Cutting edge: issues in autoimmunity

Cutting edge: issues in autoimmunity

Guest Editors: Prof Yehuda Shoenfeld and Dr Nancy Agmon-Levin

Collection published: 4 April 2013

Last updated: 1 May 2013

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.

If you would like your work to be considered as part of this article collection, you can send a pre-submission query tobmcmedicineeditorial@biomedcentral.com.

	Question and Answer    Video Q&A: what is ASIA? An interview with Yehuda Shoenfeld Yehuda ShoenfeldBMC Medicine 2013, 11:118 (1 May 2013) Abstract | Full text | PDF | PubMed| Editor’s summary
	Research article     Slow CCL2-dependent translocation of biopersistent particles from muscle to brain 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, Josette CadusseauBMC Medicine 2013, 11:99 (4 April 2013) Abstract | Full text | PDF | PubMed | Cited on BioMed Central| Editor’s summary
	Research article    Anti-ribosomal P protein IgG autoantibodies in patients with systemic lupus erythematosus: diagnostic performance and clinical profile Diana Carmona-Fernandes, Maria Santos, Helena Canhão, João FonsecaBMC Medicine 2013, 11:98 (4 April 2013) Abstract | Full text | PDF | PubMed | Cited on BioMed Central| Editor’s summary
	Research article    Associations between selected immune-mediated diseases and tuberculosis: record-linkage studies Sreeram V Ramagopalan, Raph Goldacre, Andrew Skingsley, Chris Conlon, Michael J GoldacreBMC Medicine 2013, 11:97 (4 April 2013) Abstract | Full text | PDF | PubMed | Cited on BioMed Central| Editor’s summary
	Review    Phosphodiesterase 4-targeted treatments for autoimmune diseases Neal Kumar, Ari M Goldminz, Noori Kim, Alice B GottliebBMC Medicine 2013, 11:96 (4 April 2013) Abstract | Full text | PDF | PubMed| Editor’s summary
	Review    Renal involvement in autoimmune connective tissue diseases Andreas Kronbichler, Gert MayerBMC Medicine 2013, 11:95 (4 April 2013) Abstract | Full text | PDF | PubMed | Cited on BioMed Central| Editor’s summary
	Commentary    Age-related autoimmunity Zahava Vadasz, Tharwat Haj, Aharon Kessel, Elias ToubiBMC Medicine 2013, 11:94 (4 April 2013) Abstract | Full text | PDF | PubMed | Cited on BioMed Central| Editor’s summary
	Review    Novel aspects of Sjögren’s syndrome in 2012 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, Yehuda ShoenfeldBMC Medicine 2013, 11:93 (4 April 2013) Abstract | Full text | PDF | PubMed | Cited on BioMed Central| Editor’s summary
	Research article    Coagulopathy triggered autoimmunity: experimental antiphospholipid syndrome in factor V Leiden mice Aviva Katzav, Nikolaos C Grigoriadis, Tania Ebert, Olga Touloumi, Miri Blank, Chaim G Pick, Yehuda Shoenfeld, Joab ChapmanBMC Medicine 2013, 11:92 (4 April 2013) Abstract | Full text | PDF | PubMed| Editor’s summary
	Commentary    Discoveries in the pathophysiology of neuropsychiatric lupus erythematosus: consequences for therapy Takahisa Gono, Yasushi Kawaguchi, Hisashi YamanakaBMC Medicine 2013, 11:91 (4 April 2013) Abstract | Full text | PDF | PubMed | Cited on BioMed Central| Editor’s summary
	Research article    16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus Shaye Kivity, Aviva Katzav, Maria Arango, Moran Landau-Rabi, Yaron Zafrir, Nancy Agmon-Levin, Miri Blank, Juan-Manuel Anaya, Edna Mozes, Joab Chapman, Yehuda ShoenfeldBMC Medicine 2013, 11:90 (4 April 2013) Abstract | Full text | PDF | PubMed | Cited on BioMed Central | F1000 Biology| Editor’s summary
	Research article    The thrombophilic network of autoantibodies in celiac disease Aaron Lerner, Nancy Agmon-Levin, Yinon Shapira, Boris Gilburd, Sandra Reuter, Idit Lavi, Yehuda ShoenfeldBMC Medicine 2013, 11:89 (4 April 2013) Abstract | Full text | PDF | PubMed | Cited on BioMed Central| Editor’s summary
	Review    Biologic therapy for autoimmune diseases: an update Ziv Rosman, Yehuda Shoenfeld, Gisele Zandman-GoddardBMC Medicine 2013, 11:88 (4 April 2013) Abstract | Full text | PDF | PubMed | Cited on BioMed Central| Editor’s summary
	Editorial    Novel pebbles in the mosaic of autoimmunity Carlo Perricone, Nancy Agmon-Levin, Yehuda ShoenfeldBMC Medicine 2013, 11:101 (4 April 2013) Abstract | Full text | PDF | PubMed| Editor’s summary
	Review    Requirements for innate immune pathways in environmentally induced autoimmunity Kenneth Pollard, Dwight H KonoBMC Medicine 2013, 11:100 (4 April 2013) Abstract | Full text | PDF | PubMed | Cited on BioMed Central| Editor’s summary
	Research article     How do autoimmune diseases cluster in families? A systematic review and meta-analysis Jorge Cardenas-Roldan, Adriana Rojas-Villarraga, Juan-Manuel AnayaBMC Medicine 2013, 11:73 (18 March 2013) Abstract | Provisional PDF | PubMed | Cited on BioMed Central| Editor’s summary
	Research article     Month of birth, vitamin D and risk of immune-mediated disease: a case control study Giulio Disanto, George Chaplin, Julia M Morahan, Gavin Giovannoni, Elina Hyppönen, George C Ebers, Sreeram V RamagopalanBMC Medicine 2012, 10:69 (6 July 2012) Abstract | Full text | PDF | PubMed | Cited on BioMed Central | 1 comment| Editor’s summary

Research

Open-label parallel dose tolerability study of three subcutaneous immunotherapy regimens in house dust mite allergic patients

Juliane Rieker-Schwienbacher, Marja J Nell, Zuzana Diamant, Ronald van Ree, Andreas Distler, Johan D Boot and Jörg Kleine-Tebbe

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Clinical and Translational Allergy 2013, 3:16 doi:10.1186/2045-7022-3-16

Published: 8 May 2013

Abstract (provisional)

Background

The current maintenance dose (10,000 AUeq/monthly) of a subcutaneous allergoid for house dust mite (HDM) immunotherapy has previously shown significant clinical efficacy in patients with HDM induced allergic rhinitis or rhinoconjunctivitis. In order to comply with the 2009 EMA guidelines on immunotherapy products, a study was conducted to evaluate the safety, tolerability and short-term treatment effects of up-dosing regimens with high doses (up to 40,000 AUeq) of allergoid HDM immunotherapy.

Methods

In total 48 patients with HDM-allergic rhinitis or rhinoconjunctivitis (29 M/19 F; 18--53 years) were included and enrolled into one of three up-dosing regimens (1:4:4): 1) a regular regimen with up-dosing to 40,000 AUeq followed by two maintenance doses (total duration 17 weeks), 2) an intermediate regimen (14 weeks) or 3) a fast regimen (11 weeks). Safety and tolerability were evaluated by monitoring of early and late local reactions and systemic reactions. In addition, short-term effects were assessed by conjunctival provocation test (CPT) and levels of serum allergen-specific IgE, IgG and IgG4.

Results

Thirty-nine patients completed the study according to protocol. No early local reactions occurred. Late local reactions (LLR) were observed in 12% of the injections. In total, 31 systemic reactions, all grade 1, were reported of which two needed oral antihistamine treatment. No grade 2 or higher systemic reactions were observed. Six patients (15%) did not reach the highest dose due to LLR and/or systemic reactions needing antihistamines (20% in the regular regimen, 16% in the intermediate regimen and 13% in the fast regimen). At the end of the study, an improvement in the CPT was observed in 82.1% of patients, indirectly indicating an early treatment effect at the current dose and higher doses. In addition, IgG4 immunoglobulin levels were significantly increased in all groups following treatment.

Conclusions

In this open-label study, allergoid HDM immunotherapy in doses up to 40,000 AUeq was generally well tolerated and no clinically relevant safety issues were identified. In the safety aspects of the three up-dosing regimens no clinically relevant differences were encountered. Therefore, these dose ranges and up-dosing regimens can be safely included in future dose- finding efficacy studies.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

• J Res Med Sci >
• v.17(6); Jun 2012 >
• PMC3634285

J Res Med Sci. 2012 June; 17(6): 508–512.

PMCID: PMC3634285

Association between allergic rhinitis and migraine

Alia Saberi, Shadman Nemati,¹ Reza Jafari Shakib,² Ehsan Kazemnejad,³ and Mohammadbagher Maleki⁴

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Abstract

Background:

Migraine and allergic rhinitis (AR) are two common causes of headache and facial pain that inflammatory mediators with vasoactive function play important roles in both of them. The aim of this research was to determine the prevalence of migraine in AR patients.

Materials and Methods:

In a cross-sectional comparative study performed from June to December 2010 in patients with AR sign and symptoms referred to ear, nose, throat (ENT) clinic of a university hospital in Iran-Rasht, 46 patients with positive skin prick test were compared with 60 subject without AR signs and symptoms and with negative skin test. In both the groups, history of migraine according to IHS (International Headache Society ) criteria were investigated. Analysis of data was performed by chi-sqaure and Fisher exact test by using SPSS16. Odds ratio were estimated for determining the chance of migraine in AR.

Results:

In case group (14 male, 37 female; mean age: 31.17 ± 8.31 years) and control group (23 male, 32 female; mean age: 37.58 ± 12.63 years), the prevalence of migraine was 37% and 5%, respectively. The differences in prevalence of migraine and migraine without aura between cases and controls were significant (P = 0.001). The chance of migraine in AR was 8.227 folds (95% CI: 2.38-28.42). In subjects older than 40 years old, the difference of prevalence of migraine was significant, contrary to subjects younger than 30 years old and between 30 and 39 years old.

Conclusions:

There is a correlation between migraine especially without aura and AR and this correlation is more powerful with increasing age.

Keywords: Allergic rhinitis, migraine, skin prick test test

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• Int J Gen Med >
• v.6; 2013 >
• PMC3636804

Int J Gen Med. 2013; 6: 253–265.

Published online 2013 April 17. doi:  10.2147/IJGM.S28156

PMCID: PMC3636804

Genetic polymorphisms and associated susceptibility to asthma

Michael E March,¹ Patrick MA Sleiman,¹ and Hakon Hakonarson^1,2

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Abstract

As complex common diseases, asthma and allergic diseases are caused by the interaction of multiple genetic variants with a variety of environmental factors. Candidate-gene studies have examined the involvement of a very large list of genes in asthma and allergy, demonstrating a role for more than 100 loci. These studies have elucidated several themes in the biology and pathogenesis of these diseases. A small number of genes have been associated with asthma or allergy through traditional linkage analyses. The publication of the first asthma-focused genome-wide association (GWA) study in 2007 has been followed by nearly 30 reports of GWA studies targeting asthma, allergy, or associated phenotypes and quantitative traits. GWA studies have confirmed several candidate genes and have identified new, unsuspected, and occasionally uncharacterized genes as asthma susceptibility loci. Issues of results replication persist, complicating interpretation and making conclusions difficult to draw, and much of the heritability of these diseases remains undiscovered. In the coming years studies of complex diseases like asthma and allergy will probably involve the use of high-throughput next-generation sequencing, which will bring a tremendous influx of new information as well as new problems in dealing with vast datasets.

Keywords: genome-wide association study, high-throughput next-generation sequencing, allergy, environmental irritant, allergen

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