Immunomodulatory effects of therapeutic plasma exchange on monocytes in antiphospholipid syndrome

Martirosyan,Anush; Petrek,Martin; Kishore,Amit; Manukyan,Gayane

doi:10.3892/etm.2016.3441

Immunomodulatory effects of therapeutic plasma exchange on monocytes in antiphospholipid syndrome

Authors:
- Anush Martirosyan
- Martin Petrek
- Amit Kishore
- Gayane Manukyan
View Affiliations

Affiliations: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77520, Czech Republic
Published online on: June 8, 2016 https://doi.org/10.3892/etm.2016.3441
Pages: 1189-1195

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis and recurrent fetal loss, with the persistent presence of antiphospholipid antibodies (aPLs). aPLs exert their pathogenic effect via the overproduction of tissue factor and activation of complement and several cell types, including endothelial cells, platelets and notably monocytes. As a result, a hypercoagulable state develops leading to APS‑associated obstetric complications and fetal loss. Despite being far from optimal, treatment of APS usually includes heparin and low dose aspirin. Recently, plasma exchange (PE) therapy was successfully used in patients with APS with obstetric complications who did not respond to the standard treatment. Therefore, the present study investigated the mechanism underlying PE action, and aimed to determine whether PE affects the functional activity of APS monocytes by examining the expression of 11 mRNA transcripts encoding cytokines, signaling molecules and transcription factors. Monocytes were collected prior to and following the PE treatment from women with APS who experienced recurrent pregnancy losses, as well as from healthy volunteers. Compared with control cells, APS monocytes showed deregulated expression of interleukin (IL)‑1β, IL‑6, IL‑23, chemokine (C‑C motif) ligand 2 (CCL2), C‑X‑C motif chemokine 10 (CXCL10), toll‑like receptor 2, and signal transducer and activator of transcription 3. PE treatment resulted in increased IL‑1β, IL‑6, IL‑23, CCL2, P2X7 and tumor necrosis factor‑α mRNA transcripts in APS monocytes, restoring the mRNA expression levels to within normal ranges. Furthermore, PE therapy counterbalanced the expression levels of CCL2 and CXCL10, the levels of which are indicative of T helper cell 1/2 balance. The results of the present study indicate that the altered transcriptional profile in APS monocytes was restored by the immunomodulatory effect of plasmapheresis.

View Figures

View References

1	de Jesus GR, Agmon-Levin N, Andrade CA, Andreoli L, Chighizola CB, Porter TF, Salmon J, Silver RM, Tincani A and Branch DW: 14th International congress on antiphospholipid antibodies task force report on obstetric antiphospholipid syndrome. Autoimmun Rev. 13:795–813. 2014. View Article : Google Scholar : PubMed/NCBI
2	Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, et al: International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 4:295–306. 2006. View Article : Google Scholar : PubMed/NCBI
3	Gris JC and Bouvier S: Antiphospholipid syndrome: Looking for a refocusing. Thromb Res 131 Suppl. 1:S28–S31. 2013. View Article : Google Scholar
4	Galli M, Borrelli G, Jacobsen EM, Marfisi RM, Finazzi G, Marchioli R, Wisloff F, Marziali S, Morboeuf O and Barbui T: Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study. Blood. 110:1178–1183. 2007. View Article : Google Scholar : PubMed/NCBI
5	Khamashta MA and Asherson RA: Hughes syndrome: Antiphospholipid antibodies move closer to thrombosis in 1994. Br J Rheumatol. 34:493–494. 1995. View Article : Google Scholar : PubMed/NCBI
6	Reverter JC, Tàssies D, Font J, Khamashta MA, Ichikawa K, Cervera R, Escolar G, Hughes GR, Ingelmo M and Ordinas A: Effects of human monoclonal anticardiolipin antibodies on platelet function and on tissue factor expression on monocytes. Arthritis Rheum. 41:1420–1427. 1998. View Article : Google Scholar : PubMed/NCBI
7	Kornberg A, Blank M, Kaufman S and Shoenfeld Y: Induction of tissue factor-like activity in monocytes by anti-cardiolipin antibodies. J Immunol. 153:1328–1332. 1994.PubMed/NCBI
8	Branch DW and Rodgers GM: Induction of endothelial cell tissue factor activity by sera from patients with antiphospholipid syndrome: A possible mechanism of thrombosis. Am J Obstet Gynecol. 168:206–210. 1993. View Article : Google Scholar : PubMed/NCBI
9	López-Pedrera C, Cuadrado MJ, Herández V, Buendïa P, Aguirre MA, Barbarroja N, Torres LA, Villalba JM, Velasco F and Khamashta M: Proteomic analysis in monocytes of antiphospholipid syndrome patients: Deregulation of proteins related to the development of thrombosis. Arthritis Rheum. 58:2835–2844. 2008. View Article : Google Scholar : PubMed/NCBI
10	Ruiz-Irastorza G and Khamashta MA: Management of thrombosis in antiphospholipid syndrome and systemic lupus erythematosus in pregnancy. Ann N Y Acad Sci. 1051:606–612. 2005. View Article : Google Scholar : PubMed/NCBI
11	Di Prima FA, Valenti O, Hyseni E, Giorgio E, Faraci M, Renda E, De Domenico R and Monte S: Antiphospholipid syndrome during pregnancy: The state of the art. J Prenat Med. 5:41–53. 2011.PubMed/NCBI
12	Meroni PL, Moia M, Derksen RH, Tincani A, McIntyre JA, Arnout JM, Koike T, Piette JC, Khamashta MA and Shoenfeld Y: Venous thromboembolism in the antiphospholipid syndrome: Management guidelines for secondary prophylaxis. Lupus. 12:504–507. 2003. View Article : Google Scholar : PubMed/NCBI
13	Erkan D, Ortel TL and Lockshin MD: Warfarin in antiphospholipid syndrome-time to explore new horizons. J Rheumatol. 32:208–212. 2005.PubMed/NCBI
14	Tincani A, Branch W, Levy RA, Piette JC, Carp H, Rai RS, Khamashta M and Shoenfeld Y: Treatment of pregnant patients with antiphospholipid syndrome. Lupus. 12:524–529. 2003. View Article : Google Scholar : PubMed/NCBI
15	Marson P, Bagatella P, Bortolati M, Tison T, De Silvestro G, Fabris F, Pengo V and Ruffatti A: Plasma exchange for the management of the catastrophic antiphospholipid syndrome: Importance of the type of fluid replacement. J Intern Med. 264:201–203. 2008. View Article : Google Scholar : PubMed/NCBI
16	Ibrahim RB and Balogun RA: Medications in patients treated with therapeutic plasma exchange: Prescription dosage, timing and drug overdose. Semin Dial. 25:176–189. 2012. View Article : Google Scholar : PubMed/NCBI
17	Ibrahim RB and Balogun RA: Medications and therapeutic apheresis procedures: Are we doing our best? J Clin Apher. 28:73–77. 2013. View Article : Google Scholar : PubMed/NCBI
18	Kaplan AA: Therapeutic apheresis for renal disorders. Therap Apher. 3:25–30. 1999. View Article : Google Scholar
19	Bove LL, Bednall T, Masser B and Buzza M: Understanding the plasmapheresis donor in a voluntary, nonremunerated environment. Transfusion. 51:2411–2424. 2011. View Article : Google Scholar : PubMed/NCBI
20	Crocco I, Franchini M, Garozzo G, Gandini AR, Gandini G, Bonomo P and Aprili G: Adverse reactions in blood and apheresis donors: Experience from two Italian transfusion centres. Blood Transfus. 7:35–38. 2009.PubMed/NCBI
21	Nguyen TC, Kiss JE, Goldman JR and Carcillo JA: The role of plasmapheresis in critical illness. Crit Care Clin. 28:453–468. 2012. View Article : Google Scholar : PubMed/NCBI
22	Nakanishi T, Suzuki N, Kuragano T, Nagasawa Y and Hasuike Y: Current topics in therapeutic plasmapheresis. Clin Exp Nephrol. 18:41–49. 2014. View Article : Google Scholar : PubMed/NCBI
23	Dittrich E, Schmaldienst S, Langer M, Jansen M, Hörl WH and Derfler K: Immunoadsorption and plasma exchange in pregnancy. Kidney Blood Press Res. 25:232–239. 2002. View Article : Google Scholar : PubMed/NCBI
24	Bortolati M, Marson P, Chiarelli S, Tison T, Facchinetti M, Gervasi MT, De Silvestro G and Ruffatti A: Case reports of the use of immunoadsorption or plasma exchange in high-risk pregnancies of women with antiphospholipid syndrome. Ther Apher Dial. 13:157–160. 2009. View Article : Google Scholar : PubMed/NCBI
25	Bontadi A, Ruffatti A, Marson P, Tison T, Tonello M, Hoxha A, De Silvestro G and Punzi L: Plasma exchange and immunoadsorption effectively remove antiphospholipid antibodies in pregnant patients with antiphospholipid syndrome. J Clin Apher. 27:200–204. 2012. View Article : Google Scholar : PubMed/NCBI
26	Ferrer DG, Jaldín-Fincati JR, Amigone JL, Capra RH, Collino CJ, Albertini RA and Chiabrando GA: Standardized flow cytometry assay for identification of human monocytic heterogeneity and LRP1 expression in monocyte subpopulations: Decreased expression of this receptor in nonclassical monocytes. Cytometry A. 85:601–610. 2014. View Article : Google Scholar : PubMed/NCBI
27	Manukyan G, Petrek M, Kriegova E, Ghazaryan K, Fillerova R, Fillerova R and Boyajyan A: Activated phenotype of circulating neutrophils in familial mediterranean fever. Immunobiology. 218:892–898. 2013. View Article : Google Scholar : PubMed/NCBI
28	Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29:e452001. View Article : Google Scholar : PubMed/NCBI
29	Cuadrado MJ, López-Pedrera C, Khamashta MA, Camps MT, Tinahones F, Torres A, Hughes GR and Velasco F: Thrombosis in primary antiphospholipid syndrome: A pivotal role for monocyte tissue factor expression. Arthritis Rheum. 40:834–841. 1997. View Article : Google Scholar : PubMed/NCBI
30	Wakefield TW, Strieter RM, Wilke CA, Kadell AM, Wrobleski SK, Burdick MD, Schmidt R, Kunkel SL and Greenfield LJ: Venous thrombosis-associated inflammation and attenuation with neutralizing antibodies to cytokines and adhesion molecules. Arterioscler Thromb Vasc Biol. 15:258–268. 1995. View Article : Google Scholar : PubMed/NCBI
31	Godessart N and Kunkel SL: Chemokines in autoimmune disease. Curr Opin Immunol. 13:670–675. 2001. View Article : Google Scholar : PubMed/NCBI
32	Oghumu S, Lezama-Dávila CM, Isaac-Márquez AP and Satoskar AR: Role of chemokines in regulation of immunity against leishmaniasis. Exp Parasitol. 126:389–396. 2010. View Article : Google Scholar : PubMed/NCBI
33	Gu D, Chen Z, Zhao H, Du W, Xue F, Ge J, Sui T, Wu H, Liu B, Lu S, Zhang L and Yang R: Th1 (CXCL10) and Th2 (CCL2) chemokine expression in patients with immune thrombocytopenia. Hum Immunol. 71:586–591. 2010. View Article : Google Scholar : PubMed/NCBI
34	Rotondi M, Rosati A, Buonamano A, Lasagni L, Lazzeri E, Pradella F, Fossombroni V, Cirami C, Liotta F, La Villa G, et al: High pretransplant serum levels of CXCL10/IP-10 are related to increased risk of renal allograft failure. Am J Transplant. 4:1466–1474. 2004. View Article : Google Scholar : PubMed/NCBI
35	Wegmann TG, Lin H, Guilbert L and Mosmann TR: Bidirectional cytokine interactions in the maternal-fetal relationship: Is successful pregnancy a TH2 phenomenon? Immunology Today. 14:353–356. 1993. View Article : Google Scholar : PubMed/NCBI
36	Lissauer D, Goodyear O, Khanum R, Moss PA and Kilby MD: Profile of maternal CD4 T-cell effector function during normal pregnancy and in women with a history of recurrent miscarriage. Clin Sci (Lond). 126:347–354. 2014. View Article : Google Scholar : PubMed/NCBI
37	Raghupathy R, Makhseed M, Azizieh F, Omu A, Gupta M and Farhat R: Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. Hum Reprod. 15:713–778. 2000. View Article : Google Scholar : PubMed/NCBI
38	Bernales I, Fullaondo A, Marín-Vidalled MJ, Ucar E, Martínez-Taboada V, López-Hoyos M and Zubiaga AM: Innate immune response gene expression profiles characterize primary antiphospholipid syndrome. Genes Immun. 9:38–46. 2008. View Article : Google Scholar : PubMed/NCBI
39	Laird SM, Tuckerman EM, Cork BA, Linjawi S, Blakemore AI and Li TC: A review of immune cells and molecules in women with recurrent miscarriage. Hum Reprod Update. 9:163–174. 2003. View Article : Google Scholar : PubMed/NCBI
40	Goto H, Matsuo H, Nakane S, Izumoto H, Fukudome T, Kambara C and Shibuya N: Plasmapheresis affects T helper type-1/T helper type-2 balance of circulating peripheral lymphocytes. Ther Apher. 5:494–496. 2001. View Article : Google Scholar : PubMed/NCBI
41	Shariatmadar S, Nassiri M and Vincek V: Effect of plasma exchange on cytokines measured by multianalyte bead array in thrombotic thrombocytopenic purpura. Am J Hematol. 79:83–88. 2005. View Article : Google Scholar : PubMed/NCBI
42	Haskill S, Johnson C, Eierman D, Becker S and Warren K: Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol. 140:1690–1694. 1988.PubMed/NCBI
43	Fuhlbrigge RC, Chaplin DD, Kiely JM and Unanue ER: Regulation of interleukin 1 gene expression by adherence and lipopolysaccharide. J Immunol. 138:3799–3802. 1987.PubMed/NCBI
44	Yang J, Hooper WC, Phillips DJ, Tondella ML and Talkington DF: Centrifugation of human lung epithelial carcinoma a549 cells up-regulates interleukin-1beta gene expression. Clin Diagn Lab Immunol. 9:1142–1143. 2002.PubMed/NCBI
45	Yona S and Jung S: Monocytes: subsets, origins, fates and functions. Curr Opin Hematol. 17:53–59. 2010. View Article : Google Scholar : PubMed/NCBI