Plasma from human mothers of fetuses with severe arthrogryposis multiplex congenita causes deformities in mice

Arthrogryposis multiplex congenita (AMC) is characterized by fixed joint co ntractures and other deformities, sometimes resulting in fetal death. The c ause is unknown in most cases, but some women with fetuses affected by seve re AMC have serum antibodies that inhibit fetal acetylcholine receptor (ACh R) function, and antibodies to fetal antigens might play a pathogenic role in other congenital disorders. To investigate this possibility, we have est ablished a model by injecting pregnant mice with plasma from four anti-AChR antibody-positive women whose fetuses had severe AMC. We found that human antibodies can be transferred efficiently to the mouse fetus during the las t few days of fetal life. Many of the fetuses of darns injected with AMC ma ternal plasmas or Ig were stillborn and showed fixed joints and other defor mities. Moreover, similar changes were found in mice after injection of a s erum from one anti-AChR antibody-negative mother who had had four AMC fetus es. Thus, we have confirmed the role of maternal antibodies in cases of AMC associated with maternal anti-AChR, and we have demonstrated the existence of pathogenic maternal factors in one other case. Importantly, this approa ch can be used to look at the effects of other maternal human antibodies on development of the fetus.