Plasma proteomics associated with autoimmune coagulation factor deficiencies reveals the link between inflammation and autoantibody development.

Autoimmune coagulation factor deficiency (AiCFD) is characterized by sudden excessive bleeding due to autoantibodies against coagulation factors. This occurs primarily in elderly patients with no family history or previous clotting issues. However, the detailed mechanisms underlying autoantibody development are not well understood. Here, we evaluated the plasma proteome in patients with AiCFD and compared it with that of 22 healthy controls and 17 patients with non-autoimmune acquired factor XIII deficiency (acF13D). We identified eighteen proteins whose plasma levels were higher in AiCFD than in either healthy controls or patients with acF13D. Most of these proteins were found to be acute-phase reactants or immunoglobulins. Patients with acF13D had lower levels of nine of these proteins and higher levels of the remaining nine compared to healthy controls. However, in all cases, these protein levels were much higher in patients with AiCFD than in those with acF13D. These results suggest that an inflammatory response independent of the acute inflammation caused by bleeding can occur, which may lead to the development of AiCFD. Therefore, we believe that severe and/or chronic inflammation, probably due to an underlying disease or aging, is the most important factor in autoantibody development.