Skip to main content

Advertisement

SpringerLink
Log in

The Challenge of Treating Orphan Disease

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Uncommon or orphan diseases are less frequently addressed in mainstream medical journals and, as a consequence, their understanding and clinical recognition may rely on case series or anecdotal data with limited guidelines and management directions. The study of selected underrepresented autoimmune and allergy conditions is the subject of the present issue of Clinical Reviews in Allergy and Immunology to provide peculiar perspectives on common and rare themes. First, allergy remains a major concern for physicians worldwide despite the limited developments over the past years, particularly for antigens such as mite or Alternaria alternata, and due to the increasing incidence of drug hypersensitivity. Second, the female predominance of autoimmune diseases such as systemic sclerosis is well recognized but enigmatic, and a unifying hypothesis remains elusive. Third, the management of conditions triggered by infectious agents as in Guillain-Barre syndrome or mixed cryoglobulinemia is challenging, and clinical guidelines are needed in the setting of infections and autoimmunity. Fourth, gamma-delta T cells represent major players in innate immunity and are the subject of extensive studies in autoimmune diseases to provide new therapeutic targets for disease prevention or modulation in the near future. Ultimately, we acknowledge the major developments in the broad fields of rheumatology and immunology and expect that microbiota definition, epigenetics studies, and microRNA analysis will provide new exciting avenues toward the understanding and treatment of chronic and acute inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Oliveira MJ, Borges T, Dias C (2014) 12th Medinterna International Meeting: what did we learn? Isr Med Assoc J 16:524–526

    PubMed  Google Scholar 

  2. Salvador F, Antunes AM, Cunha J, Dias C (2013) 11th Medinterna International Meeting: what did we learn? Isr Med Assoc J 15:785–788

    PubMed  Google Scholar 

  3. Islam AD, Naguwa SM, Cheema GS, Hunter JC, Gershwin ME (2013) Multicentric reticulohistiocytosis: a rare yet challenging disease. Clin Rev Allergy Immunol 45:281–289

    Article  PubMed  Google Scholar 

  4. Yang YH, Chiang BL (2014) Novel approaches to food allergy. Clin Rev Allergy Immunol 46:250–257

    Article  CAS  PubMed  Google Scholar 

  5. Verma AK, Kumar S, Das M, Dwivedi PD (2013) A comprehensive review of legume allergy. Clin Rev Allergy Immunol 45:30–46

    Article  CAS  PubMed  Google Scholar 

  6. Van Winkle RC, Chang C (2014) The biochemical basis and clinical evidence of food allergy due to lipid transfer proteins: a comprehensive review. Clin Rev Allergy Immunol 46:211–224

    Article  PubMed  Google Scholar 

  7. Shu SA, Chang C, Leung PS (2014) Common methodologies in the evaluation of food allergy: pitfalls and prospects of food allergy prevalence studies. Clin Rev Allergy Immunol 46:198–210

    Article  CAS  PubMed  Google Scholar 

  8. Sharp MF, Lopata AL (2014) Fish allergy: in review. Clin Rev Allergy Immunol 46:258–271

    Article  CAS  PubMed  Google Scholar 

  9. Kung SJ, Steenhoff AP, Gray C (2014) Food allergy in Africa: myth or reality? Clin Rev Allergy Immunol 46:241–249

    Article  CAS  PubMed  Google Scholar 

  10. Thurner L, Preuss KD, Fadle N et al (2013) Progranulin antibodies in autoimmune diseases. J Autoimmun 42:29–38

    Article  CAS  PubMed  Google Scholar 

  11. Szczeklik W, Jakiela B, Adamek D, Musial J (2013) Cutting edge issues in the Churg-Strauss syndrome. Clin Rev Allergy Immunol 44:39–50

    Article  CAS  PubMed  Google Scholar 

  12. Agmon-Levin N, Selmi C (2013) The autoimmune side of heart and lung diseases. Clin Rev Allergy Immunol 44:1–5

    Article  CAS  PubMed  Google Scholar 

  13. Zen M, Gatto M, Domeneghetti M et al (2013) Clinical guidelines and definitions of autoinflammatory diseases: contrasts and comparisons with autoimmunity—a comprehensive review. Clin Rev Allergy Immunol 45:227–235

    Article  CAS  PubMed  Google Scholar 

  14. Yazici H, Ugurlu S, Seyahi E (2012) Behcet syndrome: is it one condition? Clin Rev Allergy Immunol 43:275–280

    Article  CAS  PubMed  Google Scholar 

  15. Marzano AV, Ishak RS, Saibeni S, Crosti C, Meroni PL, Cugno M (2013) Autoinflammatory skin disorders in inflammatory bowel diseases, pyoderma gangrenosum and Sweet’s syndrome: a comprehensive review and disease classification criteria. Clin Rev Allergy Immunol 45:202–210

    Article  CAS  PubMed  Google Scholar 

  16. Chang C (2013) The pathogenesis of neonatal autoimmune and autoinflammatory diseases: a comprehensive review. J Autoimmun 41:100–110

    Article  CAS  PubMed  Google Scholar 

  17. Brooks WH (2012) Mechanisms and pathophysiology of autoimmune disease. Clin Rev Allergy Immunol 42:1–4

    Article  CAS  PubMed  Google Scholar 

  18. Avidan N, Le Panse R, Berrih-Aknin S, Miller A (2014) Genetic basis of myasthenia gravis—a comprehensive review. J Autoimmun 52:146–153

    Article  CAS  PubMed  Google Scholar 

  19. Damoiseaux J, Cohen Tervaert JW (2013) Diagnostics and treatment of cryoglobulinaemia: it takes two to tango. Clin Rev Allergy Immunol. doi:10.1007/s12016-013-8390-y

  20. Tansley S, Gunawardena H (2013). The evolving spectrum of polymyositis and dermatomyositis—moving towards clinicoserological syndromes: a critical review. Clin Rev Allergy Immunol. doi:10.1007/s12016-013-8387-6

  21. Xiao J, Simard AR, Shi FD, Hao J (2013) New strategies in the management of guillain–barré syndrome. Clin Rev Allergy Immunol. doi:10.1007/s12016-013-8388-5

  22. Coop CA (2013) Immunotherapy for mold allergy. Clin Rev Allergy Immunol. doi:10.1007/s12016-013-8389-4

  23. Cui Y (2013) Immunoglobulin E-binding epitopes of mite allergens: from characterization to immunotherapy. Clin Rev Allergy Immunol. doi:10.1007/s12016-013-8396-5

  24. Kustrzeba-Wojcicka I, Siwak E, Terlecki G, Wolanczyk-Medrala A, Medrala W (2014) Alternaria alternata and its allergens: a comprehensive review. Clin Rev Allergy Immunol. doi:10.1007/s12016-014-8447-6

  25. D’Amico F, Skarmoutsou E, Mazzarino MC (2013) The sex bias in systemic sclerosis: on the possible mechanisms underlying the female disease preponderance. Clin Rev Allergy Immunol. doi:10.1007/s12016-013-8392-9

  26. Bank I, Marcu-Malina V (2013) Quantitative peripheral blood perturbations of γδ T cells in human disease and their clinical implications. Clin Rev Allergy Immunol. doi:10.1007/s12016-013-8391-x

  27. Svendsen AJ, Hjelmborg JV, Kyvik KO et al (2013) The impact of genes on the occurrence of autoantibodies in rheumatoid arthritis. A study on disease discordant twin pairs. J Autoimmun 41:120–125

    Article  CAS  PubMed  Google Scholar 

  28. Orbach H, Zandman-Goddard G, Boaz M et al (2012) Prolactin and autoimmunity: hyperprolactinemia correlates with serositis and anemia in SLE patients. Clin Rev Allergy Immunol 42:189–198

    Article  CAS  PubMed  Google Scholar 

  29. Hewagama A, Gorelik G, Patel D et al (2013) Overexpression of X-linked genes in T cells from women with lupus. J Autoimmun 41:60–71

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Lu Q (2013) The critical importance of epigenetics in autoimmunity. J Autoimmun 41:1–5

    Article  PubMed  Google Scholar 

  31. Liu Y, Li H, Xiao T, Lu Q (2013) Epigenetics in immune-mediated pulmonary diseases. Clin Rev Allergy Immunol 45:314–330

    Article  CAS  PubMed  Google Scholar 

  32. De Santis M, Selmi C (2012) The therapeutic potential of epigenetics in autoimmune diseases. Clin Rev Allergy Immunol 42:92–101

    Article  CAS  PubMed  Google Scholar 

  33. Podda M, Selmi C, Lleo A, Moroni L, Invernizzi P (2013) The limitations and hidden gems of the epidemiology of primary biliary cirrhosis. J Autoimmun 46:81–87

    Article  PubMed  Google Scholar 

  34. Floreani A, Liberal R, Vergani D, Mieli-Vergani G (2013) Autoimmune hepatitis: contrasts and comparisons in children and adults—a comprehensive review. J Autoimmun 46:7–16

    Article  PubMed  Google Scholar 

  35. Lleo A, Oertelt-Prigione S, Bianchi I et al (2013) Y chromosome loss in male patients with primary biliary cirrhosis. J Autoimmun 41:87–91

    Article  PubMed  Google Scholar 

  36. Mitchell VL, Van Winkle LS, Gershwin LJ (2012) Environmental tobacco smoke and progesterone alter lung inflammation and mucous metaplasia in a mouse model of allergic airway disease. Clin Rev Allergy Immunol 43:57–68

    Article  CAS  PubMed  Google Scholar 

  37. Wichner K, Fischer A, Winter S et al (2013) Transition from an autoimmune-prone state to fatal autoimmune disease in CCR7 and RORgammat double-deficient mice is dependent on gut microbiota. J Autoimmun 47:58–72

    Article  CAS  PubMed  Google Scholar 

  38. Rook GA (2012) Hygiene hypothesis and autoimmune diseases. Clin Rev Allergy Immunol 42:5–15

    Article  CAS  PubMed  Google Scholar 

  39. Rinaldi M, Perricone R, Blank M, Perricone C, Shoenfeld Y (2013) Anti-Saccharomyces cerevisiae autoantibodies in autoimmune diseases: from bread baking to autoimmunity. Clin Rev Allergy Immunol 45:152–161

    Article  CAS  PubMed  Google Scholar 

  40. Henao-Mejia J, Elinav E, Thaiss CA, Licona-Limon P, Flavell RA (2013) Role of the intestinal microbiome in liver disease. J Autoimmun 46:66–73

    Article  CAS  PubMed  Google Scholar 

  41. Vatti RR, Teuber SS (2012) Asthma and pregnancy. Clin Rev Allergy Immunol 43:45–56

    Article  CAS  PubMed  Google Scholar 

  42. Ideguchi H, Ohno S, Uehara T, Ishigatsubo Y (2013) Pregnancy outcomes in Japanese patients with SLE: retrospective review of 55 pregnancies at a university hospital. Clin Rev Allergy Immunol 44:57–64

    Article  PubMed  Google Scholar 

  43. Zhao M, Liu Q, Liang G et al (2013) E4BP4 overexpression: a protective mechanism in CD4+ T cells from SLE patients. J Autoimmun 41:152–160

    Article  CAS  PubMed  Google Scholar 

  44. Zhang Y, Zhao M, Sawalha AH, Richardson B, Lu Q (2013) Impaired DNA methylation and its mechanisms in CD4(+)T cells of systemic lupus erythematosus. J Autoimmun 41:92–99

    Article  PubMed  Google Scholar 

  45. Xiao J, Liu C, Li G et al (2013) PDCD5 negatively regulates autoimmunity by upregulating FOXP3(+) regulatory T cells and suppressing Th17 and Th1 responses. J Autoimmun 47:34–44

    Article  CAS  PubMed  Google Scholar 

  46. Coit P, Jeffries M, Altorok N et al (2013) Genome-wide DNA methylation study suggests epigenetic accessibility and transcriptional poising of interferon-regulated genes in naive CD4+ T cells from lupus patients. J Autoimmun 43:78–84

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Chuang WY, Strobel P, Bohlender-Willke AL et al (2014) Late-onset myasthenia gravis—CTLA4(low) genotype association and low-for-age thymic output of naive T cells. J Autoimmun 52:122–129

    Article  CAS  PubMed  Google Scholar 

  48. Edwards LJ, Evavold BD (2013) Destabilization of peptide:MHC interaction induces IL-2 resistant anergy in diabetogenic T cells. J Autoimmun 44:82–90

    Article  CAS  PubMed  Google Scholar 

  49. Gravano DM, Hoyer KK (2013) Promotion and prevention of autoimmune disease by CD8+ T cells. J Autoimmun 45:68–79

    Article  CAS  PubMed  Google Scholar 

  50. Hillhouse EE, Lesage S (2013) A comprehensive review of the phenotype and function of antigen-specific immunoregulatory double negative T cells. J Autoimmun 40:58–65

    Article  CAS  PubMed  Google Scholar 

  51. Koristka S, Cartellieri M, Arndt C et al (2013) Retargeting of regulatory T cells to surface-inducible autoantigen La/SS-B. J Autoimmun 42:105–116

    Article  CAS  PubMed  Google Scholar 

  52. Muratori L, Longhi MS (2013) The interplay between regulatory and effector T cells in autoimmune hepatitis: Implications for innovative treatment strategies. J Autoimmun 46:74–80

    Article  CAS  PubMed  Google Scholar 

  53. Selmi C, Mackay IR, Gershwin ME (2007) The immunological milieu of the liver. Semin Liver Dis 27:129–139

    Article  CAS  PubMed  Google Scholar 

  54. Thabet Y, Le Dantec C, Ghedira I et al (2013) Epigenetic dysregulation in salivary glands from patients with primary Sjogren’s syndrome may be ascribed to infiltrating B cells. J Autoimmun 41:175–181

    Article  CAS  PubMed  Google Scholar 

  55. Quartuccio L, Isola M, Baldini C et al (2014) Biomarkers of lymphoma in Sjogren’s syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: results of a multicenter study. J Autoimmun 51:75–80

    Article  PubMed  Google Scholar 

  56. Nezos A, Papageorgiou A, Fragoulis G et al (2014) B-cell activating factor genetic variants in lymphomagenesis associated with primary Sjogren’s syndrome. J Autoimmun 51:89–98

    Article  CAS  PubMed  Google Scholar 

  57. Moriyama M, Tanaka A, Maehara T, Furukawa S, Nakashima H, Nakamura S (2014) T helper subsets in Sjogren’s syndrome and IgG4-related dacryoadenitis and sialoadenitis: a critical review. J Autoimmun 51:81–88

    Article  CAS  PubMed  Google Scholar 

  58. Lee BH, Gauna AE, Pauley KM, Park YJ, Cha S (2012) Animal models in autoimmune diseases: lessons learned from mouse models for Sjogren’s syndrome. Clin Rev Allergy Immunol 42:35–44

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Kyriakidis NC, Kapsogeorgou EK, Tzioufas AG (2014) A comprehensive review of autoantibodies in primary Sjogren’s syndrome: clinical phenotypes and regulatory mechanisms. J Autoimmun 51:67–74

    Article  CAS  PubMed  Google Scholar 

  60. Gliozzi M, Greenwell-Wild T, Jin W et al (2013) A link between interferon and augmented plasmin generation in exocrine gland damage in Sjogren’s syndrome. J Autoimmun 40:122–133

    Article  CAS  PubMed  Google Scholar 

  61. Barrera MJ, Bahamondes V, Sepulveda D et al (2013) Sjogren’s syndrome and the epithelial target: a comprehensive review. J Autoimmun 42:7–18

    Article  CAS  PubMed  Google Scholar 

  62. Longhi MS, Ma Y, Grant CR et al (2013) T-regs in autoimmune hepatitis-systemic lupus erythematosus/mixed connective tissue disease overlap syndrome are functionally defective and display a Th1 cytokine profile. J Autoimmun 41:146–151

    Article  CAS  PubMed  Google Scholar 

  63. Vandenbark AA, Meza-Romero R, Benedek G et al (2013) A novel regulatory pathway for autoimmune disease: binding of partial MHC class II constructs to monocytes reduces CD74 expression and induces both specific and bystander T-cell tolerance. J Autoimmun 40:96–110

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Moinzadeh P, Nihtyanova SI, Howell K, Ong VH, Denton CP (2012) Impact of hallmark autoantibody reactivity on early diagnosis in scleroderma. Clin Rev Allergy Immunol 43:249–255

    Article  CAS  PubMed  Google Scholar 

  65. Katzav A, Arango MT, Kivity S et al (2013) Passive transfer of narcolepsy: anti-TRIB2 autoantibody positive patient IgG causes hypothalamic orexin neuron loss and sleep attacks in mice. J Autoimmun 45:24–30

    Article  CAS  PubMed  Google Scholar 

  66. Iorio R, Fryer JP, Hinson SR et al (2013) Astrocytic autoantibody of neuromyelitis optica (NMO-IgG) binds to aquaporin-4 extracellular loops, monomers, tetramers and high order arrays. J Autoimmun 40:21–27

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Boettler T, Pagni PP, Jaffe R, Cheng Y, Zerhouni P, von Herrath M (2013) The clinical and immunological significance of GAD-specific autoantibody and T-cell responses in type 1 diabetes. J Autoimmun 44:40–48

    Article  CAS  PubMed  Google Scholar 

  68. van de Ven AA, Hoytema van Konijnenburg DP, Wensing AM, van Montfrans JM (2012) The role of prolonged viral gastrointestinal infections in the development of immunodeficiency-related enteropathy. Clin Rev Allergy Immunol 42:79–91

    Article  PubMed  Google Scholar 

  69. Singh AK, Mahlios J, Mignot E (2013) Genetic association, seasonal infections and autoimmune basis of narcolepsy. J Autoimmun 43:26–31

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. An J, Nakajima T, Shibata H, Arimura T, Yasunami M, Kimura A (2013) A novel link of HLA locus to the regulation of immunity and infection: NFKBIL1 regulates alternative splicing of human immune-related genes and influenza virus M gene. J Autoimmun 47:25–33

    Article  CAS  PubMed  Google Scholar 

  71. Bartoloni E, Alunno A, Bistoni O, Gerli R (2013) Cardiovascular risk in rheumatoid arthritis and systemic autoimmune rheumatic disorders: a suggested model of preventive strategy. Clin Rev Allergy Immunol 44:14–22

    Article  CAS  PubMed  Google Scholar 

  72. Maverakis E, Goodarzi H, Wehrli LN, Ono Y, Garcia MS (2012) The etiology of paraneoplastic autoimmunity. Clin Rev Allergy Immunol 42:135–144

    Article  CAS  PubMed  Google Scholar 

  73. Van Belle TL, Ling E, Haase C, Bresson D, Urso B, von Herrath MG (2013) NKG2D blockade facilitates diabetes prevention by antigen-specific Tregs in a virus-induced model of diabetes. J Autoimmun 40:66–73

    Article  PubMed  Google Scholar 

  74. Ito K, Baudino L, Kihara M et al (2013) Three Sgp loci act independently as well as synergistically to elevate the expression of specific endogenous retroviruses implicated in murine lupus. J Autoimmun 43:10–17

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Hintermann E, Ehser J, Bayer M, Pfeilschifter JM, Christen U (2013) Mechanism of autoimmune hepatic fibrogenesis induced by an adenovirus encoding the human liver autoantigen cytochrome P450 2D6. J Autoimmun 44:49–60

    Article  CAS  PubMed  Google Scholar 

  76. Freeman ML, Burkum CE, Lanzer KG et al (2013) Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice. J Autoimmun 42:71–79

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Borchers AT, Chang C, Gershwin ME, Gershwin LJ (2013) Respiratory syncytial virus—a comprehensive review. Clin Rev Allergy Immunol 45:331–379

    Article  CAS  PubMed  Google Scholar 

  78. Lidar M, Lipschitz N, Agmon-Levin N et al (2012) Infectious serologies and autoantibodies in hepatitis C and autoimmune disease-associated mixed cryoglobulinemia. Clin Rev Allergy Immunol 42:238–246

    Article  CAS  PubMed  Google Scholar 

  79. Agmon-Levin N, Ram M, Barzilai O et al (2009) Prevalence of hepatitis C serum antibody in autoimmune diseases. J Autoimmun 32:261–266

    Article  CAS  PubMed  Google Scholar 

  80. Stubgen JP (2013) A literature review on optic neuritis following vaccination against virus infections. Autoimmun Rev 12:990–997

    Article  CAS  PubMed  Google Scholar 

  81. Shinsuke N, Hiroshi I (2013) Overexpression of Epstein-Barr virus-induced gene 3 protein (EBI3) in MRL/lpr mice suppresses their lupus nephritis by activating regulatory T cells. Autoimmunity 46:446–454

    Article  CAS  PubMed  Google Scholar 

  82. Baldovino S, Montin D, Martino S, Sciascia S, Menegatti E, Roccatello D (2013) Common variable immunodeficiency: crossroads between infections, inflammation and autoimmunity. Autoimmun Rev 12:796–801

    Article  CAS  PubMed  Google Scholar 

  83. Selmi C, Crotti C, Meroni PL (2013) Less travelled roads in clinical immunology and allergy: drug reactions and the environmental influence. Clin Rev Allergy Immunol 45:1–5

    Article  CAS  PubMed  Google Scholar 

  84. Selmi C (2012) Cutting-edge issues in autoimmunity and allergy of the digestive system. Clin Rev Allergy Immunol 42:265–268

    Article  CAS  PubMed  Google Scholar 

  85. Leung NY, Wai CY, Shu S et al (2014) Current immunological and molecular biological perspectives on seafood allergy: a comprehensive review. Clin Rev Allergy Immunol 46:180–197

    Article  CAS  PubMed  Google Scholar 

  86. Katz Y, Gutierrez-Castrellon P, Gonzalez MG, Rivas R, Lee BW, Alarcon P (2014) A comprehensive review of sensitization and allergy to soy-based products. Clin Rev Allergy Immunol 46:272–281

    Article  CAS  PubMed  Google Scholar 

  87. Hajeb P, Selamat J (2012) A contemporary review of seafood allergy. Clin Rev Allergy Immunol 42:365–385

    Article  CAS  PubMed  Google Scholar 

  88. Chang C, Mahmood MM, Teuber SS, Gershwin ME (2012) Overview of penicillin allergy. Clin Rev Allergy Immunol 43:84–97

    Article  CAS  PubMed  Google Scholar 

  89. Chang C, Gershwin ME (2013) Integrative medicine in allergy and immunology. Clin Rev Allergy Immunol 44:208–228

    Article  CAS  PubMed  Google Scholar 

  90. Tanaka A, Takikawa H (2013) Geoepidemiology of primary sclerosing cholangitis: a critical review. J Autoimmun 46:35–40

    Article  CAS  PubMed  Google Scholar 

  91. Zisimopoulou P, Evangelakou P, Tzartos J et al (2013) A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis. J Autoimmun 52:139–45. doi:10.1016/j.jaut.2013.12.004

  92. Sinico RA, Di Toma L, Radice A (2013) Renal involvement in anti-neutrophil cytoplasmic autoantibody associated vasculitis. Autoimmun Rev 12:477–482

    Article  CAS  PubMed  Google Scholar 

  93. Sivamani RK, Goodarzi H, Garcia MS et al (2013) Biologic therapies in the treatment of psoriasis: a comprehensive evidence-based basic science and clinical review and a practical guide to tuberculosis monitoring. Clin Rev Allergy Immunol 44:121–140

    Article  CAS  PubMed  Google Scholar 

  94. Kurko J, Besenyei T, Laki J, Glant TT, Mikecz K, Szekanecz Z (2013) Genetics of rheumatoid arthritis—a comprehensive review. Clin Rev Allergy Immunol 45:170–179

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  95. Mells GF, Kaser A, Karlsen TH (2013) Novel insights into autoimmune liver diseases provided by genome-wide association studies. J Autoimmun 46:41–54

    Article  CAS  PubMed  Google Scholar 

  96. Oaks Z, Perl A (2013) Metabolic control of the epigenome in systemic Lupus erythematosus. Autoimmunity 47(4):256–64. doi:10.3109/08916934.2013.834495

  97. Zhang P, Zhao M, Liang G et al (2013) Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris. J Autoimmun 41:17–24

    Article  PubMed  Google Scholar 

  98. Selmi C, Lu Q, Humble MC (2012) Heritability versus the role of the environment in autoimmunity. J Autoimmun 39:249–252

    Article  PubMed  Google Scholar 

  99. Miller FW, Pollard KM, Parks CG et al (2012) Criteria for environmentally associated autoimmune diseases. J Autoimmun 39:253–258

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  100. Germolec D, Kono DH, Pfau JC, Pollard KM (2012) Animal models used to examine the role of the environment in the development of autoimmune disease: findings from an NIEHS Expert Panel Workshop. J Autoimmun 39:285–293

    Article  PubMed Central  PubMed  Google Scholar 

  101. Miller FW, Alfredsson L, Costenbader KH et al (2012) Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop. J Autoimmun 39:259–271

    Article  PubMed Central  PubMed  Google Scholar 

  102. Leung PS, Wang J, Naiyanetr P et al (2013) Environment and primary biliary cirrhosis: electrophilic drugs and the induction of AMA. J Autoimmun 41:79–86

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  103. Smyk D, Rigopoulou EI, Baum H, Burroughs AK, Vergani D, Bogdanos DP (2012) Autoimmunity and environment: am I at risk? Clin Rev Allergy Immunol 42:199–212

    Article  CAS  PubMed  Google Scholar 

  104. Selmi C, Invernizzi P, Zuin M, Podda M, Gershwin ME (2005) Genetics and geoepidemiology of primary biliary cirrhosis: following the footprints to disease etiology. Semin Liver Dis 25:265–280

    Article  PubMed  Google Scholar 

  105. Selmi C, Tsuneyama K (2010) Nutrition, geoepidemiology, and autoimmunity. Autoimmun Rev 9:A267–270

    Article  CAS  PubMed  Google Scholar 

  106. Salunga TL, Cui ZG, Shimoda S et al (2007) Oxidative stress-induced apoptosis of bile duct cells in primary biliary cirrhosis. J Autoimmun 29:78–86

    Article  CAS  PubMed  Google Scholar 

  107. de la Rica L, Urquiza JM, Gomez-Cabrero D et al (2013) Identification of novel markers in rheumatoid arthritis through integrated analysis of DNA methylation and microRNA expression. J Autoimmun 41:6–16

    Article  PubMed  Google Scholar 

  108. Ando Y, Yang GX, Kenny TP et al (2013) Overexpression of microRNA-21 is associated with elevated pro-inflammatory cytokines in dominant-negative TGF-beta receptor type II mouse. J Autoimmun 41:111–119

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Centro Hospitalar São João, 4200-319, Porto, Portugal

    Carlos Dias

  2. Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, Davis, CA, USA

    Carlo Selmi

  3. Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, University of Milan, via A. Manzoni 56, 20089, Rozzano, Milan, Italy

    Carlo Selmi

Authors
  1. Carlos Dias
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlo Selmi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Carlos Dias or Carlo Selmi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dias, C., Selmi, C. The Challenge of Treating Orphan Disease. Clinic Rev Allerg Immunol 47, 259–263 (2014). https://doi.org/10.1007/s12016-014-8462-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-014-8462-7

Keywords

Search

Navigation