Gestational Dermatosis Shortly after Implantation Associated with Parental Class II HLA Compatibility and Maternal Immune Activation: Preliminary Report of a Prospective Case Series

Abstract

Background: Pregnancy represents a semiallograft, subject to similar immune responses as allogeneic organ transplants. Tolerance of pregnancy appears best with maximal class II HLA heterogeneity between mother and father, while compatibilities are associated with increased pregnancy loss and maternal autoimmunity. Tolerance abnormalities often involve skin reactions. Abnormalities in tolerance of the fetal graft may do the same. Objective: To define the characteristics of a newly described dermatosis in very early pregnancy. Methods: Prospective case series of 7 couples/12 clinical episodes. Results: The dermatosis was observed in 7 out of 285 women undergoing in vitro fertilization (IVF; 2.5%; 95% CI 0.66–4.26%) and in 12 out of 277 total IVF cycles reaching embryo transfer (4.3%; 95% CI 1.93–6.73%). Prior to IVF all women reported autoimmune clinically significant allergies. All but 1 couple demonstrated class II HLA compatibility. Two of 4 pregnancies miscarried. All rashes erupted within days from embryo implantation. Conclusions: The ‘implantation rash’ reported here is uncommon but not rare. It may be the consequence of abnormal maternal immune responses to embryo implantation in women with prior immune activation, associated with class II HLA compatibility between parents. Further prospective studies are required to better define this condition.

Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation

“…Like Gleicher has pointed out in a number of publications, these unexplained conditions of pregnancy exhibit characteristics similar to immunological conditions observed in organ transplant rejection [28] and/or graft versus host disease (GVHD) [29], therefore ICP may represent the complications of normal tolerance of the fetal semi-allograft by the maternal immune system [30]. Herein, our microarray results revealed that genes associated with immune response, CXCL6 , CXCL14 and IL-7R were up-regulated in mild ICP and further up-regulated in severe ICP, while CCL3 and CCL25 were only up-regulated in severe ICP, which suggest that abnormal immune response in patients’ placentas might be positively correlated to the severity of ICP.…”

Placental ADAMTS-12 Levels in the Pathogenesis of Preeclampsia and Intrahepatic Cholestasis of Pregnancy

“…19 Likewise, Gleicher and Barad suggested that dermatosis of pregnancy including ICP may represent similar characteristics observed in allogenic graft rejection. 31 The ADAMTS-12 is already known to be required in allergic and normal inflammation, as ADAMTS-12-deficient mice exhibited more severe inflammation accompanied by neutrophilia in affected tissues. 20,32,33 The results of our study are in consistence with the above-mentioned reports, as we found significantly decreased levels of ADAMTS-12 in ICP placentas.…”