Ghirardello Anna, Gizzo Salvatore, Noventa Marco, Quaranta Michela, Vitagliano Amerigo, Gallo Nicoletta, Pantano Giorgia, Beggio Marianna, Cosma Chiara, Gangemi Michele, Plebani Mario, Doria Andrea
Division of Rheumatology, Department of Medicine, University of Padua, Padua, Italy.
Department of Woman and Child Health, Gynaecologic and Obstetric Unit, University of Padua, Padua, Italy.
J Assist Reprod Genet. 2015 Dec;32(12):1765-72. doi: 10.1007/s10815-015-0588-x. Epub 2015 Oct 14.
The aim of the present study was to evaluate the in vivo immunomodulatory effects of an acute short-term estradiol (E(2)) increase on serum levels of B cell-activating factor (BAFF), immunoglobulins (Ig), anti-nuclear antibodies (ANA), and the peripheral B cell phenotype.
We conducted, at the Infertility Center of the University of Padua, a prospective case-control study on a cohort of infertile normo-responder women (group-A, 63 patients) undergoing controlled ovarian stimulation (COS) compared with an age-matched cohort of normo-ovulatory healthy women (group-B, 39 patients). Three serial blood sample assays were conducted in both groups, at T0, hypothalamic suppression; T1, ovulation induction; and T2, βhCG test in group A, and at T0, 2nd day; T1, 14th day; and T2, 21st day of cycle in group B, and serum levels of E(2) and BAFF, BAFF/E(2) ratio, circulating IgM, IgG, and IgA, ANA titer, and peripheral B cell phenotype were measured. We compared group-A versus group-B in terms of absolute and E(2) normalized values of BAFF at baseline (T0) to verify for possible differences between healthy and infertile women, at T1 to verify for possible differences occurring after spontaneous ovulation versus COS, and at T2 to evaluate differences in serum BAFF levels between pregnant versus non-pregnant patients (considering only group-A) and between non-pregnant women after spontaneous versus COS cycles (group-B versus group-A). In group-A, we also evaluated IgM, IgG, IgA levels, ANA titer, and peripheral B cell phenotype at T0 versus T1 versus T2.
With the exception of E(2) levels at T1 (as expected), no significant differences were found between the two groups for all outcome measures. In group-A, BAFF at T0 positively correlated with IgM levels; marginal zone CD19+/CD27+/IgD+ memory B cell compartment tended to be expanded at T1 when compared with T0.
Despite several mechanistic and clinical studies supporting a stimulatory role of E(2) on autoimmunity, the acute increase of E(2) during COS for infertility treatment does not seem to have a major impact on the immune system.
本研究旨在评估急性短期雌二醇（E₂）升高对血清B细胞活化因子（BAFF）水平、免疫球蛋白（Ig）、抗核抗体（ANA）及外周B细胞表型的体内免疫调节作用。
在帕多瓦大学不孕症中心，我们对一组接受控制性卵巢刺激（COS）的不孕正常反应女性（A组，63例患者）进行了一项前瞻性病例对照研究，并与年龄匹配的正常排卵健康女性队列（B组，39例患者）进行比较。两组均在T0（下丘脑抑制）、T1（排卵诱导）和T2（A组的βhCG检测）时进行三次连续血样检测，B组在月经周期的T0（第2天）、T1（第14天）和T2（第21天）进行检测，并测量血清E₂和BAFF水平、BAFF/E₂比值、循环IgM、IgG和IgA、ANA滴度以及外周B细胞表型。我们比较了A组和B组在基线（T0）时BAFF的绝对值和E₂标准化值，以验证健康女性和不孕女性之间可能存在的差异；在T1时，验证自发排卵与COS后可能出现的差异；在T2时，评估怀孕与未怀孕患者（仅考虑A组）之间以及自发周期与COS周期后未怀孕女性（B组与A组）之间血清BAFF水平的差异。在A组中，我们还评估了T0、T1和T2时的IgM、IgG、IgA水平、ANA滴度以及外周B细胞表型。
除了T1时的E₂水平（如预期）外，两组在所有观察指标上均未发现显著差异。在A组中，T0时的BAFF与IgM水平呈正相关；与T0相比，边缘区CD19⁺/CD27⁺/IgD⁺记忆B细胞区在T1时倾向于扩大。
尽管有多项机制和临床研究支持E₂对自身免疫有刺激作用，但不孕症治疗中COS期间E₂的急性升高似乎对免疫系统没有重大影响。
