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Cutting edge: issues in autoimmunity

During the last three decades a significant increase in the prevalence of autoimmune diseases was noted. More diseases apparently thought to be either genetically or environmentally induced were found to have an autoimmune origin - for example narcolepsy, depression, duodenal ulcer, etc. However, not all the autoimmune diseases fulfill Noel Rose's criteria (Shoenfeld Y, Cervera R, Gershwin M.E. Diagnostic Criteria in Autoimmune Diseases. Humana Press, Springer Science + Business Media, LLC, USA. pp 1-593, 2008). In some of the diseases, indirect criteria allude to their autoimmune etiology, i.e. the co-appearance with other autoimmune diseases, specific HLA common to autoimmunity, presence of autoantibodies, etc. The fact that narcolepsy could be induced by autoantibodies extracted from patients to mice, fulfilled N. Rose's criteria, and therefore helped to classify narcolepsy as a classical autoimmune disease. Analyzing the mechanisms by which autoimmune disease is induced, leads to a better therapies than just immunosuppression or corticosteroids. Hence the role of the new biologics, where each type is aimed in counteracting a key point in the autoinflammatory process. Unfortunately, not all the etiologies of autoimmune diseases have been revealed. Moreover there are some autoimmune diseases such as systemic sclerosis in which the pathogenetic mechanisms have not been deciphered, and therefore these conditions are still devastating and require extensive research. The aim of this article collection is to review some of the forefront issues in autoimmunity and which may lead to better diagnosis and therapies in the future.

  1. Commentary

    Is atherosclerosis an autoimmune disease?

    Immunologic research into pathogenic mechanisms operating in autoimmune-mediated atherosclerosis initially focused on adaptive immunity. Current interest is directed to more basic inflammatory mechanisms. Chro...

    Eiji Matsuura, Fabiola Atzeni, Piercarlo Sarzi-Puttini, Maurizio Turiel, Luis R Lopez and Michael T Nurmohamed

    BMC Medicine 2014 12:47

    Published on: 18 March 2014

  2. Commentary

    Biologics, cardiovascular effects and cancer

    Rheumatoid arthritis (RA) is associated with increased cardiovascular risk. Treatment with tumor necrosis factor (TNF)-inhibitors leads to about a 50% reduction in the first cardiovascular event. TNF-inhibitor...

    Nemanja Damjanov, Michael T Nurmohamed and Zoltán Szekanecz

    BMC Medicine 2014 12:48

    Published on: 18 March 2014

  3. Commentary

    Epigenetics in the pathogenesis of rheumatoid arthritis

    An increasing number of studies show that besides the inherited genetic architecture (that is, genomic DNA), various environmental factors significantly contribute to the etiology of rheumatoid arthritis. Epig...

    Tibor T Glant, Katalin Mikecz and Tibor A Rauch

    BMC Medicine 2014 12:35

    Published on: 26 February 2014

  4. Research article

    Autoantibodies against MHC class I polypeptide-related sequence A are associated with increased risk of concomitant autoimmune diseases in celiac patients

    Overexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases. MHC class I polypeptide-related sequence A (MICA) is highly expressed in the enterocytes of patients w...

    Antonio López-Vázquez, Lourdes Mozo, Rebeca Alonso-Arias, Beatriz Suárez-Álvarez, José Ramón Vidal-Castiñeira, Eduardo Arranz, Umberto Volta, Carlos Bousoño, Marcos López-Hoyos, Luís Rodrigo and Carlos López-Larrea

    BMC Medicine 2014 12:34

    Published on: 25 February 2014

  5. Commentary

    In-/off-label use of biologic therapy in systemic lupus erythematosus

    Current therapies for systemic lupus erythematosus (SLE) include corticosteroids as a persistent mainstay and traditional immunosuppressants which are given according to disease severity, organ involvement and...

    Mariele Gatto, Emese Kiss, Yaakov Naparstek and Andrea Doria

    BMC Medicine 2014 12:30

    Published on: 17 February 2014

  6. Commentary

    Early start and stop of biologics: has the time come?

    Despite considerable advances in the management of rheumatoid arthritis, results are still not satisfactory for all patients. The treatment goal in rheumatoid arthritis is remission, and there currently are nu...

    Ronald F van Vollenhoven, György Nagy and Paul P Tak

    BMC Medicine 2014 12:25

    Published on: 6 February 2014

  7. Minireview

    What is next after the genes for autoimmunity?

    Clinical pathologies draw us to envisage disease as either an independent entity or a diverse set of traits governed by common physiopathological mechanisms, prompted by environmental assaults throughout life....

    John Castiblanco, Mauricio Arcos-Burgos and Juan-Manuel Anaya

    BMC Medicine 2013 11:197

    Published on: 4 September 2013

  8. Opinion

    The Hyperferritinemic Syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome

    Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical con...

    Cristina Rosário, Gisele Zandman-Goddard, Esther G Meyron-Holtz, David P D’Cruz and Yehuda Shoenfeld

    BMC Medicine 2013 11:185

    Published on: 22 August 2013

  9. Research article

    Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

    Vitamin D insufficiency has been implicated in autoimmunity. ChIP-seq experiments using immune cell lines have shown that vitamin D receptor (VDR) binding sites are enriched near regions of the genome associat...

    Adam E Handel, Geir K Sandve, Giulio Disanto, Antonio J Berlanga-Taylor, Giuseppe Gallone, Heather Hanwell, Finn Drabløs, Gavin Giovannoni, George C Ebers and Sreeram V Ramagopalan

    BMC Medicine 2013 11:163

    Published on: 12 July 2013

  10. Editorial

    Novel pebbles in the mosaic of autoimmunity

    Almost 25 years ago, the concept of the ‘mosaic of autoimmunity’ was introduced to the scientific community, and since then this concept has continuously evolved, with new pebbles being added regularly. We are...

    Carlo Perricone, Nancy Agmon-Levin and Yehuda Shoenfeld

    BMC Medicine 2013 11:101

    Published on: 4 April 2013

  11. Commentary

    Age-related autoimmunity

    Older persons have higher autoimmunity but a lower prevalence of autoimmune diseases. A possible explanation for this is the expansion of many protective regulatory mechanisms highly characteristic in the elde...

    Zahava Vadasz, Tharwat Haj, Aharon Kessel and Elias Toubi

    BMC Medicine 2013 11:94

    Published on: 4 April 2013

  12. Research article

    Anti-ribosomal P protein IgG autoantibodies in patients with systemic lupus erythematosus: diagnostic performance and clinical profile

    This study was devised to assess the performance of anti-ribosomal P (anti-Rib-P) antibodies in the diagnosis of systemic lupus erythematosus (SLE) and the association of these antibodies with the clinical fea...

    Diana Carmona-Fernandes, Maria José Santos, Helena Canhão and João Eurico Fonseca

    BMC Medicine 2013 11:98

    Published on: 4 April 2013

  13. Research article

    The thrombophilic network of autoantibodies in celiac disease

    Celiac disease is a life-long autoimmune condition, affecting genetically susceptible individuals that may present with thromboembolic phenomena. This thrombophilia represents a puzzle with multiple constituen...

    Aaron Lerner, Nancy Agmon-Levin, Yinon Shapira, Boris Gilburd, Sandra Reuter, Idit Lavi and Yehuda Shoenfeld

    BMC Medicine 2013 11:89

    Published on: 4 April 2013

  14. Research article

    16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus

    The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in naïve mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as wel...

    Shaye Kivity, Aviva Katzav, Maria Teresa Arango, Moran Landau-Rabi, Yaron Zafrir, Nancy Agmon-Levin, Miri Blank, Juan-Manuel Anaya, Edna Mozes, Joab Chapman and Yehuda Shoenfeld

    BMC Medicine 2013 11:90

    Published on: 4 April 2013

  15. Review

    Biologic therapy for autoimmune diseases: an update

    Biologic therapies for rheumatologic diseases, which are targeted at molecules involved in the mechanisms of the immune system, provide an alternative to the existing treatment methods of disease-modifying ant...

    Ziv Rosman, Yehuda Shoenfeld and Gisele Zandman-Goddard

    BMC Medicine 2013 11:88

    Published on: 4 April 2013

  16. Research article

    Coagulopathy triggered autoimmunity: experimental antiphospholipid syndrome in factor V Leiden mice

    We investigated interactions between genetically and autoimmune-mediated coagulopathies by inducing experimental antiphospholipid syndrome (eAPS) in mice carrying the factor V Leiden (FVL) mutation.

    Aviva Katzav, Nikolaos C Grigoriadis, Tania Ebert, Olga Touloumi, Miri Blank, Chaim G Pick, Yehuda Shoenfeld and Joab Chapman

    BMC Medicine 2013 11:92

    Published on: 4 April 2013

  17. Review

    Phosphodiesterase 4-targeted treatments for autoimmune diseases

    Advancements in phosphodiesterase (PDE)-targeted therapies have shown promise in recent years for treating patients with a variety of autoimmune diseases. This review summarizes the development of PDE4 inhibit...

    Neal Kumar, Ari M Goldminz, Noori Kim and Alice B Gottlieb

    BMC Medicine 2013 11:96

    Published on: 4 April 2013

  18. Review

    Renal involvement in autoimmune connective tissue diseases

    Connective tissue diseases (CTDs) are a heterogeneous group of disorders that share certain clinical presentations and a disturbed immunoregulation, leading to autoantibody production. Subclinical or overt ren...

    Andreas Kronbichler and Gert Mayer

    BMC Medicine 2013 11:95

    Published on: 4 April 2013

  19. Review

    Novel aspects of Sjögren’s syndrome in 2012

    Sjögren’s syndrome (SS) is a systemic progressive autoimmune disease characterized by a complex pathogenesis requiring a predisposing genetic background and involving immune cell activation and autoantibody pr...

    Angela Tincani, Laura Andreoli, Ilaria Cavazzana, Andrea Doria, Marta Favero, Maria-Giulia Fenini, Franco Franceschini, Andrea Lojacono, Giuseppe Nascimbeni, Amerigo Santoro, Francesco Semeraro, Paola Toniati and Yehuda Shoenfeld

    BMC Medicine 2013 11:93

    Published on: 4 April 2013

  20. Research article

    Slow CCL2-dependent translocation of biopersistent particles from muscle to brain

    Long-term biodistribution of nanomaterials used in medicine is largely unknown. This is the case for alum, the most widely used vaccine adjuvant, which is a nanocrystalline compound spontaneously forming micro...

    Zakir Khan, Christophe Combadière, François-Jérôme Authier, Valérie Itier, François Lux, Christopher Exley, Meriem Mahrouf-Yorgov, Xavier Decrouy, Philippe Moretto, Olivier Tillement, Romain K Gherardi and Josette Cadusseau

    BMC Medicine 2013 11:99

    Published on: 4 April 2013

  21. Research article

    Month of birth, vitamin D and risk of immune-mediated disease: a case control study

    A season of birth effect in immune-mediated diseases (ID) such as multiple sclerosis and type 1 diabetes has been consistently reported. We aimed to investigate whether season of birth influences the risk of r...

    Giulio Disanto, George Chaplin, Julia M Morahan, Gavin Giovannoni, Elina Hyppönen, George C Ebers and Sreeram V Ramagopalan

    BMC Medicine 2012 10:69

    Published on: 6 July 2012