Pub Date : 2021-06-17DOI: 10.5772/intechopen.98617
F. Nicolini, M. Mazza
The interplay between the immune system and the pleural mesothelium is crucial both for the development of malignant pleural mesothelioma (MPM) and for the response of MPM patients to therapy. MPM is heavily infiltrated by several immune cell types which affect the progression of the disease. The presence of organized tertiary lymphoid structures (TLSs) witness the attempt to fight the disease in situ by adaptive immunity which is often suppressed by tumor expressed factors. In rare patients physiological, pharmacological or vaccine-induced immune response is efficient, rendering their plasma a valuable resource of anti-tumor immune cells and molecules. Of particular interest are human antibodies targeting antigens at the tumor cell surface. Here we review current knowledge regarding MPM immune infiltration, MPM immunotherapy and the harnessing of this response to identify novel biologics as biomarkers and therapeutics through innovative screening strategies.
{"title":"The Immune System of Mesothelioma Patients: A Window of Opportunity for Novel Immunotherapies","authors":"F. Nicolini, M. Mazza","doi":"10.5772/intechopen.98617","DOIUrl":"https://doi.org/10.5772/intechopen.98617","url":null,"abstract":"The interplay between the immune system and the pleural mesothelium is crucial both for the development of malignant pleural mesothelioma (MPM) and for the response of MPM patients to therapy. MPM is heavily infiltrated by several immune cell types which affect the progression of the disease. The presence of organized tertiary lymphoid structures (TLSs) witness the attempt to fight the disease in situ by adaptive immunity which is often suppressed by tumor expressed factors. In rare patients physiological, pharmacological or vaccine-induced immune response is efficient, rendering their plasma a valuable resource of anti-tumor immune cells and molecules. Of particular interest are human antibodies targeting antigens at the tumor cell surface. Here we review current knowledge regarding MPM immune infiltration, MPM immunotherapy and the harnessing of this response to identify novel biologics as biomarkers and therapeutics through innovative screening strategies.","PeriodicalId":272660,"journal":{"name":"Rare Diseases [Working Title]","volume":"258 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124234383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-23DOI: 10.5772/intechopen.97036
M. Nita, J. Pliszczyński, A. Eljaszewicz, M. Moniuszko, T. Oldak, K. Woźniak, S. Majewski, C. Kowalewski, A. Kamiński, D. Šladowski, Z. Zimek, M. Kosieradzki, P. Fiedor
Epidermolysis bullosa (EB) is a group of hereditary skin diseases, or genodermatoses, characterized by the formation of severe, chronic blisters with painful and life-threatening complications. Despite the previous and ongoing progress in the field, there are still no effective causative treatments for EB. The treatment is limited to relieving symptoms, which—depending on disease severity—may involve skin (blisters, poorly healing wounds caused by the slightest mechanical stimuli, contractures, scarring, pseudosyndactyly) and internal organ abnormalities (esophageal, pyloric, or duodenal atresia; renal failure; and hematopoietic abnormalities). The last decade saw a series of important discoveries that paved the way for new treatment methods, including gene therapy, bone marrow transplantation, cell therapy (allogenic fibroblasts, mesenchymal stem cells [MSCs], and clinical use of induced pluripotent stem cells. Tissue engineering experts are attempting to develop skin-like structures that can facilitate the process of healing to promote skin reconstruction in injuries that are currently incurable. However, this is incredibly challenging, due to the complex structure and the many functions of the skin. Below, we characterize EB and present its potential treatment methods. Despite the cure for EB being still out of reach, recent data from animal models and initial clinical trials in humans have raised patients’, clinicians’, and researchers’ expectations. Consequently, modifying the course of the disease and improving the quality of life have become possible. Moreover, the conclusions drawn based on EB treatment may considerably improve the treatment of other genetic diseases.
{"title":"Surgical Treatment of Wounds Using Stem Cells in Epidermolysis Bullosa (EB)","authors":"M. Nita, J. Pliszczyński, A. Eljaszewicz, M. Moniuszko, T. Oldak, K. Woźniak, S. Majewski, C. Kowalewski, A. Kamiński, D. Šladowski, Z. Zimek, M. Kosieradzki, P. Fiedor","doi":"10.5772/intechopen.97036","DOIUrl":"https://doi.org/10.5772/intechopen.97036","url":null,"abstract":"Epidermolysis bullosa (EB) is a group of hereditary skin diseases, or genodermatoses, characterized by the formation of severe, chronic blisters with painful and life-threatening complications. Despite the previous and ongoing progress in the field, there are still no effective causative treatments for EB. The treatment is limited to relieving symptoms, which—depending on disease severity—may involve skin (blisters, poorly healing wounds caused by the slightest mechanical stimuli, contractures, scarring, pseudosyndactyly) and internal organ abnormalities (esophageal, pyloric, or duodenal atresia; renal failure; and hematopoietic abnormalities). The last decade saw a series of important discoveries that paved the way for new treatment methods, including gene therapy, bone marrow transplantation, cell therapy (allogenic fibroblasts, mesenchymal stem cells [MSCs], and clinical use of induced pluripotent stem cells. Tissue engineering experts are attempting to develop skin-like structures that can facilitate the process of healing to promote skin reconstruction in injuries that are currently incurable. However, this is incredibly challenging, due to the complex structure and the many functions of the skin. Below, we characterize EB and present its potential treatment methods. Despite the cure for EB being still out of reach, recent data from animal models and initial clinical trials in humans have raised patients’, clinicians’, and researchers’ expectations. Consequently, modifying the course of the disease and improving the quality of life have become possible. Moreover, the conclusions drawn based on EB treatment may considerably improve the treatment of other genetic diseases.","PeriodicalId":272660,"journal":{"name":"Rare Diseases [Working Title]","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125068001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-22DOI: 10.5772/INTECHOPEN.97080
V. Gorodetskiy
Felty’s syndrome (FS) is an uncommon subset of seropositive rheumatoid arthritis (RA) complicated by neutropenia with or without splenomegaly. The pathogenesis of neutropenia in FS is still not fully understood, but it is believed that the principal cause is neutrophil survival defect. Autoantibodies against peptidylarginine deiminase type 4 deiminated histones, glucose-6-phosphate isomerase, and eukaryotic elongation factor 1A-1 antigen may contribute to neutropenia development in FS patients. Splenic histology in FS shows non-specific findings and spleen size do not correlate with neutropenia. Cases of T-cell large granular lymphocytic leukemia with low tumor burden in blood and concomitant RA are clinically indistinguishable from FS and present a diagnostic challenge. Examination of T-cell clonality, mutations in signal transducer and activator of transcription 3 gene, and the number of large granular lymphocytes in the blood can establish a correct diagnosis. Optimal approaches to therapy for FS have not been developed, but the use of rituximab seems promising. In this chapter, the epidemiology, pathogenesis, clinical manifestations, differential diagnosis, and treatment options for FS are discussed.
{"title":"Felty’s Syndrome","authors":"V. Gorodetskiy","doi":"10.5772/INTECHOPEN.97080","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.97080","url":null,"abstract":"Felty’s syndrome (FS) is an uncommon subset of seropositive rheumatoid arthritis (RA) complicated by neutropenia with or without splenomegaly. The pathogenesis of neutropenia in FS is still not fully understood, but it is believed that the principal cause is neutrophil survival defect. Autoantibodies against peptidylarginine deiminase type 4 deiminated histones, glucose-6-phosphate isomerase, and eukaryotic elongation factor 1A-1 antigen may contribute to neutropenia development in FS patients. Splenic histology in FS shows non-specific findings and spleen size do not correlate with neutropenia. Cases of T-cell large granular lymphocytic leukemia with low tumor burden in blood and concomitant RA are clinically indistinguishable from FS and present a diagnostic challenge. Examination of T-cell clonality, mutations in signal transducer and activator of transcription 3 gene, and the number of large granular lymphocytes in the blood can establish a correct diagnosis. Optimal approaches to therapy for FS have not been developed, but the use of rituximab seems promising. In this chapter, the epidemiology, pathogenesis, clinical manifestations, differential diagnosis, and treatment options for FS are discussed.","PeriodicalId":272660,"journal":{"name":"Rare Diseases [Working Title]","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122246165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-12DOI: 10.5772/INTECHOPEN.96543
Katharina Sterlich, M. Minkov
Childhood LCH is a rare disease, affecting 4–9 per 1,000,000 children below the age of 15 years. It is driven by somatic mutations in the MAPK pathway, arising in myeloid marrow progenitors. Both genders are affected by a slight male preponderance. The clinical spectrum of LCH varies from a single lesion affecting one organ system to severe multisystem disease with dysfunction of vital organs. Likewise, variable and unpredictable is its course, spanning from self-limiting course to progression with lethal outcome. Recognized unfavorable prognostic factors are the involvement of hematopoiesis, liver, and spleen, as well as non-response to systemic treatment. Recent studies suggest that patients carrying the BRAFV600E mutation may have a more severe clinical phenotype and less favorable prognosis. The combination of prednisolone and vinblastine is the standard first-line treatment for disseminated disease. Second-line options used in clinical practice are not well evidenced. Inhibitors of the MAPK pathway are a promising alternative option.
{"title":"Childhood Langerhans Cell Histiocytosis: Epidemiology, Clinical Presentations, Prognostic Factors, and Therapeutic Approaches","authors":"Katharina Sterlich, M. Minkov","doi":"10.5772/INTECHOPEN.96543","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.96543","url":null,"abstract":"Childhood LCH is a rare disease, affecting 4–9 per 1,000,000 children below the age of 15 years. It is driven by somatic mutations in the MAPK pathway, arising in myeloid marrow progenitors. Both genders are affected by a slight male preponderance. The clinical spectrum of LCH varies from a single lesion affecting one organ system to severe multisystem disease with dysfunction of vital organs. Likewise, variable and unpredictable is its course, spanning from self-limiting course to progression with lethal outcome. Recognized unfavorable prognostic factors are the involvement of hematopoiesis, liver, and spleen, as well as non-response to systemic treatment. Recent studies suggest that patients carrying the BRAFV600E mutation may have a more severe clinical phenotype and less favorable prognosis. The combination of prednisolone and vinblastine is the standard first-line treatment for disseminated disease. Second-line options used in clinical practice are not well evidenced. Inhibitors of the MAPK pathway are a promising alternative option.","PeriodicalId":272660,"journal":{"name":"Rare Diseases [Working Title]","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132634291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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