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The immunopathogenesis of sarcoidosis remains unclear. This failure in understanding has been clinically impactful, as it has impeded the accurate diagnosis, treatment, and prevention of this disease. Unraveling the mechanisms of sarcoidosis will require input from basic and translational scientists. In order to reach this goal, scientists must have a firm grasp of the clinical aspects of the disease, including its diagnostic criteria, the immunologic defects, clinical presentations, response to therapy, risk factors, and clinical course. This manuscript will provide an overview of the clinical aspects of sarcoidosis that are particularly relevant for the basic and translational scientist. The variable phenotypic expression of the disease will be described, which may be integral in identifying immunologic disease mechanisms that may be relevant to subgroups of sarcoidosis patients. Data concerning treatment and risk factors may yield important insights concerning germane immunologic pathways involved in the development of disease. It is hoped that this manuscript will stimulate communication between scientists and clinicians that will eventually lead to improved care of sarcoidosis patients.

Knowledge related to the biology of inborn errors of immunity and associated laboratory testing methods continues to expand at a tremendous rate. Despite this, many patients with inborn errors of immunity suffer for prolonged periods of time before identification of their underlying condition, thereby delaying appropriate care. Understanding that test selection and optimal evaluation for patients with recurrent infections or unusual patterns of inflammation can be unclear, we present a document that distills relevant clinical features of immunologic disease due to inborn errors of immunity and related appropriate and available test options. This document is intended to serve the practicing clinical immunologist and, in turn, patients by describing best available test options for initial and expanded immunologic evaluations across the disease spectrum. Our goal is to demystify the process of evaluating patients with suspected immune dysfunction and to enable more rapid and accurate diagnosis of such individuals.

Background: The occurrence of left atrial appendage (LAA) thrombus formation and embolic myocardial infarction (MI) is rarely reported in the absence of atrial fibrillation (AF). In patients with a history of immunologic disease, a multidisciplinary approach is critical for prompt evaluation and treatment. Presentation: A 46-year-old woman with chest pain and lower extremity paresthesias was found to have NSTEMI. Past medical history was notable for vasculitis and multiple organ infarcts. Coronary angiogram and cardiac MRI showed no obstructive or structural disease. One month later she had recurrent chest pain with inferior ST-elevations on ECG and troponin of 24ng/mL. Investigations and Outcome: Coronary catheterization showed multiple embolic occlusions (Figure 1A and 1B). Subsequent TEE showed LAA thrombus (Figure 1C). Continuous telemetry and serial ECGs from initial presentation were negative for AF. Hypercoagulable and antiphospholipid testing was negative. Brain MRI for paresthesias showed dural enhancement and subsequent biopsy found an IgG4 inflammatory process. Treatment with warfarin, corticosteroids, and rituximab was initiated. No atrial fibrillation was detected on serial EKGs and an event monitor during one year of follow-up. There was no embolic recurrence. Conclusion: Autoimmune diseases can have complex organ involvement through lesser known mechanisms which often present as diagnostic challenges. This case identifies the potential for cardioembolic events, including myocardial infarction, in IgG4 vasculitis even in the absence of atrial fibrillation or hypercoagulability.

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic.Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.

The topics of climate change and ecosystem disruption are at the forefront of global discussion. Accordingly, there is a sense of urgency among citizens, environmental experts, and political leaders for action and policy change. While the effect of a changing climate on the environment is well recognized, its impact on the human body has not been sufficiently described. In our review, we will attempt to outline some of these effects. We will discuss how the recent surge of immunologic disease may be related to the changing profile of microorganisms and antigens in our every-day environment. We will explore how the introduction of antibiotics may result in an altered gut microbiome, and subsequently abnormal neurodevelopment. Finally, we will discuss a possible link between chemical preservatives and neoplastic disease.

The veterinary drugs used in food producing animals has led to residues occurring in animal products as (meat, milk, eggs and honey), poses a health hazard to the consumer.

During the last half-century, human beings have developed new processes to both produce and preserve food for immediate and long term consumption

The discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) and their subsequent development for gene modification has revolutionized ...

Celiac disease (CD) is an inflammatory syndrome that affects mainly the intestine, but also other organs. This ailment is also affected by the physicochemical behavior of gluten as such. From the medical standpoint, this pathology results from a combination of genetic and environmental factors. At the same time, gliadin (the alcohol-soluble fraction of gluten) along with other related oligomers, such as 33-gliadin, present high immunogenicity and are responsible for triggering of this disease. Within CD characterization, there are mainly two different approaches to carry out this study; one focuses on its chronic phase, while the other deals with its initial stages. Although the chronic phase of CD has been well characterized, the initiation of the inflammatory process is still unclear. As this process is apparently related to the aggregation of the oligomers involved in CD, the initiation of the disease could be explained by means of clarifying their self-assembly behavior. Thus, this work addresses the clinical explanation, within the chronic approach, attempting to combine it with the physicochemical techniques used for characterization of proteins aggregates as well. Fil: Benedini, Luciano Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: González Vidal, Noelia Luján. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina Fil: Gonzalez, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina

Costimulatory molecules have been identified as crucial regulators in the inflammatory response in various immunologic disease models. These molecules are classified into four different families depending on their structure. Here, we will focus on various ischemia studies that use costimulatory molecules as a target to reduce the inherent inflammatory status. Furthermore, we will discuss the relevant role of T regulatory cells in these inflammatory mechanisms and the costimulatory pathways in which they are involved.

Systemic lupus erythematosus (SLE) is a multisystem immunologic disease. Renal and neurological manifestations are frequently seen in childhood SLE. Out of the neurological features movement disorders are uncommon. A case of SLE is presented here with unusual neurological manifestation i.e. chorea associated with microphonia.

Resumo A relação entre doenças autoimunes e infeção está bem descrita na literatura. No entanto, desconhece-se qual o mecanismo patofisiológico envolvido nas infeções para o desenvolvimento de autoimunidade. Por outro lado, existem infeções que cursam transitoriamente com positividade para alguns auto-anticorpos sem nenhuma evidência de doença imunológica. A nefrite de shunt (NS) é uma glomerulonefrite mediada por imunocomplexos que surge habitualmente associada a infeção de shunt ventrículo-auricular. Raramente, a NS pode-se acompanhar de marcadores imunológicos positivos como os anticorpos antinucleares e anti-citoplasma dos neutrófilos (ANCA). Contrariamente, os anticorpos anti-DNA de cadeia dupla (anti-dsDNA) são reconhecidos pela sua especificidade para o diagnóstico de Lúpus e desconhecem-se relatos prévios da sua associação a NS. Os autores apresentam o caso de uma NS com positividade tanto para os ANCA-PR3 como para os anti-dsDNA em que não houve manifestação de doença autoimune e em que a resolução da infeção levou à descida paulatina dos autoanticorpos. Que tenhamos conhecimento, este é o primeiro caso de NS com elevação transitória de anti-dsDNA. Abstract The relationship between autoimmune disease and infection is well known in literature. However, the pathophysiologic role of infections in the development of autoimmunity is largely unknown. Furthermore, there are infections that occur with transient autoantibody positivity without any evidence of immunologic disease. Shunt nephritis (SN) is an immune complex mediated glomerulonephritis usually related with infection of ventriculoatrial shunt. Rarely, SN may be accompanied by positive immunological markers, like antinuclear and anti-neutrophil cytoplasm (ANCA) antibodies. In contrast, antibodies to double-stranded DNA (anti-dsDNA) are recognized by their specificity for the diagnosis of lupus, and have never been described in association with SN. The authors present the case of a NS with positivity for both PR3-ANCA and for anti-dsDNA in which there was no manifestation of autoimmune disease and the resolution of the infection led to the gradual decline of autoantibodies. To our knowledge this is the first report of a NS with transient elevation of anti-dsDNA.

Over the past 40 years Dr. Robert Lisak has made important contributions to our understanding of the pathophysiology and therapy of myasthenia gravis. This review will touch upon some of his work as it discusses current therapies and the potential for new treatments based on the evolving knowledge of the underlying basis of the disease. The recognition of different immune mechanisms that can cause the phenotype that we acknowledge as myasthenia gravis coincides with the introduction of monoclonal antibodies and other new therapies that can target specific aspects of the disease. This has raised our hopes for treatments that will have less side effects and be more effective. In some cases these hopes have been realized. In other instances, the situation remains a "work in progress". Dr. Lisak's work and teachings remain cogent to our modern approach to this classic immunologic disease.

Allergic rhinitis (AR) is the most common immunologic disease in industrialized societies and has a significant impact on quality of life. Most asthmatics also have rhinitis. AR may present with comorbidities, including chronic otitis media with effusion, cough, and pollen-food cross-reactivity. AR may occur in isolation or be part of a mixed rhinitis.

Specialists in allergy/immunology are often asked to evaluate patients with eosinophilia, with the general assumption of an underlying allergic or immunologic disease. We present a case of an infant referred for marked eosinophilia. Although atopic disease may be in the differential diagnosis, it is rarely associated with hypereosinophilia, and other conditions need to be investigated. Until the underlying cause is identified, systemic corticosteroid therapy may be initiated, mainly in severe cases.

Background: Allergic rhinitis (AR) is the most common immunologic disease, and it renders a considerable burden on both sufferers and society. The prevalence of AR has been increasing worldwide ove ...

In order to reproduce completely the function of an organ, past research has considered hybrid artificial organs as the only method to achieve this goal. Various attempts have been made to use cell components, whole cells, tissue, and organ sections in conjunction with artificial organ systems. However, utilization of biological preparations or tissues is not clinically practical today. In this paper disadvantages of using natural tissue preparations are outlined. Recent progress in membrane technology such as membrane plasmapheresis, particularly on-line plasma treatment by multiple reactors, on-line plasma treatment by cryogelation, or the use of a cascade membrane scheme for the selective removal of macromolecules, will provide the tools to treat and remove macromolecules which were once considered extremely difficult to treat. The historical development of membrane plasmapheresis is described, including potential applications of this type of artificial organ for practical clinical treatment of metabolic, toxic and immunologic disease states.

This article focuses on the neuroendocrine infrastructure of the adaptive response to stress and on its effects on the major endocrine axes in the body. Also discussed is the altered regulation or dysregulation of the adaptive response in various physiologic and pathophysiologic states, which may influence the growth and development of an individual and define the vulnerability of this individual to endocrine, psychiatric, or immunologic disease.

IntroductionSjogren syndrome (SS) is a systemic autoimmune disease that mainly affects the exocrine glands and usually presents as persistent dryness of the mouth and eyes due to functional impairment of the salivary and lacrimal glands (12). In the absence of an associated systemic autoimmune

The ability to accurately quantitate and experimentally examine epigenetic modifications across the human genome has exploded in the past decade. This has given rise to a wealth of new information concerning the contributions of epigenetic regulatory networks to the pathogenesis of human disease. In particular, immunological disorders have strong developmental roots in chromatin regulatory pathways. In this review, we focus on the epigenetic signatures and new discoveries revealing the epigenetic compositions of specific immunological cancers and autoimmune diseases. We also comment on the conserved epigenetic roots among diverse immunological disorders and suggest inhibition strategies that may be relevant for future treatment. Finally, we highlight emerging experimental tools with the capability to examine the mechanisms of chromatin regulatory enzymes with a high level of temporal control. The knowledge of genetic and epigenetic defects in immunological disease combined with new experimental approaches will elucidate the contribution of individual enzymes in complex epigenetic regulatory networks. This could lead to new diagnostic and therapeutic approaches for some very diverse and difficult to treat human diseases.

Lichen planus (LP) is a chronic inflammatory disorder that most often affects middle-aged adults. LP can involve the skin or mucous membranes including the oral, vulvovaginal, esophageal, laryngeal, and conjunctival mucosa. It has different variants based on the morphology of the lesions and the site of involvement. The literature suggests that certain presentations of the disease such as esophageal or ophthalmological involvement are underdiagnosed. The burden of the disease is higher in some variants including hypertrophic LP and erosive oral LP, which may have a more chronic pattern. LP can significantly affect the quality of life of patients as well. Drugs or contact allergens can cause lichenoid reactions as the main differential diagnosis of LP. LP is a T-cell mediated immunologic disease but the responsible antigen remains unidentified. In this paper, we review the history, epidemiology, and clinical subtypes of LP. We also review the histopathologic aspects of the disease, differential diagnoses, immunopathogenesis, and the clinical and genetic correlations.

結核は慢性感染症である.しかしその病態は,マクロファージとヘルパーT細胞1 (TH1)が主体の遅延型アレルギーである.すなわち,結核菌体の刺激によりTH1指向性のサイトカインが感染局所に過剰産生され,菌体蛋白抗原特異的なTH1細胞が誘導される.その結果,マクロファージが活性化されて類上皮細胞, Langhans巨細胞を経て,結核結節や結核性空洞形成へと進む.

Parkinsonism is a rare feature of immunological diseases. We describe a 67-year-old man with Caplan's syndrome (CS) and parkinsonism. CS is an immunologic disease characterised by the presence of rheumatoid arthritis associated with a specific form of pneumoconiosis. Parkinsonism as a manifestation of involvement of the central nervous system in this condition has never been reported. Following immunosuppressive treatment both the CS and the parkinsonian signs and symptoms showed a marked improvement. The role of immune mechanisms in these parkinsonian syndromes is discussed.

Bronchoalveolar lavage (BAL) has become an invaluable diagnostic tool with important clinical implications in both opportunistic infections and the pulmonary pathology of immunologic disease. Until recently, the use of BAL was limited primarily to two areas: the study of interstitial lung diseases and the diagnosis of lung infections by opportunistic microorganisms in severely immunocompromised patients with lung infiltrates. Over the past decade, the use of BAL has been expanded to include the conventional diagnosis of bacterial pneumonia in non-immunocompromised patients. In the past, different clinical studies proposed using BAL to quantify cultures in the sample obtained as a means of increasing the tool's effectiveness. Recent developments have led to a number of newer applications of BAL, such as bronchoscopic BAL, non-bronchoscopic BAL and protected BAL. The most important use of BAL in the non-immunocompromised patient is the diagnosis of pneumonia in the mechanically ventilated patient.

CD is an immunologic disease of the small intestine which is precipitated by ingestion of wheat gliadin. Most patients carry the HLA-DQ (α1 ∗ 0501,β1 ∗ 0201) (DQ2) heterodimer. We recently reported that a prepoderance of gliadin-specific T cells from the small intestinal mucosa of DQ2-positive CD patients were restricted by this DQ heterodimer. However, a small percentage of CD patients do not carry this DQ heterodimer, and most of them instead carry DQ (α1 ∗ 0301,β1 ∗ 0302) (DQ8). Here we report that a majority of gliadin-specific T cells from the small intestinal mucosa of a DR4,DQ7/DR4,DQ8 heterozygous CD patient are restricted by DQ8. Thus, preferential presentation of gliadin-derived peptides to T cells by the CD-associated DQ2 and DQ8 molecules may be an initial and important immunopathogenic step in CD. Human Immunology 41, 285–291 (1994)

Systemic lupus erythematosus (SLE) is an immunologic disease that is multisystemic and as a result can manifest itself in various organs. In general, the hematologic manifestations of the disease c...

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Publisher Summary This chapter appraises the use of mathematical modeling to enhance drug discovery and development for several diseases characterized by dysfunction of the immune system. Immunological modeling provides useful insights throughout the pharmaceutical process, from early-stage drug discovery such as target prioritization to development efforts. These are aimed at optimizing treatment schedules and personalizing treatment approaches. Further, models allow the researcher to simulate biological processes and analyze the consequences of manipulating the underlying biology. The study of immunological diseases is challenged by the diversity and complexity of immune responses to environmental and endogenous stresses. Effective and safe treatment of immunologic diseases remains a challenging goal because of the complex, context-dependent function of numerous immunologic components. The techniques of systems biology have been applied to the study of immunologic diseases to integrate disparate datasets, formulate and test new hypotheses, and further scientific understanding of complex biological processes. Applications of mathematical modeling in the areas of infectious disease, cancer, allergy and autoimmunity have also been discussed. This study illustrates how mathematical models can be used to guide drug discovery and development. Although modeling and simulation will continue to have increasing roles in immunologic research, drug discovery and development, caution should be used when using model predictions in the absence of supporting in-vitro and in-vivo data. Cross-disciplinary collaboration among engineers, mathematicians, researchers and clinicians is essential to sound model development and interpretation of the results of simulations. As systems biology approaches are applied and refined continued advances in understanding of immunologic disease processes can be anticipated.

Absorption of small amounts of various dietary antigens in an intact state is a normal phenomenon in humans. This article discusses the normal mechanisms of excess antigen exclusion, examples of the states in which absorption can occur, and some of the immunologic consequences that have been documented.