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Multipl skleroz ve otoimmünite üzerine cinsiyet faktörünün etkisi

Year 2016, Volume: 2 Issue: 2, 158 - 164, 01.06.2016

Bilge Piri Çınar , Halil Güllüoğlu Yüksel Güven Yorgun

Abstract

Otoimmün bir hastalık olan multipl sklerozun (MS) etyopatogenezi tam aydınlatılamamış olsa da T ve B lenfositlerin, doğal öldürücü (NK) hücrelerin,makrofajların ve sitokinlerin atak-remisyon dönemlerinde ve progresyonda önemli rolü olduğu bilinmektedir. Kadınlarda otoimmün hastalık gelişmeriski erkeklere oranla daha fazladır. Multipl sklerozda yardımcı T 1 hücre (Th1) aktivitesi ön plandadır ve kadınlarda Th1 hücre yanıtı erkeklerden dahabaskındır. Bu durum MS gibi diğer otoimmün hastalıkların kadınlarda neden daha sık olduğunu kısmen açıklamaktadır. Düşük östrojen düzeyleri Th1tipi proenflamatuar yanıtı artırırken, yüksek östrojen ve progesteron düzeyleri Th2 tipi yanıtı artırır. Kadınlarda menstrüasyon döneminden önce MSataklarında alevlenme olduğu ve östrojen ve progesteron düzeylerinin çok düşük olduğu saptanmıştır. Progesteron ve östrojenin çok yüksek olduğugebeliğin son trimesterinde atak oranı anlamlı olarak azalırken, doğum sonrası dönemde atak sıklığı ve şiddeti artmaktadır. Progestreron reaktifgliozisi düşürür, remiyelinizasyonu artırır ve mikroglial enflamatuar aktivasyonu azaltır. Östrojen proenflamatuar sinyalleri azaltmaktadır. Kadınlarda,tekrarlayan ve düzelen MS tipi daha sık görülmekle birlikte, erkeklerde daha ciddi düzeyde disabilite ve daha kısa sürede progresif forma geçişsaptanmaktadır. Manyetik rezonans görüntülemelerde erkeklerde daha az enflamatuvar aktivite gözlenirken, aksonal kayıp ve nörodejenerasyonungöstergesi olan kara delik görüntüsüne daha sık rastlanmaktadır. Bu klinik ve radyolojik farklılıklar, seks hormonlarının MS patolojisi üzerine olan etkisiolduğu düşüncesini desteklemektedir.

Keywords

Autoimmunity gender multiple sclerosis

References

  • 1. Probert L, Akassoglou K, Pasparakis M, Kontogeorgos G, Kollias G. Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor alpha. Proc Natl Acad Sci U S A 1995;92:11294-8.
  • 2. Griot C, Vandevelde M, Richard A, Peterhans E, Stocker R. Selective degeneration of oligodendrocytes mediated by reactive oxygen species. Free Radic Res Commun 1990;11:181-93.
  • 3. Linington C, Bradl M, Lassmann H, Brunner C, Vass K. Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 1988;130:443-54.
  • 4. Lucchinetti CF, Parisi J, Bruck W. The pathology of multiple sclerosis. Neurol Clin 2005;23:77-105.
  • 5. Argaw AT, Zhang Y, Snyder BJ, Zhao ML, Kopp N, Lee SC, et al. IL-1beta regulates blood-brain barrier permeability via reactivation of the hypoxiaangiogenesis program. J Immunol 2006;177:5574-84.
  • 6. D’Souza S, Alinauskas K, McCrea E, Goodyer C, Antel JP. Differential susceptibility of human CNSderived cell populations to TNF-dependent and independent immune-mediated injury. J Neurosci 1995;15:7293-300.
  • 7. Brosnan CF, Raine CS. Mechanisms of immune injury in multiple sclerosis. Brain Pathol 1996;6:243-57.
  • 8. Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996;17:138-46.
  • 9. Podojil JR, Miller SD, Immunopathological mechanisms in multiple sclerosis. Drug Discov Today Dis Mech 2006;3:177-84.
  • 10. Panitch HS. Interferons in multiple sclerosis. A review of the evidence. Drugs 1992;44:946-62.
  • 11. Sharief MK, Hentges R. Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis. N Engl J Med 1991;325:467-72.
  • 12. Drenth JP, Van Uum SH, Van Deuren M, Pesman GJ, Van der Ven-Jongekrijg J, Van der Meer JW. Endurance run increases circulating IL-6 and IL-1ra but downregulates ex vivo TNF-alpha and IL-1 beta production. J Appl Physiol (1985) 1995;79:1497-503.
  • 13. Gardner RV, McKinnon E, Poretta C, Leiva L. Hemopoietic function after use of IL-1 with chemotherapy or irradiation. J Immunol 2003;171:1202-6.
  • 14. Dinarello CA. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol 2002;20:1-13.
  • 15. Crome SQ, Wang AY, Levings MK. Translational minireview series on Th17 cells: function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol 2010;159:109-19.
  • 16. Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, et al. Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol 2006;177:36-9.
  • 17. Fossiez F, Djossou O, Chomarat P, Flores-Romo L, Ait-Yahia S, Maat C, et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 1996;183:2593- 603.
  • 18. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006;126:1121-33.
  • 19. Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev 2008;223:87-113.
  • 20. Fainardi E, Castellazzi M, Bellini T, Manfrinato MC, Baldi E, Casetta I, et al. Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis. Mult Scler 2006;12:294-301.
  • 21. Collison LW, Pillai MR, Chaturvedi V, Vignali DA. Regulatory T cell suppression is potentiated by target T cells in a cell contact, IL-35- and IL-10-dependent manner. J Immunol 2009;182:6121-8.
  • 22. Beissert S, Schwarz A, Schwarz T. Regulatory T cells. J Invest Dermatol 2006;126:15-24.
  • 23. Nie J, Li YY, Zheng SG, Tsun A, Li B. FOXP3(+) Treg Cells and Gender Bias in Autoimmune Diseases. Front Immunol 2015;6:493.
  • 24. Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003;4:337-42.
  • 25. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003;299:1057-61.
  • 26. Qin Y, Duquette P, Zhang Y, Talbot P, Poole R, Antel J. Clonal expansion and somatic hypermutation of V(H) genes of B cells from cerebrospinal fluid in multiple sclerosis. J Clin Invest 1998;102:1045-50.
  • 27. Owens GP, Ritchie AM, Burgoon MP, Williamson RA, Corboy JR, Gilden DH. Single-cell repertoire analysis demonstrates that clonal expansion is a prominent feature of the B cell response in multiple sclerosis cerebrospinal fluid. J Immunol 2003;171:2725-33.
  • 28. Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 2004;14:164-74.
  • 29. Howell OW, Reeves CA, Nicholas R, Carassiti D, Radotra B, Gentleman SM, et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 2011;134:2755-71.
  • 30. Yoshizaki A, Miyagaki T, DiLillo DJ, Matsushita T, Horikawa M, Kountikov EI, et al. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature 2012;491:264-8.
  • 31. Eidinger D, Garrett TJ. Studies of the regulatory effects of the sex hormones on antibody formation and stem cell differentiation. J Exp Med 1972;136:1098-116.
  • 32. Weinstein Y, Ran S, Segal S. Sex-associated differences in the regulation of immune responses controlled by the MHC of the mouse. J Immunol 1984;132:656-61.
  • 33. Amadori A, Zamarchi R, De Silvestro G, Forza G, Cavatton G, Danieli GA, et al. Genetic control of the CD4/CD8 T-cell ratio in humans. Nat Med 1995;1:1279-83.
  • 34. Özakba S, ‹diman E, Paköz B, Uysal U. Multipl sklerozda seyir özellikleri: 420 olgunun klinik özellikleri. Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi 2003;17:205-11.
  • 35. Miller AE, Lublin FD, Coyle PK, editors. Multiple sclerosis in clinical practice. London: Martin Dunitz; 2003.
  • 36. Kim S, Liva SM, Dalal MA, Verity MA, Voskuhl RR. Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis. Neurology 1999;52:1230-8.
  • 37. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med 2000;343:938-52.
  • 38. Gilmore W, Weiner LP, Correale J. Effect of estradiol on cytokine secretion by proteolipid protein-specific T cell clones isolated from multiple sclerosis patients and normal control subjects. J Immunol 1997;158:446-51.
  • 39. Villard-Mackintosh L, Vessey MP. Oral contraceptives and reproductive factors in multiple sclerosis incidence. Contraception 1993;47:161-8.
  • 40. Smith R, Studd JW. A pilot study of the effect upon multiple sclerosis of the menopause, hormone replacement therapy and the menstrual cycle. J R Soc Med 1992;85:612-3.
  • 41. Argyriou AA, Makris N. Multiple sclerosis and reproductive risks in women. Reprod Sci 2008;15:755-64.
  • 42. Damek Shuster EA. Pregnancy and multiple sclerosis. Mayo Clin Proc 1997;72:977-89.
  • 43. Jansson L, Holmdahl R. Estrogen-mediated immunosuppression in autoimmune diseases. Inflamm Res 1998;47:290-301.
  • 44. Whitaker JN. Effects of pregnancy and delivery on disease activity in multiple sclerosis. N Engl J Med 1998;339:339-40.
  • 45. Foroughipour A, Norbakhsh V, Najafabadi SH, Meamar R. Evaluating sex hormone levels in reproductive age women with multiple sclerosis and their relationship with disease severity. J Res Med Sci 2012;17:882-5.
  • 46. Tomassini V, Onesti E, Mainero C, Giugni E, Paolillo A, Salvetti M, et al. Sex hormones modulate brain damage in multiple sclerosis: MRI evidence. J Neurol Neurosurg Psychiatry 2005;76:272-5.
  • 47. Wei T, Lightman SL. The neuroendocrine axis in patients with multiple sclerosis. Brain 1997;120:1067-76.
  • 48. Dalal M, Kim S, Voskuhl RR. Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response. J Immunol 1997;159:3-6.
  • 49. Roberts E, Fauble TJ. Oral DHEA in multiple sclerosis: results of a phase one, open study. In: Kalimi M, Regelson W, editors. The Biologic Role of DHEA. New York: Walter De Gruyter; 1990. p. 81-93.
  • 50. Bovolenta P, Wandosell F, Nieto-Sampedro M. CNS glial scar tissue: a source of molecules which inhibit central neurite outgrowth. Prog Brain Res 1992;94:367-79.
  • 51. Alonso A, Hernán MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology 2008;71:129-35.
  • 52. Confavreux C, Vukusic S, Adeleine P. Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain 2003;126:770-82.
  • 53. Weinshenker BG, Rice GP, Noseworthy JH, Carriere W, Baskerville J, Ebers GC. The natural history of multiple sclerosis: a geographically based study. 4. Applications to planning and interpretation of clinical therapeutic trials. Brain 1991;114:1057-67.
  • 54. Pozzilli C, Tomassini V, Marinelli F, Paolillo A, Gasperini C, Bastianello S. 'Gender gap' in multiple sclerosis: magnetic resonance imaging evidence. Eur J Neurol 2003;10:95-7.
  • 55. Luchetti S, van Eden CG, Schuurman K, van Strien ME, Swaab DF, Huitinga I. Gender differences in multiple sclerosis: induction of estrogen signaling in male and progesterone signaling in female lesions. J Neuropathol Exp Neurol 2014;73:123-35.
  • 56. Spence RD, Voskuhl RR. Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol 2012;33:105-15.
  • 57. Gold SM, Voskuhl RR. Estrogen and testosterone therapies in multiple sclerosis. Prog Brain Res 2009;175:239-51.

Year 2016, Volume: 2 Issue: 2, 158 - 164, 01.06.2016

Bilge Piri Çınar , Halil Güllüoğlu Yüksel Güven Yorgun

Abstract

References

  • 1. Probert L, Akassoglou K, Pasparakis M, Kontogeorgos G, Kollias G. Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor alpha. Proc Natl Acad Sci U S A 1995;92:11294-8.
  • 2. Griot C, Vandevelde M, Richard A, Peterhans E, Stocker R. Selective degeneration of oligodendrocytes mediated by reactive oxygen species. Free Radic Res Commun 1990;11:181-93.
  • 3. Linington C, Bradl M, Lassmann H, Brunner C, Vass K. Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 1988;130:443-54.
  • 4. Lucchinetti CF, Parisi J, Bruck W. The pathology of multiple sclerosis. Neurol Clin 2005;23:77-105.
  • 5. Argaw AT, Zhang Y, Snyder BJ, Zhao ML, Kopp N, Lee SC, et al. IL-1beta regulates blood-brain barrier permeability via reactivation of the hypoxiaangiogenesis program. J Immunol 2006;177:5574-84.
  • 6. D’Souza S, Alinauskas K, McCrea E, Goodyer C, Antel JP. Differential susceptibility of human CNSderived cell populations to TNF-dependent and independent immune-mediated injury. J Neurosci 1995;15:7293-300.
  • 7. Brosnan CF, Raine CS. Mechanisms of immune injury in multiple sclerosis. Brain Pathol 1996;6:243-57.
  • 8. Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996;17:138-46.
  • 9. Podojil JR, Miller SD, Immunopathological mechanisms in multiple sclerosis. Drug Discov Today Dis Mech 2006;3:177-84.
  • 10. Panitch HS. Interferons in multiple sclerosis. A review of the evidence. Drugs 1992;44:946-62.
  • 11. Sharief MK, Hentges R. Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis. N Engl J Med 1991;325:467-72.
  • 12. Drenth JP, Van Uum SH, Van Deuren M, Pesman GJ, Van der Ven-Jongekrijg J, Van der Meer JW. Endurance run increases circulating IL-6 and IL-1ra but downregulates ex vivo TNF-alpha and IL-1 beta production. J Appl Physiol (1985) 1995;79:1497-503.
  • 13. Gardner RV, McKinnon E, Poretta C, Leiva L. Hemopoietic function after use of IL-1 with chemotherapy or irradiation. J Immunol 2003;171:1202-6.
  • 14. Dinarello CA. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol 2002;20:1-13.
  • 15. Crome SQ, Wang AY, Levings MK. Translational minireview series on Th17 cells: function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol 2010;159:109-19.
  • 16. Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, et al. Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol 2006;177:36-9.
  • 17. Fossiez F, Djossou O, Chomarat P, Flores-Romo L, Ait-Yahia S, Maat C, et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 1996;183:2593- 603.
  • 18. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006;126:1121-33.
  • 19. Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev 2008;223:87-113.
  • 20. Fainardi E, Castellazzi M, Bellini T, Manfrinato MC, Baldi E, Casetta I, et al. Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis. Mult Scler 2006;12:294-301.
  • 21. Collison LW, Pillai MR, Chaturvedi V, Vignali DA. Regulatory T cell suppression is potentiated by target T cells in a cell contact, IL-35- and IL-10-dependent manner. J Immunol 2009;182:6121-8.
  • 22. Beissert S, Schwarz A, Schwarz T. Regulatory T cells. J Invest Dermatol 2006;126:15-24.
  • 23. Nie J, Li YY, Zheng SG, Tsun A, Li B. FOXP3(+) Treg Cells and Gender Bias in Autoimmune Diseases. Front Immunol 2015;6:493.
  • 24. Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003;4:337-42.
  • 25. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003;299:1057-61.
  • 26. Qin Y, Duquette P, Zhang Y, Talbot P, Poole R, Antel J. Clonal expansion and somatic hypermutation of V(H) genes of B cells from cerebrospinal fluid in multiple sclerosis. J Clin Invest 1998;102:1045-50.
  • 27. Owens GP, Ritchie AM, Burgoon MP, Williamson RA, Corboy JR, Gilden DH. Single-cell repertoire analysis demonstrates that clonal expansion is a prominent feature of the B cell response in multiple sclerosis cerebrospinal fluid. J Immunol 2003;171:2725-33.
  • 28. Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 2004;14:164-74.
  • 29. Howell OW, Reeves CA, Nicholas R, Carassiti D, Radotra B, Gentleman SM, et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 2011;134:2755-71.
  • 30. Yoshizaki A, Miyagaki T, DiLillo DJ, Matsushita T, Horikawa M, Kountikov EI, et al. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature 2012;491:264-8.
  • 31. Eidinger D, Garrett TJ. Studies of the regulatory effects of the sex hormones on antibody formation and stem cell differentiation. J Exp Med 1972;136:1098-116.
  • 32. Weinstein Y, Ran S, Segal S. Sex-associated differences in the regulation of immune responses controlled by the MHC of the mouse. J Immunol 1984;132:656-61.
  • 33. Amadori A, Zamarchi R, De Silvestro G, Forza G, Cavatton G, Danieli GA, et al. Genetic control of the CD4/CD8 T-cell ratio in humans. Nat Med 1995;1:1279-83.
  • 34. Özakba S, ‹diman E, Paköz B, Uysal U. Multipl sklerozda seyir özellikleri: 420 olgunun klinik özellikleri. Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi 2003;17:205-11.
  • 35. Miller AE, Lublin FD, Coyle PK, editors. Multiple sclerosis in clinical practice. London: Martin Dunitz; 2003.
  • 36. Kim S, Liva SM, Dalal MA, Verity MA, Voskuhl RR. Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis. Neurology 1999;52:1230-8.
  • 37. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med 2000;343:938-52.
  • 38. Gilmore W, Weiner LP, Correale J. Effect of estradiol on cytokine secretion by proteolipid protein-specific T cell clones isolated from multiple sclerosis patients and normal control subjects. J Immunol 1997;158:446-51.
  • 39. Villard-Mackintosh L, Vessey MP. Oral contraceptives and reproductive factors in multiple sclerosis incidence. Contraception 1993;47:161-8.
  • 40. Smith R, Studd JW. A pilot study of the effect upon multiple sclerosis of the menopause, hormone replacement therapy and the menstrual cycle. J R Soc Med 1992;85:612-3.
  • 41. Argyriou AA, Makris N. Multiple sclerosis and reproductive risks in women. Reprod Sci 2008;15:755-64.
  • 42. Damek Shuster EA. Pregnancy and multiple sclerosis. Mayo Clin Proc 1997;72:977-89.
  • 43. Jansson L, Holmdahl R. Estrogen-mediated immunosuppression in autoimmune diseases. Inflamm Res 1998;47:290-301.
  • 44. Whitaker JN. Effects of pregnancy and delivery on disease activity in multiple sclerosis. N Engl J Med 1998;339:339-40.
  • 45. Foroughipour A, Norbakhsh V, Najafabadi SH, Meamar R. Evaluating sex hormone levels in reproductive age women with multiple sclerosis and their relationship with disease severity. J Res Med Sci 2012;17:882-5.
  • 46. Tomassini V, Onesti E, Mainero C, Giugni E, Paolillo A, Salvetti M, et al. Sex hormones modulate brain damage in multiple sclerosis: MRI evidence. J Neurol Neurosurg Psychiatry 2005;76:272-5.
  • 47. Wei T, Lightman SL. The neuroendocrine axis in patients with multiple sclerosis. Brain 1997;120:1067-76.
  • 48. Dalal M, Kim S, Voskuhl RR. Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response. J Immunol 1997;159:3-6.
  • 49. Roberts E, Fauble TJ. Oral DHEA in multiple sclerosis: results of a phase one, open study. In: Kalimi M, Regelson W, editors. The Biologic Role of DHEA. New York: Walter De Gruyter; 1990. p. 81-93.
  • 50. Bovolenta P, Wandosell F, Nieto-Sampedro M. CNS glial scar tissue: a source of molecules which inhibit central neurite outgrowth. Prog Brain Res 1992;94:367-79.
  • 51. Alonso A, Hernán MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology 2008;71:129-35.
  • 52. Confavreux C, Vukusic S, Adeleine P. Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain 2003;126:770-82.
  • 53. Weinshenker BG, Rice GP, Noseworthy JH, Carriere W, Baskerville J, Ebers GC. The natural history of multiple sclerosis: a geographically based study. 4. Applications to planning and interpretation of clinical therapeutic trials. Brain 1991;114:1057-67.
  • 54. Pozzilli C, Tomassini V, Marinelli F, Paolillo A, Gasperini C, Bastianello S. 'Gender gap' in multiple sclerosis: magnetic resonance imaging evidence. Eur J Neurol 2003;10:95-7.
  • 55. Luchetti S, van Eden CG, Schuurman K, van Strien ME, Swaab DF, Huitinga I. Gender differences in multiple sclerosis: induction of estrogen signaling in male and progesterone signaling in female lesions. J Neuropathol Exp Neurol 2014;73:123-35.
  • 56. Spence RD, Voskuhl RR. Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol 2012;33:105-15.
  • 57. Gold SM, Voskuhl RR. Estrogen and testosterone therapies in multiple sclerosis. Prog Brain Res 2009;175:239-51.
There are 57 citations in total.

Details

Journal Section Review
Authors

Bilge Piri Çınar

Halil Güllüoğlu This is me

Yüksel Güven Yorgun This is me

Publication Date June 1, 2016
Published in Issue Year 2016 Volume: 2 Issue: 2

Cite

APA Çınar, B. P., Güllüoğlu, H., & Güven Yorgun, Y. (2016). Multipl skleroz ve otoimmünite üzerine cinsiyet faktörünün etkisi. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi, 2(2), 158-164. https://doi.org/10.5606/fng.btd.2016.029
AMA Çınar BP, Güllüoğlu H, Güven Yorgun Y. Multipl skleroz ve otoimmünite üzerine cinsiyet faktörünün etkisi. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi. June 2016;2(2):158-164. doi:10.5606/fng.btd.2016.029
Chicago Çınar, Bilge Piri, Halil Güllüoğlu, and Yüksel Güven Yorgun. “Multipl Skleroz Ve otoimmünite üzerine Cinsiyet faktörünün Etkisi”. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi 2, no. 2 (June 2016): 158-64. https://doi.org/10.5606/fng.btd.2016.029.
EndNote Çınar BP, Güllüoğlu H, Güven Yorgun Y (June 1, 2016) Multipl skleroz ve otoimmünite üzerine cinsiyet faktörünün etkisi. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi 2 2 158–164.
IEEE B. P. Çınar, H. Güllüoğlu, and Y. Güven Yorgun, “Multipl skleroz ve otoimmünite üzerine cinsiyet faktörünün etkisi”, İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi, vol. 2, no. 2, pp. 158–164, 2016, doi: 10.5606/fng.btd.2016.029.
ISNAD Çınar, Bilge Piri et al. “Multipl Skleroz Ve otoimmünite üzerine Cinsiyet faktörünün Etkisi”. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi 2/2 (June 2016), 158-164. https://doi.org/10.5606/fng.btd.2016.029.
JAMA Çınar BP, Güllüoğlu H, Güven Yorgun Y. Multipl skleroz ve otoimmünite üzerine cinsiyet faktörünün etkisi. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi. 2016;2:158–164.
MLA Çınar, Bilge Piri et al. “Multipl Skleroz Ve otoimmünite üzerine Cinsiyet faktörünün Etkisi”. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi, vol. 2, no. 2, 2016, pp. 158-64, doi:10.5606/fng.btd.2016.029.
Vancouver Çınar BP, Güllüoğlu H, Güven Yorgun Y. Multipl skleroz ve otoimmünite üzerine cinsiyet faktörünün etkisi. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi. 2016;2(2):158-64.
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