Nathalie C. Lambert

INSERM UMRs 1097 Arthritides, Microchimerism and Inflammations (ARTHEMIS), Aix Marseille University, Marseille, France

The idea that semi-allogeneic cells resulting from feto-maternal exchanges might play a role in autoimmune diseases was first suggested in 1893, when a German pathologist, Georg Schmorl, discovered fetal placental cells in the lungs of mothers who had died of eclampsia. A century later, in 1996, J. Lee Nelson revisited this hypothesis, asking whether autoimmune diseases might in fact be semi-alloimmune in nature. She sparked interest by demonstrating that the peripheral blood of women with scleroderma more frequently and abundantly contained male cells—presumed to be of fetal origin—than that of age- and pregnancy-matched controls. This phenomenon, known as fetal microchimerism (Mc), became the focus of extensive correlation studies linking Mc levels to various autoimmune conditions.

But does the mere presence of these cells in higher quantities among patients truly establish their causal role in disease? Could other cells arising from placental exchanges participate also ?  Do maternal, fetal and sibling microchimeric cells exert pathogenic effects only within specific genetic contexts in families?

In a cohort of patients with rheumatoid arthritis, we have recently identified specific genetic patterns across three generations that may influence the levels of microchimerism. We, along with others, have shown that microchimerism can represent a genetic risk factor for developing the disease in hosts who do not carry a known predisposition. Finally, using a mouse model, we have analyzed the ability of different microchimeric sources to produce autoantibodies and to contribute to pathogenesis. Does this represent a worrying biological phenomenon—or, conversely, an exciting therapeutic opportunity?