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Molecular Neurobiology

, Volume 56, Issue 10, pp 7056–7073 | Cite as

Upregulation of the Intestinal Paracellular Pathway with Breakdown of Tight and Adherens Junctions in Deficit Schizophrenia

  • Michael MaesEmail author
  • Sunee Sirivichayakul
  • Buranee Kanchanatawan
  • Aristo Vodjani
Article

Abstract

In 2001, the first author of this paper reported that schizophrenia is associated with an increased frequency of the haptoglobin (Hp)-2 gene. The precursor of Hp-2 is zonulin, a molecule that affects intercellular tight junction integrity. Recently, we reported increased plasma IgA/IgM responses to Gram-negative bacteria in deficit schizophrenia indicating leaky gut and gut dysbiosis. The current study was performed to examine the integrity of the paracellular (tight and adherens junctions) and transcellular (cytoskeletal proteins) pathways in deficit versus non-deficit schizophrenia. We measured IgM responses to zonulin, occludin, E-cadherin, talin, actin, and vinculin in association with IgA responses to Gram-negative bacteria, CCL-11, IgA responses to tryptophan catabolites (TRYCATs), immune activation and IgM to malondialdehyde (MDA), and NO-cysteinyl in 78 schizophrenia patients and 40 controls. We found that the ratio of IgM to zonulin + occludin/talin + actin + viculin (PARA/TRANS) was significantly greater in deficit than those in non-deficit schizophrenia and higher in schizophrenia than those in controls and was significantly associated with increased IgA responses to Gram-negative bacteria. IgM responses to zonulin were positively associated with schizophrenia (versus controls), while IgM to occludin was significantly associated with deficit schizophrenia (versus non-deficit schizophrenia and controls). A large part of the variance (90.8%) in negative and PHEM (psychosis, hostility, excitation, and mannerism) symptoms was explained by PARA/TRANS ratio, IgA to Gram-negative bacteria, IgM to E-cadherin and MDA, and memory dysfunctions, while 53.3% of the variance in the latter was explained by PARA/TRANS ratio, IgA to Gram-negative bacteria, CCL-11, TRYCATs, and immune activation. The results show an upregulated paracellular pathway with breakdown of the tight and adherens junctions and increased bacterial translocation in deficit schizophrenia. These dysfunctions in the intestinal paracellular route together with lowered natural IgM, immune activation, and production of CCL-11 and TRYCATs contribute to the phenomenology of deficit schizophrenia.

Keywords

Schizophrenia Leaky gut Neuro-immune Inflammation Oxidative stress TRYCATs Inflammation 

Notes

Acknowledgements

The study was supported by the Asahi Glass Foundation, Chulalongkorn University Centenary Academic Development Project and Ratchadapiseksompotch Funds, Faculty of Medicine, Chulalongkorn University, grant numbers RA60/042 (to BK) and RA61/050 (to MM).

Author Contributions

All the contributing authors have participated in the manuscript. MM and BK designed the study. BK recruited patients and completed diagnostic interviews and rating scale measurements. MM carried out the statistical analyses. All authors (BK, MM, SS, and AV) contributed to interpretation of the data and writing of the manuscript. All authors approved the final version of the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors have no conflict of interest with any commercial or other association in connection with the submitted article.

References

  1. 1.
    Maes M, Delanghe J, Bocchio Chiavetto L, Bignotti S, Tura GB, Pioli R, Zanardini R, Altamura CA (2001) Haptoglobin polymorphism and schizophrenia: Genetic variation on chromosome 16. Psychiatry Res 104(1):1–9Google Scholar
  2. 2.
    Ritzmann SE, Daniels JC (1976) Haptoglobin, in serum protein abnormalities: Diagnostic and clinical aspects. Little, Brown, BostonGoogle Scholar
  3. 3.
    Dalan R, Liew H, Goh LL, Gao X, Chew DE, Boehm BO, Leow MK (2016) The haptoglobin 2-2 genotype is associated with inflammation and carotid artery intima-media thickness. Diab Vasc Dis Res 13(5):373–376Google Scholar
  4. 4.
    Lazalde B, Huerta-Guerrero HM, Simental-Mendía LE, Rodríguez-Morán M, Guerrero-Romero F (2014) Haptoglobin 2-2 genotype is associated with TNF-α and IL-6 levels in subjects with obesity. Dis Markers 2014:912756Google Scholar
  5. 5.
    Marvasti TB, Moody AR, Singh N, Maraj T, Tyrrell P, Afshin M (2017) Haptoglobin 2-2 genotype is associated with presence and progression of MRI depicted atherosclerotic intraplaque hemorrhage. Int J Cardiol Heart Vasc 18:96–100Google Scholar
  6. 6.
    Fasano A (2012) Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci 1258:25–33Google Scholar
  7. 7.
    Fasano A (2012) Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol 42(1):71–78Google Scholar
  8. 8.
    Smith RS, Maes M (1995) The macrophage-T-lymphocyte theory of schizophrenia: Additional evidence. Med Hypotheses 45:135–141Google Scholar
  9. 9.
    Noto MN, Maes M, Nunes SO, Ota VK, Rossaneisf AC, Verri Jr WA, Cordeiro Q, Belangero SI et al (2018) Activation of the immune-inflammatory response system and the compensatory immune-regulatory reflex system in antipsychotic naive first episode psychosis. Preprints Preprints 201809.0314.v2.Google Scholar
  10. 10.
    Roomruangwong C, Noto C, Kanchanatawan B, Anderson G, Kubera M, Carvalho AF, Maes M (2018) The role of aberrations in the immune-inflammatory response system (IRS) and the compensatory immune-regulatory reflex system (CIRS) in different phenotypes of schizophrenia: The IRS-CIRS theory of schizophrenia. Preprint, September 2018.  https://doi.org/10.20944/preprints201809.0289.v1
  11. 11.
    Maes M, Carvalho AF (2018) The compensatory immune-regulatory reflex system (CIRS) in depression and bipolar disorder. Mol Neurobiol 55(12):8885–8903Google Scholar
  12. 12.
    Davis J, Moylan S, Harvey BH, Maes M, Berk M (2014) Neuroprogression in schizophrenia: Pathways underpinning clinical staging and therapeutic corollaries. Aust N Z J Psychiatry 48:512–529Google Scholar
  13. 13.
    Davis J, Eyre H, Jacka FN, Dodd S, Dean O, McEwen S, Debnath M, McGrath J et al (2016) A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis. Neurosci Biobehav Rev 65:185–194Google Scholar
  14. 14.
    Kanchanatawan B, Hemrungrojn S, Thika S, Sirivichayakul S, Ruxrungtham K, Carvalho AF, Geffard M, Anderson G et al (2018) Changes in tryptophan catabolite (TRYCAT) pathway patterning are associated with mild impairments in declarative memory in schizophrenia and deficits in semantic and episodic memory coupled with increased false-memory creation in deficit schizophrenia. Mol Neurobiol 55(6):5184–5201Google Scholar
  15. 15.
    Sirivichayakul S, Kanchanatawan B, Thika S, Carvalho AF, Maes M (2018) A new schizophrenia model: Immune activation is associated with induction of different neurotoxic products which together determine memory impairments and schizophrenia symptom dimensions. CNS Neurol Disord Drug Targets.  https://doi.org/10.2174/1871527317666181119115532
  16. 16.
    Sirivichayakul S, Kanchanatawan B, Thika S, Carvalho AF, Maes M (2019) Eotaxin, an endogenous cognitive deteriorating chemokine (ECDC), is a major contributor to cognitive decline in Normal people and to executive, memory, and sustained attention deficits, formal thought disorders, and psychopathology in schizophrenia patients. Neurotox Res 35(1):122–138Google Scholar
  17. 17.
    Maes M, Kanchanatawan B, Sirivichayakul S, Carvalho AF (2018) In schizophrenia, deficits in natural IgM isotype antibodies including those directed to malondialdehyde and azelaic acid strongly predict negative symptoms, neurocognitive impairments, and the deficit syndrome. Mol Neurobiol.  https://doi.org/10.1007/s12035-018-1437-6
  18. 18.
    Binder CJ (2012) Naturally occurring IgM antibodies to oxidation-specific epitopes. Adv Exp Med Biol 750:2–13Google Scholar
  19. 19.
    Weismann D, Binder CJ (2012) The innate immune response to products of phospholipid peroxidation. Biochim Biophys Acta 1818:2465–2475Google Scholar
  20. 20.
    Díaz-Zaragoza M, Hernández-Ávila R, Viedma-Rodríguez R, Arenas-Aranda D, Ostoa-Saloma P (2015) Natural and adaptive IgM antibodies in the recognition of tumor-associated antigens of breast cancer (review). Oncol Rep 34:1106–1114Google Scholar
  21. 21.
    Thiagarajan D, Frostegård AG, Singh S, Rahman M, Liu A, Vikström M, Leander K, Gigante B, Hellenius ML, Zhang B, Zubarev RA, de Faire U, Lundström SL, Frostegård J (2016) Human IgM antibodies to malondialdehyde conjugated with albumin are negatively associated with cardiovascular disease among 60-year-olds. J Am Heart Assoc 5(12).  https://doi.org/10.1161/JAHA.116.004415
  22. 22.
    McMahon M, Skaggs B (2016) Autoimmunity: Do IgM antibodies protect against atherosclerosis in SLE? Nat Rev Rheumatol 12:442–444Google Scholar
  23. 23.
    Aziz M, Holodick NE, Rothstein TL, Wang P (2015) The role of B-1 cells in inflammation. Immunol Res 63:153–166Google Scholar
  24. 24.
    Roomruangwong C, Barbosa DS, de Farias CC, Matsumoto AK, Baltus THL, Morelli NR, Kanchanatawan B, Duleu S et al (2018) Natural regulatory IgM-mediated autoimmune responses directed against malondialdehyde regulate oxidative and nitrosative pathways and coupled with IgM responses to nitroso adducts attenuate depressive and physiosomatic symptoms at the end of term pregnancy. Psychiatry Clin Neurosci 72:116–130Google Scholar
  25. 25.
    Maes M, Kanchanatawan B, Sirivichayakul S, Carvalho AF (2018) In schizophrenia, increased plasma IgM/IgA responses to gut commensal Bacteria are associated with negative symptoms, neurocognitive impairments, and the deficit phenotype. Neurotox Res 35:684–698.  https://doi.org/10.1007/s12640-018-9987-y Google Scholar
  26. 26.
    Rothstein TL, Griffin DO, Holodick NE, Quach TD, Kaku H (2013) Human B-1 cells take the stage. Ann N Y Acad Sci 1285:97–114Google Scholar
  27. 27.
    Lucas K, Maes M (2013) Role of the toll like receptor (TLR) radical cycle in chronic inflammation: Possible treatments targeting the TLR4 pathway. Mol Neurobiol 48:190–204Google Scholar
  28. 28.
    Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Tóth M, Korecka A, Bakocevic N et al (2014) The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med 6(263):263ra158Google Scholar
  29. 29.
    Zakaria R, Wan Yaacob WM, Othman Z, Long I, Ahmad AH, Al-Rahbi B (2017) Lipopolysaccharide-induced memory impairment in rats: A model of Alzheimer’s disease. Physiol Res 66:553–565Google Scholar
  30. 30.
    Muraca M, Putignani L, Fierabracci A, Teti A, Perilongo G (2015) Gut microbiota-derived outer membrane vesicles: Under-recognized major players in health and disease? Discov Med 19:343–348Google Scholar
  31. 31.
    Anand D, Chaudhuri A (2016) Bacterial outer membrane vesicles: New insights and applications. Mol Membr Biol 33:125–137Google Scholar
  32. 32.
    Ellis TN, Kuehn MJ (2010) Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbiol Mol Biol Rev 74:81–94Google Scholar
  33. 33.
    Ellis TN, Leiman SA, Kuehn MJ (2010) Naturally produced outer membrane vesicles from Pseudomonas aeruginosa elicit a potent innate immune response via combined sensing of both lipopolysaccharide and protein components. Infect Immun 78:3822–3831Google Scholar
  34. 34.
    Vojdani A, Vojdani E (2019) Food-associated autoimmunities: When food turns your immune system against you. In pressGoogle Scholar
  35. 35.
    Maes M, Mihaylova I, Leunis JC (2007) Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord 99(1–3):237–240Google Scholar
  36. 36.
    Maes M, Kubera M, Leunis JC (2008) The gut-brain barrier in major depression: Intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett 29(1):117–124Google Scholar
  37. 37.
    Kirkpatrick B, Buchanan RW, McKenney PD, Alphs LD, Carpenter WT Jr (1989) The Schedule for the Deficit Syndrome: An instrument for research in schizophrenia. Psychiatry Res 30:119–123Google Scholar
  38. 38.
    Kittirathanapaiboon P, Khamwongpin M (2005) The validity of the Mini international neuropsychiatric interview (M.I.N.I.) Thai version. J Ment Health Thailand 13(3):125–135Google Scholar
  39. 39.
    Kay SR, Fiszbein A, Opler LA (1987) The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276Google Scholar
  40. 40.
    Andreasen NC (1989) The Scale for the Assessment of Negative Symptoms (SANS): Conceptual and theoretical foundations. Br J Psychiatry Suppl 7:49–58Google Scholar
  41. 41.
    Overall JE, Gorham DR (1962) The Brief Psychiatric Rating Scale. Psychol Rep 10:799–812Google Scholar
  42. 42.
    Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62Google Scholar
  43. 43.
    Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32(1):50–55Google Scholar
  44. 44.
    Zachrisson O, Regland B, Jahreskog M, Kron M, Gottfries CG (2002) A rating scale for fibromyalgia and chronic fatigue syndrome (the FibroFatigue scale). J Psychosom Res 52(6):501–509Google Scholar
  45. 45.
    Kanchanatawan B, Thika S, Sirivichayakul S, Carvalho AF, Geffard M, Maes M (2018) In schizophrenia, depression, anxiety, and Physiosomatic symptoms are strongly related to psychotic symptoms and excitation, impairments in episodic memory, and increased production of neurotoxic tryptophan catabolites: A multivariate and machine learning study. Neurotox Res 33(3):641–655Google Scholar
  46. 46.
    CERAD (1986) CERAD—An overview: The consortium to establish a registry for Alzheimer’s disease; http://cerad.mc.duke.edu/. Accessed 4 Apr 2019
  47. 47.
    Duleu S, Mangas A, Sevin F, Veyret B, Bessede A, Geffard M (2010) Circulating antibodies to IDO/THO pathway metabolites in Alzheimer’s disease. Int J Alzheimers Dis 15:2010Google Scholar
  48. 48.
    Roomruangwong C, Kanchanatawan B, Sirivichayakul S, Anderson G, Carvalho AF, Duleu S, Geffard M, Maes M (2017) IgA/IgM responses to tryptophan and tryptophan catabolites (TRYCATs) are differently associated with prenatal depression, physio-somatic symptoms at the end of term and premenstrual syndrome. Mol Neurobiol 54(4):3038–3049Google Scholar
  49. 49.
    Roomruangwong C, Kanchanatawan B, Carvalho AF, Sirivichayakul S, Duleu S, Geffard M, Maes M (2018) Body image dissatisfaction in pregnant and non-pregnant females is strongly predicted by immune activation and mucosa-derived activation of the tryptophan catabolite (TRYCAT) pathway. World J Biol Psychiatry 19:200–209Google Scholar
  50. 50.
    Kanchanatawan B, Sirivichayakul S, Ruxrungtham K, Carvalho AF, Geffard M, Ormstad H, Anderson G, Maes M (2018) Deficit, but not nondeficit, schizophrenia is characterized by mucosa-associated activation of the tryptophan catabolite (TRYCAT) pathway with highly specific increases in IgA responses directed to picolinic, xanthurenic, and quinolinic acid. Mol Neurobiol 55(2):1524–1536Google Scholar
  51. 51.
    Daverat P, Geffard M, Orgogozo JM (1989) Identification and characterization of anti-conjugated azelaic acid antibodies in multiple sclerosis. J Neuroimmunol 22(2):129–134Google Scholar
  52. 52.
    Boullerne A, Petry KG, Geffard M (1996) Circulating antibodies directed against conjugated fatty acids in sera of patients with multiple sclerosis. J Neuroimmunol 65(1):75–81Google Scholar
  53. 53.
    Amara A, Constans J, Chaugier C, Sebban A, Dubourg L, Peuchant E, Pellegrin JL, Leng B et al (1995) Autoantibodies to malondialdehyde-modified epitope in connective tissue diseases and vasculitides. Clin Exp Immunol 101(2):233–238Google Scholar
  54. 54.
    Faiderbe S, Chagnaud JL, Geffard M (1992) Anti-phosphoinositide auto-antibodies in sera of cancer patients: Isotypic and immunochemical characterization. Cancer Lett 66(1):35–41Google Scholar
  55. 55.
    Geffard M, Bodet D, Dabadie MP, Arnould L (2003) Identification of antibodies in sera of breast cancer patients. Immuno-Analyse & Biologie Special 18:248–253Google Scholar
  56. 56.
    Boullerne AI, Petry KG, Meynard M, Geffard M (1995) Indirect evidence for nitricoxide involvement in multiple sclerosis by characterization of circulating antibodies directed against conjugated S-nitrosocysteine. J Neuroimmunol 60(1–2):117–124Google Scholar
  57. 57.
    Boullerne AI, Rodriguez JJ, Touil T, Brochet B, Schmidt S, Abrous ND, Le Moal M, Pua JR et al (2002) Anti-S-nitrosocysteine antibodies are a predictive marker for demyelination in experimental autoimmune encephalomyelitis: Implications for multiple sclerosis. J Neurosci 22(1):123–132Google Scholar
  58. 58.
    Ringle CM, da Silva D, Bido D (2014) Structural equation modeling with the SmartPLS. Brazilian Journal of Marketing—BJM Revista Brasileira de Marketing—ReMark Edição Especial 13(2):56–73Google Scholar
  59. 59.
    Cepeda-Carrion G, Cegarra-Navarro J-G, Cillo V (2018) Tips to use partial least squares structural equation modelling (PLS-SEM) in knowledge management. J Knowl Manag 23:67–89.  https://doi.org/10.1108/JKM-05-2018-0322 Google Scholar
  60. 60.
    Yu AS, McCarthy KM, Francis SA, McCormack JM, Lai J, Rogers RA, Lynch RD, Schneeberger EE (2005) Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells. Am J Physiol Cell Physiol 288(6):C1231–C1241Google Scholar
  61. 61.
    Suzuki T, Elias BC, Seth A, Shen L, Turner JR, Giorgianni F, Desiderio D, Guntaka R et al (2009) PKC eta regulates occludin phosphorylation and epithelial tight junction integrity. Proc Natl Acad Sci U S A 106(1):61–66Google Scholar
  62. 62.
    Elias BC, Suzuki T, Seth A, Giorgianni F, Kale G, Shen L, Turner JR, Naren A et al (2009) Phosphorylation of Tyr-398 and Tyr-402 in occludin prevents its interaction with ZO-1 and destabilizes its assembly at the tight junctions. J Biol Chem 284(3):1559–1569Google Scholar
  63. 63.
    Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S (1993) Occludin: A novel integral membrane protein localizing at tight junctions. J Cell Biol 123(6 Pt 2):1777–1788Google Scholar
  64. 64.
    Balda MS, Matter K (2000) Transmembrane proteins of tight junctions. Semin Cell Dev Biol 11(4):281–289Google Scholar
  65. 65.
    Cummins PM (2012) Occludin: One protein, many forms. Mol Cell Biol 32(2):242–250Google Scholar
  66. 66.
    Saitou M, Furuse M, Sasaki H, Schulzke JD, Fromm M, Takano H, Noda T, Tsukita S (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11(12):4131–4142Google Scholar
  67. 67.
    McCarthy KM, Skare IB, Stankewich MC, Furuse M, Tsukita S, Rogers RA, Lynch RD, Schneeberger EE (1996) Occludin is a functional component of the tight junction. J Cell Sci 109(Pt 9):2287–2298Google Scholar
  68. 68.
    Balda MS, Whitney JA, Flores C, González S, Cereijido M, Matter K (1996) Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein. J Cell Biol 134(4):1031–1049Google Scholar
  69. 69.
    Edelblum KL, Turner JR (2009) The tight junction in inflammatory disease: Communication breakdown. Curr Opin Pharmacol 9(6):715–720Google Scholar
  70. 70.
    van Roy F, Berx G (2008) The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci 65(23):3756–3788Google Scholar
  71. 71.
    Gomez GA, McLachlan RW, Wu SK, Caldwell BJ, Moussa E, Verma S, Bastiani M, Priya R et al (2015) An RPTPα/Src family kinase/Rap1 signaling module recruits myosin IIB to support contractile tension at apical E-cadherin junctions. Mol Biol Cell 26(7):1249–1262Google Scholar
  72. 72.
    Brüser L, Bogdan S (2017) Adherens junctions on the move-membrane trafficking of E-cadherin. Cold Spring Harb Perspect Biol 1:9(3)Google Scholar
  73. 73.
    Hartsock A, Nelson WJ (2008) Adherens and tight junctions: Structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 1778(3):660–669Google Scholar
  74. 74.
    Dominguez R, Holmes KC (2011) Actin structure and function. Annu Rev Biophys 40:169–186Google Scholar
  75. 75.
    Burridge K, Connell L (1983) Talin: A cytoskeletal component concentrated in adhesion plaques and other sites of actin-membrane interaction. Cell Motil 3(5–6):405–417Google Scholar
  76. 76.
    Balda MS, Matter K (1989) Tight junctions. J Cell Sci 111(Pt 5):541–547Google Scholar
  77. 77.
    Kuwabara H, Kokai Y, Kojima T, Takakuwa R, Mori M, Sawada N (2001) Occludin regulates actin cytoskeleton in endothelial cells. Cell Struct Funct 26(2):109–116Google Scholar
  78. 78.
    Wan C, La Y, Zhu H, Yang Y, Jiang L, Chen Y, Feng G, Li H et al (2007) Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene. Amino Acids 32(1):101–108Google Scholar
  79. 79.
    Dohan FC, Grasberger JC (1973) Relapsed schizophrenics: Earlier discharge from the hospital after cereal-free, milk-free diet. Am J Psychiatry 130(6):685–688Google Scholar
  80. 80.
    Ergün C, Urhan M, Ayer A (2018) A review on the relationship between gluten and schizophrenia: Is gluten the cause? Nutr Neurosci 21(7):455–466Google Scholar
  81. 81.
    Rowland LM, Demyanovich HK, Wijtenburg SA, Eaton WW, Rodriguez K, Gaston F, Cihakova D, Talor MV et al (2017) Antigliadin antibodies (AGA IgG) are related to neurochemistry in schizophrenia. Front Psych 8:104Google Scholar
  82. 82.
    Nguyen TT, Kosciolek T, Maldonado Y, Daly RE, Martin AS, McDonald D, Knight R, Jeste DV (2019) Differences in gut microbiome composition between persons with chronic schizophrenia and healthy comparison subjects. Schizophr Res 204:23–29.  https://doi.org/10.1016/j.schres.2018.09.014
  83. 83.
    Al-Sadi R, Ye D, Boivin M, Guo S, Hashimi M, Ereifej L, Ma TY (2014) Interleukin-6 modulation of intestinal epithelial tight junction permeability is mediated by JNK pathway activation of claudin-2 gene. PLoS One 9(3):e85345Google Scholar
  84. 84.
    Al-Sadi R, Boivin M, Ma T (2009) Mechanism of cytokine modulation of epithelial tight junction barrier. Front Biosci (Landmark Ed) 14:2765–2778Google Scholar
  85. 85.
    Utech M, Mennigen R, Bruewer M (2010) Endocytosis and recycling of tight junction proteins in inflammation. J Biomed Biotechnol 2010:484987Google Scholar
  86. 86.
    Bruewer M, Samarin S, Nusrat A (2006) Inflammatory bowel disease and the apical junctional complex. Ann N Y Acad Sci 1072:242–252Google Scholar
  87. 87.
    Grönwall C, Vas J, Silverman GJ (2012) Protective roles of natural IgM antibodies. Front Immunol 3:66Google Scholar
  88. 88.
    Sokoloff AV, Bock I, Zhang G, Hoffman S, Dama J, Ludtke JJ, Cooke AM, Wolff JA (2001) Specific recognition of protein carboxy-terminal sequences by natural IgM antibodies in normal serum. Mol Ther 3(6):821–830Google Scholar
  89. 89.
    Manfredini E, Nobile-Orazio E, Allaria S, Scarlato G (1995) Anti-alpha- and beta-tubulin IgM antibodies in dysimmune neuropathies. J Neurol Sci 133(1–2):79–84Google Scholar

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Authors and Affiliations

  1. 1.Department of Psychiatry, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  2. 2.Department of PsychiatryMedical University of PlovdivPlovdivBulgaria
  3. 3.IMPACT Strategic Research Center, Barwon HealthDeakin UniversityGeelongAustralia
  4. 4.Faculty of MedicineChulalongkorn UniversityBangkokThailand
  5. 5.Immunosciences Laboratory, Inc.Los AngelesUSA
  6. 6.Cyrex Laboratories, LLCPhoenixUSA
  7. 7.Department of Preventive MedicineLoma Linda UniversityLoma LindaUSA

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