Effect of IgG Therapy on Lymphocyte Subpopulations in the Peripheral Blood of Kuwaiti Women Experiencing Recurrent Pregnancy Loss

Abstract

Intravenously administered polyspecific IgG is being increasingly used as an immunomodulating therapy with controversial beneficial outcome. The aim of this study was to evaluate the effects of IgG infusion on peripheral T-cell subpopulations in women with recurrent pregnancy loss (RPL). Fifteen women with a history of three previous RPL between 6 and 22 weeks of gestation and positivity for the antiphospholipid antibody syndrome (APS) were randomized to one of two treatment groups: (a) an intravenous immunoglobulin therapy group (RPL-IVIg; 7 patients), 500 mg IVIg/kg/month and (b) a placebo-treated group given multivitamins (8 patients). Control groups comprised either normal pregnant women without APS (10 patients) or non-pregnant women. The T-cell markers were characterized using a monoclonal antibody panel including CD3, CD4, CD8, CD25, CD29, CD38, CD45RA, CD45RO, CD54 and HLA-DR. Analysis was performed with a two-color fluorescent-activated flow cytometer. In the first trimester, the percentage of CD4+CD25+, CD4+CD45RO+, CD8+HLA-DR+, and CD8+CD38+ populations were reduced in the multivitamin group compared to normal pregnant women (p < 0.05) while in the RPL-IVIg group only CD4+CD25+ cells were reduced (p < 0.05). By the second trimester, CD3+CD16+CD56+ was significantly higher in multivitamin- than in IVIg-treated women (p < 0.05). The percentage of CD4+HLA-DR+ was significantly higher in the two RPL groups compared to normal pregnant women (p < 0.05). IVIg therapy in women with RPL was associated with a significant reduction in CD3+CD16+CD56+ and CD4+CD25+. This may contribute to the suppression of immune-mediated processes contributing to premature abortion.

The Effects of Intravenous Immunoglobulins in Women with Recurrent Miscarriages: A Systematic Review of Randomised Trials with Meta-Analyses and Trial Sequential Analyses Including Individual Patient Data

“…We included 11 randomised clinical trials described in 19 publications in our systematic review [ 5 , 9 – 15 , 17 , 38 , 39 ].…”

“…Two trials enrolled only women with primary RM [ 11 , 12 ], two trials enrolled only women with secondary RM [ 15 , 17 ], and six trials enrolled women with primary or secondary RM [ 5 , 9 , 10 , 13 , 14 , 39 ]. One trial did not report whether the women had primary or secondary RM [ 38 ].…”

“…Dosage and number of infusions varied between trials. Eight trials initiated the intervention when the pregnancy was detected by a positive pregnancy test or by ultrasound [ 5 , 10 – 12 , 14 , 17 , 38 , 39 ] and three trials initiated the intervention before the women became pregnant [ 9 , 13 , 15 ].…”

“…Saline is not considered an adequate placebo as it can be distinguished visually from the IVIg. Two trials used treatment as usual with multivitamin and subcutaneous heparin plus low-dose aspirin, respectively, as control interventions [ 38 , 39 ]. These two control interventions could easily be distinguished from IVIg as they are applied differently.…”

Association of Selected Phenotypic Markers of Lymphocyte Activation and Differentiation with Perinatal Human Immunodeficiency Virus Transmission and Infant Infection

“…Likewise, use of prenatal IVIG in other disorders is not associated with lymphocyte activation or premature maturation of the neonatal immune system (26). While specific immunological effects of HIVIG in pregnancy have not been studied, IVIG treatment in pregnancy does not appear to affect levels of CD3ϩCD8 ϩ or CD3 ϩ lymphocytes (17,30), but does reduce peripheral blood NK cells (15). IVIG appears to exert its therapeutic effects in autoimmune and alloimmune disorders by down-regulation of costimulatory molecules associated with modulation of cytokine secretion, with resultant inhibition of autoreactive and alloreactive T-cell activation and proliferation (2); by reduction of intact B cell and monocyte cell numbers, modulation of surface molecule expression on B cells, and deletion of B and T cells by apoptosis with resultant inhibition of optimal T-cell activation (34); and by inhibition of cytokine-induced NF-B activation and blocking of Fc␥RIII on cell membranes (11,12).…”