Female infertility due to abnormal autoimmunity: Frequently overlooked and greatly underappreciated. Part I

Expert Review of Obstetrics and Gynecology

Volumn 2, Issue 4, 2007, Pages 453-464

  Gleicher, Norbert ^a   Weghofer, Andrea ^b   Barad, David ^b  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

antibodies; autoimmune polyglandular syndrome; autoimmunity; infertility; miscarriage; polycystic ovarian disease; premature ovarian aging; premature ovarian failure

Indexed keywords

EID: 61549122262     PISSN: 17474108     EISSN: 17474116     Source Type: Journal    
DOI: 10.1586/17474108.2.4.453     Document Type: Article

References (123)

1. Hornstein MD. Antiphospholipid antibodies in patients undergoing IVF: the data do not support testing. Fertil. Steril. 74, 635–636 (2000).
2. Hill GA, Scott RT Jr. Immunologic tests and IVF: “please enough already”. Fertil. Steril. 74, 439–442 (2000).
3. ASRM Practice Committee Report. Antiphospholipid Antibodies Do Not Affect IVF Success. American Society for Reproductive Medicine, AL, USA (1999).
4. ASRI Antiphospholipid Antibody Committee. A rational basis for antiphospholipid antibody testing and selective immunotherapy in assisted reproduction: a rebuttal to the American Society for Reproductive Medicine Practice Committee Opinion. Fertil. Steril. 74, 631–634 (2000).
5. Kamradt T, Avrion Mitchison N. Tolerance and autoimmunity. N. Engl. J. Med. 344, 655–664 (2001).
6. Davidson A, Diamond B. Autoimmune diseases. N. Engl. J. Med. 345, 340–350 (2001).
7. Townsend A, Bodmer. Antigenic recognition by Class I restricted T lymphocytes. Annu. Rev. Immunol. 7, 601–624 (1989).
8. Ortonne JP. Recent developments in the understanding of the pathogenesis of psoriasis. Br. J. Dermatol. 140 (Suppl. 54), 1–7 (1999).
9. Kukreja A, MacLaren NK. Autoimmunity and diabetes. J. Clin. Endocrinol. Metab. 84, 4371–4378 (1999).
10. Gregersen PK. Genetic analysis of rheumatic diseases. In: Textbook of Rheumatology (5th Edition, Volume 1). Kelly WN, Harris ED Jr, Ruddy S, Sledge CB (Eds). WB Saunders, PA, USA 209–227 (1997).
11. Gleicher N, Weiner R, Vietzke M. The impact of abnormal autoimmune function on reproduction: maternal and fetal consequences. J. Autoimmun. 27, 161–165 (2006).
12. Hayashi T, Fustman DL. Role of defective apoptosis in type 1 diabetes and other autoimmune diseases. Rec. Prog. Hormone Res. 58, 131–153 (2003).
13. Encinas JA, Kuchroo VK. Mapping and identification of autoimmunity genes. Curr. Opin. Immunol. 12, 691–697 (2000).
14. Becker KG. Comparative genetics of Type 1 diabetes and autoimmune disease: common loci, common pathways? Diabetes 48, 1353–1358 (1999).
15. Klein J, Sato A. The HLA system. N. Engl. J. Med. 343, 782–786 (2000).
16. Rose NR. Mechanisms of autoimmunity. Sem. Liver Dis. 22, 387–394 (2001).
17. Brix TH, Kyvik KO, Christensen K, Hegedus L. Evidence for a major role of heredity in Grave’s disease: a population-based study of two Danish twin cohorts. J. Clin. Endocrinol. Metab. 86, 930–934 (2001).
18. Yuki N. Pathogenesis of Guillaine–Barre and Miller Fisher syndromes subsequent to Campylobacter jejuni enteritis. Jpn J. Infect. Dis. 52, 99–105 (1999).
19. Regner M, Lambert P. Autoimmunity through infection or immunization? Nat. Immun. 2, 185–188 (2001).
20. Fairweather D, Rose NR. Type 1 diabetes: virus infection or autoimmune disease? Nat. Immun. 3, 338–340 (2002).
21. Wucherpfennig KW. Structural basis for molecular mimicry. J. Autoimmun. 16, 293–302 (2001).
22. Rose NR, Mackay IR. Molecular mimicry: a critical look at exemplary instances in human disease. Cell Molec. Life Sci. 57, 542–551 (2000).
23. Zhao ZS, Granucci F, Yeh L, Schaffer PA, Cantor H. Molecular mimicry by herpes simplex virus-type-1: autoimmune disease after viral infection. Science 279, 1344–1347 (1998).
24. Galvin JE, Hemric ME, Ward K, Cunningham MW. Cytotoxic mAb rheumatic carditis recognizes heart valves and laminin. J. Clin. Invest. 106, 217–224 (2000).
25. Guilherem L, Cunha-Neto E, Coelho V et al. Human heart infiltrating T-cell clones from rheumatic heart disease patients recognize both streptococcal and cardiac proteins. Circulation 92, 415–420 (1995).
26. Tough DF, Borrow P, Sprent J. Induction of bystander T cell proliferation by viruses and type 1 interferon in vivo. Science 272, 1947–1950 (1996).
27. Horwitz MS, Bradley LM, Harbertson J, Krahl T, Lee J, Sarvetnik N. Diabetes induced by coxsackievirus: initiation by bystander damage and not molecular mimicry. Nat. Med. 4, 781–785 (1998).
28. Gleicher N, Pratt D, Dudkiewicz A. What do we really know about autoantibody abnormalities and reproductive failure: a critical review. Autoimmunity 16, 115–140 (1993).
29. El-Roeiy A, Gleicher N. Definition of normal autoantibody levels in an apparently healthy population. Obstet. Gynecol. 72, 596–602 (1988).
30. National Institutes of Health. Autoimmune Disease. Coordinating Committee Report, 2002. The Institutes, MD, USA (2002).
31. Da Silva JAP. Sex hormones, glucocorticoids and autoimmunity: facts and hypothesis. Ann. Rheum. Dis. 54, 6–16 (1995).
32. Whitacre CC. Sex differences in autoimmune disease. Nat. Immunol. 2, 777–780 (2001).
33. McCarthy M. The “gender gap” in autoimmune disease. Lancet 356, 1088 (2000).
34. Ackerman LS. Sex hormones and the genesis of autoimmune disease. Arch. Dermatol. 142, 371–376 (2006).
35. Cutolo M. Estrogen metabolites: increasing evidence for their role in rheumatoid arthritis and systemic lupus erythematosus. J. Rheumatol. 31, 419–421 (2004).
36. Gleicher N, Barad DH. Gender as a risk factor for autoimmune disease. J. Autoimmun. 28, 1–6 (2007).
37. Van Vollenhofen RF. Dehyrdoepiandrosterone for the treatment of systemic lupus erythematosus. Expert Opin. Pharmacother. 3, 23–31 (2003).
38. Barad D, Gleicher N. Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum. Reprod. 21, 2845–2849 (2006).
39. Gleicher N, Weghofer A, Barad D. Adrenal function in women with premature aging ovaries. Fertil. Steril. 86 (Suppl. 2), S401 (2006).
40. Lockshin MD. Sex ratio and rheumatic disease. IMAJ 3, 511–516 (2001).
41. Starzl DE, Demetris AJ, Murase N, Ildstad S, Ricodi C, Trucco M. Cell migration, chimerism, and graft acceptance. Lancet 339, 1579–1582 (1992).
42. Quaini F, Urbanek K, Beltrami AP et al. Chimerism of the transplanted heart. N. Engl. J. Med. 346, 5–15 (2002).
43. Raulet DH. Does a low level of expression of HLA molecules engender autoimmunity? N. Engl. J. Med. 340, 314–315 (1999).
44. Gleicher N. Graft-versus-host disease (GVHD) and graft rejection, a feature of pregnancy and preeclampsia: a unifying hypothesis and implications for diagnosis and treatment. (2007) (In Press).
45. Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, DeMaria MA. Male fetal progenitor cells persist in maternal blood for as long as 27 years post-partum. Proc. Natl Acad. Sci. USA 93, 705–708 (1996).
46. Artlett AM, Smith B, Jimenez SA. Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N. Engl. J. Med. 338, 1186–1191 (1998).
47. Lambert NC, Evans PC, Hashizumi TL et al. Persistent fetal microchimerism in T lymphocytes is associated with HLA-DQA*0501: implications in autoimmunity. J. Immunol. 164, 5545–5548 (2000).
48. Nelson JL. Microchimerism and autoimmune disease. N. Engl. J. Med. 338, 1224–1225 (1998).
49. Gleicher N. Modern obstetrical and infertility care may increase the prevalence of disease: an evolutionary concept. Fertil. Steril. 79, 249–252 (2003).
50. Gleicher N, Barad D. An evolutionary concept of polycystic ovarian disease: does evolution favour reproductive success over survival? Reprod. Biomed. Online 5, 587–589 (2006).
51. Meyer JM, Evans TI, Small RE et al. HLA-DRB1 genotype influences risk and severity of rheumatoid arthritis. J. Rheumatol. 26, 1024–1034 (1999).
52. + regulatory T cells for immunologic self- tolerance and negative control of immune responses. Annu. Rev. Immunol. 22, 531–562 (2004).
53. Kita M, Goulis DG, Avramides A. Post partum thyroiditis in a Mediterranean population. J. Endocrinol. Invest. 25, 513–519 (2002).
54. Elkayam U, Akhter MW, Singh H et al. Pregnancy associated cardiomyopathy. Clinical characteristics and a comparison between early and late presentation. Circulation 111, 2050–2055 (2005).
55. Ansari AA, Fett JD, Carraway RE, Mayne AE, Onlamoon N, Sundstrom JC. Autoimmune mechanisms as the basis for human peripartum cardiomyopathy. Clin. Rev. Allergy Immunol. 23, 301–324 (2002).
56. Argarwal RK, Chan C-C, Wiggert B, Caspi RR. Pregnancy ameliorates induction and expression of experimental autoimmune uveitis. J. Immunol. 162, 2648–2654 (1999).
57. Gogas H, Ioannovich J, Dafni U et al. prognostic significance of autoimmunity during treatment of melanoma with interferon. N. Engl. J. Med. 354, 708–719 (2006).
58. Scott JS. Immunological diseases and pregnancy. Br. Med. J. 1, 1559–1567 (1966).
59. Shoenfeld Y, Segol G, Segol O et al. Detection of antibodies to histones and their subfractions in systemic lupus erythematosus patients and their asymptomatic relatives. Arthritis Rheum. 30, 169–175 (1987).
60. Hardy CJ, Palmer BP, Morton SJ, Muir KR, Powell RJ. Pregnancy outcome and family size in systemic lupus erythematosus: a case control study. Rheumatology 38, 559–563 (1999).
61. Arbuckle MR, McClain MT, Rubertone MV et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N. Engl. J. Med. 349, 1526–1533 (2003).
62. Shmerling RH. Autoantibodies in systemic lupus erythematosus – there before you know it. N. Engl. J. Med. 349, 1499 (2003).
63. Scofield RH. Autoantibodies as predictors of disease. Lancet 363, 1544–1546 (2004).
64. Gleicher N. Reproductive failure prior to the onset of clinical autoimmune disease. Rheumatology 38, 485–487 (1999).
65. Cowchock S, Smith JB, Gocial B. Antibodies to phospholipids and nuclear antigens in patients with repeated abortions. Am. J. Obstet. Gynecol. 155, 1002–1010 (1986).
66. Gleicher N, El-Roeiy A, Confino E, Friberg J. Reproductive failure because of autoantibodies: unexplained infertility and pregnancy wastage. Am. J. Obstet. Gynecol. 160, 1376–1385 (1989).
67. Sher G, Matzner W, Chong P, Ching W. The generalizability of antiphospholipid testing? Fertil. Steril. 74, 611–612 (2000).
68. Practice Committee of the American Society for Reproductive Medicine. Aging and infertility in women: a Committeee Opinion. Fertil. Steril. 78, 2159 (2002).
69. Choudhury A, Mukherjee P, Basu SK, George A, Rath S, Bal V. Disruption of T cell tolerance to self-immunoglobulin causes polyclonal B cell stimulation followed by inactivation of responding autoreactive T cells. J. Immunol. 164, 1713–1721 (2000).
70. Fritzler MJ, Pauls JD, Kinsella TD, Bowen TJ. Antinuclear, anticytoplasmic, and anti-Sjögren’s syndrome antigen A (SS-A/Ro) antibodies in female blood donors. Clin. Immunol. Immunopathol. 36, 120–128 (1985).
71. Bach JF, Kouyouzov S. New clues to systemic lupus. Lancet 350 (Suppl. 3), 11 (1997).
72. Suzuki N, Mihara S, Sakane T. Development of pathogenic anti-DNA antibodies in patients with systemic lupus erythematosus. FASEB J. 11, 1033–1038 (1997).
73. Harger JH, Rabin BS, Marchese SG. The prognostic value of antinuclear antibodies in women with recurrent pregnancy losses: a prospective controlled study. Obstet. Gynecol. 73, 419–424 (1998).
74. Gleicher N, El Roeiy A, Confino E, Friberg J. Is endometriosis an autoimmune disease? Obstet. Gynecol. 70, 115–122 (1987).
75. Taylor PV, Campbell JM, Scott JS. Presence of autoantibodies in women with unexplained infertility. Am. J. Obstet. Gynecol. 161, 377–379 (1989).
76. Hill GA. It’s not what you don’t know that makes you look like a fool. It’s what you do know that ain’t so. Fertil. Steril. 74, 637–638 (2000).
77. Kay A, Bash F. Subfertility before and after development of rheumatoid arthritis in women. Ann. Rheum. Dis. 24, 169–173 (1965).
78. Nelson JL, Koepsell TD, Dugowson CE, Voigt LF, Daling JR, Hansen JA. Fecundity before disease onset in women with rheumatoid arthritis. Arthritis Rheum. 36, 7–14 (1993).
79. Silman AJ, Black C. Increased incidence of spontaneous abortion and infertility in women with scleroderma before disease onset: a controlled study. Ann. Rheum. 47, 441–444 (1988).
80. Gleicher N, Barad D. Unexplained infertility: does it really exist? Hum. Reprod. 21, 1951–1955 (2006).
81. Scott RT Jr. Déja vu all over again. Fertil. Steril. 74, 639–640 (2000).
82. Lubbe WF, Bulter WS, Palmer SJ. Lupus anticoagulant in pregnancy. Br. J. Obstet. Gynaecol. 91, 357–363 (1984).
83. Gleicher N, Friberg J. IgM gammopathy and lupus anticoagulant syndrome in habitual aborters. JAMA 253, 3278–3281 (1985).
84. Lockwood CJ, Reece EA, Romero R, Hobbins JC. Antiphospholipid antibody and pregnancy wastage. Lancet 2, 742–743 (1986).
85. Lockwood CJ, Romero R, Feinberg RF, Clyne LP, Coster B, Hobbins J. The prevalence and biological significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population. Am. J. Obstet. Gynecol. 161, 369–373 (1989)
86. Balasch J, Font J, Lopez-Sota A et al. Antiphospholipid antibodies in unselected patients with repeated abortion. Hum. Reprod. 5, 43–46 (1990).
87. Gleicher N. Autoantibodies and pregnancy loss. Lancet 343, 747–748 (1994).
88. Pratt D, Novotny M, Kaberlein G, Dudkiewicz A, Gleicher N. Antithyroid antibodies and the association with non-organ-specific antibodies in recurrent pregnancy loss. Am. J. Obstet. Gynecol. 168, 837–841 (1993).
89. Petri M, Golbus M, Anderson R, Whiting-O’Keefe Q, Corash L, Hellmann D. Antinuclear antibody, lupus anticoagulant, and anticardiolipin antibody in women with idiopathic habitual abortion. Arthritis Rheum. 30, 601–606 (1987).
90. Eroglu GE, Scopelites E. Antinuclear and antiphospholipid antibodies in healthy women with recurrent spontaneous abortion. Am. J. Reprod. Immunol. 31, 1–6 (1994).
91. Shoenfeld Y, Carp HJ, Molina V et al. Autoantibodies and prediction of reproductive failure. Am. J. Reprod. Immunol. 56, 337–344 (2006).
92. Lockshin MD. Antiphospholipid antibody syndrome. Rheum. Dis. Clin. North Am. 20, 45–59 (1994).
93. Khamashta MA, Cuadrado MJ, Mujic F et al. The management of thrombosis in the antiphospolipid antibody syndrome. N. Engl. J. Med. 332, 993–997 (1995).
94. Triplet DA. Antiphospholipid antibodies and thrombosis. A consequence, coincidence, or cause. Arch. Path. Lab. Med. 117, 78–88 (1993).
95. Gleicher N, El Roeiy A. The reproductive autoimmune failure syndrome (RAFS). Am. J. Obstet. Gynecol. 159, 223–227 (1988).
96. Weed JC, Arguembourg PC. Endometriosis: can it produce an autoimmune response resulting in infertility? Clin. Obstet. Gynecol. 23, 885–893 (1980).
97. Fish B, Rikover Y, Shohat L et al. The relationship between in vitro fertilization and naturally occurring antibodies: evidence for increased production of antiphospholipid antibodies. Fertil. Steril. 56, 718–724 (1991).
98. Gleicher N, Liu HC, Dudkiewicz A et al. Autoantibody profiles and immunoglobulin levels as predictors of in vitro fertilization success. Am. J. Obstet. Gynecol. 170, 1145–1149 (1994).
99. Geva E, Yaron Y, Lessing JB et al. Circulating autoimmune antibodies may be responsible for implantation failure in in vitro fertilization. Fertil. Steril. 62, 802–806 (1994).
100. Geva E, Amit A, Lerner-Geva L, Azem F, Yovel Y, Lessing JB. Autoimmune disorders: another possible cause for in vitro fertilization and embryo transfer failure. Hum. Reprod. 10, 101–104 (1995).
101. Gleicher N, Vidali A, Karande V. The immunological “Wars of the Roses”: disagreements amongst reproductive immunologists. Hum. Reprod. 17, 539–542 (2002).
102. Hornstein MD, Davis OK, Massey JB et al. Antiphospholipid antibodies and in vitro fertilization success: a meta analysis. Fertil. Steril. 73, 330–333 (2000).
103. Blank M, Cohen J, Toder V, Shoenfeld Y. Induction of antiphospholipid syndrome in naïve mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies. Proc. Natl Acad. Sci. USA 88, 3069–3073 (1991).
104. Geva E, Amit A, Lerner-Geva L, Lessing JB. Autoimmunity and reproduction. Fertil. Steril. 67, 599–611 (1997).
105. Aoki K, Dudkiewicz AB, Matsuura E, Novotny M, Kaberlein G, Gleicher N. Clinical significance of β2-glycoprotein I-dependent anticardiolipin antibodies in the reproductive autoimmune failure syndrome: correlation with conventional antiphospholipid antibody detection systems. Am. J. Obstet. Gynecol. 172, 926–931 (1995).
106. Coulam C, Kaider B, Janovicz P, Roussev R. Antiphospholipid antibodies associated with implantation failure after IVF/ET. J. Assist. Reprod. Genet. 14, 603–608 (1997).
107. Peaceman AM, Silver RK, MacGregor SN, Socol ML. Interlaboratory variation in antiphospholipid antibody testing. Am. J. Obstet. Gynecol. 166, 1780–1787 (1992).
108. Harris EN. Special report: the second international anti-cardiolipin standardization workshop/the Kingston Antiphospholipid Antibody Study (KAPS) group. Am. J. Clin. Pathol. 94, 476–484 (1990).
109. Coulam CB, McIntyre JR, Wagenknecht D, Rote N. Inter-laboratory inconsistencies in detection of anticardiolipin antibodies. Lancet 335, 865 (1990).
110. Harries EN, Gharavi E, Patel SP, Hughes GRV. Evaluation of the anti-cardiolipin antibody test: report of an international workshop held April 4, 1986. Clin. Exp. Immunol. 68, 215–222 (1987).
111. Gleicher N, Harlow L, Zilberstein M. Regulatory effect of antiphospholipid antibodies on signal transduction. Am. J. Obstet. Gynecol. 167, 637–642 (1992).
112. Ware-Branch D, Rodgers GM. Induction of endothelial cell tissue factor activity by sera from patients with antiphospholipid syndrome: a possible mechanism for thrombosis. Am. J. Obstet. Gynecol. 168, 206–210 (1993).
113. Peaceman AM, Rehnberg KA. The immunoglobulin G fraction from plasma containing antiphospholipid antibodies causes increased placental thromboxane production. Am. J. Obstet. Gynecol. 167, 1543–1547 (1992).
114. Adler RR, Ng A-K, Rote NS. Monoclonal antiphosphatidylserine antibody inhibits intercellular fusion of the choriocarcinoma line. JAR Biol. Reprod. 53, 905–910 (1995).
115. Wolfe F, Caplan L, Michaud K. Treatment of rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum. 54, 628–634 (2006).
116. Brannagan TH 3rd. Intravenous gammaglobulin (IVIg) for treatment of CIDP and related immune-mediated neuropathies. Neurology 59 (Suppl. 6), S33 –S40 (2002).
117. Sher G, Matzner W, Feinman M et al. The selective use of heparin/aspirin therapy, alone or in combination with intravenous immunoglobulin G, in the management of antiphospholipid antibody positive women undergoing in vitro fertilization. Am. J. Reprod. Immunol. 40, 74–82 (1998).
118. Sher G, Zouves C, Feinman M et al. A rational basis for the use of heparin/aspirin and IV-IG immunotherapy in the treatment of recurrent IVF failure associated with antiphospholipid antibodies. Am. J. Reprod. Immunol. 39, 391–394 (1998).
119. Many A, Pauzner R, Carp H, Langevitz P, Martinowitz U. Treatment of patients with antiphospholipid antibodies during pregnancy. Am. J. Reprod. Immunol. 28, 216–218 (1992).
120. Hasegawa I, Takakuwa K, Goto S et al. Effectiveness of prednisolone/aspirin therapy for recurrent aborters with antiphospholipid antibody. Hum. Reprod. 7, 203–207 (1992).
121. De Carolis C, Greco E, Guarino MD et al. Anti-thyroid antibodies and antiphospholipid syndrome: evidence of reduced fecundity and of poor pregnancy outcome in recurrent spontaneous aborters. Am. J. Reprod. Immunol. 52, 263–266 (2004).
122. Angier N. Studying the autoimmune disease puzzle www.nytimes.com/201/06/19/health/19auto.html
123. Hughes’ syndrome www.hughes-syndrome.org/what1.htm