Immunomediated Diseases Research Articles

ADVANCED STAGE CHRONIC SCLEROSING SIALOADENITIS (KÜTTNER TUMOR)

Kuttner tumor chronic sclerosing sialadenitis is graded in 4 stages, but most of the lesions are usually diagnosed in the 2 intermediary stages. We present a case affecting a female patient, 57 years old and white, who sought the oral medicine service because of a small tendered nodule on the buccal mucosa. Intraoral examination revealed a sessile, painless, and normal-colored fluctuating nodule, resembling a mucocele. After excisional biopsy, the material was submitted to a microscopic evaluation that revealed dilated salivary ducts with ectasia and peripheral fibrosis with intense hyalinization in addition to a discrete periductal lymphocytic infiltrate in the middle of a stroma of adipose tissue of usual appearance. That suggested diagnosis of advanced stage chronic sclerosing sialadenitis (Kuttner tumor). Further clinical and laboratory examinations ruled out the other immunomediated diseases. Postoperative follow-up showed no signs of recurrence, and the patient was released.

BEAM Vs Cyclophosphamide-Based Conditioning Regimen in Aggressive Multiple Sclerosis: A Retrospective Analysis of European Blood and Marrow Transplantation Society

Background Multiple Sclerosis (MS) is a chronic, immuno-mediated disease of Central Nervous System (CNS), mostly affecting young adults and frequently resulting in a progressive, irreversible disability despite the administration of approved Disease Modifying Treatments (DMTs). Autologous HSCT was shown to induce a high rate of sustained, treatment-free remissions in cases of aggressive MS, seldom associated to a partial reversal of disability. Toxicity of Conditioning Regimen is still a major concern. We retrospectively analyzed the outcome of 926 MS patients reported to the EBMT Registry who underwent autologous HSCT following the two most frequent CRs for this indication in the last 20 years. Patients and Methods Patient data were extracted from both the EBMT database and a disease-specific database developed by the EBMT Autoimmune Diseases Working Party (ADWP). Patients were selected for having received either BEAM + ATG (BEAM) or HD-Cyclophosphamide + ATG (CYC) as conditioning regimen. Hematological toxicity was assessed through Neutrophil (PMN) engraftment and 100-days (early) mortality (eTRM). MS forms at HSCT were reported as Relapsing-Remitting (RR), Secondary Progressive (SP), Primary Progressive (PP) and Progressive-Relapsing (PR). The impact of variables related to both patients (age, gender, year of HSCT, EDSS at HSCT) and disease characteristics (MS form, interval diagnosis-HSCT) at HSCT in the two groups were also evaluated. Results The utilization of conditioning regimens along the observed time period (1998-2018) was variable, with an increase of the HSCT activity in general after 2010 (230 vs 697 procedures) and a prevalence of BEAM before 2010 (205 BEAM vs 25 CYC) and of CYC thereafter (205 BEAM vs 492 CYC, p=0.001). Also, RR forms of MS prevailed over Progressive forms after 2010 (p=0.001) which is reflected in the different distribution across the two regimens, with RR significantly more frequently treated with CYC-based regimen (p<0.001). Gender distribution and age at HSCT was similar in the two groups (p=ns), whilst the interval between diagnosis and HSCT was longer in BEAM group than CYC (8.47 years ± 5.9 vs 7.57 ±5.5, mean ± SD, p=0.012). PMN engraftment in BEAM/ATG- and CYC/ATG-treated patients occurred at +11.0 (8-42) and +10.9 (8-95) days, respectively (median and range, p=ns). Overall eTRM was low (1.4%), but slightly higher in BEAM over CYC (8/402, 2% vs 5/517, 1%, p=ns). Discussion Although autologous HSCT is increasingly used as a treatment in highly active MS, toxicity remains a principal concern in the neurological community despite a marked decrease of TRM over time. The intensity of conditioning regimens has varied in the literature, but the best toxicity/efficacy ratio remains unclear. The non-myeloablative regimen CYC-ATG has become the most common conditioning regimen despite a lack of comparative data with more intense regimens. In our large retrospective analysis of the two most frequent conditioning regimens in the EBMT Registry, there was no significant difference in major toxicity indicators despite differences in chronological period and patients characteristics in the two groups. Comparative analysis of neurological efficacy is currently ongoing and will inform the toxicity/efficacy ratio and clinical choice of conditioning regimen in autologous HSCT in MS. Disclosures Mielke: Bellicum: Consultancy, Honoraria, Other: Travel (via institution); Jazz Pharma: Honoraria, Other: Travel support, Speakers Bureau; IACH: Other: Travel support; Kiadis Pharma: Consultancy, Honoraria, Other: Travel support (via institution), Speakers Bureau; Miltenyi: Consultancy, Honoraria, Other: Travel and speakers fee (via institution), Speakers Bureau; DGHO: Other: Travel support; GILEAD: Consultancy, Honoraria, Other: travel (via institution), Speakers Bureau; Celgene: Honoraria, Other: Travel support (via institution), Speakers Bureau; ISCT: Other: Travel support; EBMT/EHA: Other: Travel support.

The role of gut microbiota and nutrition features in the pathogenesis of multiple sclerosis and its course

The study of the role of microbiota in the pathogenesis of autoimmune and demyelinating diseases is of a particular importance. Experimental data obtained during the last 10 years shows a close connection between the immune system and the gut microbiota. In the analyzed literature, additional evidence was found that microbial involvement in immunoregulation and the influence of gut microbiota on the development of various immunomediated diseases: rheumatoid arthritis, psoriasis, Sjogren syndrome, multiple sclerosis, metabolic syndrome, autoimmune hepatitis, type 1 diabetes, spondylarthritis and inflammatory bowel disease. Studies from recent years have shown that intestinal microbiota with the help of numerical microbial compounds, autonomic nervous system of the allocation of neurometabolites, signaling molecules, neurotransmitters has an effect on the functioning of the central nervous system, in connection with which the model of the intestinal‑cerebral axis was proposed, which involves the interregulation between CNS and intestinal microbiota. Detection of the influence of microbiota on the functioning of the immune and nervous systems raised the interest in microbiota of the intestine as an etiopathogenetic factor in the development of autoimmune diseases such as multiple sclerosis. However, during studies analysis, it was established that because of the nature and composition of microbiota in patients with multiple sclerosis, it is impossible to say with certainty which type of microorganisms is associated with the onset of the disease and its course. Therefore further research is aimed at the study of microbiota and the interdependence of the species composition of microorganisms necessary for clarification of the influence on methods of correction of disorders in patients with multiple sclerosis. It has been established that an important element of the study of microbiota composition is the study of the nutrition, as the dietetic pattern determines the enterotype of a person and affects the concentration and distribution of microorganisms in the intestine. That is why it is necessary to combine modern methods of studying the composition of microbiota and to compare with the type of dietary pattern found in the patient.

Signaling from Intestine to the Host: How Bile Acids Regulate Intestinal and Liver Immunity.

Primary bile acids (BAs) are generated in the liver as the end products of cholesterol catabolism; they are then conjugated and accumulated in the gallbladder. After a meal ingestion, BAs are reversed into the duodenum to facilitate the lipid absorption. At the intestinal level, the 95% of BAs are reabsorbed and redirected into enterohepatic circulation; indeed only a small amount of them are then subjected to chemical modifications by the intestinal microbiota, which plays a very important role in the generation of secondary bile acids and in regulating host's metabolism and activity of the immune system. Behind their role in nutrients absorption, bile acids act as signaling molecules, activating several receptors, known as bile acid-activated receptors (BARs), including the farnesoid-X-receptor (FXR) and the G protein-coupled bile acid receptor 1 (GPBAR1 or Takeda G-protein receptor 5). Both receptors appear to contribute to maintain the tolerogenic state of the liver and intestine immunity. In particular, FXR and GPBAR1 are highly expressed in cells of innate immunity including intestinal and liver macrophages, dendritic cells, and natural killer T cells. In this chapter, we provide an overview on mechanisms through which FXR and GPBAR1 modulate the signaling between microbiota and intestinal and liver innate immune system. This overview could help to explain beneficial effects exerted by GPBAR1 and FXR agonists in the treatment of metabolic and immuno-mediated diseases.

The prevalence of dysphonia and dysphagia in patients affected by immunomediated diseases and the role of psychometric tests.

This cross-sectional investigation examined the prevalence and severity of dysphonia, globus pharyngeus, and dysphagia in patients affected by immunomediated (IM) diseases. Seventy subjects were administered the Voice Handicap Index (VHI) (scale 0-4), Glasgow-Edinburgh Throat Scale (GETS) (scale from 0 to 7) for globus pharyngeus assessment, and modified Swallowing Outcomes After Revised Laryngectomy (SOAL) (scale 0, 1, 2) to test swallowing symptoms. VHI: the mean percentage of answers with a score greater than 1 (corresponding to a frequency of situation's occurrence "sometimes," "almost always," or "always") was 25.7, 26.7, and 44.1% for functional, emotional, and physical groups of sub-items respectively. GETS: the mean percentage of answers with a score ≥ 3 was 60.85%, significantly higher if compared with that of answers with a score < 3 (40.14%). The mean percentages of answers with a score 0-2, 3-4, and 5-7 were 40.1, 16.7, and 43.7% respectively. SOAL: a mean of 57.9% of answers gained a symptomatic score (1 ["a little"] or 2 ["a lot"]) and 41.9%, the score 0. The difference was statistically significant (p < 0.05). The first two most recurrent items with a score 2 ("a lot") were "Do you have a problem swallowing dry food?" (46%) and "Do you have a problem swallowing solid food?" (36%). The study represents the first to describe the globus pharyngeus symptoms in IM population. Moreover, it allows to confirm the recurrence of dysphonia and dysphagia in this type of patients. Particularly, it has been demonstrated that the alteration of swallowing function is related to solid and dry food. The self-assessment questionnaires proved as a useful tool to early detection of dysfunctions in order to avoid further deterioration of quality of life and to prevent serious life-threatening complications.

332i - Immunochip Analysis Revealed HLA Mechanism in Collagenous Colitis and Overlapping Genes with Immunomediated Diseases

332i - Immunochip Analysis Revealed HLA Mechanism in Collagenous Colitis and Overlapping Genes with Immunomediated Diseases

Biológicos y cáncer: ¿una relación peligrosa?

Anti-TNF agents have shown to be effective treating immuno-mediated diseases. The first cases of lymphoma diagnosed after the approval of anti-TNF focused their attention on the role of these drugs in the risk of tumor development. In patients with inflammatory bowel disease and other immune-mediated diseases, especially rheumatoid arthritis, anti-TNF drugs do not appear to increase the risk of developing malignancies. Conflicting results were only observed in the case of risk of lymphoma and skin cancer. However, if the treatment with anti-TNF drugs increases the risk of development of these tumors, the magnitude of effect and the absolute number of cases would be very low, so that the benefit of these treatments clearly exceeds the potential risks. Finally, the effect of anti-TNF in patients with a history of neoplasia is poorly known; current evidence suggests there is no increased risk of tumor recurrence in patients exposed to these drugs. However, because data about this issue are scarce, it would be prudent to assess each case individually, taking into account the history of cancer and the available alternatives for the control of inflammatory bowel disease.

NMR-based metabolomic approach to study urine samples of chronic inflammatory rheumatic disease patients.

The nuclear magnetic resonance (NMR)-based metabolomic approach was used as analytical methodology to study the urine samples of chronic inflammatory rheumatic disease (CIRD) patients. The urine samples of CIRD patients were compared to the ones of both healthy subjects and patients with multiple sclerosis (MS), another immuno-mediated disease. Urine samples collected from 39 CIRD patients, 25 healthy subjects, and 26 MS patients were analyzed using 1H NMR spectroscopy, and the NMR spectra were examined using partial least squares-discriminant analysis (PLS-DA). PLS-DA models were validated by a double cross-validation procedure and randomization tests. Clear discriminations between CIRD patients and healthy controls (average diagnostic accuracy 83.5 ± 1.9%) as well as between CIRD patients and MS patients (diagnostic accuracy 81.1 ± 1.9%) were obtained. Leucine, alanine, 3-hydroxyisobutyric acid, hippuric acid, citric acid, 3-hydroxyisovaleric acid, and creatinine contributed to the discrimination; all of them being in a lower concentration in CIRD patients as compared to controls or to MS patients. The application of NMR metabolomics to study these still poorly understood diseases can be useful to better clarify the pathologic mechanisms; moreover, as a holistic approach, it allowed the detection of, by means of anomalous metabolic traits, the presence of other pathologies or pharmaceutical treatments not directly connected to CIRDs, giving comprehensive information on the general health state of individuals. Graphical abstract NMR-based metabolomic approach as a tool to study urine samples in CIRD patients with respect to MS patients and healthy controls.

Diabetes mellitus in childhood: an emerging condition in the 21st century.

The International Diabetes Federation (IDF-2015) estimates the existence of 30,900 children under 15 years old with type 1 diabetes mellitus (DM1) in Brazil, and an increase of 3.0% per year is expected. This review focused on meta-analysis and pediatric diabetes update articles in order to draw attention to the need of planning coping strategies to support this serious public health problem in coming years. DM1 is considered an immuno-mediated disease with a complex transmission influenced by genetic and environmental factors responsible for a gradual destruction of the insulin producing pancreatic beta cells. Seroconversion to DM1-associated autoantibodies and abnormalities in metabolic tests that assess insulin secretion and glucose tolerance can be used as predictive criteria of beta cells functional reserve and the onset of the clinical disease. Symptomatic DM1 treatment is complex and the maintenance of good metabolic control is still the only effective strategy for preserving beta cell function. Disease duration and hyperglycemia are both risk factors for the onset of chronic vascular complications that negatively affect the quality of life and survival of these patients. In this regard, health teams must be trained to provide the best possible information on pediatric diabetes, through continuing education programs focused on enabling these young people and their families to diabetes self-management.

Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic immuno-mediated disease primarily affecting the joints, characterized by persistent high-grade systemic inflammation. Cardiovascular morbidity and mortality are significantly increased in RA, with >50% of premature deaths attributable to cardiovascular disease. In particular, RA patients were twice as likely to experience sudden cardiac death compared with non-RA subjects, pointing to an increased propensity to develop malignant ventricular arrhythmias. Indeed, ventricular repolarization (QT interval) abnormalities and cardiovascular autonomic nervous system dysfunction, representing two well-recognized risk factors for life-threatening ventricular arrhythmias in the general population, are commonly observed in RA. Moreover, large population-based studies seem to indicate that also the prevalence of atrial fibrillation is significantly higher in RA subjects than in the general population, thus suggesting that these patients are characterized by an abnormal diffuse myocardial electrical instability. Although the underlying mechanisms accounting for the pro-arrhythmogenic substrate in RA are probably intricate, the leading role seems to be played by chronic systemic inflammatory activation, able to promote arrhythmias both indirectly, by accelerating the development of ischaemic heart disease and congestive heart failure, and directly, by affecting cardiac electrophysiology. In this integrated mechanistic view, lowering the inflammatory burden through an increasingly tight control of disease activity may represent the most effective intervention to reduce arrhythmic risk in these patients. Intriguingly, these considerations could be more generally applicable to all the diseases characterized by chronic systemic inflammation, and could help elucidate the link between low-grade chronic inflammation and arrhythmic risk in the general population.

Allergic diseases among children: nutritional prevention and intervention.

Allergic diseases comprise a genetically heterogeneous group of chronic, immunomediated diseases. It has been clearly reported that the prevalence of these diseases has been on the rise for the last few decades, but at different rates, in various areas of the world. This paper discusses the epidemiology of allergic diseases among children and their negative impact on affected patients, their families, and societies. These effects include the adverse effects on quality of life and economic costs. Medical interest has shifted from tertiary or secondary prevention to primary prevention of these chronic diseases among high-risk infants in early life. Being simple, practical, and cost-effective are mandatory features for any candidate methods delivering these strategies. Dietary therapy fits this model well, as it is simple, practical, and cost-effective, and involves diverse methods. The highest priority strategy is feeding these infants breast milk. For those who are not breast-fed, there should be a strategy to maintain beneficial gut flora that positively influences intestinal immunity. We review the current use of probiotics, prebiotics, and synbiotics, and safety and adverse effects. Other dietary modalities of possible potential in achieving this primary prevention, such as a Mediterranean diet, use of milk formula with modified (hydrolyzed) proteins, and the role of micronutrients, are also explored. Breast-feeding is effective in reducing the risk of asthma, allergic rhinitis, and atopic eczema among children. In addition, breast milk constitutes a major source of support for gut microbe colonization, due to its bifidobacteria and galactooligosaccharide content. The literature lacks consensus in recommending the addition of probiotics to foods for prevention and treatment of allergic diseases, while prebiotics may prove to be effective in reducing atopy in healthy children. There is insufficient evidence to support soy formulas or amino acid formulas for prevention of allergic disease. A healthy diet, such as the Mediterranean diet, may have a protective effect on the development of asthma and atopy in children. In children with asthma and allergic diseases, vitamin D deficiency correlates strongly with asthma, allergic rhinitis, and wheezing.

Biologic Therapy in Inflammatory Immunomediated Systemic Diseases: Safety Profile.

The discovery of some key molecular mechanisms underlying the dysregulation of the immune system responsible for inflammatory systemic diseases as severe as Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), and Systemic Vasculitides, led to the development and subsequent introduction into clinical practice of biological drugs which are significantly improving the management of such complex disorders. This novel molecular targeted therapeutics represents in fact a valid alternative or complementary treatment to conventional immunosuppressive strategies, characterized by broad, unspecific actions and severe adverse effects. Main advantages of the use of biologic drugs reside in their steroid-sparing effect and in the ability of inducing remission of refractory disease states or curing specific organ involvements. Aim of this article is to review and briefly discuss the scientific evidence supporting the use of biologics in these diseases, with a particular emphasis on their efficacy and safety profile compared to the canonical drugs.

Hypovitaminosis D and Low Bone Mineral Density in Inflammatory Bowel Disease Patients

Background: Increasing evidences suggest that hypovitaminosis D can play an important role in immuno-mediated diseases, such as Inflammatory Bowel Diseases (IBD). The hypovitaminosis D is an established risk factor for the development of osteopenia, osteoporosis and pathological fractures. Studies have reported a correlation between hypovitaminosis D, disease history and clinical features in Crohn's Disease (CD) and Ulcerative Colitis (UC). The aim of this study is to evaluate the vitamin D serum levels and the prevalence of bone mineral density (BMD) alterations in a population of Italian IBD patients and to correlate the prevalence of hypovitaminosis D with disease history and clinical features. Method: Between October 2013 and November 2014 we enrolled patients from our center that were affected by UC or CD. Exclusion criteria were age below 18 and over 60, concomitant vitamin D replacement therapy and concomitant gastrointestinal or endocrinological diseases which may alter vitamin D metabolism. All patients underwent 25-OH-vitamin D, ESR, C-reactive protein (CRP), PTH, serum calcium and phosphorus, β-CTX, alkaline phosphatase (bone isoenzyme) plasma assay and bone mass density (BMD) evaluation by lumbar and femoral dual-energy X-ray absorptiometry (DXA) scan. Both measurements were made at the same time, during the autumn and winter months. Following 2012 Osteoporosis Italian Society Guidelines, we defined as hypovitaminosis D plasmatic values <30 ng/mL, vitamin D levels were considered as insufficient if between 20 and 30 ng/ mL and deficient if <20 ng/mL. We collected data regarding patients’ life habits and clinical history, disease course and disease clinical activity at enrollment. For BMD evaluation T-score and/or Z-score were calculated for each patient at lumbar (L1-L4) and femoral neck level, and the diagnosis of osteopenia or osteoporosis was made according to international guidelines. Results: We enrolled 88 patients (62 CD, 26 UC); median age at enrollment was 42 years for CD and 43 years for UC. Mean Body Mass Index (BMI) was 22.6 in CD and 23.7 in UC patients. Age at diagnosis was 29.8 years for CD and 33.5 years for UC, with mean disease duration of 12.8 years for CD and 9.1 years for UC.Hypovitaminosis D was observed in 84.1% of the patients. Of these, 31.8% had insufficient vitamin D levels, whereas 57.3% deficient. Mean vitamin D level was 20.4 ng/mL, but there was no difference with respect to sex or disease type. Indeed, there was no correlation between hypovitaminosis D and disease duration or patients age at diagnosis. A statistically significant correlation was found between hypovitaminosis D and history of steroid-dependancy (p=0.03), need of therapy with anti- TNF-α drugs (p=0.01) and cigarette smoke habit in CD patients (p=0.01). In CD patients we also found a correlation, at the limit of statistical significance (p=0.05), between hypovitaminosis D, high CRP values and HarveyBradshaw Index (HBI) at enrollment.70 patients underwent the lumbar DXA analysis, 67 the femoral DXA. Lumbar BMD was found to be below the normal range in 37.1% of the patients, suggesting that 24.2% and 12.9% were affected by osteopenia or osteoporosis, irrespective of sex and disease type (CD or UC). Similarly, femoral BMD was below the normal range for age in 43.3% of the patients. This figure is consistent with osteopenia or osteoporosis in 34.3% and 9%, irrespective of sex and disease type and femoral Z-score that was found significantly lower in CD than UC patients (p=0.03). Reduced BMD correlated with lower BMI and hypovitaminosis D. Conclusion: In our study we found a high prevalence of hypovitaminosis D in an IBD population irrespective of patients' sex, type and duration of disease. Our data show a strong correlation between hypovitaminosis D and a more aggressive disease course in terms of history of steroiddependancy, need of therapy with anti TNF-α drugs and smoke habit in CD patients. Hypovitaminosis D may play a crucial role in causing a more severe clinical behavior of IBD. Alteration of bone metabolism is a concern in IBD patients. We observed a high prevalence of BMD alterations in both men and women affected by UC and CD, even if of young age and with a short disease duration, irrespective of the type of IBD. Such patients may be prescribed lumbar and femoral, especially in cases of hypovitaminosis D and low BMI. This would allow an early diagnosis of BMD alterations, to start specific therapy and to prevent further complications.

Association of Crohn's Disease and Celiac Disease: Causal link or only coincidence?

Crohn’s disease (CD) is a chronic inflammatory bowel disease that affects any part of the gastrointestinal tract, most commonly terminal ileum and proximal colon; and Celiac Disease (CeD) is immuno-mediated systemic disease caused by gluten and similar prolamins in genetically susceptible individuals. Concomitant occurrence of CD and CeD is rare and there are limited literature data regarding the association of CeD to CD. Although, recent findings propose shared mechanisms, genetics and functional pathways. Herein, we report a case that has co-occurrence of CD and CeD and rewiew the literature of the association between these two diseases.

Dermatomyositis: A Rare Extra-intestinal Manifestation of Ulcerative Colitis

Inflammatory myositis as an extra-intestinal manifestation of inflammatory bowel disease (IBD) is rare. Coexistence of immuno-mediated diseases in patients with IBD and myositis suggests a common etiopathogenic mechanism underlying these conditions. The current report refers to a rare case of a 45-year-old Korean female with ulcerative colitis (UC) who developed dermatomyositis. She presented with skin rash and proximal muscle weakness, and her disease activity of UC was in remission state. Electromyography, magnetic resonance imaging, and deltoid muscle biopsy were performed. She was diagnosed with dermatomyositis associated with UC and treatment with glucocorticoids and azathioprine resulted in improvement in muscle power and skin rash. Clinicians should be aware of this unusual extra-intestinal manifestation. (J Rheum Dis 2016;23:183-186)

NET amyloidogenic backbone in human activated neutrophils.

Activated human neutrophils produce a fibrillar DNA network [neutrophil extracellular traps (NETs)] for entrapping and killing bacteria, fungi, protozoa and viruses. Our results suggest that the neutrophil extracellular traps show a resistant amyloidogenic backbone utilized for addressing reputed proteins and DNA against the non-self. The formation of amyloid fibrils in neutrophils is regulated by the imbalance of reactive oxygen species (ROS) in the cytoplasm. The intensity and source of the ROS signal is determinant for promoting stress-associated responses such as amyloidogenesis and closely related events: autophagy, exosome release, activation of the adrenocorticotrophin hormone/α-melanocyte-stimulating hormone (ACTH/α-MSH) loop and synthesis of specific cytokines. These interconnected responses in human activated neutrophils, that have been evaluated from a morphofunctional and quantitative viewpoint, represent primitive, but potent, innate defence mechanisms. In invertebrates, circulating phagocytic immune cells, when activated, show responses similar to those described previously for activated human neutrophils. Invertebrate cells within endoplasmic reticulum cisternae produce a fibrillar material which is then assembled into an amyloidogenic scaffold utilized to convey melanin close to the invader. These findings, in consideration to the critical role played by NET in the development of several pathologies, could explain the structural resistance of these scaffolds and could provide the basis for developing new diagnostic and therapeutic approaches in immunomediated diseases in which the innate branch of the immune system has a pivotal role.

Refractory epilepsy responsive to nonspecific immunossupression: autoimmune or auto inflammatory disease? A case report and review of literature

Over the past few years, some epilepsies have been found to be associated with immunomediated disorders. The presence of antibodies against intracellular and extracellular proteins especially in refractory epilepsy provides additional evidence of immunomediated diseases in the brain. In refractory epilepsy, autoantibodies against NMDAR, GAD and the VGKC-complex can be found in 2 to 16% of patients. The definition of autoinflammatory diseases was first introduced by Kastner et al in 2009 after the discovery of a homozygous mutation in the gene MEV1, responsible for Mediterranean Fever. After that, the recognition of inflammassome and interleukin 1 as the main actors in the innate immune system responsible for inflammation in these diseases has changed the treatment for some rare disorders.

Microbes as trigger/sustainers of chronic immuno-mediated inflammatory diseases

Microbes as trigger/sustainers of chronic immuno-mediated inflammatory diseases

Welcome to a new era for Clinical and Molecular Allergy.

Welcome to a new era for Clinical and Molecular Allergy.

Anti-neutrophlic cytoplasmic antibody Elastase, Lactoferrin, Cathapsin G,and Lysozyme in a sample of Iraqi patients with Rheumatoid Arthritis

mucosal secretions as well as in secondary granules of polymorphonuclear leukocytes. Anti-Elastase antibodies, anti-Lactoferrin antibodies,anti-Cathapsin G antibodies and anti-Lysozyme antibodies, which belong to Perinuclear Anti-Neutrophil Cytoplasmic Antibodies(pANCA) have been described in several immunomediated diseases, including Rheumatoid Arthritis .Objectives: Investigate the prevalence of anti-Elastase antibodies, anti-Lactoferrin antibodies,anti-Cathapsin G antibodies , anti- Lysozyme antibodies and rheumatoid factor in patients with rheumatoid arthritis in comparison to healthy control.Patients &amp;Methods: The study involved 40 Rheumatoid Arthritis patients who were referred to Immunological Department in Teaching laboratory \ Medical City during period of (1st of January – 31st of June) 2011 and 25 apparently healthy individual used as a control group were investeged to rheumatic factor IgG, IgM ,IgA isotypes and Elastase antibodies, Lactoferrin antibodies, Cathapsin G antibodies , and lysozyme antibodies were measured by using enzyme immunoassay technique.Results : Anti- Elastase, Abs anti-Cathapsin G Abs ,and anti-lysozyme Abs showed significant correlation with RF screen, and the mean concentration for these antibodies in rheumatoid arthritis patients with significant difference if compare it with the healthy control group. While anti-Lactoferrin Abs showed no significant correlation with RF screen. This study showed a association between the positive results of anti- Cathapsin G Abs with RF IgG and RF IgM only .Anti- Elastase Abs, Anti-Lactoferrin Abs and Antilysozyme Abs showed neither a significant correlation with RF IgG, RF IgM nor with RF IgA.Conclusion:A significant correlation was found between Elastase antibodies, Cathapsin G antibodies , lysozyme antibodies and patients with rheumatiod arthritis Cathapsin G antibodies has a significant association with RF IgG and RF IgM