Change of serum B-cell activating factor level in patients with positive antiphospholipid antibodies and previous adverse pregnancy outcomes and its significance

Abstract BACKGROUND: The Sapporo criteria for the diagnosis of the antiphospholipid syndrome (APS) are based on the presence of antiphospholipid antibodies (APLA) and clinical criteria. Although pre-eclampsia, intra-uterine growth restriction (IUGR), late fetal loss and placental abruption, collectively termed “placenta mediated complications”, are recognized as clinical criteria for the APS, their association with APLA remains controversial. OBJECTIVE: This review was conducted to evaluate the association between APLA (anticardiolipin antibodies, lupus anticoagulant, anti B2 glycoprotein 1 antibodies) and placenta mediated complications in untreated women without autoimmune diseases. METHODS: We performed a systematic review of published case-control, cohort and cross sectional studies using MEDLINE (1975 to October week 2 2007), EMBASE 16 (1980 to 2007 week 42) and all EBM Reviews (3rd quarter of 2007). For eligible studies, the rates of adverse pregnancy outcomes were compared between patients with and without specific APLA. Pooled odds ratios with 95% CI were generated using random-effects models. RESULTS: Our search strategy identified 1204 potentially relevant studies. Twenty five were included in the final analysis. Results are outlined in table 1. CONCLUSION: The association between various APLA and pregnancy complications is for the most part weak and inconsistent. There is currently insufficient data to support a significant link between anti-B2 glycoprotein 1 antibodies and pregnancy morbidity. Caution should be used when establishing a diagnosis of APS based on the presence of any APLA, particularly anti-B2 glycoprotein 1 antibodies, in the setting of late pregnancy complications. Table 1 Association Between APLA and Adverse Pregnancy Outcomes Pre-eclampsia OR (95%CI) # studies / participants IUGR OR (95%CI) # studies / participants Placental abruption OR (95%CI) # studies / participants Late fetal loss OR (95%CI) # studies / participants LA: Lupus anticoagulant; aCL: Anticardiolipin antibodies; Anti-B2 GP1 antibodies: Anti-B2 glycoprotein 1 antibodies italic characters indicate statistically significant associations LA 2.88 (1.42, 5.87)  11 / 6085 3.51 (1.38, 8.93)  4 / 3232 0.78 (0.13, 4.80)  2 / 226 3.56 (0.12, 106.05)  3 / 3870 aCL (IgG/IgM) 1.71 (1.09, 2.70)  21 / 9722 2.31 (0.74, 7.17)  6 / 5753 1.35 (0.45, 4.02)  4 / 1274 3.86 (1.14, 13.07)  7 / 5963 aCL IgG 1.65 (0.84, 3.22)  15 / 3627 6.16 (2.50, 15.18)  2 / 1006 1.87 (0.21, 16.83)  2 / 500 10.06 (0.88, 114.96)  2 / 1006 aCL IgM 1.36 (0.93, 1.97)  13 / 5397 0.75 (0.19, 2.93)  2 / 3002 0.96 (0.24, 3.85)  2 / 500 1.37 (0.42, 4.46)  3 / 3212 anti- B2GP1 (IgG/IgM) 2.97 (0.47, 18.69)  4 / 2225 20.03 (4.59, 87.43)  1 / 1108 2.64 (0.14, 50.63)  1 / 510 6.74 (0.24, 191.23)  3 / 1828 anti- B2GP1 IgG 0.87 (0.38, 2.01)  2 / 607 N/A  0 / 0 N/A  0 / 0 0.52 (0.02, 11.02)  1 / 212 anti- B2GP1 IgM 0.37 (0.16, 0.85)  1 / 400 N/A  0 / 0 N/A  0 / 0 1.32 (0.24, 7.42)  1 / 210

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Low Preconception Complement Levels Are Associated with Adverse Pregnancy Outcomes in a Multicenter Study of 260 Pregnancies in 197 Women with Antiphospholipid Syndrome or Carriers of Antiphospholipid Antibodies

Biomedicines ◽

10.3390/biomedicines9060671 ◽

2021 ◽

Vol 9 (6) ◽

pp. 671

Author(s):

Cecilia Nalli ◽

Daniele Lini ◽

Laura Andreoli ◽

Francesca Crisafulli ◽

Micaela Fredi ◽

...

Keyword(s):

Antiphospholipid Syndrome ◽

Multicenter Study ◽

Pregnancy Outcomes ◽

Antiphospholipid Antibodies ◽

Pregnancy Loss ◽

Fetal Loss ◽

Adverse Pregnancy Outcomes ◽

Experimental Animal Models ◽

Increased Risk ◽

Adverse Pregnancy

Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated with pregnancy complications in patients with antiphospholipid syndrome (APS), but these results are not unanimously confirmed. To investigate if the detection of low C3/C4 could be considered a risk factor for adverse pregnancy outcomes (APO) in APS and aPL carriers’ pregnancies we performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed (p = 0.008). A subgroup analysis focusing on triple aPL-positive patients found that preconception low C3 and/or C4 levels were associated with an increased rate of pregnancy loss (p = 0.05). Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. This has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss.

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