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.

OBJECTIVES: 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.