Abnormal immunoglobulin subclass patterns in women with a history of recurrent miscarriage

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Slide 1 : Abnormal immunoglobulin subclass patterns in women with a history of recurrent miscarriage R Wilson, M Maclean, C Jenkins, D Kinane, J Mooney, JJ Walker
Slide 2 : Introduction Miscarriage affects approximately 1% of all pregnancies and a proportion of these women will suffer recurrent miscarriages. Although the causes of recurrent miscarriage are not fully understood, immunological mechanisms are thought to play an important role. The effector T cell response is divided into two subsets: Th1 cells, which produce gamma interferon (IFNg) and IL-12, and Th2 cells, which produce IL-4, 5, and 13 (1). A successful pregnancy is associated with TH2 type cytokines while Th1 type cytokines are associated with miscarriage (2, 3). Changes in immunoglobulin subclasses have been reported in normal pregnancy. This study has considered the changes occurring in women with a history of recurrent miscarriage (at least three previous miscarriages) about whom very little is known.
Slide 3 : MATERIALS AND METHODS Patient Groups The ethical committee approved the study, and all women gave informed consent. The study comprised 4 patient groups; Group 1 comprised of 10 healthy non pregnant women. Group 2 comprised of 10 first trimester (8.1 ± 1.3 weeks gestation) pregnant women. All pregnancies went to term. Group 3 comprised of eight first trimester pregnant women (7.6 ± 1.5 weeks gestation) with a history of recurrent miscarriage. on this occasion all pregnancies went to term. Group 4 comprised of 10 first trimester pregnant women (7.1 ± 1.1weeks gestation) with a history of recurrent miscarriage. All pregnancies again failed later in the first trimester. Methods Titres of IgG subclasses were measured by ELISA (4) in serum collected from the 4 patient groups
Slide 4 : RESULTS - 1 The results (Table 1) showed; Compared with non pregnant women, women in Group 2 had significantly increased total IgG production and significantly increased levels of IgG subclasses 1, 2, and 3. Women in Group 3, (a past history of recurrent miscarriage, but whose pregnancies on this occasion continued to term), showed similar IgG subclass patterns to those in Group 2. Group 4, (women whose pregnancies again ended in miscarriage) showed significantly reduced levels of total IgG and IgG subclasses 1, 2, 3, and 4 compared with women in Group 2.
Slide 5 : Table 1 Immunoglobulin subclasses in pregnant and non pregnant women
Slide 6 : Legend to Table 1 Results are given as mean ± 1 standard deviation Group 1 = non pregnant Group 2 = pregnant Group 3 = miscarriage - successful Group 4 = miscarriage - unsuccessful agroup 2 vs. Group 1 bGroup 4 vs. Group2 cGroup 4 vs. Group 3
Slide 7 : RESULTS - 2 IgG 1 levels were found to be significantly higher in serum from women in Group 3 compared with Group 4 patients, and there was no overlap between the two groups (Fig. 1). It is worth noting that all patients were pregnant at the time of sampling, although all women in group 4 miscarried later in the first trimester
Slide 8 : Figure 1 IgG 1 levels in pregnant women with a history of recurrent miscarriage 0 1 2 3 4 5 6 7 Successful Miscarriage Pregnancy IgG 1 LEVEL (MG/ML)
Slide 9 : Discussion 1 This study has shown that; Normal pregnancy is associated with significant changes in IgG subclasses. Pregnant women who miscarried later in the first trimester showed different IgG subclass patterns to those pregnant women whose pregnancies continued to term. This would suggest that in these women, changes leading to miscarriage occur at an early stage in the pregnancy
Slide 10 : Discussion - 2 The changes in IgG subclass production can be linked to the immunological events that occur. Pregnancy is associated with the production of Th2 type cytokines (IL-10 and IL-4) while miscarriage is associated with the production of Th1 type cytokines (IFNg, IL-12) (2,3). IL-4 causes human peripheral blood cells to become activated and switch to IgG 4 production and IL-10 has been show in vitro to increase total IgG production (7). IFNg inhibits these processes (6). .
Slide 11 : Conclusion Pregnancies that ended in miscarriage showed a different pattern of IgG subclasses than those that continued to term. The changes seen in immunoglobulin patterns could be linked to changes in cytokine production.
Slide 12 : References Wegnman TG, et al. Immunol Today 93; 11: 353–6 Jenkins C, et al. Fertil Steril 2000; 73: 1206–8. Lim KJ, et al. Fertil Steril 2000; 73: 136–42. Kinnane DF, et al. Oral Microbiol 1993; 8: 65–8. Del Prete G, et al J Immunol 1988; 140: 4193–8 Kitaya K, et al Biol Hum Reprod 2000; 63: 683–7. Lorente L, et al J Exp Med 1995; 181: 839–44

 


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