Autoimmune Diseases The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Clinical and Immunologic Profiles in Incomplete Lupus Erythematosus and Improvement with Hydroxychloroquine Treatment Wed, 28 Dec 2016 12:31:12 +0000 Objective. The study goals were to evaluate performance of SLE classification criteria, to define patients with incomplete lupus erythematosus (ILE), and to probe for features in these patients that might be useful as indicators of disease status and hydroxychloroquine response. Methods. Patients with ILE () and SLE () defined by the 1997 American College of Rheumatology criteria were reclassified using the 2012 Systemic Lupus International Collaborating Clinics criteria. Disease activity, patient reported outcomes, and levels of Type I interferon- (IFN-) inducible genes, autoantibodies, and cytokines were measured. Subgroups treated with hydroxychloroquine (HCQ) were compared to patients not on this drug. Results. The classification sets were correlated (). ILE patients were older () with lower disease activity scores () and greater dissatisfaction with health status () than SLE patients. ILE was associated with lower levels of macrophage-derived cytokines and levels of expressed Type I IFN-inducible genes. Treatment of ILE with HCQ was associated with better self-reported health status scores and lower expression levels of Type I IFN-inducible genes than ILE patients not on HCQ. Conclusion. The 2012 SLICC SLE classification criteria will be useful to define ILE in trials. Patients with ILE have better health status and immune profiles when treated with HCQ. Nancy J. Olsen, Carl McAloose, Jamie Carter, Bobby Kwanghoon Han, Indu Raman, Quan-Zhen Li, and Duanping Liao Copyright © 2016 Nancy J. Olsen et al. All rights reserved. GAKG-RGEKG an Epitope That Provokes Immune Cross-Reactivity between Prevotella sp. and Human Collagen: Evidence of Molecular Mimicry in Chronic Periodontitis Sun, 25 Dec 2016 08:48:44 +0000 Periodontal disease afflicts 20% of world population. This process usually occurs in the form of being lethargic and chronic, and consequently this disease is known as chronic process. All chronic diseases constantly cause activation of the immune system, and therefore the presentation of microbial peptides which are presented to lymphocytes by professional antigen presenting cells can present microbial peptides very similar to important structures of human economy causing autoimmune diseases, process known as molecular mimicry. Thus, the aim of this study was to verify the presence of molecular mimicry phenomenon between periodontopathogens and human proteins. Blasting microbes of Socransky periodontal complexes against human collagen were performed and then the proteins with similarities were modelled and were screened in the MHI binding virtual methods. The epitopes selected were produced and plasma of chronic periodontal volunteers was obtained and a dot immunobinding assay was performed. Hypothetical protein of Prevotella sp. and human collagen epitopes with high similarities were positive for dot immunobinding assay. With this result it can be suggested that the mimicry phenomena can occur on periodontal disease. Gustavo Alberto Obando-Pereda Copyright © 2016 Gustavo Alberto Obando-Pereda. All rights reserved. Infiltrating CD16+ Are Associated with a Reduction in Peripheral CD14+CD16++ Monocytes and Severe Forms of Lupus Nephritis Tue, 13 Dec 2016 14:30:45 +0000 Our aim was to characterize glomerular monocytes (Mo) infiltration and to correlate them with peripheral circulating Mo subsets and severity of lupus nephritis (LN). Methods. We evaluated 48 LN biopsy samples from a referral hospital. Recognition of Mo cells was done using microscopic view and immunohistochemistry stain with CD14 and CD16. Based on the number of cells, we classified LN samples as low degree of diffuse infiltration (<5 cells) and high degree of diffuse infiltration (≥5 cells). Immunophenotyping of peripheral Mo subsets was done using flow cytometry. Results. Mean age was years and the mean SLEDAI was . The most common SLE manifestations were proteinuria (91%) and hypocomplementemia (75%). Severe LN was found in 70% of patients (Class III, 27%; Class IV, 43%). Severe LN patients and patients with higher grade of CD16+ infiltration had lower levels of nonclassical (CD14+CD16++) Mo in peripheral blood. Conclusions. Our results might suggest that those patients with more severe forms of LN had a higher grade of CD14+CD16+ infiltration and lower peripheral levels of nonclassical (CD14+CD16++) Mo and might reflect a recruitment process in renal tissues. However, given the small sample, our results must be interpreted carefully. Anabel Barrera García, José A. Gómez-Puerta, Luis F. Arias, Catalina Burbano, Mauricio Restrepo, Adriana L. Vanegas, Carlos H. Muñoz, Mauricio Rojas, Luis A. González, and Gloria Vásquez Copyright © 2016 Anabel Barrera García et al. All rights reserved. Presence of DQ2.2 Associated with DQ2.5 Increases the Risk for Celiac Disease Wed, 30 Nov 2016 11:35:20 +0000 Background. Celiac disease (CD) is a genetically determined immune-mediated disorder in which gluten immunogenic peptides are presented to CD4 T cells by HLA-DQ2.5, DQ8, DQ2.2, and their combinations. Our aim is to establish a risk gradient for celiac disease based on HLA-DQ profile in a brazilian representative population and the relevance of DQ2.2 in celiac disease development. Materials and Methods. 237 celiac patients and 237 controls (both groups with 164 females and 73 males) were included. All samples were tested for the presence of predisposing HLA-DQ alleles using the PCR-SSP method. Results were considered significant when . Disease risk was expressed as 1 :  for each HLA-DQ category described at this study. Results. DQ2.5 and/or DQ8 were detected in 224 celiac patients (94.5%) and 84 controls (35.4%). Eight celiac patients (3.4%) and 38 controls (16%) disclosed only DQ2.2. Even though DQ2.2 (β2/β2 or β2/x) showed a low CD risk of 1 : 251 and 1 : 550, respectively, the genotype DQ2.5/DQ2.2 (β2/β2) showed high CD risk of 1 : 10 (). The disease risk gradient ranged from 1 : 3014 to 1 : 7. Conclusion. Our study allowed the determination of a risk gradient for celiac disease development in at-risk population, showing that DQ2.2 variant was relevant when associated with DQ2.5. Lucas Malta Almeida, Lenora Gandolfi, Riccardo Pratesi, Rosa Harumi Uenishi, Fernanda Coutinho de Almeida, Nicole Selleski, and Yanna Karla de Medeiros Nóbrega Copyright © 2016 Lucas Malta Almeida et al. All rights reserved. The Prevalence of S. aureus Skin and Soft Tissue Infections in Patients with Pemphigus Sun, 09 Oct 2016 07:08:01 +0000 Pemphigus vulgaris are autoimmune blistering diseases that may result in significant morbidity and death. Immunosuppressive therapy of pemphigus vulgaris would predispose the patients to infections. The aim of this study was to assess the prevalence of S. aureus infection and PVL gene in patients with pemphigus admitted to dermatology clinic. Materials and Methods. This descriptive study was conducted on 196 pemphigus vulgaris patients (119 males, 77 females) admitted to dermatology clinic between 2014 and 2015. In this study, the diagnosis of pemphigus vulgaris was made by histology, immunofluorescence pattern of perilesional skin, and indirect immunofluorescence testing of serum. Data were collected through a questionnaire. Results. 59.1% of pemphigus vulgaris patients had S. aureus infection. 49 out of 116 were methicillin-resistant. PVL gene was detected in 25 out of 116 S. aureus positive patients. Conclusion. This is the first report of S. aureus infection in pemphigus patients in Iran. More than forty percent of isolates were methicillin-resistant S. aureus. PVL gene carried by methicillin-resistant S. aureus was high in this study. Zeinab Fagheei Aghmiyuni, Ahmad Khorshidi, Rezvan Moniri, Tahereh Soori, and Seyed Gholam Abbas Musavi Copyright © 2016 Zeinab Fagheei Aghmiyuni et al. All rights reserved. [18F]-Fluoro-Deoxy-Glucose Positron Emission Tomography Scan Should Be Obtained Early in Cases of Autoimmune Encephalitis Sun, 31 Jul 2016 10:04:02 +0000 Introduction. Autoimmune encephalitis (AE) is a clinically challenging diagnosis with nonspecific neurological symptoms. Prompt diagnosis is important and often relies on neuroimaging. We present a case series of AE highlighting the importance of an early [18F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET) scan. Methods. Retrospective review of seven consecutive cases of autoimmune encephalitis. Results. All patients had both magnetic resonance imaging (MRI) and FDG-PET scans. Initial clinical presentations included altered mental status and/or new onset seizures. Six cases had serum voltage-gated potassium channel (VGKC) antibody and one had serum N-methyl-D-aspartate (NMDA) antibody. MRI of brain showed mesial temporal lobe hyperintensity in five cases of VGKC. The other two patients with VGKC or NMDA AE had restiform body hyperintensity on MRI brain or a normal MRI, respectively. Mesial temporal lobe hypermetabolism was noted in three cases on FDG-PET, despite initial unremarkable MRI. Malignancy workup was negative in all patients. Conclusion. A high index of suspicion for AE should be maintained in patients presenting with cognitive symptoms, seizures, and limbic changes on neuroimaging. In cases with normal initial brain MRI, FDG-PET can be positive. Additionally, extralimbic hyperintensity on MRI may also be observed. C. R. Newey, A. Sarwal, and S. Hantus Copyright © 2016 C. R. Newey et al. All rights reserved. Correlation of Serum Soluble Interleukin-7 Receptor and Anti-C1q Antibody in Patients with Systemic Lupus Erythematosus Wed, 16 Mar 2016 09:10:19 +0000 Background. Serum concentrations of soluble interleukin-7 receptor (sIL-7R) and anti-C1q antibody have recently been identified as unique serological markers for lupus nephritis (LN) in patients with systemic lupus erythematosus (SLE). In this study, we evaluated the correlation of serum sIL-7R and anti-C1q in SLE patients. Methods. Sera from 134 patients with SLE and 84 healthy cohorts were tested for levels of sIL-7R and anti-C1q antibodies in terms of ELISA. Correlations of the sIL-7R and anti-C1q autoantibodies were evaluated. Results. The serum concentrations of sIL-7R and anti-C1q antibodies were significantly higher in SLE patients and LN patients in comparison with healthy individuals/controls and SLE patients with non-LN, respectively. In addition, both sIL-7R and anti-C1q concentrations were found to significantly correlate with the SLE disease activity as evaluated by SLEDAI scores. Interestingly, the serum sIL-7R concentration was strongly correlated with the level of anti-C1q antibodies (, ) but not statistically correlated with other serological markers, including the anti-dsDNA and complements C3 and C4 concentrations in SLE patients. Conclusion. Both serum sIL-7R and anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that they may be reliable serological markers for identification of SLE patients with active diseases and LN. Shuhong Chi, Jing Xue, Feng Li, Caixia Zhu, Yunxia Yu, Haibo Li, Xuemei Wang, Yurong Zhang, Jijuan Yang, Shaolan Zhou, Lijuan Yang, Chen Ji, and Xiaoming Liu Copyright © 2016 Shuhong Chi et al. All rights reserved. Increased Circulating Th17 Cells, Serum IL-17A, and IL-23 in Takayasu Arteritis Sun, 13 Mar 2016 11:09:59 +0000 Introduction. Th17, γδT, NK, and NKT cells in peripheral blood and serum IL-17 and IL-23 in Takayasu arteritis (TA) were measured and correlated with disease activity. Methods. Th17 (anti-CD3APC, CD4PECy7, and IL-17PE), NKT, NK (anti-CD3APC, CD56FITC), and γδT (anti-CD3FITC and γδTCRAPC) cells were enumerated by flow cytometry in peripheral blood of 30 patients with TA (ACR1990 criteria) and 20 healthy controls, serum IL-17 and IL-23 measured by ELISA. Relation with disease activity (NIH criteria, ITAS2010) was analyzed (using nonparametric tests, median with interquartile range). Results. Mean age of patients was years (25 females); mean symptom duration was years. 13 were not on immunosuppressants; 12 were active (ITAS2010 ≥ 4). The percentage of Th17 cells was significantly expanded in TA (patients 2.1 (1.5–3.2) versus controls 0.75 (0.32–1.2); ) with no differences in other cell populations. Serum IL-17 and IL-23 (pg/mL) in patients (6.2 (4.6–8.5) and 15 (14.9–26.5), resp.) were significantly higher () than controls (3.9 (3.9–7.3) and undetectable median value, resp.). Subgroup analysis revealed no correlation of Th17 cells, serum IL-17, and IL-23 with disease activity or medications, nor any significant difference before and after medication. Conclusions. There is significant expansion of Th17 cells and elevated serum IL-17 and IL-23 levels in TA patients compared to healthy controls. Durga Prasanna Misra, Smriti Chaurasia, and Ramnath Misra Copyright © 2016 Durga Prasanna Misra et al. All rights reserved. Mechanism of Xinfeng Capsule on Adjuvant-Induced Arthritis via Analysis of Urinary Metabolomic Profiles Thu, 18 Feb 2016 11:19:27 +0000 We aimed to explore the potential effects of Xinfeng capsule (XFC) on urine metabolic profiling in adjuvant-induced arthritis (AA) rats by using gas chromatography time-of-flight mass spectrometry (GC-TOF/MS). GC-TOF/MS technology was combined with multivariate statistical approaches, such as principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal projections to latent structures discriminant analysis (OPLS-DA). These methods were used to distinguish the healthy group, untreated group, and XFC treated group and elucidate potential biomarkers. Nine potential biomarkers such as hippuric acid, adenine, and L-dopa were identified as potential biomarkers, indicating that purine metabolism, fat metabolism, amino acid metabolism, and energy metabolism were disturbed in AA rats. This study demonstrated that XFC is efficacious for RA and explained its potential metabolomics mechanism. Hui Jiang, Jian Liu, Ting Wang, Jia-rong Gao, Yue Sun, Chuan-bing Huang, Mei Meng, and Xiu-juan Qin Copyright © 2016 Hui Jiang et al. All rights reserved. Prooxidant-Antioxidant Balance in Patients with Systemic Lupus Erythematosus and Its Relationship with Clinical and Laboratory Findings Tue, 26 Jan 2016 12:57:26 +0000 Aim. This study was aimed at evaluating prooxidant-antioxidant balance (PAB) in patients with systemic lupus erythematosus (SLE) and its relationship with laboratory findings and clinical manifestations. Methods. In this case-control study, 60 patients with SLE and 60 healthy individuals were enrolled. The blood samples were collected and their sera were separated. Subsequently, the prooxidant-antioxidant balance value was evaluated using PAB assay for each sample. Results. The mean of PAB values in SLE patients was significantly higher than healthy controls ( versus  HK, ). Furthermore, in SLE patients, there was a positive significant correlation between the PAB and erythrocyte sedimentation rate (ESR) (, ). In addition, the PAB values in patients with alopecia, discoid rash, oral ulcers, arthritis, and nephritis were significantly higher than those without these manifestations. Conclusion. The findings of current study showed that the mean of PAB was significantly higher in SLE patients and PAB was correlated with ESR. Moreover increased PAB was found in SLE patients with alopecia, discoid rash, oral ulcers, arthritis, and nephritis. These findings suggest that the measurement of PAB may be useful to show oxidative stress condition in SLE patients. Seyyed Mehdi Jafari, Saeedeh Salimi, Alireza Nakhaee, Hamed Kalani, Shima Tavallaie, Farzaneh Farajian-Mashhadi, Zahra Zakeri, and Mahnaz Sandoughi Copyright © 2016 Seyyed Mehdi Jafari et al. All rights reserved. Risk Factors and Adverse Events Poorly Predict Infections and Hypogammaglobulinemia in Granulomatosis with Polyangiitis Patients Receiving Rituximab Mon, 18 Jan 2016 09:34:08 +0000 Background. 29 GPA patients from the Northern Norway vasculitis disease registry received rituximab (RTX) induction and maintenance. 24% and 31% had, respectively, severe and chronic infections while 45% had hypogammaglobulinemia and 28% discontinued RTX due to hypogammaglobulinemia. The aim of the study was to examine how known predictors and adverse events interacted with adverse events using structural statistical methods. Methods. Five predictors (age, cyclophosphamide, total Ig and CD4/CD8 ratio prior RTX, and type of RTX maintenance regimen) and 4 adverse events (severe and chronic infections, hypogammaglobulinemia, and RTX discontinuation) were modeled in principal component and redundancy analyses. Results. The 5 predictors explained 51% of the variance of the GPA cohort. Models including cyclophosphamide exposure and total Ig level predicted best adverse events. However total Ig level has low squared. The 2 best combinations of adverse events explained 13% of the variance of the predictors and adverse events. Only chronic infections were associated with combination of all adverse events (). Hypogammaglobulinemia did not seem associated with the other adverse events. Conclusions. Traditional risk factors for infections and hypogammaglobulinemia seemed to poorly predict adverse events in our GPA cohort. Emilio Besada Copyright © 2016 Emilio Besada. All rights reserved. Pentraxin 3 Plasma Levels and Disease Activity in Systemic Lupus Erythematosus Tue, 03 Nov 2015 11:03:24 +0000 SLE is an autoimmune disorder that involves polyclonal autoimmunity against multiple autoantigens. PTX3, a marker of the acute-phase inflammatory response, plays an important role in innate immunity and in modulation of the adaptive immune response. Our study tried to resolve some rather controversial aspects of the use of PTX3 as a biomarker of disease activity in SLE patients. We demonstrated that plasma PTX3 concentration of the SLE patients was significantly higher than the healthy control groups and reflected disease activity. ROC curve analysis was used to determine best cut-off point (2.8 ng/mL) with a good sensitivity and specificity. In patients with SLE, PTX3 concentrations were correlated with SLEDAI. Trend to remission (TTR) curve was created by plotting PTX3 levels and SLEDAI and we applied the curve as a model for the analysis of two patients with different follow-up. PTX3 plasma levels declined significantly and this decline occurred parallel to the clinical improvement with a complete remission of disease. In patients who experienced a clinical relapse, an increase in PTX3 levels followed the lupus flare. The proposal of PTX3 cut-off associated with TTR and monitoring of PTX3 plasma levels could be an innovative approach to follow-up of SLE patients. Roberto Assandri, Marta Monari, Anna Colombo, Alessandra Dossi, and Alessandro Montanelli Copyright © 2015 Roberto Assandri et al. All rights reserved. Immunological Parameters Associated With Vitiligo Treatments: A Literature Review Based on Clinical Studies Thu, 17 Sep 2015 09:28:42 +0000 Vitiligo, a depigmentary disorder, caused by the loss of melanocytes, affects approximately 1% of the world population, irrespective of skin type, with a serious psychological impact on the patient quality of life. So far, the origin of vitiligo has not been traced and the pathogenesis is complex, involving the interplay of a multitude of variables. Although there is no treatment that ensures the complete cure of the disorder, there are some pharmacological, phototherapy, and surgical therapies available. A series of variables can affect treatment outcome, such as individual characteristics, emotional issues, type of vitiligo, stability of the lesions, and immunological status. The present literature review identified the main immunological parameters associated with treatments for vitiligo. Cytotoxic CD8+ T lymphocytes are the main cell type involved in treatment success, as fewer cells in skin lesions are associated with better results. Other parameters such as cytokines and regulatory T cells may also be involved. Further clinical scientific studies are needed to elucidate the complex mechanisms underlying vitiligo and its treatments, in order to expand the range of therapeutic approaches for each individual case. Ana Cláudia Guimarães Abreu, Gabriela Guy Duarte, Juliana Yasmin Pains Miranda, Daniel Gontijo Ramos, Camila Gontijo Ramos, and Mariana Gontijo Ramos Copyright © 2015 Ana Cláudia Guimarães Abreu et al. All rights reserved. The Attenuated Live Yellow Fever Virus 17D Infects the Thymus and Induces Thymic Transcriptional Modifications of Immunomodulatory Genes in C57BL/6 and BALB/C Mice Thu, 17 Sep 2015 08:46:37 +0000 Thymus is involved in induction of self-tolerance in T lymphocytes, particularly due to Aire activity. In peripheral tissues, Treg cells and immunomodulatory molecules, like the major histocompatibility complex (MHC) class Ib molecules, are essential for maintenance of autotolerance during immune responses. Viral infections can trigger autoimmunity and modify thymic function, and YFV17D immunization has been associated with the onset of autoimmunity, being contraindicated in patients with thymic disorders. Aiming to study the influence of YFV17D immunization on the transcriptional profiles of immunomodulatory genes in thymus, we evaluated the gene expression of AIRE, FOXP3, H2-Q7 (Qa-2/HLA-G), H2-T23 (Qa-1/HLA-E), H2-Q10, and H2-K1 following immunization with 10,000 LD50 of YFV17D in C57BL/6 and BALB/c mice. The YFV17D virus replicated in thymus and induced the expression of H2-Q7 (Qa-2/HLA-G) and H2-T23 (Qa-1/HLA-E) transcripts and repressed the expression of AIRE and FOXP3. Transcriptional expression varied according to tissue and mouse strain analyzed. Expression of H2-T23 (Qa-1/HLA-E) and FOXP3 was induced in thymus and liver of C57BL/6 mice, which exhibited defective control of viral load, suggesting a higher susceptibility to YFV17D infection. Since the immunization with YFV17D modulated thymus gene expression in genetically predisposed individuals, the vaccine may be related to the onset of autoimmunity disorders. Breno Luiz Melo-Lima, Danillo Lucas Alves Espósito, Benedito Antônio Lopes da Fonseca, Luiz Tadeu Moraes Figueiredo, Philippe Moreau, and Eduardo Antonio Donadi Copyright © 2015 Breno Luiz Melo-Lima et al. All rights reserved. Association of IFN-γ : IL-10 Cytokine Ratio with Nonsegmental Vitiligo Pathogenesis Wed, 09 Sep 2015 11:24:40 +0000 Background and Objectives. Cytokines regulate immune response and inflammation and play a crucial role in depigmentation process of vitiligo. The present study aimed to estimate the serum levels of pro- and anti-inflammatory cytokines, IFN-γ and IL-10, and their ratios in nonsegmental vitiligo patients and healthy individuals from India. Methods. Blood samples were collected from 280 subjects and serum IFN-γ and IL-10 levels were measured using standard ELISA. Results. Nonsegmental vitiligo patients showed increased levels of IFN-γ ( versus  pg/mL) and decreased levels of IL-10 ( versus  pg/mL) compared to controls. Ratio of IFN-γ : IL-10 differed significantly from patients to controls (). IFN-γ concentrations and IFN-γ : IL-10 ratio varied significantly with respect to clinical variants, disease stability, and social habits (smoking and alcohol consumption) and showed a positive correlation with disease duration. Family history of vitiligo was significantly associated with IFN-γ : IL-10 ratio but not with their individual levels. Conclusion. The ratio of IFN-γ : IL-10 serum levels may be considered as one of the promising immunological markers in nonsegmental vitiligo. This is the first study considering multiple aspects in relation to ratio of cytokine levels. Similar studies with large samples are warranted to confirm our observations. Yaswanth Ala, Mohammed Khalid Pasha, Raja Narasimha Rao, Prasanna Latha Komaravalli, and Parveen Jahan Copyright © 2015 Yaswanth Ala et al. All rights reserved. Social Support and Self-Reported Stress Levels in a Predominantly African American Sample of Women with Systemic Lupus Erythematosus Wed, 09 Sep 2015 09:06:03 +0000 Lupus patients should avoid stress because physical or emotional stress can affect overall physical health. It has been suggested that social support has a positive influence on health status, but there is a lack of information in the literature on the association between the two among lupus patients. The current study investigated the association between social support and self-reported stress and coping status among African American women with lupus using data collected from two linked cross-sectional surveys. No social support differences in groups of high and low stress/coping were revealed; a duplicate study with a larger sample size is required. Edith Marie Williams, Jiajia Zhang, Judith Anderson, Larisa Bruner, and Laurene Tumiel-Berhalter Copyright © 2015 Edith Marie Williams et al. All rights reserved. Hepatic but Not CNS-Expressed Human C-Reactive Protein Inhibits Experimental Autoimmune Encephalomyelitis in Transgenic Mice Thu, 03 Sep 2015 12:54:54 +0000 We recently demonstrated that human C-reactive protein (CRP), expressed hepatically in transgenic mice (CRPtg), improved the outcome of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The liver is the primary site of CRP synthesis in humans and in CRPtg mice but is also expressed by both at low levels in the CNS. To determine if CNS expression of human CRP is sufficient to impact EAE, we generated neuronal CRP transgenic mice (nCRPtg) wherein human CRP expression is driven by the neuron-specific Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) gene promoter. We found that hepatically expressed/blood-borne CRP, but not CNS expressed CRP, lessened EAE severity. These outcomes indicate that the protective actions of human CRP in EAE are manifested in the periphery and not in the CNS and reveal a previously unappreciated site specificity for the beneficial actions of CRP in CNS disease. Tyler T Wright, Rachel V. Jimenez, Todd E. Morgan, Namrata Bali, Xiaogang Hou, Mark A. McCrory, Caleb E. Finch, and Alexander J. Szalai Copyright © 2015 Tyler T Wright et al. All rights reserved. Detection of Antibodies against Human and Plant Aquaporins in Patients with Multiple Sclerosis Sun, 26 Jul 2015 11:10:28 +0000 Multiple sclerosis (MS) is an autoimmune disease that affects the body’s central nervous system. Around 90% of MS sufferers are diagnosed with relapsing-remitting MS (RRMS). We used ELISA to measure IgG, IgA, and IgM antibodies against linear epitopes of human and plant aquaporins (AQP4) as well as neural antigens in RRMS patients and controls to determine whether patients suffering from RRMS have simultaneous elevations in antibodies against these peptides and antigens. In comparison to controls, significant elevations in isotype-specific antibodies against human and plant AQP4 and neural antigens such as MBP, MOG, and S100B were detected in RRMS patients, indicating a high correlation in antibody reaction between plant aquaporins and brain antigens. This correlation between the reactivities of RRMS patients with various tested antigens was the most significant for the IgM isotype. We conclude that a subclass of patients with RRMS reacts to both plant and human AQP4 peptides. This immune reaction against different plant aquaporins may help in the development of dietary modifications for patients with MS and other neuroimmune disorders. Aristo Vojdani, Partha Sarathi Mukherjee, Joshua Berookhim, and Datis Kharrazian Copyright © 2015 Aristo Vojdani et al. All rights reserved. Therapeutic Effect of Saponin Rich Fraction of Achyranthes aspera Linn. on Adjuvant-Induced Arthritis in Sprague-Dawley Rats Sun, 26 Jul 2015 06:45:06 +0000 Objective. Achyranthes aspera Linn. (AA) is used in folklore for the treatment of various inflammatory ailments and arthritis like conditions. Anti-inflammatory activity of saponin rich (SR) fraction of AA has been previously reported. The objective of this study was to assess the antiarthritic effect of SR fraction of Achyranthes aspera in adjuvant-induced arthritic rats. Methods. Arthritis was assessed by arthritis score, paw volume, changes in tibiotarsal joint thickness, hyperalgesic parameters, and spleen and thymus index. Haematological, serum, biochemical, and inflammatory cytokine and in vivo antioxidant parameters were measured on the last day of the study. Results. SR fraction significantly suppressed paw swelling and arthritic score and improved the pain threshold in motility and stair climbing tests. There was a reversal in the levels of altered parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and antioxidant parameters like superoxide dismutase, catalase, glutathione, malondialdehyde, and nitric oxide. SR fraction significantly decreased plasma levels of tumor necrosis factor-alpha and interleukin-6. Moreover, histopathology revealed a significant reduction in synovial hyperplasia, inflammatory cell infiltration, and bone destruction in the joints. Conclusion. These observations explain the therapeutic benefit of SR fraction of AA in suppressing the progression of adjuvant-induced arthritis in rats. Pankaj S. Kothavade, Vipin D. Bulani, Dnyaneshwar M. Nagmoti, Padmini S. Deshpande, Nitin B. Gawali, and Archana R. Juvekar Copyright © 2015 Pankaj S. Kothavade et al. All rights reserved. Understanding and Managing Pregnancy in Patients with Lupus Sun, 12 Jul 2015 09:08:40 +0000 Systemic lupus erythematosus (SLE) is a chronic, multisystemic autoimmune disease that occurs predominantly in women of fertile age. The association of SLE and pregnancy, mainly with active disease and especially with nephritis, has poorer pregnancy outcomes, with increased frequency of preeclampsia, fetal loss, prematurity, growth restriction, and newborns small for gestational age. Therefore, SLE pregnancies are considered high risk condition, should be monitored frequently during pregnancy and delivery should occur in a controlled setting. Pregnancy induces dramatic immune and neuroendocrine changes in the maternal body in order to protect the fetus from immunologic attack and these modifications can be affected by SLE. The risk of flares depends on the level of maternal disease activity in the 6–12 months before conception and is higher in women with repeated flares before conception, in those who discontinue useful medications and in women with active glomerulonephritis at conception. It is a challenge to differentiate lupus nephritis from preeclampsia and, in this context, the angiogenic and antiangiogenic cytokines are promising. Prenatal care of pregnant patients with SLE requires close collaboration between rheumatologist and obstetrician. Planning pregnancy is essential to increase the probability of successful pregnancies. Guilherme Ramires de Jesus, Claudia Mendoza-Pinto, Nilson Ramires de Jesus, Flávia Cunha dos Santos, Evandro Mendes Klumb, Mario García Carrasco, and Roger Abramino Levy Copyright © 2015 Guilherme Ramires de Jesus et al. All rights reserved. Urine Monocyte Chemoattractant Protein-1 and Lupus Nephritis Disease Activity: Preliminary Report of a Prospective Longitudinal Study Sun, 12 Jul 2015 09:05:56 +0000 Objective. This longitudinal study aimed to determine the urine monocyte chemoattractant protein-1 (uMCP-1) levels in patients with biopsy-proven lupus nephritis (LN) at various stages of renal disease activity and to compare them to current standard markers. Methods. Patients with LN—active or inactive—had their uMCP-1 levels and standard disease activity markers measured at baseline and 2 and 4 months. Urinary parameters, renal function test, serological markers, and renal SLE disease activity index-2K (renal SLEDAI-2K) were analyzed to determine their associations with uMCP-1. Results. A hundred patients completed the study. At each visit, uMCP-1 levels (pg/mg creatinine) were significantly higher in the active group especially with relapses and were significantly associated with proteinuria and renal SLEDAI-2K. Receiver operating characteristic (ROC) curves showed that uMCP-1 was a potential biomarker for LN. Whereas multiple logistic regression analysis showed that only proteinuria and serum albumin and not uMCP-1 were independent predictors of LN activity. Conclusion. uMCP-1 was increased in active LN. Although uMCP-1 was not an independent predictor for LN activity, it could serve as an adjunctive marker when the clinical diagnosis of LN especially early relapse remains uncertain. Larger and longer studies are indicated. Sabah Alharazy, Norella C. T. Kong, Marlyn Mohd, Shamsul A. Shah, Arbaiyah Ba’in, and Abdul Halim Abdul Gafor Copyright © 2015 Sabah Alharazy et al. All rights reserved. Association between Secondary and Primary Sjögren’s Syndrome in a Large Collection of Lupus Families Sun, 12 Jul 2015 08:23:51 +0000 Objective. Systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS) share clinical and immunogenetic features and may occur together. We undertook this study to determine the risk of primary SS among SLE-unaffected relatives of SLE patients and whether or not primary and secondary SS tended to occur in the same families. Methods. We collected clinical and serological data on 2694 SLE patients, 7390 SLE-unaffected relatives of the SLE patients, and 1470 matched controls. Results. Of the 2694 subjects with SLE, 548 had secondary SS, while 71 of their 7390 SLE-unaffected relatives had primary SS. None of the 1470 controls had SS as defined herein ( compared to SLE-unaffected relatives). Of the 71 SLE-unaffected relatives with primary SS, 18 (25.3%) had an SLE-affected family member with secondary SS, while only 530 of the 7319 (7.2%) SLE-unaffected relatives without SS did so (). Conclusion. Among families identified for the presence of SLE, primary and secondary SS tend to occur within the same families. These results highlight the commonalities between these two forms of SS, which in fact correspond to the same disease. Rachna Aggarwal, Juan-Manuel Anaya, Kristi A. Koelsch, Biji T. Kurien, and R. Hal Scofield Copyright © 2015 Rachna Aggarwal et al. All rights reserved. Predisposition to Cervical Atypia in Systemic Lupus Erythematosus: A Clinical and Cytopathological Study Thu, 09 Jul 2015 12:42:17 +0000 Introduction. Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course, and prognosis. The female genital tract may be a potential target organ in SLE since cervical inflammation may be associated with disease activity. An increase in cervical dysplasia, a precursor of cervical cancer, has been reported in females with SLE. Aim of the Work. This work aimed to study the prevalence of abnormal cervicovaginal smears in patients with systemic lupus erythematosus (SLE) and to correlate abnormal smear findings with exposure to infection with human papilloma virus (HPV) in SLE patients. Patients and Methods. Thirty-two patients with SLE, fulfilling the 1997 revised criteria for the classification of SLE, were included in this study. They were subjected to full history taking, clinical examination, laboratory investigations, and cervicovaginal smearing. Twenty healthy subjects not known to suffer from any rheumatological disease were used as controls, and they were subjected to cervicovaginal smearing. Results. Four out of 32 SLE patients showed abnormal Pap smears (12.5%) compared to none showing any cervical changes in the control group (0%). Among these 4 patients, 3 were having ASCU and one was having LSIL (HPV). Conclusion. Cervicovaginal smearing is an easy, economic, safe, repeatable, and noninvasive technique for screening and early detection of cervical neoplastic lesions in SLE. Hend Hilal Al-Sherbeni, Ahmed Mohamed Fahmy, and Nadine Sherif Copyright © 2015 Hend Hilal Al-Sherbeni et al. All rights reserved. Pathophysiological Relationship between Infections and Systemic Vasculitis Tue, 07 Jul 2015 11:50:55 +0000 The development of autoimmune disorders requires a combination of genetic, immunological, and environmental factors. Infectious agents, such as viruses and bacteria, can trigger autoimmunity through different mechanisms, and for systemic vasculitis in particular, microbial agents have been suggested to be involved in its pathogenesis. Although the exact mechanisms have not been fully elucidated, different theories have been postulated. This review considers the role of infections in the etiology of primary vasculitis, emphasizing their related immunological events. Carolina Muñoz-Grajales and Juan C. Pineda Copyright © 2015 Carolina Muñoz-Grajales and Juan C. Pineda. All rights reserved. Gender and Ethnicity Based Differences in Clinical and Laboratory Features of Myasthenia Gravis Sun, 14 Jun 2015 06:32:14 +0000 Background. Previous reports describe ethnicity based differences in clinical and laboratory features between Caucasians and African Americans with myasthenia gravis. However, it is not known whether these findings apply to other ethnicities. Methods. Retrospective analysis of all patients treated for myasthenia gravis during a three-year period at a community based medical center. Results. A total of 44 patients were included, including 19 of Hispanic, 16 of African American, 6 of Caucasian, and 3 of Asian ethnicities. Female gender was more common among those with Hispanic, Asian, and African American ethnicities compared to Caucasian ethnicity (). Anti-acetylcholine receptor antibody subtypes demonstrated no significant ethnicity based differences in either generalized or ocular myasthenia gravis. A trend was noted towards greater frequency of blocking antibodies among Hispanics (52.6%) compared to African American (37.5%) and Caucasian (33.3%) patients (). Generalized but not ocular myasthenia patients showed greater frequency of anti-muscle specific kinase antibodies in Asians and Hispanics compared to African Americans and Caucasians (). Conclusions. The results of this study support the existence of ethnicity based differences in clinical and laboratory features of myasthenia gravis. Further study of genetic factors influencing clinical features of myasthenia gravis is indicated. Fawzi Abukhalil, Bijal Mehta, Erin Saito, Sejal Mehta, and Aaron McMurtray Copyright © 2015 Fawzi Abukhalil et al. All rights reserved. Slipping through the Cracks: Linking Low Immune Function and Intestinal Bacterial Imbalance to the Etiology of Rheumatoid Arthritis Thu, 12 Mar 2015 12:47:42 +0000 Autoimmune diseases (ADs) are considered to be caused by the host immune system which attacks and destroys its own tissue by mistake. A widely accepted hypothesis to explain the pathogenic mechanism of ADs is “molecular mimicry,” which states that antibodies against an infectious agent cross-react with a self-antigen sharing an identical or similar antigenic epitope. However, this hypothesis was most likely established based on misleading antibody assay data largely influenced by intense false positive reactions involved in immunoassay systems. Thus reinvestigation of this hypothesis using an appropriate blocking agent capable of eliminating all types of nonspecific reactions and proper assay design is strongly encouraged. In this review, we discuss the possibility that low immune function may be the fundamental, common defect in ADs, which increases the susceptibility to potential disease causative pathogens located in the gastrointestinal tract (GI), such as bacteria and their components or dietary components. In addition to these exogenous agents, aberrations in the host’s physical condition may disrupt the host defense system, which is tightly orchestrated by “immune function,” “mucosal barrier function,” and “intestinal bacterial balance.” These disturbances may initiate a downward spiral, which can lead to chronic health problems that will evolve to an autoimmune disorder. Kuniaki Terato, Christopher T. Do, and Hiroshi Shionoya Copyright © 2015 Kuniaki Terato et al. All rights reserved. Environmental Triggers and Autoimmunity Wed, 24 Dec 2014 09:20:21 +0000 Aristo Vojdani, K. Michael Pollard, and Andrew W. Campbell Copyright © 2014 Aristo Vojdani et al. All rights reserved. Intravenous Immunoglobulin Treatment in Chronic Neurological Diseases: Do We Have Maintenance Dose Right? Thu, 18 Dec 2014 00:10:36 +0000 Objectives. We tried to define, on individual basis, minimal effective maintenance dose of intravenous immunoglobulins (IVIG) in 26 patients with chronic neurological conditions requiring long-term IVIG treatment. Methods. Clinical criteria were reviewed in individual cases (Phase 1) followed by titration phase (Phase 2, 12 months) and posttitration/follow-up phase (Phase 3, 3 months). Objective neurological examination and patient self-reports were used for clinical follow-up. Results. 69.2% of patients reported condition as stable, 26.9% as better, and 3.9% as mildly worse. Original mean monthly dose was 1 g/kg; over the period of 12 months we reduced dose of IVIG to mean dose 0.67 g/kg (range 0.3–2.5 g/kg, which meant reduction by 36.4%. We identified 4 nonresponders and diagnosis in one case was reclassified to degenerative disease. In follow-up phase we reduced dose further to 0.60 g/kg. Cumulative monthly dose dropped from 2040 g to 1298 g and to 991 g, respectively. Financial expenses were reduced significantly (by −36.4% during titration phase and by −51.4% during follow-up phase) (comparing with baseline) . Conclusion. Individual dose titration leads to significant maintenance IVIG dose reduction with preserved clinical efficacy. Maintenance dose below 1 g/kg (in our study around 0.7 g/kg) has acceptable risk/benefit ratio. Ondrej Dolezal Copyright © 2014 Ondrej Dolezal. All rights reserved. The Prevalence of Antinuclear Antibodies in Patients with Sarcoidosis Wed, 17 Dec 2014 12:53:26 +0000 Introduction. Sarcoidosis, which is a chronic inflammatory granulomatous disease, can mimic different rheumatologic diseases including connective tissue diseases. Antinuclear antibodies are the markers used for connective tissue diseases. Aim. To determine antinuclear antibody frequency and any possible correlation with clinical and laboratory data in sarcoidosis patients. Material and Method. Forty-two sarcoidosis patients, 45 rheumatoid arthritis patients, and 45 healthy volunteers who were followed up in rheumatology outpatient clinic were included in this study. Demographic, clinical, serological, and radiological data of all patients were recorded. Antinuclear antibodies were determined with indirect immunofluorescent method and 1/100 titration was accepted as positive. The cases that were ANA positive were evaluated with immunoblot method. Results. Average age of the 42 patients (10 males) with sarcoidosis was 45.2 (20–70 years), and average disease duration was 3.5 years. ANA positivity was detected in 12 (28.5%) patients with sarcoidosis (1/100 in 10 patients, 1/320 in two patients), in 19 of RA patients (42.2%), and in two of healthy volunteers in low titer (). In the subgroup analysis made by immunblot test, one patient had anticentromere antibody, one had anti-Ro antibody, one had anti-Scl-70 antibody, one had anti-dsDNA antibody, and eight patients were negative. The two patients who had anticentromere and anti-Scl-70 antibodies had also Sjögren’s syndrome and scleroderma diagnosis, respectively. Discussion. The prevalence of ANA in patients with sarcoidosis was found to be significantly higher than healthy control group and lower than RA patients. This result shows that ANA may have an important role in the pathogenesis of sarcoidosis and also could be important in revealing the overlap syndromes of sarcoidosis-connective tissue diseases. Further studies with larger series are necessary in this subject. Senol Kobak, Hatice Yilmaz, Fidan Sever, Arzu Duran, Nazime Sen, and Ahmet Karaarslan Copyright © 2014 Senol Kobak et al. All rights reserved. Serum Leptin Levels in Treatment-Naive Patients with Clinically Isolated Syndrome or Relapsing-Remitting Multiple Sclerosis Wed, 19 Nov 2014 09:38:22 +0000 Several studies have investigated leptin levels in patients with multiple sclerosis (MS) with somewhat conflicting results. They have all focused on patients with established relapsing-remitting (RR) MS but have not specifically looked at patients with clinically isolated syndrome (CIS) suggestive of MS, in the early stages of disease. In this study, serum leptin levels were measured in 89 treatment-naïve patients with CIS (53 patients) or RRMS (36 patients) and 73 controls searching for differences between the groups and for associations with several disease parameters. The expected significant sexual dimorphism in leptin levels (higher levels in females) was observed in both MS patients and controls. Increased leptin levels were found in female patients with RRMS compared to female controls () and female CIS patients (). Female CIS patients had comparable levels to controls. Leptin levels correlated positively to disease duration, but not to EDSS, in female patients with RRMS. The results of the present study do not indicate involvement of leptin in the early stages of MS. Normal leptin levels in patients with CIS suggest that leptin does not have a pathogenic role. The ratio leptin/BMI increases during disease course in female MS patients in a time-dependent and disability-independent manner. Maria Eleftheria Evangelopoulos, Georgios Koutsis, and Manolis Markianos Copyright © 2014 Maria Eleftheria Evangelopoulos et al. All rights reserved.