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Objective. To determine the outcome of pregnancy in women with rheumatoid arthritis (RA) in relation to disease activity and medication use during the pregnancy.Methods. In a prospective study, pregnant women with RA were evaluated before conception (when possible), during each trimester of the pregnancy, and postpartum. Clinical characteristics, disease activity, medication use, and pregnancy outcome were analyzed. To examine the independent influence of prednisone use and disease activity on birth weight, regression analyses were performed, with adjustments for gestational age of the child at delivery, the sex of the newborn, and the mother's smoking status, education level, parity, and use of an assisted reproduction technique. KaplanMeier curve analyses were performed to examine the association between medication use and gestational age at delivery.Results. Data from 152 Caucasian RA patients with singleton pregnancies were available. Both the mean ؎ SD birth weight (3,379 ؎ 564 gm) and the mean ؎ SD birth weight standard deviation score (SDS; ؉0.1 ؎ 1.1), which is the birth weight adjusted for the gestational age and sex of the newborn, were comparable with those in the general population. On multiple linear regression analyses of birth weight and birth weight SDS, both of which were adjusted for covariates, only disease activity was associated with lower birth weight (P ‫؍‬ 0.025). The gestational age at delivery was significantly lower in women who were taking prednisone (38.8 versus 39.9 weeks; P ‫؍‬ 0.001), and their delivery was more often premature (<37 weeks; P ‫؍‬ 0.004). Conclusion. Pregnancy outcome in women with well-controlled RA is comparable with that in the general population. The effect of prednisone on birth weight is mediated by a lower gestational age at delivery, whereas a higher level of disease activity independently influences birth weight negatively, suggesting an immune-mediated mechanism.

It is a longstanding question which bone marrow-derived cell seeds the thymus and to what level this cell is committed to the T-cell lineage. We sought to elucidate this issue by examining gene expression, lineage potential, and self-renewal capacity of the 2 most immature subsets in the human thymus, namely CD34 ؉ CD1a ؊ and CD34 ؉ CD1a ؉ thymocytes. DNA microarrays revealed the presence of several myeloid and erythroid transcripts in CD34 ؉ CD1a ؊ thymocytes but not in CD34 ؉ CD1a ؉ thymocytes. Lineage potential of both subpopulations was assessed using in vitro colony assays, bone marrow stroma cultures, and in vivo transplantation into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The CD34 ؉ CD1a ؊ subset contained progenitors with lymphoid (both T and B), myeloid, and erythroid lineage potential. Remarkably, development of CD34 ؉ CD1a ؊ thymocytes toward the T-cell lineage, as shown by T-cell receptor ␦ gene rearrangements, could be reversed into a myeloid-cell fate. In contrast, the CD34 ؉ CD1a ؉ cells yielded only T-cell progenitors, demonstrating their irreversible commitment to the T-cell lineage. Both CD34 ؉ CD1a ؊ and CD34 ؉ CD1a ؉ thymocytes failed to repopulate NOD/SCID mice. We conclude that the human thymus is seeded by multipotent progenitors with a much broader lineage potential than previously assumed. These cells resemble hematopoietic stem cells but, by analogy with murine thymocytes, apparently lack sufficient self-renewal capacity. IntroductionThe thymic microenvironment is exceptional in its ability to sustain production of T cells. 1 However, hematopoietic stem cells (HSCs) that will eventually give rise to T cells are derived from the bone marrow (BM). The nature of the thymus-seeding cell and its relation to several BM progenitors has remained elusive, despite being the subject of intense investigation. Furthermore, it is controversial whether cells commit to the T-cell lineage prethymically or intrathymically. 2,3 Aided by modern cell-sorting techniques, many studies in the mouse have recently readdressed these issues. Adult murine BM has been demonstrated to contain precursors with a restricted T-/B-lymphoid potential, so-called common lymphoid progenitors (CLPs). 2,4 However, the earliest thymic immigrants were shown to differ from CLPs in several aspects. 5 In peripheral blood, T-lineage potential appeared to be restricted to Lin Ϫ Sca-1 ϩ c-Kit ϩ (LSK) progenitor populations, rather than to CLPs. 6 Recently, two detailed analyses of the earliest subpopulations in the murine thymus showed variable lineage potential of different subsets. 7,8 Together, these studies point toward a model in which a range of BM-derived progenitors colonize the thymus, probably including multipotent progenitors and more lineage-restricted precursor cells. 9 For the human system, comparable experimental data are lacking. Determining lineage potential of early thymocytes will help to unveil the identity of the thymus-seeding cell in humans.In both humans and mice, the most immature ce...

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