http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Wed, 22 May 2013 11:04:10 +0000 http://www.hindawi.com/journals/ad/2013/593493/ Serum adrenal androgens (AAs), including androstenedione (Δ4A) and dehydroepiandrosterone sulfate (DHEAS), have been reported to be lower in female rheumatoid arthritis (RA) patients with early disease. Few data are available on hormonal status of women before the onset of clinical rheumatoid arthritis (pre-RA). A broad baseline panel of serum adrenal and sex steroids was compared in 36 female pre-RA to 144 matched cohort control (CN) subjects to determine differences in their mean values and in patterns of hormonal correlations. Study subjects having lower versus higher baseline serum cortisol levels than the total group's mean value were also analyzed separately to investigate differences in their hormonal levels and correlational patterns. In total subjects, mean (±SE) Δ4A level (nmol/L) was lower () in 28 pre-RA cases () versus 108 CN (). The significant () difference was restricted to 9 pre-RA versus 53 CN subjects having lower cortisol levels ( versus  nmol/L, resp.). In total subjects, no significant difference was found between study subjects in their bivariate correlations of the hormonal panel variables, unlike results found in the subgroups stratified by lower versus higher cortisol levels. A subgroup of pre-RA females may have relative adrenal cortical insufficiency, as reflected by lower Δ4A, especially observed among those subjects with lower cortisol levels. Alfonse T. Masi, Kevin B. Elmore, Azeem A. Rehman, Robert T. Chatterton, Ned J. Goertzen, and Jean C. Aldag Copyright © 2013 Alfonse T. Masi et al. All rights reserved. Sun, 19 May 2013 11:24:48 +0000 http://www.hindawi.com/journals/ad/2013/621417/ Kamal D. Moudgil, Stephen J. Thompson, Fabiana Geraci, Boel De Paepe, and Yehuda Shoenfeld Copyright © 2013 Kamal D. Moudgil et al. All rights reserved. Mon, 13 May 2013 18:26:46 +0000 http://www.hindawi.com/journals/ad/2013/728720/ We have tested serum samples from 24 patients with multifocal motor neuropathy (MMN) for reactivity to ganglioside GM1 and to Gal(β1–3)GalNAc-bearing glycoproteins isolated from human peripheral nerve and from Campylobacter jejuni (Cj) serotype O:19. IgM anti-GM1 antibodies were detected by ELISA in 11 patients (45.8%) with MMN and in only one subject (4%) from the control group. Western blots showed positive reactivity of sera from 6 patients (25%) with MMN to several Gal(β1–3)GalNAc-bearing glycoproteins from human peripheral nerve and from Cj O:19 isolates. Sera from three patients (12.5%) with MMN showed positively reactive bands with similar electrophoretic mobility in all isolates (60–62 kDa, 48–51 kDa, 42 kDa, and 38 kDa). All six patients showed positive reactivity to 48–52 kDa protein isolated from human peripheral nerve. Increased titer of IgG antibodies to 60–62 kDa protein isolated from Cj O:19 associated with Guillain-Barré syndrome was detected in three patients, and their serum showed also IgG positive reactivity to peripheral nerve antigen with the same electrophoretic mobility. One of these patients had a previous history of Cj infection which suggests the possibility that Cj may be also involved in the pathogenesis of MMN. Ljubica Suturkova, Katerina Brezovska, Ana Poceva-Panovska, Aleksandra Grozdanova, Sladjana Knežević Apostolski, and Ivana Basta Copyright © 2013 Ljubica Suturkova et al. All rights reserved. Thu, 14 Mar 2013 09:37:39 +0000 http://www.hindawi.com/journals/ad/2013/813256/ Heat shock proteins (HSPs) are important molecules required for ideal protein function. Extensive research on the functional properties of HSPs indicates that HSPs may be implicated in a wide range of physiological functions including immune function. In the immune system, HSPs are involved in cell proliferation, differentiation, cytokine release, and apoptosis. Therefore, the ability of the immune system, in particular immune cells, to function optimally and in unison with other physiological systems is in part dependent on signaling transduction processes, including bidirectional communication with HSPs. Regulatory T cells (Tregs) are important T cells with suppressive functions and impairments in their function have been associated with a number of autoimmune disorders. The purpose of this paper is to examine the relationship between HSPs and Tregs. The interrelationship between cells and proteins may be important in cellular functions necessary for cell survival and expansion during diseased state. E. W. Brenu, D. R. Staines, L. Tajouri, T. Huth, K. J. Ashton, and S. M. Marshall-Gradisnik Copyright © 2013 E. W. Brenu et al. All rights reserved. Tue, 05 Mar 2013 16:20:47 +0000 http://www.hindawi.com/journals/ad/2013/548064/ The present study investigated posttranslational reactions in the salivary glands of patients with Sjögren’s syndrome. We analysed the biopsies of primary Sjögren’s patients using immunohistochemistry and a tag-purified anticyclic citrullinated protein (CCP) antibody to detect citrullinated peptides, and the presence of peptidylarginine deiminase 2 (PAD2) was assessed simultaneously. The present work demonstrated the weak presence of the PAD2 enzyme in some normal salivary glands, although PAD2 expression was increased considerably in Sjögren’s patients. The presence of citrullinated proteins was also detected in the salivary tissues of Sjögren’s patients, which strongly supports the in situ posttranslational modification of proteins in this setting. Furthermore, the mutual expression of CCP and PAD2 suggests that this posttranslational modification is enzyme dependent. In conclusion, patients with Sjögren’s syndrome expressed the catalytic machinery to produce posttranslational reactions that may result in autoantigen triggering. Rafael Herrera-Esparza, Mayra Rodríguez-Rodríguez, María Elena Pérez-Pérez, Martha Adriana Badillo-Soto, Felipe Torres-del-Muro, Juan José Bollain-y-Goytia, Deyanira Pacheco-Tovar, and Esperanza Avalos-Díaz Copyright © 2013 Rafael Herrera-Esparza et al. All rights reserved. Sun, 24 Feb 2013 09:23:28 +0000 http://www.hindawi.com/journals/ad/2013/761046/ Background. The persistent presence of antiphospholipid antibodies (APA) may lead to the development of primary or secondary antiphospholipid syndrome. Although the genetic basis of APA has been suggested, the identity of the underlying genes is largely unknown. In this study, we have performed a genome-wide association study (GWAS) in an effort to identify susceptibility loci/genes for three main APA: anticardiolipin antibodies (ACL), lupus anticoagulant (LAC), and anti-β2 glycoprotein I antibodies (anti-β2GPI). Methods. DNA samples were genotyped using the Affymetrix 6.0 array containing 906,600 single-nucleotide polymorphisms (SNPs). Association of SNPs with the antibody status (positive/negative) was tested using logistic regression under the additive model. Results. We have identified a number of suggestive novel loci with . Although they do not meet the conservative threshold of genome-wide significance, many of the suggestive loci are potential candidates for the production of APA. We have replicated the previously reported associations of HLA genes and APOH with APA but these were not the top loci. Conclusions. We have identified a number of suggestive novel loci for APA that will stimulate follow-up studies in independent and larger samples to replicate our findings. M. Ilyas Kamboh, Xingbin Wang, Amy H. Kao, Michael M. Barmada, Ann Clarke, Rosalind Ramsey-Goldman, Susan Manzi, and F. Yesim Demirci Copyright © 2013 M. Ilyas Kamboh et al. All rights reserved. Tue, 05 Feb 2013 09:07:25 +0000 http://www.hindawi.com/journals/ad/2013/651497/ Neutrophils are the first line of defense of the immune system against infection. Among their weaponry, they have the ability to mix and extrude their DNA and bactericidal molecules creating NET-like structures in a unique type of cell death called NETosis. This process is important in order to control extracellular infections limiting collateral damage. Its aberrant function has been implicated in several human diseases including sepsis and autoimmune disease. The purpose of the present paper is to give a general introduction to this concept. Miguel Antonio Mesa and Gloria Vasquez Copyright © 2013 Miguel Antonio Mesa and Gloria Vasquez. All rights reserved. Tue, 08 Jan 2013 12:53:01 +0000 http://www.hindawi.com/journals/ad/2013/859145/ Inflammasomes are cytosolic sensors that detect pathogens and danger signals in the innate immune system. The NLRP3 inflammasome is currently the most fully characterized inflammasome and is known to detect a wide array of microbes and endogenous damage-associated molecules. Possible involvement of the NLRP3 inflammasome (or inflammasomes) in the development of multiple sclerosis (MS) was suggested in a number of studies. Recent studies showed that the NLRP3 inflammasome exacerbates experimental autoimmune encephalomyelitis (EAE), an animal model of MS, although EAE can also develop without the NLRP3 inflammasome. In this paper, we discuss the NLRP3 inflammasome in MS and EAE development. Makoto Inoue and Mari L. Shinohara Copyright © 2013 Makoto Inoue and Mari L. Shinohara. All rights reserved. Sun, 30 Dec 2012 14:32:41 +0000 http://www.hindawi.com/journals/ad/2012/160830/ Multiple Sclerosis is a multifactorial disease with several pathogenic mechanisms and pathways. Successful MS management and medical care requires early accurate diagnosis along with specific treatment protocols based upon multifunctional nanotechnology approach. This paper highlights advances in nanotechnology that have enabled the clinician to target the brain and CNS in patient with multiple sclerosis with nanoparticles having therapeutic and imaging components. The multipartite theranostic (thera(py) + (diag)nostics) approach puts forth strong implications for medical care and cure in MS. The current nanotheranostics utilize tamed drug vehicles and contain cargo, targeting ligands, and imaging labels for delivery to specific tissues, cells, or subcellular components. A brief overview of nonsurgical nanorepair advances as future perspective is also described. Considering the potential inflammatory triggers in MS pathogenesis, a multifunctional nanotechnology approach will be needed for the prognosis. Ajay Vikram Singh, Manish Khare, W. N. Gade, and Paolo Zamboni Copyright © 2012 Ajay Vikram Singh et al. All rights reserved. Sun, 30 Dec 2012 12:14:57 +0000 http://www.hindawi.com/journals/ad/2012/957802/ In a retrospective review of patients with acquired demyelinating disorders of the central nervous system, 133 patients (5.6%) whose diseases started in childhood, were selected from 2369 patients, who had medical records in the Neurology Department of Dokuz Eylul University. Out of 133, 98 had relapsing remitting multiple sclerosis, 21 had secondary progressive multiple sclerosis, 8 had clinically isolated syndrome, 3 had neuromyelitis optica, 2 had Marburg disease, and 1 had radiologically isolated syndrome. In 55 patients (41.3%), disease onset was before age 16. Polysymptomatic presentation (22.6%) was the most common initial feature. The EDSS scores ranged from 0 to 9 with a median of 2.0 () for 126 patients. MRI records of 111 patients were obtained. 97 patients had clinically definite multiple sclerosis. 11 MS patients (11.3%) did not initially present the diagnostic MRI features. All of the remaining multiple sclerosis patients fulfilled Barkhof-Tintore criteria (100%) and 88.7% fulfilled KIDMUS criteria. Cranial MRI of NMO patients was normal. Our findings demonstrate some important clinical and paraclinical features that can help the literature on acquired demyelinating disorders of childhood by utilizing data from Western Turkey. Derya Kaya, Egemen İdiman, and Serkan Özakbaş Copyright © 2012 Derya Kaya et al. All rights reserved. Thu, 20 Dec 2012 08:20:11 +0000 http://www.hindawi.com/journals/ad/2012/296214/ Senear-Usher syndrome or pemphigus erythematosus is a pathology that overlaps clinically and serologically with pemphigus foliaceus and lupus erythematosus. Skin biopsies of patients with pemphigus erythematosus reveal acantholysis and deposits of immunoglobulins in desmosomes, and they are positive in the lupus band test. In the present paper, we determined whether the autoantibodies associated with pemphigus erythematosus targeted a single antigen or multiple antigens as a result of the stimulation of independent B cell clones. Our present paper demonstrates that patients with pemphigus erythematosus produce both antiepithelial antibodies specific for desmoglein 1 and 3 and antinuclear antibodies specific for Ro, La, Sm, and double-stranded DNA antigens. After eluting specific anti-epithelial or anti-nuclear antibodies, which were recovered and tested using double-fluorescence assays, a lack of cross-reactivity was demonstrated between desmosomes and nuclear and cytoplasmic lupus antigens. This result suggests that autoantibodies in pemphigus erythematosus are directed against different antigens and that these autoantibodies are produced by independent clones. Given these clinical and serological data, we suggest that pemphigus erythematosus behaves as a multiple autoimmune disease. María Elena Pérez-Pérez, Esperanza Avalos-Díaz, and Rafael Herrera-Esparza Copyright © 2012 María Elena Pérez-Pérez et al. All rights reserved. Mon, 17 Dec 2012 12:36:30 +0000 http://www.hindawi.com/journals/ad/2012/617213/ Heat shock protein 70 (HSP70) has previously been described as a potent antitumour vaccine. The mechanism relied on the ability of tumour derived HSP70 to associate with antigenic peptides, which, when cross presented, elicited a T cell mediated antitumour response. Subsequently, HSP70 was incorrectly described as a potent adjuvant of innate immunity, and although mistakes in the experimental approaches were exposed and associated with endotoxin contamination in the recombinant HSP70 specimen, questions still remain regarding this matter. Here we review only publications that have cautiously addressed the endotoxin contamination problem in HSP70 in order to reveal the real immunological function of the protein. Accordingly, “endotoxin free” HSP70 stimulates macrophages and delivers antigenic peptides to APCs, which effectively prime T cells mediating an antitumour reaction. Conversely, HSP70 has potent anti-inflammatory functions as follows: regulating T cell responses, reducing stimulatory capacity of DCs, and inducing development of immunosuppressive regulatory T cells. These activities were further associated with the immune evasive mechanism of tumours and implicated in the modulation of immune reactivity in autoimmune diseases and transplant-related clinical conditions. Consequently, the role of HSP70 in immune regulation is newly emerging and contrary to what was previously anticipated. Pawel Stocki and Anne M. Dickinson Copyright © 2012 Pawel Stocki and Anne M. Dickinson. All rights reserved. Mon, 17 Dec 2012 11:57:39 +0000 http://www.hindawi.com/journals/ad/2012/357101/ Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper provides readers with an overview of the molecular and structural bases of integrin activation as well as rationale for using anti-alpha4 integrin therapy for multiple sclerosis and then chronicles the rise and fall of this treatment strategy using natalizumab, a humanized anti-alpha4 integrin. Eiji Kawamoto, Susumu Nakahashi, Takayuki Okamoto, Hiroshi Imai, and Motomu Shimaoka Copyright © 2012 Eiji Kawamoto et al. All rights reserved. Mon, 17 Dec 2012 09:24:19 +0000 http://www.hindawi.com/journals/ad/2012/836519/ Heat shock proteins (Hsp) play critical roles in the body’s self-defense under a variety of stresses, including heat shock, oxidative stress, radiation, and wounds, through the regulation of folding and functions of relevant cellular proteins. Exercise increases the levels of Hsp through elevated temperature, hormones, calcium fluxes, reactive oxygen species (ROS), or mechanical deformation of tissues. Isotonic contractions and endurance- type activities tend to increase Hsp60 and Hsp70. Eccentric muscle contractions lead to phosphorylation and translocation of Hsp25/27. Exercise-induced transient increases of Hsp inhibit the generation of inflammatory mediators and vascular inflammation. Metabolic disorders (hyperglycemia and dyslipidemia) are associated with type 1 diabetes (an autoimmune disease), type 2 diabetes (the common type of diabetes usually associated with obesity), and atherosclerotic cardiovascular disease. Metabolic disorders activate HSF/Hsp pathway, which was associated with oxidative stress, increased generation of inflammatory mediators, vascular inflammation, and cell injury. Knock down of heat shock factor-1 (HSF1) reduced the activation of key inflammatory mediators in vascular cells. Accumulating lines of evidence suggest that the activation of HSF/Hsp induced by exercise or metabolic disorders may play a dual role in inflammation. The benefits of exercise on inflammation and metabolism depend on the type, intensity, and duration of physical activity. Earl G. Noble and Garry X. Shen Copyright © 2012 Earl G. Noble and Garry X. Shen. All rights reserved. Wed, 12 Dec 2012 14:06:08 +0000 http://www.hindawi.com/journals/ad/2012/312817/ Autoimmune hepatitis (AIH) is a unique form of immune-mediated disease that attacks the liver through a variety of immune mechanisms. The outcomes of AIH are either acute liver disease, which can be fatal, or, more commonly, chronic progressive liver disease, which can lead to decompensated liver cirrhosis if left untreated. AIH has characteristic immunological, and pathological, features that are important for the establishment of the diagnosis. More importantly, most patients with AIH have a favorable response to treatment with prednisolone and azathioprine, although some patients with refractory AIH or more aggressive disease require more potent immune-suppressant agents, such as cyclosporine or Mycophenolate Mofetil. In this paper, we discuss the immunological, pathological and clinical features of AIH, as well as the standard and alternative treatments for AIH. Hind I. Fallatah and Hisham O. Akbar Copyright © 2012 Hind I. Fallatah and Hisham O. Akbar. All rights reserved. Tue, 11 Dec 2012 15:22:13 +0000 http://www.hindawi.com/journals/ad/2012/502813/ Heat shock proteins (HSPs) are a highly conserved group of proteins that are constitutively expressed and function as molecular chaperones, aiding in protein folding and preventing the accumulation of misfolded proteins. In the arterial wall, HSPs have a protective role under normal physiologic conditions. In disease states, however, HSPs expressed on the vascular endothelial cell surface can act as targets for detrimental autoimmunity due to their highly conserved sequences. Developing therapeutic strategies for atherosclerosis based on HSPs is challenged by the need to balance such physiologic and pathologic roles of these proteins. This paper summarizes the role of HSPs in normal vascular wall processes as well as in the development and progression of atherosclerosis. The potential implications of HSPs in clinical therapies for atherosclerosis are also discussed. Arman Kilic and Kaushik Mandal Copyright © 2012 Arman Kilic and Kaushik Mandal. All rights reserved. Tue, 11 Dec 2012 11:25:05 +0000 http://www.hindawi.com/journals/ad/2012/683212/ Simone Appenzeller, Yehuda Shoenfeld, and Jozélio Freire de Carvalho Copyright © 2012 Simone Appenzeller et al. All rights reserved. Tue, 11 Dec 2012 11:07:34 +0000 http://www.hindawi.com/journals/ad/2012/841085/ Aims. The aim of the study was to describe and compare (1) the types and prevalence of complementary and alternative medicine (CAM) treatments used among individuals with multiple sclerosis (MS) in the Nordic countries; (2) the types of conventional treatments besides disease-modifying medicine for MS that were used in combination with CAM treatments; (3) the types of symptoms/health issues addressed by use of CAM treatments. Methods. An internet-based questionnaire was used to collect data from 6455 members of the five Nordic MS societies. The response rates varied from 50.9% in Norway to 61.5% in Iceland. Results. A large range of CAM treatments were reported to be in use in all five Nordic countries. Supplements of vitamins and minerals, supplements of oils, special diet, acupuncture, and herbal medicine were among the CAM treatment modalities most commonly used. The prevalence of the overall use of CAM treatments within the last twelve months varied from 46.0% in Sweden to 58.9% in Iceland. CAM treatments were most often used in combination with conventional treatments. The conventional treatments that were most often combined with CAM treatment were prescription medication, physical therapy, and over-the-counter (OTC) medications. The proportion of CAM users who reported exclusive use of CAM (defined as use of no conventional treatments besides disease-modifying medicine for MS) varied from 9.5% in Finland to 18.4% in Norway. In all five Nordic countries, CAM treatments were most commonly used for nonspecific/preventative purposes such as strengthening the body in general, improving the body’s muscle strength, and improving well-being. CAM treatments were less often used for the purpose of improving specific symptoms such as body pain, problems with balance, and fatigue/lack of energy. Conclusions. A large range of CAM treatments were used by individuals with MS in all Nordic countries. The most commonly reported rationale for CAM treatment use focused on improving the general state of health. The overall pattern of CAM treatment use was similar across the five countries. L. Skovgaard, P. H. Nicolajsen, E. Pedersen, M. Kant, S. Fredrikson, M. Verhoef, and D. W. Meyrowitsch Copyright © 2012 L. Skovgaard et al. All rights reserved. Sun, 09 Dec 2012 16:05:44 +0000 http://www.hindawi.com/journals/ad/2012/565039/ Objective. Although two recent randomized placebo-controlled trials of rituximab (RTX) failed to demonstrate efficacy in systemic lupus erythematosus (SLE), clinicians continue to use off-label RTX for cases refractory to current treatments. We evaluated the effectiveness and safety of rituximab for patients with refractory SLE in Korea. Methods. We retrospectively analyzed multicenter patients treated with RTX in Korea. Results. 39 SLE patients treated with RTX were included in the following manner: lupus nephritis 43.6%, hematologic 33.3%, arthritis 7.8%, myositis 7.8%, and others 7.7%. All patients had responded poorly to at least one conventional immunosuppressive agent (mean , cyclophosphamide 43.6%, mycophenolate mofetil 48.7%, and other drugs) before RTX. Clinical improvements (complete or partial remission) occurred in patients with renal disease, hematologic disease, arthritis, myositis, and other manifestations at 6 months after RTX. The SLEDAI score was significantly decreased from at baseline to at 6 months, at 12 months, and at 24 months after RTX (). Among 28 clinical responders, 4 patients experienced a relapse of disease at months. Infections were noted in 3 patients (7.7%). Conclusion. RTX could be an effective and relatively safe therapeutic option in patients with severe refractory SLE until novel B-cell depletion therapy is available. So-Young Bang, Chang Keun Lee, Young Mo Kang, Hyoun-Ah Kim, Chang-Hee Suh, Won Tae Chung, Yong-Beom Park, Jung-Yoon Choe, Tae-Jong Kim, Yong-Wook Park, Dae-Hyun Yoo, Sang-Cheol Bae, and Hye-Soon Lee Copyright © 2012 So-Young Bang et al. All rights reserved. Thu, 06 Dec 2012 15:50:17 +0000 http://www.hindawi.com/journals/ad/2012/784364/ Objective. To provide a current and comprehensive understanding of the cost-effectiveness of DMTs for the treatment of MS by quantitatively evaluating the quality of recent cost-effectiveness studies and exploring how the field has progressed from past recommendations. Methods. We assessed the quality of studies that met our systematic literature search criteria using the Quality of Health Economic Studies validated instrument. Results. Of the 82 studies that met our initial search criteria, we included 22 in this review. Four studies (18%) achieved quality category 2, three studies (14%) achieved quality category 3, and 15 studies (68%) achieved the highest quality category 4. 91% of studies were simulation models. 13 studies (59%) had quality-adjusted life years (QALYs) as the primary outcome measure, included a societal perspective in the analysis, and utilized time horizons of 10 years to lifetime. Conclusions. To continue to improve the cost-effectiveness evidence of DMTs, we recommend: lifetime horizons, societal perspectives, and QALYs; supplemental evidence with shorter horizons, payer perspectives, and clinical outcomes to inform multiple decision makers; development of modeling and input standards for comparability; head-to-head RCTs between DMTs and long-term prospective studies; and comprehensive cost-effectiveness studies that compare all appropriate DMTs. David Yamamoto and Jonathan D. Campbell Copyright © 2012 David Yamamoto and Jonathan D. Campbell. All rights reserved. Wed, 05 Dec 2012 09:24:47 +0000 http://www.hindawi.com/journals/ad/2012/815753/ Hiroshi Okamoto, Ricard Cervera, Tatiana S. Rodriguez-Reyna, Hiroyuki Nishimura, and Taku Yoshio Copyright © 2012 Hiroshi Okamoto et al. All rights reserved. Wed, 05 Dec 2012 08:43:00 +0000 http://www.hindawi.com/journals/ad/2012/814048/ Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the production of antibodies against a variety of self-antigens including nucleic acids. These antibodies are cytotoxic, catalytic (hydrolyzing DNA, RNA, and protein), and nephritogenic. Current methods for investigating catalytic activities of natural abzymes produced by individuals suffering from autoimmunity are mostly discontinuous and often employ hazardous reagents. Here we demonstrate the utility of dual-labeled, fluorogenic DNA hydrolysis probes in highly specific, sensitive, continuous, fluorescence-based measurement of DNA hydrolytic activity of anti-ssDNA abzymes purified from the serum of patients suffering from SLE. An assay for the presence and levels of antibodies exhibiting hydrolytic activity could facilitate disease diagnosis, prediction of flares, monitoring of disease state, and response to therapy. The assay may allow indirect identification of additional targets of anti-DNA antibodies and the discovery of molecules that inhibit their activity. Combined, these approaches may provide new insights into molecular mechanisms of lupus pathogenesis. Michelle F. Cavallo, Anna M. Kats, Ran Chen, James X. Hartmann, and Mirjana Pavlovic Copyright © 2012 Michelle F. Cavallo et al. All rights reserved. Sun, 02 Dec 2012 17:12:54 +0000 http://www.hindawi.com/journals/ad/2012/403915/ Here we analyzed the molecular targets associated with myasthenia gravis (MG) immune responses, enabled by an immune epitope database (IEDB) inventory of approximately 600 MG-related epitopes derived from 175 references. The vast majority of epitopes were derived from the α-subunit of human AChR suggesting that other MG-associated autoantigens should be investigated further. Human α-AChR was mostly characterized in humans, whereas reactivity primarily to T. californica AChR was examined in animal models. While the fine specificity of T-cell response was similar in the two systems, substantial antibody reactivity to the C-terminus was detected in the nonhuman system, but not in humans. Further analysis showed that the reactivity of nonhuman hosts to the C-terminus was eliminated when data were restricted to hosts tested in the context of autoimmune disease (spontaneous or induced), demonstrating that the epitopes recognized in humans and animals were shared when disease was present. Finally, we provided data subsets relevant to particular applications, including those associated with HLA typing or restriction, sets of epitopes recognized by monoclonal antibodies, and epitopes associated with modulation of immunity or disease. In conclusion, this analysis highlights gaps, differences, and similarities in the epitope repertoires of humans and animal models. Kerrie Vaughan, Yohan Kim, and Alessandro Sette Copyright © 2012 Kerrie Vaughan et al. All rights reserved. Thu, 22 Nov 2012 14:11:03 +0000 http://www.hindawi.com/journals/ad/2012/567324/ Background. Mind-body therapies are used to manage physical and psychological symptoms in many chronic health conditions. Objective. To assess the published evidence for using mind-body techniques for symptom management of multiple sclerosis. Methods. MEDLINE, PsycINFO, and Cochrane Clinical Trials Register were searched from inception to March 24, 2012. Eleven mind-body studies were reviewed (meditation, yoga, biofeedback, hypnosis, relaxation, and imagery). Results. Four high quality trials (yoga, mindfulness, relaxation, and biofeedback) were found helpful for a variety of MS symptoms. Conclusions. The evidence for mind-body medicine in MS is limited, yet mind-body therapies are relatively safe and may provide a nonpharmacological benefit for MS symptoms. Angela Senders, Helané Wahbeh, Rebecca Spain, and Lynne Shinto Copyright © 2012 Angela Senders et al. All rights reserved. Mon, 19 Nov 2012 13:52:41 +0000 http://www.hindawi.com/journals/ad/2012/863041/ Heat shock proteins (HSPs) have been known for decades for their ability to protect cells under stressful conditions. In the 1980s a new role was ascribed for several HSPs given their ability to elicit specific immune responses in the setting of cancer and infectious disease. These immune responses have primarily been harnessed for the immunotherapy of cancer in the clinical setting. However, because of the ability of HSPs to prime diverse immune responses, they have also been used for modulation of immune responses during autoimmunity. The apparent dichotomy of immune responses elicited by HSPs is discussed here on a molecular and cellular level. The potential clinical application of HSP-mediated immune responses for therapy of autoimmune diseases is reviewed. Robert J. Binder, Yu Jerry Zhou, Michelle N. Messmer, and Sudesh Pawaria Copyright © 2012 Robert J. Binder et al. All rights reserved. Sun, 11 Nov 2012 07:29:23 +0000 http://www.hindawi.com/journals/ad/2012/683829/ Anti-DNA autoantibodies are responsible for tissue injury in lupus. A subset of DNA-specific antibodies capable of DNA cleavage can be even more harmful after entering the living cells by destroying nuclear DNA. Origins of anti-DNA autoantibodies are not fully understood, and the mechanism of induction of DNA-cleaving activity remains speculative. The autoantibody BV04-01 derived from lupus-prone mouse is the only DNA-hydrolyzing immunoglobulin with known 3D structure. Identification and analysis of antibodies homologous to BV04-01 may help to understand molecular bases and origins of DNA-cleaving activity of autoantibodies. BLAST search identified murine anti-DNA autoantibody MRL-4 with sequences of variable region genes highly homologous to those of autoantibody BV04-01. Despite significant homology to BV04-01, not only MRL-4 had no DNA-cleaving activity, but also reversion of its unusual P23 mutation to the germline alanine resulted in a dramatic loss of affinity to DNA. Contrary to this effect, transfer of the P23 mutation to the BV04-01 has resulted in a significant drop in DNA binding and almost complete loss of catalytic activity. In the present paper we analyzed the properties of two homologous autoantibodies and mutants thereof and discussed the implications of unusual somatic mutations for the development of autoantibodies with DNA-binding and DNA-hydrolyzing activity. A. V. Kozyr, A. V. Kolesnikov, A. E. Khlyntseva, A. G. Bogun, G. A. Savchenko, I. G. Shemyakin, and A. G. Gabibov Copyright © 2012 A. V. Kozyr et al. All rights reserved. Wed, 07 Nov 2012 08:36:32 +0000 http://www.hindawi.com/journals/ad/2012/563989/ Objectives. In the present study, we aimed to compare the childhood and adult onset multiple sclerosis patients prospectively in their adulthood on the basis of clinical and magnetic resonance imaging (MRI) findings and cognitive impairment, which have not been performed before. Patients and Methods. Forty-six patients in whom the disease onset occurred before 16 years of age were included in the present study. Study subjects were compared with 64 randomly included adult onset patients. Results. Mean disease duration, clinical course, and female to male ratio did not differ in the groups. Cerebellar/brainstem and spinal involvement at onset were significantly higher in EOMS than in AOMS. Difference in MSFC between baseline and at the end of the 5th year was significantly worse in EOMS population (). The most significant difference was found in Paced Auditory Serial Addition Test (PASAT) (). Differences between baseline and at the end of the 5th year on the basis of T1 hypointense lesions were significantly higher in early onset MS than in adult onset MS patients (). Conclusions. Early onset MS seems to have worse prognosis than that of adult onset MS on the basis of clinical manifestation, cognitive impairment, and MRI parameters. Serkan Ozakbas, Derya Kaya, and Egemen Idiman Copyright © 2012 Serkan Ozakbas et al. All rights reserved. Sun, 04 Nov 2012 08:52:11 +0000 http://www.hindawi.com/journals/ad/2012/232139/ Background. Multiple Sclerosis (MS) and Guillain Barre Syndrome (GBS) are autoimmune demyelinating disorders of Central and Peripheral Nervous system, respectively. The coexistence of these two syndromes in an individual's life span is rare. Objectives. To inspect throughout Isfahan MS society (IMSS) records for MS cases who had history of documented GBS whether before the onset of MS or after it. Methods. This retrospective survey was carried out by analyzing the clinical records of 3,522 MS patients who were registered with IMSS, from April 2003 to July 2010. Eligible cases were requested to attend to IMSS for final clinical/paraclinical examinations. Results. Among 3,522 (2,716 women and 806 men) MS subjects, we could identify seven patients (six females and one male) with documented diagnosis of GBS. Six patients (five women and one man) had developed MS within (range: 1–16) years after being diagnosed with GBS and one (a woman) had developed GBS three years after the diagnosis of MS. Conclusion. It seems that the development of MS in individuals with history of GBS is more than a simple incidental event. Masoud Etemadifar, Peyman Roomizadeh, Seyed-Hossein Abtahi, Sepideh Sajjadi, Amin Abedini, Aryan Golabbakhsh, Mahboobeh Fereidan-Esfahani, and Mojtaba Akbari Copyright © 2012 Masoud Etemadifar et al. All rights reserved. Wed, 31 Oct 2012 08:41:48 +0000 http://www.hindawi.com/journals/ad/2012/874680/ Acquired myasthenia gravis is a relatively uncommon disorder, with prevalence rates that have increased to about 20 per 100,000 in the US population. This autoimmune disease is characterized by muscle weakness that fluctuates, worsening with exertion, and improving with rest. In about two-thirds of the patients, the involvement of extrinsic ocular muscle presents as the initial symptom, usually progressing to involve other bulbar muscles and limb musculature, resulting in generalized myasthenia gravis. Although the cause of the disorder is unknown, the role of circulating antibodies directed against the nicotinic acetylcholine receptor in its pathogenesis is well established. As this disorder is highly treatable, prompt recognition is crucial. During the past decade, significant progress has been made in our understanding of the disease, leading to new treatment modalities and a significant reduction in morbidity and mortality. Annapurni Jayam Trouth, Alok Dabi, Noha Solieman, Mohankumar Kurukumbi, and Janaki Kalyanam Copyright © 2012 Annapurni Jayam Trouth et al. All rights reserved. Wed, 24 Oct 2012 19:16:45 +0000 http://www.hindawi.com/journals/ad/2012/812138/ Female patients in reproductive age with systemic lupus erythematosus and fertility complications together are observed by rheumatologists, gynecologists, and reproductive immunologists. The paper notes the presence of autoantibodies to zona pellucida, to phospholipids (phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl inositol, phosphatidyl glycerol, phosphatidic acid, annexin V, beta-2 glycoprotein I, and cardiolipin) and of isoantibodies to sperm cells. Isoantibodies to sperm cells are not significantly predominant, but autoimmunity is well expressed in IgG positivity against phosphatidyl inositol, phosphatidyl ethanolamine, phosphatidyl serine, cardiolipin, and beta-2 glycoprotein I, as well as antizona pellucida antibodies in IgG isotype. According to the levels of autoantibodies we have to choose preventive treatment to protect mother and her foetus. Zdenka Ulcova-Gallova, Alice Mockova, and Miroslava Cedikova Copyright © 2012 Zdenka Ulcova-Gallova et al. All rights reserved.