Recombinant HBsAg of the Wild-Type and the G145R Escape Mutant, included in the New Multivalent Vaccine against Hepatitis B Virus, Dramatically Differ in their Effects on Leukocytes from Healthy Donors In Vitro.

Immune-escape hepatitis B virus (HBV) mutants play an important role in HBV spread. Recently, the multivalent vaccine Bubo®-Unigep has been developed to protect against both wild-type HBV and the most significant G145R mutant. Here, we compared the effects of recombinant HBsAg antigens, wild-type and mutated at G145R, both included in the new vaccine, on activation of a human high-density culture of peripheral blood mononuclear cells (PBMC) in vitro. The antigens were used either alone or in combination with phytohemagglutinin (PHA). None of the antigens alone affected the expression of CD40, HLA-DR or CD279. Wild-type HBsAg enhanced CD86 and CD69 expression, and induced TNF-α, IL-10, and IFN-γ, regardless of the anti-HBsAg status of donor. In the presence of PHA, wild-type HBsAg had no effect on either of the tested surface markers, but increased IFN-γ and IL-10 and inhibited IL-2. In contrast, the G145R mutant alone did not affect CD86 expression, it induced less CD69, and stimulated IL-2 along with lowering levels of TNF-α, IL-10, and IFN-γ. The G145R mutant also suppressed PHA-induced activation of CD69. The dramatic differences in the immune responses elicited by wild-type HBsAg and the G145R mutant HBsAg suggest distinct adaptive capabilities of the G145R mutant HBV.

Prediction of spontaneous preterm delivery in women presenting with premature labor: a comparison of placenta alpha microglobulin-1, phosphorylated insulin-like growth factor binding protein-1, and cervical length.

BACKGROUND: Placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 have been studied in patients at risk for preterm birth with signs and symptoms of preterm labor. However, a direct comparison between these 2 biomarkers, alone or in combination with cervical length measurement with an adequate sample size, has been lacking to date. OBJECTIVE: The purpose of this study was to compare the placental alpha microglobulin-1 test and the phosphorylated insulin-like growth factor-binding protein-1 test alone and in combination with cervical length measurement for the prediction of imminent spontaneous preterm birth of testing in pregnant women with symptoms of preterm labor in a tertiary care setting. STUDY DESIGN: Four hundred three patients with intact amniotic membranes and cervical dilation ≤3 cm, without recent intercourse or cerclage, between gestational weeks of 20+0 and 36+6 were recruited prospectively from 3 international centers. Placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 tests were conducted before cervical length measurement via transvaginal ultrasound scanning. Caregivers were blinded to the biomarker test results. Medically indicated deliveries within 14 days of testing were excluded. Standard performance statistics with 95% confidence intervals were calculated and compared based on pairwise estimates from a generalized model. RESULTS: Of 403 subjects who were enrolled in the study cohort, 94% (383/403 women) met the inclusion criteria. Median gestational age and cervical length at presentation were 30+5 weeks and 27 mm, respectively; 6.8% women (26/383 women) had spontaneous birth ≤7 days from testing. The placental alpha microglobulin-1 test was positive in 7.8% of the women (30/383 women); the phosphorylated insulin-like growth factor-binding protein-1 test was positive in 29.5% women (113/383 women). Positive predictive value for placental alpha microglobulin-1, phosphorylated insulin-like growth factor-binding protein-1, and cervical length <25 mm for the prediction of spontaneous preterm birth in the overall cohort was 60.0% (18/30 women), 18.6% (21/113 women), 11.8% (18/152 women), respectively. The negative predictive value was 97.7% (345/353 women), 98.2% (265/270 women), 96.5% (223/231 women), respectively. The prevalence of spontaneous preterm birth in this group was 6.8% (26/383 women). The positive likelihood ratios were 20.6, 3.1, and 1.8, respectively. The negative likelihood ratio were 0.3, 0.3, and 0.5, respectively. Positive predictive values for placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 tests in patients with cervical length shortening of 15-30 mm for the prediction of spontaneous preterm birth were 60.9% (14/23 women) and 28.1% (16/57 women), respectively. The negative predictive values were 97.1% (168/173 women) and 97.8% (136/139 women), respectively. The prevalence of spontaneous preterm birth in the 15-30 mm cohort was 9.7% (19/196 women). The positive likelihood ratios were 14.5 and 3.6, respectively. The negative likelihood ratios were 0.3 and 0.2, respectively. CONCLUSION: Placental alpha microglobulin-1 is significantly more specific than phosphorylated insulin-like growth factor-binding protein-1 for the prediction of spontaneous preterm birth ≤7 days (P<.0001), whereas both tests have comparable sensitivity. In patients with cervical length 15-30 mm, although placental alpha microglobulin-1 has a significantly higher positive predictive value and specificity compared with phosphorylated insulin-like growth factor-binding protein-1 for the prediction of spontaneous preterm birth at ≤7 days (P<.01), both tests have a comparable sensitivity and negative predictive value. In conclusion, placental alpha microglobulin-1 is a better predictor of imminent spontaneous preterm birth when compared with phosphorylated insulin-like growth factor-binding protein-1 alone or in combination with cervical length measurement. In patients with shortening of cervical length of 15-30 mm, the placental alpha microglobulin-1 test is a significantly better predictor of imminent spontaneous preterm birth within 7 days of testing than is phosphorylated insulin-like growth factor-binding protein-1.

Combined value of placental alpha microglobulin-1 detection and cervical length via transvaginal ultrasound in the diagnosis of preterm labor in symptomatic patients.

AIM: We aimed to evaluate the combined value of placental alpha microglobulin-1 (PAMG-1) and cervical length (CL) via transvaginal ultrasound for assessing risk of imminent spontaneous preterm delivery in patients presenting with threatened preterm labor (PTL). METHODS: Clinical exam, PAMG-1 test, cardiotocography, and CL measurement via transvaginal ultrasound were performed on all patients meeting inclusion criteria. Ninety-nine patients at 22+0 -36+6 gestational weeks with the symptoms of PTL were included. The interval between sample collection and delivery was measured for each method. RESULTS: Performance metrics were calculated for PAMG-1 test, CL < 25 mm, and contractions ≥ 8/h. The sensitivity, specificity, positive predictive value, and negative predictive value for the PAMG-1 test were 100%, 95%, 75%, 100% and 100%, 98%, 88%, 100% for 7 and 14 days, respectively; the respective values for CL < 25 mm were 83%, 59%, 22%, 96% and 79%, 59%, 24%, 94% for 7 and 14 days; and those for contractions ≥ 8/h were 42%, 38%, 8%, 83% and 43%, 38%, 10%, 80% for 7 and 14 days. Specificity for the PAMG-1 test was statistically significant (P < 0.001) in pairwise comparisons for all other methods. Patients were divided into four groups for analysis of PAMG-1 test performance as follows: CL < 15 mm (100%, 100%, 100%, 100% and 100%, 100%, 100%, 100% for 7 and 14 days, respectively); CL < 25 mm (100%, 94%, 83%, 100% and 100%, 97%, 92%, 100% for 7 and 14 days, respectively); CL of 15-30 mm (100%, 95%, 64%, 100% and 100%, 97%, 82%, 100% for 7 and 14 days, respectively); and CL ≥ 30 mm (100%, 100%, 100%, 100% and 100%, 100%, 100%, 100% for 7 and 14 days, respectively). CONCLUSION: The use of the PAMG-1 test in patients with a CL of 15-30 mm is highly predictive of imminent spontaneous preterm delivery in women presenting with threatened PTL and could save hospital resources.