Journal of autoimmunity
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Journal of autoimmunity · Nov 2014
ReviewNovel approaches to the development of targeted therapeutic agents for systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a chronic multisystem disease in which various cell types and immunological pathways are dysregulated. Current therapies for SLE are based mainly on the use of non-specific immunosuppressive drugs that cause serious side effects. There is, therefore, an unmet need for novel therapeutic means with improved efficacy and lower toxicity. ⋯ Two of the peptides (P140 and hCDR1) were tested in clinical trials and were reported to be safe and well tolerated. Thus, synthetic peptides are attractive potential means for the specific treatment of lupus patients. In this review we discuss the various biological treatments that have been developed for lupus with a special focus on the tolerogenic peptides.
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Journal of autoimmunity · Aug 2014
ReviewMyasthenia Gravis: paradox versus paradigm in autoimmunity.
Myasthenia Gravis (MG) is a paradigm of organ-specific autoimmune disease (AID). It is mediated by antibodies that target the neuromuscular junction. The purpose of this review is to place MG in the general context of autoimmunity, to summarize the common mechanisms between MG and other AIDs, and to describe the specific mechanisms of MG. ⋯ The implication of AIRE, a key factor in central tolerance is also discussed. Finally, if MG is a prototype of AIDS, it has a clear specificity compared to the other AIDS, by the fact that the target organ, the muscle, is not the site of immune infiltration and B cell expansion, but exclusively that of antibody-mediated pathogenic mechanisms. By contrast, the thymus in the early onset subtype frequently undergoes tissue remodeling, resulting in the development of ectopic germinal centers surrounded by high endothelial venules (HEV), as observed in the target organs of many other AIDs.
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Journal of autoimmunity · May 2014
ReviewNarcolepsy, 2009 A(H1N1) pandemic influenza, and pandemic influenza vaccinations: what is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants.
The vaccine safety surveillance system effectively detected a very rare adverse event, narcolepsy, in subjects receiving AS03-adjuvanted A(H1N1) pandemic vaccine made using the European inactivation/purification protocol. The reports of increased cases of narcolepsy in non-vaccinated subjects infected with wild A(H1N1) pandemic influenza virus suggest a role for the viral antigen(s) in disease development. However, additional investigations are needed to better understand what factor(s) in wild influenza infection trigger(s) narcolepsy in susceptible hosts. ⋯ This review article provides a brief background on narcolepsy, outlines the different types of vaccine preparations including the ones for influenza, reviews the accumulated evidence for the safety of adjuvants, and explores the association between autoimmune diseases and natural infections. It concludes by assimilating the historical observations and recent clinical studies to formulate a feasible hypothesis on why vaccine-associated narcolepsy may not be solely linked to the AS03 adjuvant but more likely be linked to how the specific influenza antigen component of the European AS03-adjuvanted pandemic vaccine was prepared. Careful and long-term epidemiological studies of subjects who developed narcolepsy in association with AS03-adjuvanted A(H1N1) pandemic vaccine prepared with the European inactivation/purification protocol are needed.
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Journal of autoimmunity · May 2014
A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the Pandemrix vaccination campaign in Sweden 2009-2010.
Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). ⋯ In conclusion, following the 2009 influenza pandemic vaccination, A/H1N1 antibody levels were associated with young age-at-onset narcolepsy patients positive for HLA-DQB1*06:02. The possibility that TRIB2 is an autoantigen in narcolepsy remains to be clarified. We could verify autoantibody responses against TRIB2 which needs to be determined in larger patient cohorts and control populations.
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Journal of autoimmunity · Feb 2014
ReviewThe classification and diagnostic criteria of ankylosing spondylitis.
Ankylosing spondylitis is the prototype of immune-mediated inflammatory rheumatic diseases grouped under the term spondyloarthritis (SpA). An early diagnosis has now become increasingly important because effective therapies are available and anti-TNF drugs are even more effective if used in early stages of the disease. In ankylosing spondylitis, the 1984 modified New York criteria have been used widely in clinical studies and daily practice but are not applicable in early disease when the characteristic radiographic signs of sacroiliitis are not visible but active sacroiliitis is readily detectable by magnetic resonance imaging (MRI). ⋯ New classification criteria for the wider group of SpA have been proposed by ASAS (Assessment of Spondylo Arthritis International Society); and the patients are sub-grouped into (1) a predominantly axial disease, termed axial SpA including AS and non-radiographic axial SpA; (2) peripheral SpA. The clinical course and disease process of non-radiographic axial spondyloarthritis remains unclear. However the development of the SpA criteria by ASAS particularly for axial SpA, is an important step for early diagnosis and better management of these patients.