1 University Departments of Medicine, Glasgow Royal Infirmary and 2 Department of Obstetrics, St James Hospital, Leeds, UK
3 To whom correspondence should be addressed at: Department of Medicine, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK. e-mail: gcl025{at}clinmed.gla.ac.uk
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: immune function/interleukin-2 receptor/recurrent miscarriage
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The aim of this study was to compare IL-2R levels in a group of women with a history of recurrent miscarriage, but who were not pregnant at the time of sampling, with levels found in a group of non-pregnant women with no history of miscarriage to see if there was any residual immune dysfunction.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Venous blood samples were obtained from the two patient groups. Group 1 comprised 49 non-pregnant women of mean age 32 ± 6.9 years with a previous history of recurrent miscarriage. All women had suffered at least three unexplained previous miscarriages, with the group having suffered a mean of 4.2 ± 2.3 previous miscarriages and no live births. All patients had had an antiphospholipid syndrome (APS) screen comprised of anticardiolipin IgG autoantibody and lupus anticoagulant. The lupus anticoagulant screen was comprised of activated partial thromboplastin time (APPT), kaolin clotting time (KCT) and dilute Russell viper venom test (DRVVT). If any two of these tests were positive, or one was positive with a positive anticardiolipin antibody (ACL), the lupus screen was said to be positive. Antinuclear antibody with a titre of 1:40 on two occasions was considered positive. The presence of Chlamydia in the blood denoting past exposure was assessed. There were no karyotype abnormalities. At the time of sampling, it had been at least 3 months since any of the women had suffered a miscarriage. Since sampling, 21 subsequently have become pregnant: 14 have had a successful pregnancy and seven have miscarried (four miscarried embryos and three miscarried fetuses).
Group 2 comprised 22 healthy non-pregnant women of mean age 28 ± 8 years with no history of miscarriage, or autoimmune disease. All of the women had already had at least one previous successful pregnancy.
Serum was stored at 70°C until analysed using enzyme-linked immunosorbent asay (ELISA) kits purchased from Laboratory Impex (Impex House, Wimbourne, Dorset, UK).
Statistics
Results are given as the mean ± SD, and were analysed for statistical significance using a MannWhitney test.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Many previous studies have investigated the response of the maternal immune system to pregnancy and have found that the response differs in women who miscarry (Clark et al., 1991; Reinhard et al., 1998
). Previous studies have found that relatively low levels of IL-2R early in pregnancy are associated with obstetric success (Kilpatrick, 1992
; MacLean et al., 2002
). Increased IL-2R levels have been found at the time of delivery and are associated with the immune activation known to occur at this time (Burns et al., 1999
).
We previously have found levels of IL-2R to be increased in first trimester women with a history of recurrent miscarriage, whilst in on-going pregnancies IL-2R levels did not differ significantly from the non-pregnant state (MacLean et al., 2002). The results reported here show that in some non-pregnant women with a history of recurrent miscarriage, IL-2R levels are also elevated, suggesting that they have not returned to normal after miscarriage and there is still activation of the immune system. Although a wide range of IL-2R levels were found in women in Group 1, the levels were not predictive of a successful outcome in the next pregnancy. Whilst few studies have looked at immune function pre-pregnancy, Kilpatrick (1992
) also found levels of IL-2R to be elevated in non-pregnant women with a history of recurrent miscarriage, but the results did not reach statistical significance. What distinguishes the present study is that follow-up data were available on some of the women involved.
![]() |
Acknowledgement |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Clark, D.A., Lea, R.G., Podor, T,. Daya, S., Banwatt, D. and Harley, C. (1991) Cytokines determine the success or failure of miscarriage. Ann. NY Acad. Sci., 626, 524536.[Medline]
Kilpatrick, D.C. (1992) Soluble interleukin-2 receptor levels in recurrent miscarriage and the effect of leucocyte immunotherapy. Immunol. Lett., 34, 201206.[CrossRef][ISI][Medline]
MacLean, M.A., Wilson, R., Jenkins, C., Miller, H. and Walker J.J. (2002) Interleukin 2 receptor concentrations in pregnant women with a history of recurrent miscarriage. Hum. Reprod., 17, 219220.
Matthiesen, L., Berg, G., Ernerudh, J. and Hakansson, L. (1996) Lymphocyte subsets and mitogen stimulation of blood lymphocytes in normal pregnancy. Am. J. Reprod. Immunol., 35, 7079.[ISI][Medline]
Quack, K.C., Vassiliadou, N., Pudney, J., Anderson, D.J. and Hill, J.A. (2001) Leukocyte activation in the deciduas of chromosomally normal and abnormal fetuses from women with recurrent abortion. Hum. Reprod., 16, 949955.
Reinhard, G., Noll, A., Schlebusch, H., Mallmann, P. and Ruecker, A.V. (1998) Shifts in the Th1/Th2 balance during human pregnancy correlate with apoptotic changes. Biochem. Biophys. Res. Commun., 245, 933938.[CrossRef][ISI][Medline]
Vassiliadou, N., Searle, R.F. and Bulmer, J.N. (1999) Elevated expression of activation molecules by decidual lymphocytes in women suffering spontaneous early pregnancy loss. Hum. Reprod., 14, 11942000.
Submitted on September 2, 2002; resubmitted on January 17, 2003; accepted on March 26, 2003.