Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Expession of B Cell Subsets in SLE Pregnancy: Correlation with Preterm Birth.
Clowse1, Megan E. B., Sparks2, Sara, Allgood2, Sallie, Lanasa2, Mark, Pisetsky3, David S.
Pregnancy demands significant shifts in immunologic function to maintain tolerance to the fetus. Women with systemic lupus erythematosus (SLE), particularly active SLE, have a several-fold higher rate of preterm birth and miscarriage compared to healthy women, suggesting that immune systems changes in SLE affect maternal-fetal tolerance and thereby promote pregnancy complications. To investigate this possibility, we tested whether alterations in the B cell compartment associated with SLE (increased plasmablasts and plasma cells and decrease naïve B cells) are associated with SLE activity and pregnancy outcomes.
Pregnant women with rheumatologic disease were consecutively enrolled in a prospective cohort. Disease activity using the SLE pregnancy disease activity index (SLEPDAI), and blood for autoantibody levels and peripheral blood mononuclear cells were collected in the first trimester, at a mid-pregnancy visit (between 2026 weeks gestation) and at least 6 weeks post-partum. Flow cytometry was performed and data analyzed using Flowjo. Plasmablasts were identified as CD27++, CD38++, and IgD- cells. Plasma cells, memory B cells, and naive B cells were delineated based on the degree of CD27 positivity. T tests and Fisher's exact test were used to determine statistical significance.
The cohort included 25 pregnant women: 19 with SLE and 6 with rheumatoid arthritis (RA). Extractable nuclear antigens were identified in 68% and the anti-dsDNA antibody was positive in 42% of the women with SLE. Five women had active disease, determined by a SLEPDAI >=8. Three of the SLE pregnancies resulted in a pregnancy loss. Of the live births, 37% of SLE pregnancies were delivered preterm (<37 weeks gestation). All of the RA pregnancies resulted in a live birth at term.
Pregnant women with RA had a higher percentage of naive B cells than women with SLE both at mid-pregnancy (RA 88% vs SLE 80%, p=0.07) and post-partum (RA 88% vs SLE 80%, p=0.007). Women with a positive anti-dsDNA antibody had a higher percentage of plasmablasts (p=0.03), plasma cells (p=0.07), and memory B cells (p=0.08), but fewer naive B cells (p=0.09) than other women with SLE. Compared to values post-partum, in the 1st trimester women with SLE had a trend toward fewer lymphocytes, a higher percentage of B cells, fewer memory B cells and more naive B cells (see Table).
Table. Comparison of B cell subsets for pregnant women with SLE.
|Total white blood cell count||6.7 × 109 cells/mm2||6.3 × 109 cells/mm2||0.65|
|Lymphocyte count||1.5 × 109 cells/mm2||2.2 × 109 cells/mm2||0.07|
|B cells (% of lymphocytes)||5.3%||3.3%||0.09|
|Memory B cells (% of B cells)||9.5%||12%||0.07|
|Naïve B cells (% of B cells)||85%||80%||0.03|
|Plasma cells (% of B cells)||0.56%||0.69%||0.89|
|Plasmablasts (% of B cells)||0.55%||0.53%||0.67|
The week of delivery correlated negatively with the percentage of plasmablasts in the 1st trimester (r -0.7, p=0.02) and trended towards a negative correlation with plasma cells (r -0.5, p=0.07). SLE activity and pregnancy loss were not correlated with any B cell subset.
Women with SLE have altered B cell homeostasis in the 1st trimester which may reflect the immunologic changes of pregnancy that allow fetal tolerance. In women with SLE, increased numbers of plasmablasts in the first trimester were associated with preterm delivery.
To cite this abstract, please use the following information:
Clowse, Megan E. B., Sparks, Sara, Allgood, Sallie, Lanasa, Mark, Pisetsky, David S.; Expession of B Cell Subsets in SLE Pregnancy: Correlation with Preterm Birth. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1192