title: Detection of Polyclonal Increases in Immunoglobulin G4 Subclass by Distinct Patterns on Capillary Serum Protein Electrophoresis:  Diagnostic Pitfalls and Clinical Observations in a Study of 303 Cases.
abstract: OBJECTIVE
  Autoimmunity, hypersensitivity, and the recently recognized set of syndromes collectively termed immunoglobulin G4-related disease (IgG4-RD) may be associated with increased serum IgG4 levels. We reviewed our experience detecting increased IgG4 by distinct serum protein electrophoresis (SPEP) patterns.
  
  
  METHODS
  We studied 303 capillary SPEP cases with dome-like anodal γ changes and increased measured serum IgG4.
  
  
  RESULTS
  IgG4 ranged from 208 to 6,670 mg/dL (normal, <201 mg/dL). Seventeen of 91 cases evaluated by immunosubtraction appeared monotypic (16 κ, 1 λ), but all five cases further analyzed by isoelectric focusing appeared polyclonal. Six cases with markedly increased IgG4 had presumptive evidence of IgG4-RD. Sixteen of 45 assessed patients had autoantibodies.
  
  
  CONCLUSIONS
  Increased polyclonal IgG4 has a characteristic SPEP pattern that may mimic monoclonal gammopathy, even on immunosubtraction. κ Pseudo-restriction might reflect the naturally high κ/λ ratio of the IgG4 subclass. Autoantibodies were common, and the greatest IgG4 increases had clinical features of IgG4-RD.
authors.affiliation: From the Warde Medical Laboratory, Ann Arbor, MI Department of Pathology, University of Michigan, Ann Arbor. finnwg@trinity-health.org.
authors.forename: William G
authors.initials: WG
authors.lastname: Finn
authors.affiliation: From the Warde Medical Laboratory, Ann Arbor, MI.
authors.forename: Ronald
authors.initials: R
authors.lastname: Gulbranson
authors.affiliation: From the Warde Medical Laboratory, Ann Arbor, MI.
authors.forename: Sondra
authors.initials: S
authors.lastname: Fisher
authors.affiliation: From the Warde Medical Laboratory, Ann Arbor, MI.
authors.forename: Lynn
authors.initials: L
authors.lastname: Rae Sample
authors.affiliation: From the Warde Medical Laboratory, Ann Arbor, MI.
authors.forename: Renee
authors.initials: R
authors.lastname: Shalhoub
authors.affiliation: From the Warde Medical Laboratory, Ann Arbor, MI.
authors.forename: Deborah
authors.initials: D
authors.lastname: Hedstrom
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor.
authors.forename: David F
authors.initials: DF
authors.lastname: Keren
mesh_terms: D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000276:immunology; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D003937:Diagnosis, Differential; D019075:Electrophoresis, Capillary / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis* / Q000276:immunology; D007525:Isoelectric Focusing / Q000379:methods; D010265:Paraproteinemias / Q000175:diagnosis* / Q000276:immunology
chemical_list: D003176:Complement C3; D003181:Complement C4; D007074:Immunoglobulin G
keywords: Autoimmune; IgG4; IgG4-related disease; Serum protein electrophoresis