However, it seems reasonable to propose that low-affinity binding between multiple pairs of HCs could mediate the aggregation of HC·HAs seen in synovial fluids from rheumatoid arthritis patients (23) and that this, combined with more stable interactions between HCs and pentraxin 3 (26), underpins the formation and cross-linking of the cumulus extracellular matrix during COC expansion. This evidence concerns the gene PTX3 and rheumatoid arthritis.