Microchimerism in autoimmune disease: more questions than answers?

Abstract

Recent studies indicate cell traffic occurs between the fetus and mother during pregnancy and that low numbers of fetal cells commonly persist in the maternal circulation for years thereafter. Microchimerism refers to a small number of cells or DNA from one individual harbored in another individual. Autoimmune diseases are more common among women and often increase in incidence following reproductive years. Chronic graft vs. host disease is an iatrogenic form of chimerism with similarities to some autoimmune diseases for which the HLA relationship of donor and host are of central importance. When considered together, these observations led to the hypothesis that microchimerism and HLA relationships of host and non-host cells are involved in autoimmune disease. The hypothesis is applicable to men, children and women without pregnancies because there are other sources of microchimerism, including from a twin, the mother or a blood transfusion. Microchimerism has now been investigated in a number of different diseases with some results supporting a potential role in disease pathogenesis. However, fetal and maternal microchimerism are also found in organs affected by non-autoimmune conditions. Moreover, microchimerism is commonly detected in the peripheral blood of healthy individuals raising the intriguing question of whether these cells are simple remnants of pregnancy or whether they might also have beneficial effects for the host.

Introduction

Recent application of molecular techniques to the study of human pregnancy has revealed that there is bi-directional traffic of cells between the fetus and mother [1]. Fetal cells have been found to persist in the maternal circulation for many years after pregnancy [2]. An iatrogenic form of chimerism, chronic graft vs. host disease (cGvHD) is a complication of hematopoietic cell transplantation, that has clinical similarities with systemic sclerosis (SSc), primary biliary cirrhosis (PBC), Sjögrens syndrome, and occasionally myositis and systemic lupus [3]. The HLA relationship of a donor and host is known to be of central importance in the development of cGvHD. Considering these observations together, derived from differing areas of medical research, led to the hypothesis that microchimerism and HLA-relationships of host and non-host cells are involved in autoimmune disease [4]. Autoimmune manifestation of cGvHD had been described years earlier, but had not previously been considered in connection with fetal–maternal cell transfer during pregnancy.

Maternal cells have long been known to persist in immunodeficient infants, but recent studies indicate persistent maternal microchimerism also occurs in immune competent offspring. By targeting non-inherited maternal-specific HLA genes and also using fluorescence in situ hybridization for X- and Y-chromosomes in male adults, investigators were able to demonstrate persistence of maternal microchimerism into adult life both in SSc and in some healthy individuals [5]. Other potential sources of persistent microchimerism include from a twin [6] or from a blood transfusion [7]. It is presumed that persistent fetal microchimerism can occur after a spontaneous or induced abortion since substantial levels of fetal DNA are detected in the circulation of women undergoing elective termination [8]. It is possible that microchimerism might also occur from an older sibling, transferred via the maternal circulation or possibly from sexual intercourse, but these possibilities remain to be investigated.