000379:methods / Q000592:standards*; D015331:Cohort Studies; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D012189:Retrospective Studies
chemical_list: D006454:Hemoglobins; D007074:Immunoglobulin G
keywords: Hypogammaglobulinemia; Immunofixation electrophoresis; Monoclonal protein; Serum protein electrophoresis