The study introduces an advanced liquid chromatography-mass spectrometry (LC-MS) method to profile the IgG1 Fab fragments of autoantibodies, specifically focusing on anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). This approach allows for molecular-resolution analysis of the autoantibody repertoire, revealing its complexity and uniqueness to each patient. Each patient's ACPA repertoire is dominated by a few antibody clones, characterized by extensive Fab glycosylation, with a significant fraction of antibodies harboring two or more glycans. The method also highlights the glyco-heterogeneity within ACPA IgG1, where different glycovariants of the same clone can be detected. This detailed analysis provides insights into the nature and dynamics of autoantibody responses in RA, emphasizing the importance of considering both the molecular diversity and clonal dominance of autoantibodies.The study introduces an advanced liquid chromatography-mass spectrometry (LC-MS) method to profile the IgG1 Fab fragments of autoantibodies, specifically focusing on anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). This approach allows for molecular-resolution analysis of the autoantibody repertoire, revealing its complexity and uniqueness to each patient. Each patient's ACPA repertoire is dominated by a few antibody clones, characterized by extensive Fab glycosylation, with a significant fraction of antibodies harboring two or more glycans. The method also highlights the glyco-heterogeneity within ACPA IgG1, where different glycovariants of the same clone can be detected. This detailed analysis provides insights into the nature and dynamics of autoantibody responses in RA, emphasizing the importance of considering both the molecular diversity and clonal dominance of autoantibodies.