Retrospective details of false-positive and false-negative results in non-invasive prenatal testing for fetal trisomies 21, 18 and 13.

OBJECTIVE: Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT). STUDY DESIGN: A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth. RESULTS: Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21. CONCLUSION: These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT.

A Large Pure Uterine Lipoma: Its Diagnosis by Pelvic MRI and Histopathology.

The patient is a 74-year-old female previously diagnosed with an ovarian tumor at age 55. No changes were noted for one year; however, she was lost to follow-up. Eighteen years later, she presented to a local clinic complaining of diffuse abdominal and flank pain. Abdominal and pelvic ultrasound, CT, and gynecological examination showed a fatty pelvic tumor of approximately 12 cm in diameter. A left ovarian teratoma was suspected, and per the patient's request, she was transferred to Kobe Adventist Hospital for further evaluation and treatment. Pelvic MRI revealed no ovarian enlargement; however, a mass in the uterine body was appreciated with a high signal on T1 and T2 images and signal dropout in the fat suppression images, a finding most consistent with a uterine lipoma. A total hysterectomy and bilateral salpingo-oophorectomy was performed, and histopathological examination confirmed the preliminary diagnosis. No complications were observed during the postoperative period. A pure uterine lipoma is an extremely rare tumor with only a few cases reported worldwide. It is a benign tumor; however, it can sometimes be misdiagnosed as a malignant neoplasm. Pelvic MRI appears to be a useful tool in order to make the correct diagnosis preoperatively.

Successful reduction of acute puerperal uterine inversion with the use of a bakri postpartum balloon.

Uterine inversion is a state wherein the endometrial surface is inverted. Although this condition may be observed in nonpregnant women, it most commonly develops at the time of delivery. In the present case, a 37-year-old woman without any remarkable history developed acute puerperal uterine inversion after the successful induction of labor. Following the delivery, she complained twice of severe lower abdominal pain; subsequently, hemorrhage was noted at the site of partial detachment of the placenta. These findings led to a diagnosis of placenta accreta, and the patient developed a state of shock. A Bakri postpartum balloon was inserted into the uterine cavity under ultrasonographic guidance and was filled with physiological saline for treatment of this condition. With this procedure, the uterine inversion was completely reduced and the hemorrhage was stopped. Moreover, no reinversion was observed in the postoperative period. These findings suggest that a Bakri postpartum balloon can be used to noninvasively reduce uterine inversion and prevent its recurrence.

Successful management of a cesarean scar defect with dehiscence of the uterine incision by using wound lavage.

Cesarean scar defects (CSDs) that can be visualized using transvaginal ultrasonography (TVUS) may cause prolonged menstruation, irregular genital bleeding, and secondary infertility; surgical repair is sometimes necessary. We present a case of CSD, with dehiscence of the uterine incision, which was managed using wound lavage. A 38-year-old woman (gravida 4, para 4) had delivered her third and fourth children by cesarean section. Upon the resumption of menstruation, 9 months after her second cesarean section, she demonstrated prolonged menstruation and the presence of a menstrual fistula due to dehiscence of the cesarean section incision from the myometrium to the serosa. We treated the defect by lavaging with a physiological saline solution. After lavaging the wound 3 times, spontaneous healing of the dehiscent muscle layer was successfully achieved. The treatment was complication-free and the healing of the muscle layer has been maintained for more than 8 months.

IL-4Ralpha polymorphism in regulation of IL-4 synthesis by T cells: implication in susceptibility to a subset of murine lupus.

To thoroughly understand the role of IL-4 in the pathogenesis of systemic lupus erythematosus (SLE), a prototypic antibody-mediated systemic autoimmune disease, we examined the potential of in vitro IL-4 production by anti-CD3 mAb-stimulated splenic T cells in SLE model of NZB, BXSB and related mouse strains. Unexpectedly, both SLE-prone NZB and BXSB mice had a limited potential to produce IL-4, while disease-free NZW mice had a high potential. Levels in (NZB x NZW) F1 and (NZW x BXSB) F1 were in between. Genome-wide search for quantitative trait loci (QTL) controlling this variation identified a single significant QTL in the vicinity of IL-4Ralpha gene on chromosome 7. Sequence analysis of IL-4Ralpha cDNA revealed that there are 17 nucleotide substitutions resulting in eight amino acid changes between NZB and NZW strains. BXSB showed the identical sequence, as did NZB. Thus, it was suggested that the NZW-type polymorphism controls a high potential and the NZB/BXSB-type polymorphism controls a low potential for IL-4 production by T cells. Linkage studies using NZW x (NZW x BXSB) F1 male and (NZB x NZW) F1 x NZW female back-cross mice revealed that the BXSB/NZB-type IL-4Ralpha polymorphism significantly linked to BXSB, but not to (NZB x NZW) F1 lupus. Thus, the low IL-4-producing phenotype appears to predispose to SLE in BXSB, but not NZB-related strains, suggesting that the role of IL-4 in the pathogenesis may differ between certain subsets of SLE, even if they show similar disease phenotypes.

Identification of 2 major loci linked to autoimmune hemolytic anemia in NZB mice.

Using a cohort of C57BL/6 (B6) x (NZB x B6)F1 backcross male mice bearing the Yaa (Y-linked autoimmune acceleration) mutation, we mapped and characterized the NZB-derived susceptibility loci predisposing to the development of autoimmune hemolytic anemia (AHA). Our analysis identified 2 major loci on NZB chromosome 7 and chromosome 1 linked with Coombs antierythrocyte autoantibody production, and their contributions were confirmed by the analysis of B6.Yaa mice (B6 mice bearing the Yaa mutation) congenic for each NZB-derived susceptibility interval. A newly identified Aia3 (autoimmune anemia 3) locus present on NZB chromosome 7 selectively regulated Coombs antibody responses, while the second locus, directly overlapping with Nba2 (NZB autoimmunity 2) on chromosome 1, promoted the development of AHA, likely as part of its effect on overall production of lupus autoantibodies. A higher incidence of Coombs antibody production in B6.Aia3 congenic mice (B6 mice bearing the NZB-Aia3 locus) than B6.Nba2 mice (B6 mice bearing the NZB-Nba2 locus) indicated a major role for Aia3 in AHA. Notably, lack of expansion of B1 cells in B6.Aia3 congenic mice argued against the involvement of this subset in AHA. Finally, our analysis of BC mice also demonstrated the presence of a B6-derived H2-linked locus on chromosome 17 that apparently regulated the production of Coombs antibodies as a result of its overall autoimmune promoting effect.

Differential role of three major New Zealand Black-derived loci linked with Yaa-induced murine lupus nephritis.

By assessing the development of Y-linked autoimmune acceleration (Yaa) gene-induced systemic lupus erythematosus in C57BL/6 (B6) x (New Zealand Black (NZB) x B6.Yaa)F(1) backcross male mice, we mapped three major susceptibility loci derived from the NZB strain. These three quantitative trait loci (QTL) on NZB chromosomes 1, 7, and 13 differentially regulated three different autoimmune traits: anti-nuclear autoantibody production, gp70-anti-gp70 immune complex (gp70 IC) formation, and glomerulonephritis. Contributions to the disease traits were further confirmed by generating and analyzing three different B6.Yaa congenic mice, each carrying one individual NZB QTL. The chromosome 1 locus that overlapped with the previously identified Nba2 (NZB autoimmunity 2) locus regulated all three traits. A newly identified chromosome 7 locus, designated Nba5, selectively promoted anti-gp70 autoantibody production, hence the formation of gp70 IC and glomerulonephritis. B6.Yaa mice bearing the NZB chromosome 13 locus displayed increased serum gp70 production, but not gp70 IC formation and glomerulonephritis. This locus, called Sgp3 (serum gp70 production 3), selectively regulated the production of serum gp70, thereby contributing to the formation of nephritogenic gp70 IC and glomerulonephritis, in combination with Nba2 and Nba5 in NZB mice. Among these three loci, a major role of Nba2 was demonstrated, because B6.Yaa Nba2 congenic male mice developed the most severe disease. Finally, our analysis revealed the presence in B6 mice of an H2-linked QTL, which regulated autoantibody production. This locus had no apparent individual effect, but most likely modulated disease severity through interaction with NZB-derived susceptibility loci.

Differential control of CD22 ligand expression on B and T lymphocytes, and enhanced expression in murine systemic lupus.

OBJECTIVE: CD22, a B cell-restricted transmembrane glycoprotein, regulates B cell antigen receptor signaling upon interaction with alpha2,6-linked sialic acid-bearing glycans, which act as ligands and are expressed on B and T cells. In this study, we investigated how the expression of CD22 ligand (CD22L) is modulated following lymphocyte activation or during the course of systemic lupus erythematosus (SLE). METHODS: The expression levels of CD22L on B and T cells in nonautoimmune mice were assessed by flow cytometric analysis using a soluble recombinant form of CD22, following stimulation with antigen or mitogen in vitro. In addition, the expression levels of CD22L on circulating lymphocytes were correlated with the progression of SLE in lupus-prone mice. RESULTS: We observed a constitutive expression of CD22L on mature B cells, but not T cells, in nonautoimmune mice. However, CD22L levels were up-regulated selectively on T cells (but not B cells) stimulated with antigens in vitro, while their expression levels on B cells was up-modulated following polyclonal activation with lipopolysaccharide. Furthermore, expression of CD22L was increased on circulating B cells (and to a lesser extent on T cells) in parallel with progression of SLE in several different lupus-prone mice and in a cohort of (C57BL/6 x [NZB x C57BL/6.Yaa]F(1)) backcross mice. CONCLUSION: The expression of CD22L is differentially regulated in B and T cells, and high expression of CD22L on circulating B cells is a marker for development of severe SLE, suggesting a role for CD22-CD22L interactions in SLE as well as in the regulation of humoral immunity.