An Early Pregnancy Factor Detected in Human Serum by the Rosette Inhibition Test

Unfolding the relationship between secreted molecular chaperones and macrophage activation states

“…Possibly one of the quickest revolutions was of the paradigm that molecular chaperones are intracellular proteins. Indeed, some 30 years ago, 1 year before the discovery of the first molecular chaperone, a circulating immunosuppressive activity, termed early pregnancy factor (EPF), was discovered (Morton et al 1977). This turned out to be the molecular chaperone, chaperonin (Cpn)/heat shock protein (Hsp)10, a mitochondrial protein (Cavanagh and Morton 1994).…”

“…It is found in the blood during the first trimester of pregnancy (Morton et al 1977) and was rapidly recognised as an immunosuppressive factor (Noonan et al 1979). Recombinant human Hsp10 inhibits experimental autoimmune encephalomyelitis in Lewis rats (Harness et al 2003) and graft versus host disease (Johnson et al 2005).…”

Early Pregnancy Factor (EPF): A Link between Fertilization and Immunomodulation

“…Further investigations demonstrated the appearance ofEPF in serum during pregnancy in all species studied and, although the time course varies, EPF can be found within 24-48 h of a fertile mating until at least the mid-term of pregnancy (Morton et al 1977(Morton et al , 1979a(Morton et al , 1979bNancarrow et al 1981;Smart et al 1982b;Koch et al 1983;Tinneberg et al 1984). During the preimplantation stage of pregnancy EPF is produced by maternal tissue in response to a signal from the conceptus, and its continuing presence is directly related to the presence of a fertilized ovum Cavanagh et al 1982).…”

“…In all cases of established pregnancy, the continuing presence of EPF has been noted for at least the first half of pregnancy, but the length of time EPF remains in the circulation shows considerable variation. Some women had no detectable EPF during the third trimester, whereas in others EPF was present until just before parturition (Morton et al 1977;Smart et al 1982c). Similar variation has been shown in ewes (Morton et al 1979b), while all sows tested had EPF present throughout pregnancy .…”

“…Data has been presented from cases of spontaneous or induced abortion of established pregnancies in women, which demonstrate that EPF is lost from the circulation either before, or within 24 h after, loss of the conceptus (Morton et al 1977;Rolfe 1982;Smart et al 1982b). …”