Pre-disease pregnancy complications and systemic sclerosis: pathogenic or pre-clinical?

to many autoimmune diseases with a strong female predominance, relationships between pre-disease preg-nan cies and subsequent development of systemic sclerosis (SSc) have been the source of a great deal of study, often with confl icting results. Fetal microchimerism – the bidirectional transfer of cells between mother and fetus during gestation and delivery, followed by perpetuation of small amounts of foreign cells or DNA in the host for years or decades, potentially leading to a graft-versus-host-like eff ect – has been implicated in the pathogenesis of SSc based upon epidemiologic and immunological studies. While the fetal micro chimerism theory of SSc carries compelling biologic plausibility given the clinical resemblance of diff use cutaneous SSc and graft-versus-host disease, as well as the increased presence of fetal cells in women with SSc, purely epidemiologic studies without trans-lational, immuno logical, or cellular correlates cannot directly support a causal association. Th e current study by van Wyk and colleagues is an excellent example of a well-performed epidemiologic study identifying a positive association between pregnancy complications (hypertensive disorders of pregnancy (HTN) and intrauterine growth restriction (IUGR)) prior to diagnosis and the future development of SSc [1]. Th e authors conducted a case–control study of parous women with SSc compared with healthy women. Repro ductive history was obtained through questionnaires. Th e mean age at enrollment was 57 years, approximately 30 years after the fi rst pregnancy for both groups. Results showed a statistically signifi cant increase of HTN as well as IUGR among women who later developed SSc. Notably, the rates of HTN and IUGR among women in this study who were later diagnosed with SSc were not demonstrably diff erent from the rates reported for women with pre-existing SSc (22.9% HTN [2] and 5 to 20% IUGR [2,3]). Despite the merits of this study, it remains diffi cult to interpret the results as directly supportive of fetal micro-chimerism. Certainly, many pregnancy complica tions increase maternal–fetal cellular traffi cking. However, maternal–fetal cellular transfer is seen in almost all pregnancies, and is increased in other pregnancy disorders not reported in this study including preterm labor and pregnancy termination [4]. Other modes of microchimerism, including blood transfusions, are not assessed in the study. What perhaps may be more relevant to understanding the relationship between prior pregnancy complications and future diagnosis of SSc is to uncover whether fetal cells are perpetuated in maternal blood and tissues and to identify …