Comprehensive identification and profiling of antigens in immune complexes (IC antigens) is useful to provide insights into pathophysiology and could form the basis for novel diagnostic and treatment strategies for many immune-related diseases. Immune complexome analysis is the method for comprehensively identifying and profiling IC antigens in biological fluids (such as serum, cerebrospinal fluid, urine, and saliva). Here, we describe IC-antigens detection method; specifically, ICs in biological fluids are captured by using Protein G- or Protein A-coated beads, are subjected to papain-digestion elution and tryptic digestion, and are analyzed by nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS).