Comprehensive discovery of Immune Complex Antigens (IC-antigens) is helpful for elucidating pathophysiology and may serve as the foundation for new diagnostic and therapeutic approaches for a variety of immune-related disorders. A technique for completely recognising and analysing IC-antigens in bodily fluids is immune complexome analysis (such as serum and cerebrospinal fluid). We used this method to examine circulating ICs in cancer, viral illnesses, and autoimmune disorders such as rheumatoid arthritis, Sjogren's syndrome, systemic scleroderma, and systemic lupus erythematosus. Proteins are fluorogenic derivatized, followed by HPLC of the derivatized proteins, isolation of the proteins differentially expressed in a particular group, enzymatic digestion of the isolated proteins, and LC-tandem MS employing a database-searching algorithm for protein identification.