Skip to main content
Top
Published in: BMC Pregnancy and Childbirth 1/2019

Open Access 01-12-2019 | Ectopic Pregnancy | Research article

B cell activation factor (BAFF) induces inflammation in the human fallopian tube leading to tubal pregnancy

Authors: Jianying Xu, Xingguang Luo, Shihao Qu, Guiyan Yang, Nianchun Shen

Published in: BMC Pregnancy and Childbirth | Issue 1/2019

Login to get access

Abstract

Background

Tubal pregnancy is recognized as one of the most common ectopic pregnancy types. Salpingitis may result in tubal pregnancy by causing fallopian tube occlusion and hydrosalpinx. B cell activation factor (BAFF) is a proinflammatory cytokine that helps regulate both innate and adaptive immune responses. Our previous study firstly showed that BAFF immunostaining appeared on the cellular membrane and in the cytoplasm of tubal epithelial cells, and both BAFF protein and mRNA in human inflamed fallopian tubes had higher expression levels than those in normal fallopian tubes. This study aimed to elucidate the association between the expression of BAFF gene and the inflammation in the human fallopian tube leading to tubal pregnancy.

Methods

We examined 70 patients undergoing salpingectomy for salpingitis (n = 35) and tubal pregnancy (n = 35). Twenty patients with benign uterine diseases undergoing complete hysterectomy and salpingectomy were recruited into control group. BAFF mRNA and protein in tissue samples were detected by qPCR and Western blotting methods. Furthermore, serum levels of BAFF, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were measured using ELISA kits.

Results

We found statistically significantly elevated expressions of BAFF mRNA or protein in whole tissue samples, and serum levels of BAFF, TNF-α and IL-6 in whole blood samples from patients with salpingitis and tubal pregnancy, in comparison to the control group.

Conclusion

Based on the results, high expression of BAFF gene might induce inflammation in the human fallopian tube, suggesting its possible role in the tubal pregnancy process.
Literature
1.
go back to reference Stutz A, Golenbock DT, Latz E. Inflammasomes: too big to miss. J Clin Invest. 2009;119(12):3502–11.CrossRef Stutz A, Golenbock DT, Latz E. Inflammasomes: too big to miss. J Clin Invest. 2009;119(12):3502–11.CrossRef
2.
go back to reference Thompson JS, Bixler SA, Qian F, Vora K, Scott ML, Cachero TG, et al. BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF. Science. 2001;293(5537):2108–11.CrossRef Thompson JS, Bixler SA, Qian F, Vora K, Scott ML, Cachero TG, et al. BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF. Science. 2001;293(5537):2108–11.CrossRef
3.
go back to reference Nardelli B, Belvedere O, Roschke V, Moore PA, Olsen HS, Migone TS, et al. Synthesis and release of B-lymphocyte stimulator from myeloid cells. Blood. 2001;97(1):198–204.CrossRef Nardelli B, Belvedere O, Roschke V, Moore PA, Olsen HS, Migone TS, et al. Synthesis and release of B-lymphocyte stimulator from myeloid cells. Blood. 2001;97(1):198–204.CrossRef
4.
go back to reference Bossen C, Schneider P. BAFF, APRIL and their receptors: structure, function and signaling. Semin Immunol. 2006;18(5):263–75.CrossRef Bossen C, Schneider P. BAFF, APRIL and their receptors: structure, function and signaling. Semin Immunol. 2006;18(5):263–75.CrossRef
5.
go back to reference Bolkun L, Lemancewicz D, Jablonska E, Kulczynska A, Bolkun-Skornicka U, Kloczko J, et al. BAFF and APRIL as TNF superfamily molecules and angiogenesis parallel progression of human multiple myeloma. Ann Hematol. 2014;93(4):635–44.CrossRef Bolkun L, Lemancewicz D, Jablonska E, Kulczynska A, Bolkun-Skornicka U, Kloczko J, et al. BAFF and APRIL as TNF superfamily molecules and angiogenesis parallel progression of human multiple myeloma. Ann Hematol. 2014;93(4):635–44.CrossRef
6.
go back to reference Koizumi M, Hiasa Y, Kumagi T, Yamanishi H, Azemoto N, Kobata T, et al. Increased B cell-activating factor promotes tumor invasion and metastasis in human pancreatic cancer. PLoS One. 2013;8(8):e71367.CrossRef Koizumi M, Hiasa Y, Kumagi T, Yamanishi H, Azemoto N, Kobata T, et al. Increased B cell-activating factor promotes tumor invasion and metastasis in human pancreatic cancer. PLoS One. 2013;8(8):e71367.CrossRef
7.
go back to reference Uzzan M, Colombel JF, Cerutti A, Treton X, Mehandru S. B cell-activating factor (BAFF)-targeted B cell therapies in inflammatory bowel diseases. Dig Dis Sci. 2016;61(12):3407–24.CrossRef Uzzan M, Colombel JF, Cerutti A, Treton X, Mehandru S. B cell-activating factor (BAFF)-targeted B cell therapies in inflammatory bowel diseases. Dig Dis Sci. 2016;61(12):3407–24.CrossRef
8.
go back to reference Gümüş P, Nizam N, Lappin DF, Buduneli N. Saliva and serum levels of B-cell activating factors and tumor necrosis factor-α in patients with periodontitis. J Periodontol. 2014;85(2):270–80.CrossRef Gümüş P, Nizam N, Lappin DF, Buduneli N. Saliva and serum levels of B-cell activating factors and tumor necrosis factor-α in patients with periodontitis. J Periodontol. 2014;85(2):270–80.CrossRef
9.
go back to reference Sanges S, Guerrier T, Launay D, Lefèvre G, Labalette M, Forestier A, et al. Role of B cells in the pathogenesis of systemic sclerosis. Rev Med Interne. 2017;38(2):113–24.CrossRef Sanges S, Guerrier T, Launay D, Lefèvre G, Labalette M, Forestier A, et al. Role of B cells in the pathogenesis of systemic sclerosis. Rev Med Interne. 2017;38(2):113–24.CrossRef
10.
go back to reference Guo WJ, Qu X, Yang MX, Zhang WD, Liang L, Shao QQ, Kong BH. Expression of BAFF in the trophoblast and decidua of normal early pregnant women and patients with recurrent spontaneous miscarriage. Chin Med J. 2008;121(4):309–15.CrossRef Guo WJ, Qu X, Yang MX, Zhang WD, Liang L, Shao QQ, Kong BH. Expression of BAFF in the trophoblast and decidua of normal early pregnant women and patients with recurrent spontaneous miscarriage. Chin Med J. 2008;121(4):309–15.CrossRef
11.
go back to reference Stohl HE, Lee RH, Manetta J, Kikly K, Korst LM, Stohl W. Maternal serum B-cell activating factor levels: candidate early biomarker for hypertensive disorders of pregnancy. Hypertension. 2017;70(5):1007–13.CrossRef Stohl HE, Lee RH, Manetta J, Kikly K, Korst LM, Stohl W. Maternal serum B-cell activating factor levels: candidate early biomarker for hypertensive disorders of pregnancy. Hypertension. 2017;70(5):1007–13.CrossRef
12.
go back to reference Xu JY, Yang GY, Kuang GC, Huang JL. Expression and change of B cell activation factor of the TNF family (BAFF) gene between human Normal and inflamed fallopian tubes. J Reprod Contracept. 2014;25(1):12–7. Xu JY, Yang GY, Kuang GC, Huang JL. Expression and change of B cell activation factor of the TNF family (BAFF) gene between human Normal and inflamed fallopian tubes. J Reprod Contracept. 2014;25(1):12–7.
13.
go back to reference Juhasz A, Frankel P, Cheng C, Rivera H, Vishwanath R, Chiu A, et al. Quantification of chemotherapeutic target gene mRNA expression in human breast cancer biopsies: comparison of real-time reverse transcription-PCR vs. relative quantification reverse transcription-PCR utilizing DNA sequencer analysis of PCR products. J Clin Lab Anal. 2003;17(5):184–94.CrossRef Juhasz A, Frankel P, Cheng C, Rivera H, Vishwanath R, Chiu A, et al. Quantification of chemotherapeutic target gene mRNA expression in human breast cancer biopsies: comparison of real-time reverse transcription-PCR vs. relative quantification reverse transcription-PCR utilizing DNA sequencer analysis of PCR products. J Clin Lab Anal. 2003;17(5):184–94.CrossRef
14.
go back to reference Corpa JM. Ectopic pregnancy in animals and humans. Reproduction. 2006;131(4):631–40.CrossRef Corpa JM. Ectopic pregnancy in animals and humans. Reproduction. 2006;131(4):631–40.CrossRef
15.
go back to reference Schlabritz-Loutsevitch NE, Hubbard GB, Frost PA, Cummins LB, Dick EJ Jr, Nathanielsz PW, et al. Abdominal pregnancy in a baboon: a first case report. J Med Primatol. 2004;33(1):55–9.CrossRef Schlabritz-Loutsevitch NE, Hubbard GB, Frost PA, Cummins LB, Dick EJ Jr, Nathanielsz PW, et al. Abdominal pregnancy in a baboon: a first case report. J Med Primatol. 2004;33(1):55–9.CrossRef
16.
go back to reference Shao R, Feng Y, Zou S, Li X, Cui P, Billig H. Quantitative analysis of hormones and inflammatory cytokines in chlamydia trachomatis-infected women with tubal ectopic pregnancy and early intrauterine pregnancy. Data Brief. 2015;6:135–42.CrossRef Shao R, Feng Y, Zou S, Li X, Cui P, Billig H. Quantitative analysis of hormones and inflammatory cytokines in chlamydia trachomatis-infected women with tubal ectopic pregnancy and early intrauterine pregnancy. Data Brief. 2015;6:135–42.CrossRef
17.
go back to reference Rausch ME, Barnhart KT. Serum biomarkers for detecting ectopic pregnancy. Clin Obstet Gynecol. 2012;55(2):418–23.CrossRef Rausch ME, Barnhart KT. Serum biomarkers for detecting ectopic pregnancy. Clin Obstet Gynecol. 2012;55(2):418–23.CrossRef
18.
go back to reference Huang HY, Chan SH, Wu CH, Wang CW, Lai CH, Soong YK. Interleukin-1 system messenger ribonucleic acid and protein expression in human fallopian tube may be associated with ectopic pregnancy. Fertil Steril. 2005;84(5):1484–92.CrossRef Huang HY, Chan SH, Wu CH, Wang CW, Lai CH, Soong YK. Interleukin-1 system messenger ribonucleic acid and protein expression in human fallopian tube may be associated with ectopic pregnancy. Fertil Steril. 2005;84(5):1484–92.CrossRef
19.
go back to reference Islam A, Fawad A, Shah AA, Jadoon H, Sarwar I, Abbasi AU. Analysis of two years cases of ectopic pregnancy. J Ayub Med Coll Abbottabad. 2017;29(1):65–7.PubMed Islam A, Fawad A, Shah AA, Jadoon H, Sarwar I, Abbasi AU. Analysis of two years cases of ectopic pregnancy. J Ayub Med Coll Abbottabad. 2017;29(1):65–7.PubMed
20.
go back to reference Chu J, Harb HM, Gallos ID, Dhillon R, Al-Rshoud FM, Robinson L, et al. Salpingostomy in the treatment of hydrosalpinx: a systematic review and meta-analysis. Hum Reprod. 2015;30(8):1882–95.CrossRef Chu J, Harb HM, Gallos ID, Dhillon R, Al-Rshoud FM, Robinson L, et al. Salpingostomy in the treatment of hydrosalpinx: a systematic review and meta-analysis. Hum Reprod. 2015;30(8):1882–95.CrossRef
21.
go back to reference Shao R, Zhang SX, Weijdegård B, Zou S, Egecioglu E, Norström A, et al. Nitric oxide synthases and tubal ectopic pregnancies induced by chlamydia infection: basic and clinical insights. Mol Hum Reprod. 2010;16(12):907–15.CrossRef Shao R, Zhang SX, Weijdegård B, Zou S, Egecioglu E, Norström A, et al. Nitric oxide synthases and tubal ectopic pregnancies induced by chlamydia infection: basic and clinical insights. Mol Hum Reprod. 2010;16(12):907–15.CrossRef
22.
go back to reference Shaw JL, Dey SK, Critchley HO, Horne AW. Current knowledge of the aetiology of human tubal ectopic pregnancy. Hum Reprod Update. 2010;16(4):432–44.CrossRef Shaw JL, Dey SK, Critchley HO, Horne AW. Current knowledge of the aetiology of human tubal ectopic pregnancy. Hum Reprod Update. 2010;16(4):432–44.CrossRef
23.
go back to reference Luo HJ, Xiao XM, Zhou J, Wei W. Therapeutic influence of intraperitoneal injection of Wharton's jelly-derived mesenchymal stem cells on oviduct function and fertility in rats with acute and chronic salpingitis. Genet Mol Res. 2015;14(2):3606–17.CrossRef Luo HJ, Xiao XM, Zhou J, Wei W. Therapeutic influence of intraperitoneal injection of Wharton's jelly-derived mesenchymal stem cells on oviduct function and fertility in rats with acute and chronic salpingitis. Genet Mol Res. 2015;14(2):3606–17.CrossRef
24.
go back to reference Yousefian E, Novin MG, Fathabadi FF, Farahani RM, Kachouei EY. The expression of IL-6Rα and Gp130 in fallopian tubes bearing an ectopic pregnancy. Anat Cell Biol. 2013;46(3):177–82.CrossRef Yousefian E, Novin MG, Fathabadi FF, Farahani RM, Kachouei EY. The expression of IL-6Rα and Gp130 in fallopian tubes bearing an ectopic pregnancy. Anat Cell Biol. 2013;46(3):177–82.CrossRef
25.
go back to reference Soriano D, Hugol D, Quang NT, Darai E. Serum concentrations of interleukin-2R (IL-2R), IL-6, IL-8, and tumor necrosis factor alpha in patients with ectopic pregnancy. Fertil Steril. 2003;79(4):975–80.CrossRef Soriano D, Hugol D, Quang NT, Darai E. Serum concentrations of interleukin-2R (IL-2R), IL-6, IL-8, and tumor necrosis factor alpha in patients with ectopic pregnancy. Fertil Steril. 2003;79(4):975–80.CrossRef
26.
go back to reference Rajendiran S, Senthil Kumar GP, Nimesh A, Dhiman P, Shivaraman K, Soundararaghavan S. Diagnostic significance of IL-6 and IL-8 in tubal ectopic pregnancy. J Obstet Gynaecol. 2016;36(7):909–11.CrossRef Rajendiran S, Senthil Kumar GP, Nimesh A, Dhiman P, Shivaraman K, Soundararaghavan S. Diagnostic significance of IL-6 and IL-8 in tubal ectopic pregnancy. J Obstet Gynaecol. 2016;36(7):909–11.CrossRef
27.
go back to reference Alsaleh G, Messer L, Semaan N, Boulanger N, Gottenberg JE, Sibilia J, et al. BAFF synthesis by rheumatoid synoviocytes is positively controlled by alpha5beta1 integrin stimulation and is negatively regulated by tumor necrosis factor alpha and toll-like receptor ligands. Arthritis Rheum. 2007;56(10):3202–14.CrossRef Alsaleh G, Messer L, Semaan N, Boulanger N, Gottenberg JE, Sibilia J, et al. BAFF synthesis by rheumatoid synoviocytes is positively controlled by alpha5beta1 integrin stimulation and is negatively regulated by tumor necrosis factor alpha and toll-like receptor ligands. Arthritis Rheum. 2007;56(10):3202–14.CrossRef
28.
go back to reference Lee GH, Lee J, Lee JW, Choi WS, Moon EY. B cell activating factor-dependent expression of vascular endothelial growth factor in MH7A human synoviocytes stimulated with tumor necrosis factor-α. Int Immunopharmacol. 2013;17(1):142–7.CrossRef Lee GH, Lee J, Lee JW, Choi WS, Moon EY. B cell activating factor-dependent expression of vascular endothelial growth factor in MH7A human synoviocytes stimulated with tumor necrosis factor-α. Int Immunopharmacol. 2013;17(1):142–7.CrossRef
29.
go back to reference Moisini I, Davidson A. BAFF: a local and systemic target in autoimmune diseases. Clin Exp Immunol. 2009;158(2):155–63.CrossRef Moisini I, Davidson A. BAFF: a local and systemic target in autoimmune diseases. Clin Exp Immunol. 2009;158(2):155–63.CrossRef
30.
go back to reference Papathanasiou A, Djahanbakhch O, Saridogan E, Lyons RA. The effect of interleukin-6 on ciliary beat frequency in the human fallopian tube. Fertil Steril. 2008;90(2):391–4.CrossRef Papathanasiou A, Djahanbakhch O, Saridogan E, Lyons RA. The effect of interleukin-6 on ciliary beat frequency in the human fallopian tube. Fertil Steril. 2008;90(2):391–4.CrossRef
31.
go back to reference Plewka D, Kowalczyk AE, Jakubiec-Bartnik B, Morek M, Bogunia E, Kmiec A, et al. Immunohistochemical visualization of pro-inflammatory cytokines and enzymes in ovarian tumors. Folia Histochem Cytobiol. 2014;52(2):124–37.CrossRef Plewka D, Kowalczyk AE, Jakubiec-Bartnik B, Morek M, Bogunia E, Kmiec A, et al. Immunohistochemical visualization of pro-inflammatory cytokines and enzymes in ovarian tumors. Folia Histochem Cytobiol. 2014;52(2):124–37.CrossRef
32.
go back to reference Jin CH, Yi KW, Ha YR, Jin CH, Yi KW, Ha YR, et al. Chemerin expression in the peritoneal fluid, serum, and ovarian Endometrioma of women with endometriosis. Am J Reprod Immunol. 2015;74(4):379–86.CrossRef Jin CH, Yi KW, Ha YR, Jin CH, Yi KW, Ha YR, et al. Chemerin expression in the peritoneal fluid, serum, and ovarian Endometrioma of women with endometriosis. Am J Reprod Immunol. 2015;74(4):379–86.CrossRef
33.
go back to reference Hever A, Roth RB, Hevezi P, Marin ME, Acosta JA, Acosta H, et al. Human endometriosis is associated with plasma cells and overexpression of B lymphocyte stimulator. Proc Natl Acad Sci U S A. 2007;104(30):12451–6.CrossRef Hever A, Roth RB, Hevezi P, Marin ME, Acosta JA, Acosta H, et al. Human endometriosis is associated with plasma cells and overexpression of B lymphocyte stimulator. Proc Natl Acad Sci U S A. 2007;104(30):12451–6.CrossRef
34.
go back to reference Do MS, Jeong HS, Choi BH, Hunter L, Langley S, Pazmany L, et al. Inflammatory gene expression patterns revealed by DNA microarray analysis in TNF-alpha-treated SGBS human adipocytes. Yonsei Med J. 2006;47(5):729–36.CrossRef Do MS, Jeong HS, Choi BH, Hunter L, Langley S, Pazmany L, et al. Inflammatory gene expression patterns revealed by DNA microarray analysis in TNF-alpha-treated SGBS human adipocytes. Yonsei Med J. 2006;47(5):729–36.CrossRef
35.
go back to reference Kim DH, Do MS. BAFF knockout improves systemic inflammation via regulating adipose tissue distribution in high-fat diet-induced obesity. Exp Mol Med. 2015;47:e129.CrossRef Kim DH, Do MS. BAFF knockout improves systemic inflammation via regulating adipose tissue distribution in high-fat diet-induced obesity. Exp Mol Med. 2015;47:e129.CrossRef
Metadata
Title
B cell activation factor (BAFF) induces inflammation in the human fallopian tube leading to tubal pregnancy
Authors
Jianying Xu
Xingguang Luo
Shihao Qu
Guiyan Yang
Nianchun Shen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2019
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/s12884-019-2324-5

Other articles of this Issue 1/2019

BMC Pregnancy and Childbirth 1/2019 Go to the issue