27.futuro centros


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27.futuro centros

  1. 1. El Mosaico de la AutoinmunidadYehuda Shoenfeld, MD, FRCPJefe, Departamento de Medicina B y CentroZabludowicz para Enfermedades Autoinmunes,Centro Médico Sheba (Afiliado a la Universidad deTel-Aviv), y Titular de la Cátedra de InvestigaciónLaura Schwarz-Kipp en EnfermedadesAutoinmunes, Universidad de Tel-Aviv, Israel. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  2. 2. Autoimmune diseases The enemy from within Yehuda Shoenfeld MD FRCP TAU 03 03 11
  3. 3. Allergy and AID Yehuda Shoenfeld, MD,FRCP ( Hon.)
  4. 4. First Autoimmune Disease Yehuda Shoenfeld, MD,FRCP ( Hon.)
  5. 5. Paul Ehrlich (14.3.1854)Virtuoso of test tubeDifferential staining of blood cellsDiagnosis of leukemia (CLL vs CML)Acid fast staining of TBAnti-serum therapy of diphtheriaChemotherapy and “Magic bullet” (Abs)Salvarsan (compound 606) for syphilisNobel Prize“Horror autotoxicus” Yehuda Shoenfeld, MD,FRCP ( Hon.)
  6. 6. History of Autoimmunity1945: Anti-red blood cell autoantibodies and AIHA.1950: Harrington -ITP plasma self infusion induced severe thrombocytopenia. Still: Autoantibodies referred as “factors”, SLE , RA-”connective tissue”, “collagen” diseases. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  7. 7. History of Autoimmunity1959: The first animal model of a spontaneous AI disease: NZB=AIHA.  (NZB/NZW) F1= SLE (genetic basis for AI diseases)MD,FRCP ( Hon.) Yehuda Shoenfeld,
  8. 8. LE CELL-1948 Yehuda Shoenfeld, MD,FRCP ( Hon.)
  9. 9. Autoimmunity1) Why Ms. X develops SLE at the ageof 30?2) Why Mr. Y presents withGoodpasture’s Syndrome at the age of 50? a) Why he and she? b) Why the specific disease? c) Why at that specific time? Yehuda Shoenfeld, MD,FRCP ( Hon.)
  10. 10. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  11. 11. Anti- TSH-RYehuda Shoenfeld, MD,FRCP ( Hon.)
  12. 12. Exophthalmus Yehuda Shoenfeld, MD,FRCP ( Hon.)
  13. 13. MyxedemaHypothyroidism Yehuda Shoenfeld, MD,FRCP ( Hon.)
  14. 14. Anti- DesmogleinYehuda Shoenfeld, MD,FRCP ( Hon.)
  15. 15. Acantholysis - intraepidermal blister Pemphigus vulgaris (PV) – Pemphigus foliaceous (PF) –blisterblister in suprabasal epidermal layers in superficial epidermis Yehuda Shoenfeld, MD,FRCP ( Hon.)
  16. 16. Anti- Topoisomerase-I Correlation of serum anti-DNA topoisomerase I antibody levels with disease severity and activity in systemic sclerosis. Hu PQ, et.al.. .Arthritis Rheum. 2003;48:1363-73 Yehuda Shoenfeld, MD,FRCP ( Hon.)
  17. 17. Myasthenia Gravis Yehuda Shoenfeld, MD,FRCP ( Hon.)
  18. 18. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  19. 19. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  20. 20. Vanda Lennonwith electric eel Yehuda Shoenfeld, MD,FRCP ( Hon.)
  21. 21. Myasthenia Gravis – pre and post thymectomy Yehuda Shoenfeld, MD,FRCP ( Hon.)
  22. 22. Polymyositis-Ovarian cancer Sjogren syndrome and lymphoma Paraneoplastic syndromes Small cell ca of the lungYehuda Shoenfeld, MD,FRCP ( Hon.)
  23. 23. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  24. 24. Type-I Insulin-Dependent Diabetes Melitus – IDDM Organ specific, T-cell mediated autoimmune disease Yehuda Shoenfeld, MD,FRCP ( Hon.)
  25. 25. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  26. 26. The original classification of autoimmune diseases into organ-specific and non-organ- specific Simmonds MJ & Gough SCL. British Medical Bulletin. 2005; 71Organ-specific Non-organ-specificHashimoto’s thyroiditis Sjogren’s syndromeGraves’ disease APECEDPernicious anaemia Rheumatoid arthritisAddisons disease Systemic lupus erythematosusMyasthenia gravisType 1 diabetesMultiple sclerosis Yehuda Shoenfeld, MD,FRCP ( Hon.)
  27. 27. Autoantibodies Predictive 2005Precede overt autoimmune diseasePredict specific clinical manifestationPredict pregnancy loss. Yehuda Shoenfeld Yehuda Shoenfeld, MD,FRCP ( Hon.)
  28. 28. Autoantibodies as Predictors Of Diseases Scofield RH. Lancet. 2004,8;363:1544-6 . Shoenfeld Y. Autoimmunity. 2004 (in press) RA: anti-ccp, IgM-RF-4.5y., NPV-75%, PPV-100%. Nielen MM, et.al. Arthritis Rheum, 2004;50:380-6 Rantapaa-Dahlqvist S, et.al. Arthritis Rheum. 2003;48:2741-9. SLE: α DNA, 2.5-10y. α Ro,α Sm Arbuckle MR, et.al. N Engl J Med. 2003;349:1526-33 PBC: α PDH-30y. Kisand KE. J Gastroenterol. 2001;36:248-54. Addison’s disease: α adrenal cortical and α 21 hydroxilase Ketchum CH, et.al.J Clin Endocrinol Metab. 1984;58:1166-70. Laureti S, et.al. J Clin Endocrinol Metab. 1998;83:3507-11. DM type I: α GAD, α Insulin, α IA-2A. Siblings, general. 99.5% specific, 50% PPV. Kupila A, et.al. Diabetologia. 2001;44:290-7. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  29. 29. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  30. 30. AUTOANTIBODY EXPLOSION IN SLE More than 100 Different Antibodies Found in SLE PatientsY. Sherer,A. Gorstein,M. J. Fritzler Y. Shoenfeld; Sem A@R 2004 Yehuda Shoenfeld, MD,FRCP ( Hon.)
  31. 31. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  32. 32. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  33. 33. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  34. 34. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  35. 35. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  36. 36. Message to Congress to pay attention to autoimmunity According to AARDA, approximately 50 million Americans, 20 percent of the population or one in five people suffer from some 80 autoimmune diseases. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  37. 37. Prevalence of autoimmune diseases The seventh leading cause of death by disease among females ages one to 14. The fifth leading cause of death by disease among females ages 15 to 44. The seventh leading cause of death by disease among females ages 45 to 65. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  38. 38. Epidemiology of autoimmune diseases in Denmark Eaton WW et al. J Autoimmun. 2007; 29: 1-9Table 1: Lifetimeprevalence of 31autoimmune diseasesfrom two reviews andamong 5,472,032persons in Denmark in2001 per 1000population Yehuda Shoenfeld, MD,FRCP ( Hon.)
  39. 39. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  40. 40. PL Meroni Yehuda Shoenfeld, MD,FRCP ( Hon.)
  41. 41. New congresses Yehuda Shoenfeld, MD,FRCP ( Hon.)
  42. 42. Witebsky-Rose (Koch) criteria for classical autoimmune disease Defining the autoantigen (e.g., AchR, gpllb, cadherin, MBP). Defining the autoantibody or autoreactive T cell (anti- RBC anti-Tg, TSH). Induction of the disease by active immunization of the autoantigen with adjuvant (e.g. thyroiditis, collagen arthritis, myasthenia). Induction of the disease by passive transfer of the autoantibody (or autoreactive T cell), e.g. ITP, myasthenia, AIHA. Transfer of autoimmune disease from the sick mother of the offspring, e.g. congenital myasthenia, thyrotoxicosis, pemphigus, ITP. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  43. 43. New autoimmune diseases Endometriosis Duodenal ulcer Alopecia Psoriasis Autism Neuroleptic malignant Depression Schizophrenia Epilepsy (10% of 543 APS pts.) ( Hon.) Yehuda Shoenfeld, MD,FRCP
  44. 44. Autoantibodies- Anti P ribosomal Causing behavioral changesNovel aspects of the pathogenicity ofautoantibodies -psychiatric conditions. Pathways; therapy; compound, peptides Yehuda Shoenfeld, MD,FRCP ( Hon.)
  45. 45. Anti P ribosomal can inducedepression in an animal model. Anti P Ribosomal Abs Depression Yehuda Shoenfeld, MD,FRCP ( Hon.)
  46. 46. Forced swimming test Anti P rib. Ab Control mice injected mice 350 300 control APS anti-P Immobility time (sec) 250 200 150 100 50 0 Yehuda Shoenfeld, MD,FRCP ( Hon.) first 120-sec last 240-sec total 360-sec
  47. 47. Autoantibodies in atrial fibrillation: actor, biomaker or bystander? Baba A, Fu M. Autoimmunity . 2008; 41:470-2 At least three types of autoantibody have been found in AF: the anti-myosin heavy chain autoantibody, the anti-M2 muscarinic receptor autoantibody and the anti-heat shock protein autoantibody. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  48. 48. Autoimmunity1) Why does Ms. X develop SLE at theage of 30?2) Why does Mr. Y present withGoodpasture’s Syndrome at the age of50? a) Why he and she? b) Why the specific disease? c) Why at that specific time? Yehuda Shoenfeld, MD,FRCP ( Hon.)
  49. 49. The major pieces of the mosaic of autoimmunityCenetics: Increased incidence of the disease in families. Increased incidence of autoantibodies in first-degree relatives of a patient. Increased incidence of the disease in monozygotic twins. HLA studies – increased incidence of HLA-B8, DR2, DR3, DR4 in some diseases. A protective effect, e.g. HLA DR2 in type 1 diabetes. Increased incidence of common idiotype of autoantibodies in patients and first-degree relatives, Gm-allotypes. Complement component deficiencies. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  50. 50. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  51. 51. Marco Salvetti et alYehuda Shoenfeld, MD,FRCP ( Hon.)
  52. 52. Triplets with SLE Kamat SS, et al. Arthritis Rheum. 2003;48:3176-80. The first case report of identical triplets who developed systemic lupus erythematosus (SLE). The children were diagnosed at ages 8, 9, and 11 years. Each sibling manifested different clinical signs and symptoms. Findings of laboratory studies were similar, including antinuclear antibodies, anti-native DNA, and anti-double-stranded DNA, as well as low levels of complement. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  53. 53. HLA risk for SLE A1, B8, DR3 is associated with a 10 - fold increase (Primary link with C4 null allele). Yehuda Shoenfeld, MD,FRCP ( Hon.)
  54. 54. Evidence for a susceptibility gene (SLEH1) on chromosome 11q14 for systemic lupus erythematosus (SLE) families with hemolytic anemiaKelly JA, et.al. Proc Natl Acad Sci U S A 2002 ;99:11766-71 Yehuda Shoenfeld, MD,FRCP ( Hon.)
  55. 55. The major pieces of the Mosaic of AutoimmunityDefects in immune system: IgA deficiency. Complement component deficiencies (e.g.C1q, C2, C4). Qualitative and quantitative defects in T suppressors (CD4+25+) ( Treg). Defects in natural killer (NK) cells. Defects in apoptosis (Fas) or phagocytosis. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  56. 56. Selective IgA deficiency in children and adults with systemic lupus erythematosus Cassidy JT et al. Lupus. 2007; 16: 647-5012/77 SLESimilar clinical presentation Yehuda Shoenfeld, MD,FRCP ( Hon.)
  57. 57. The major pieces of the Mosaic of Autoimmunity Sex and autoimmunity Females have, on the average, higher Ig levels than males. Females have an enhanced antibody production to both primary and secondary Ag stimulation. Females have a higher CMI response (e.g. homograft rejection). Males are more prone to infections . In male animals, it is easier to produce immune tolerance. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  58. 58. Cutolo M et al. J Clin Ezndocrinol Metab 1996;81:820-827 Yehuda Shoenfeld, MD,FRCP ( Hon.)
  59. 59. Synovial tissue Macrophages stained for ER Cultured synovial Macrophages stained for ERSynovial tissue Macrophages stained for AR Cultured synovial Macrophages stained for AR Yehuda Shoenfeld, MD,FRCP ( Hon.) Cutolo M et al. J Clin Ezndocrinol Metab 1996;81:820-827
  60. 60. monocytes Estrogen Receptors lymphocytes Yehuda Shoenfeld, MD,FRCP ( Hon.)
  61. 61. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  62. 62. Beneficial effects of the anti- oestrogen tamoxifen on systemic lupus erythematosus of (NZBxNZW)F1 female mice areassociated with specific reduction of IgG3 autoantibodies. Sthoeger ZM, Zinger H, Mozes E. Ann Rheum Dis 2003 ;62:341-6 Yehuda Shoenfeld, MD,FRCP ( Hon.)
  63. 63. The major pieces of the Mosaic of Autoimmunity Environmental: Infecting agents: viruses, bacteria, parasites. Drugs (e.g. idiopathic thrombocytopenia purpura, myasthenia, SLE). Toxins (e.g. scleroderma). Cosmetics (e.g. silicone). UV light (e.g. SLE). Smoking (e.g. Goodpasture’s syndrome,RA,Thyr). Stress (e.g. SLE) Nutritional influence (e.g. RA, SLE). Yehuda Shoenfeld, MD,FRCP ( Hon.)
  64. 64. Hepatitis-C and Autoimmune Diseases1) Mixed cryoglobulinemia.2) Ch. Active hepatitis.3) Polyarteritis nodosa.4) Leukocytoclastic vasculitis.5) Autoimmune thyroid disease.6) Glomerulonephritis.7) Polymyositis + anti-Jo-1 Ab.8) Formation of autoantibodies and CIC (A@R. 3: 437, 1995). Yehuda Shoenfeld, MD,FRCP ( Hon.)
  65. 65. The infectious origin of the antiphospholipid syndrome (APS): induction of exp.APS bypassive transfer of anti-β 2GPI Abs induced by common bacteria 1 Blank M, 1Krause I, 1Levy Y, 2Fridkin M, Keller N and 1Y Shoenfeld 3 J Clin Invest 109;797-804,2002 Yehuda Shoenfeld, MD,FRCP ( Hon.)
  66. 66. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  67. 67. EBV genetics and autoimmune diseases EBVAutoimmune HLA-DR15 gene Multiple sclerosis Late EBV Infection EBVAutoimmune HLA-DR3 gene Late EBV Autoimmune Infection thyroid disease Yehuda Shoenfeld, MD,FRCP ( Hon.)
  68. 68. Influence of HLA-DR phenotype on the risk of hepatitis C virus-associated mixed cryoglobulinemia. Cacoub P, et.al. Arthritis Rheum 2001 ;44:2118-24 The presence of the DR11 phenotype is associated with a significantly increased risk for the development of type II MC in patients with chronic HCV infection. In contrast, HLA-DR7 appears to protect against the production of type II MC. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  69. 69. Smoking and GoodpastureCigarette smoking and lung hemorrhage inglomerulonephritis caused by autoantibodies toglomerular basement membrane. Lancet 1983 : 2 : 1390-3Diffuse alveolar hemorrhage developed: # 20% of non-smokers. # 80% of smokers. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  70. 70. Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells Makrygiannakis D et al. Ann Rheum Dis. 2008; 67: 1488-92 Smoking enhances PAD2 expression in the bronchial mucosal and alveolar compartment, with consequent generation of citrullinated proteins in the latter. Smoking is an environmental factor that may lead to citrulline autoimmunity in genetically susceptible subjects. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  71. 71. Lipstick consumption and systemic lupuserythematosus: nothing to gloss over Kurien BT, Scofield RH. Clin Rheumatol . 2008; 27: 1339-40 Yehuda Shoenfeld, MD,FRCP ( Hon.)
  72. 72. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  73. 73. Multiple autoantibodies in patients with silicone breast implantsBar-Meir E, Teuber SS, Lin HC, Alosacie I, Goddard G, Terrybery J, Barka N, Shen B, Peter JB, Blank M, Gershwin ME, Shoenfeld Y. J Autoimmunity 8: 267-277, 1995 Yehuda Shoenfeld, MD,FRCP ( Hon.)
  74. 74. Systemic lupus erythematosus afteralpha-interferon therapy for chronic hepatitis C :a case report and review of the literature Fukuyama S, et al. Am J Gastroenterol 2000 : 95: 310 - 2 Yehuda Shoenfeld, MD,FRCP ( Hon.)
  75. 75. Occupational risk factors for the development of systemic lupus erythematosus Cooper GS, et al. J Rheumatol. 2004; 31: 1928-33 Associations were seen with self-reported occupational exposure to mercury (OR 3.6, 95% CI 1.3, 10.0), mixing pesticides for agricultural work (OR 7.4, 95% CI 1.4, 40.0), and among dental workers (OR 7.1, 95% CI 2.2, 23.4). Yehuda Shoenfeld, MD,FRCP ( Hon.)
  76. 76. Geographical clustering of scleroderma in south and west London. Silman AJ, et al. Br J Rheumatol 1990 ;29:93-6 Living in close proximity to an air- port may be a marker for an environmental hazard for scleroderma although the magnitude of any effect appears to be very small. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  77. 77. ,Reifen R, Blank M, Afek A ,Kopilowiz Y, Sklan D ,Gershwin ME, German B .Yoshida S, Shoenfeld Y Dietary polyunsaturated fatty acids decrease anti-dsDNA and anti-cardiolipin antibodies production in idiotype induced .mouse model of SLE .Lupus 7, 192-197, 1998 ,Reifen R. Amital H, Blank M, Sklan D .Berkovich Z, Gershwin E, Shoenfeld Y Diet and Linseed Oil suppressesAutoimmunity the antiB2GPI in .experimental APS .J Autoimmun 15: 381-385, 2000 Yehuda Shoenfeld, MD,FRCP ( Hon.)
  78. 78. The mosaic of autoimmunity Yehuda Shoenfeld MD Genetic ,HLA) Immune GM Environmental deficienccy Allotype ,infection) state Idiotype Drugs, UVIgA def. Trg) smoking( C‘ def., NK Hormonal Estrogen) ( Testosterone Yehuda Shoenfeld, MD,FRCP ( Hon.)
  79. 79. The mosaic of autoimmunity.A classical case of inhalation of a polyclonal activating factor in a genetically and hormonally susceptible patient leading to multiple autoimmune diseases. Rahamim-Cohen D, Shoenfeld Y. Isr Med Assoc J. 2001;3:381-2. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  80. 80. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  81. 81. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  82. 82. Galileo Galilei Page 72 Opere GallileiOmnium rerum origo ipsa suiimmunis, donec res contraria reperitur. “Everything isautoimmune until proven otherwise” Yehuda Shoenfeld, MD,FRCP ( Hon.)
  83. 83. Systemic autoimmune diseasesSystemic diseases Reiter’s disease Reiter’Systemic lupus erythematosus Sneddons diseaseAntiphospholipid syndrome Autoimmune polyendocrinopathy, candidiasis-ectodermalRheumatoid arthritis dystropyJuvenile Rheumatoid arthritis Essential cryoglobulinemic vasculitisFelty’s syndromeFelty’ Cutaneous leukocytoclastic angiitisLarge granular lymphocytosis (LGL) Lyme diseaseSjogren’s syndromeSjogren’ Rheumatic fever and heart diseaseSystemic sclerosis (scleroderma) Eosinophilic fasciitisCrest syndrome Paroxysmal cold hemoglobinuriaMixed connective tissue disease Polymyalgia rheumaticaPolymyositis/ dermatomyositis FibromyalgiaGoodpasture’s DiseaseGoodpasture’ POEMS syndrome (polyneuropathy, organomegaly,Wegener’s granulomatosis endocrinopathy, M-spot and skin changes)Wegener’ Relapsing polychondritisChurg-Strauss syndromeHenoch-Schonlein purpura Autoimmune lymphoproliferative syndrome TINU syndrome (acute tubulointerstitial nephritis andMicroscopic polyangiatis uveitis)Periarteritis nodosa Autoimmunity associated with immunodeficiencyBechet’s syndromeBechet’ Common variable immunodeficiencyAtherosclerosis TAP (transporter associated with antigen presentation)Temporal (giant) cell arteritis deficiencyTakayasu arteritis Omenn syndromeKawasaki disease HyperIgM syndromeAnkylosing spondilitis BTK agammaglobulinemia Human immunodeficiency virus Post bone-marrow-transplant Yehuda Shoenfeld, MD,FRCP ( Hon.)
  84. 84. Organ specific autoimmune diseasesNeurological Dermatology ReproductiveMyasthenia Gravis Pemphigus Vulgaris Autoimmune premature ovarian failureCongenital myasthenia gravis Pemphigus Foliaceus AzoospermiaMultiple sclerosis Bullous phemphigoid/ Pemphigoid gestationis HypogonadismStiff-man syndrome Cicatrical pemphigoid Male infertility associated with spermTropical spastic paraparesis Dermatitis herpetiformis autoantibodiesRasmussen’s encephalitisRasmussen’ Epidermal bullosa acquisita Autoimmune orchitisAcute motor axonal neuropathy Erythema multiforme Premature ovarian failureAcute sensory-motor axonal neuropathy Herpes gestatonis Autoimmune oophoritisDorsal root ganglion neuritis Vitiligo OcularAcute pan-autonomic neuropathy Chronic urticaria UveitisBrachial neuritis Discoid lupus RetinitisAcute necrotizing hemorrhagic lekoencephalitis Alopecia universalis/Areata Sympathetic ophthalmiaSporadic necrotizing myelopathy Psoriasis Birdshot retinochoroidopathyParaneoplastic cerebellar degeneration Hepatobiliary Vogt-Koyanagi-Harada granulomatous uveitisGuillain-Barre syndrome Autoimmune hepatitis Retinal degenerationLimbic encephalitis Primary biliary cirrhosis Lens-induced uveitisOpsoclonus-myoclonus ataxia Chronic active hepatitis Optic neuritisSensory neuronitis Chronic active hepatitits/ Primary biliary cirrhosis VestibulocochlearAutonomic neuropathy overlap syndrome Autoimmune sensorineural hearing lossDemyelinating neuropathy Primary sclerosing cholangitis Meniere’s disease Meniere’AIDS-dementia complex. Hematopoeitic CardiacTourette’s syndromeTourette’ Autoimmune hemolytic anemia Autoimmune myocarditisMiller-Fisher syndrome Idiopathic thrombocytopenic purpura Congenital heart block (neonatal lupus)Alzheimer’s diseaseAlzheimer’ Evans syndrome Chagas’ disease Chagas’Endocrine Heparin-induced thrombocytopenia Adriamycin cardiotoxicityGraves’ DiseaseGraves’ Primary autoimmune neutropenia Dressler’s myocarditis syndrome Dressler’Hashimoto’s thyroiditisHashimoto’ Autoimmune (primary) neutropenia of infancy Respiratory RespiratoryPostpartum thyroiditis Autoimmune neutropenia following bone marrow Bronchial asthma transplant Interstitial fibrosing lung diseaseFocal thyroiditis Acquired autoimmune hemophilia NephrologyJuvenile thyroiditisIdiopathic hypothyroidism Gastroenterlogy Rapidly progressive glomerulonephritis Autoimmune gastritis and pernicious anemia Autoimmune tubulointerstitial nephritisType I (insulin dependent) diabetes mellitus Coeliac diseaseAddison’s diseaseAddison’Hypophysitis Crohn’s disease Crohn’Autoimmune diabetes insipidus Ulcerative colitisHypoparathyroidism Sialadenitis Yehuda Shoenfeld, MD,FRCP ( Hon.)
  85. 85. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  86. 86. Pet dogs owned by lupus patients are at a higher risk of developing lupus Chiou SH, et al. Lupus. 2004; 13: 442-9 Among 59 pet dogs owned by 37 SLE patients, 11 (18%) were ANA positive, and three (5%) had SLE. Of 187 pet dogs owned by non-SLE households, nine (4.81%) were ANA positive, and none (0%) had SLE. Pet dogs with human SLE contact were at a higher risk of developing SLE. A common environmental factor or zoonotic agent may be involved in the development of human and canine SLE. Yehuda Shoenfeld, MD,FRCP ( Hon.)
  87. 87. Yehuda Shoenfeld, MD,FRCP ( Hon.)