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Prospective study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis

  1. Zhen Yan1,*,
  2. Nathalie C. Lambert2,
  3. Monika ØStensen3,
  4. Kristina M. Adams4,
  5. Katherine A. Guthrie1,
  6. J. Lee Nelson4

Article first published online: 27 JUN 2006

DOI: 10.1002/art.21966

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 54, Issue 7, pages 2069–2073, July 2006

Additional Information

How to Cite

Yan, Z., Lambert, N. C., ØStensen, M., Adams, K. M., Guthrie, K. A. and Nelson, J. L. (2006), Prospective study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis. Arthritis & Rheumatism, 54: 2069–2073. doi: 10.1002/art.21966

Author Information

  1. 1

    Fred Hutchinson Cancer Research Center, Seattle, Washington

  2. 2

    Fred Hutchinson Cancer Research Center, Seattle, Washington, and INSERM U639, Marseilles, France

  3. 3

    University Hospital, Bern, Switzerland

  4. 4

    Fred Hutchinson Cancer Research Center, Seattle, Washington, and University of Washington, Seattle

*Immunogenetics D2-100, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19024, Seattle, WA 98109

Publication History

  1. Issue published online: 27 JUN 2006
  2. Article first published online: 27 JUN 2006
  3. Manuscript Accepted: 6 APR 2006
  4. Manuscript Received: 28 DEC 2005

Funded by

  • NIH. Grant Numbers: AI-41721, AR-39282, AI-45659
  • Washington Women's Foundation

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Abstract

Objective

Rheumatoid arthritis (RA) usually improves during pregnancy and recurs postpartum. Fetal cells and cell-free DNA reach the maternal circulation during normal pregnancy. The present study investigated dynamic changes in levels of fetal DNA in serum from women with RA and inflammatory arthritis during and after pregnancy to test the hypothesis that the levels of circulating fetal DNA correlate with arthritis improvement.

Methods

Twenty-five pregnant patients were prospectively studied. A real-time quantitative polymerase chain reaction panel targeting unshared, paternally transmitted HLA sequences, a Y chromosome–specific sequence, or an insertion sequence within the glutathione S-transferase M1 gene was used to measure cell-free fetal DNA. Results were expressed as fetal genomic equivalents per milliliter (gE/ml) of maternal serum. Physical examinations were conducted during and after pregnancy.

Results

Levels of fetal DNA in women with improvement in or remission of arthritis were higher than those in women with active disease, especially in the third trimester. Overall, an inverse relationship between serum fetal DNA levels and disease activity was observed (P < 0.001). Serum fetal DNA increased with advancing gestation, reaching median levels of 24 gE/ml (range 0–334), 61 gE/ml (range 0–689), and 199 gE/ml (range 0–2,576) in the first, second, and third trimesters, respectively, with fetal DNA clearance observed postpartum. Arthritis improvement was initially noted in the first trimester for most patients, increased further or was sustained with advancing gestation, and was active postpartum.

Conclusion

Changes in serum fetal DNA levels correlated with arthritis improvement during pregnancy and recurrence postpartum. Immunologic mechanisms by which pregnancy might modulate RA activity are described.

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