In the last decade, the significance of aPL persistency and accumulation (the co-presence of aPL criteria: aCL, anti-β2-GPI of the IgG or IgM subtypes and circulating LAC) was evaluated, especially regarding the risk of APS evolvement, although their functional role for assessment of the specific APS-related manifestations is not always clear. This evidence concerns the gene CD40LG and autoimmune polyendocrinopathy.