RESUMEN
Hypersensitivity to mosquito bites (HMB) is a rare disease characterized by transient intense skin reaction and systemic inflammation. Clinical presentation of HMB resembles other mosquito allergic responses, and it can also be difficult to clinically distinguish HMB from other severe allergic reactions. However, a distinctive pathophysiology underlies HMB. HMB belongs to a category of Epstein-Barr virus (EBV)-associated natural killer (NK) cell lymphoproliferative disorders (LPD). Hence, HMB may progress to systemic diseases, such as hemophagocytic lymphohistiocytosis, chronic active EBV disease, and EBV-associated malignancies. A triad of elevated serum IgE, NK lymphocytosis, and detection of EBV DNA in peripheral blood is commonly observed, and identification of EBV-infected NK cells usually facilitates the diagnosis. However, the effective treatment is limited, and its precise etiology remains unknown. Local CD4+ T cell proliferation triggered by mosquito bites appears to help induce EBV reactivation and EBV-infected NK-cell proliferation. These immunological interactions may explain the transient HMB signs and symptoms and the disease progression toward malignant LPD. Further research to elucidate the mechanism of HMB is warranted for better diagnosis and treatment of HMB and other forms of EBV-associated LPD.
Asunto(s)
Culicidae , Infecciones por Virus de Epstein-Barr , Hipersensibilidad , Trastornos Inmunoproliferativos , Inflamación , Mordeduras y Picaduras de Insectos/complicaciones , Neoplasias , Animales , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/etiología , Infecciones por Virus de Epstein-Barr/virología , Humanos , Hipersensibilidad/epidemiología , Hipersensibilidad/etiología , Hipersensibilidad/virología , Trastornos Inmunoproliferativos/etiología , Trastornos Inmunoproliferativos/inmunología , Trastornos Inmunoproliferativos/virología , Inflamación/epidemiología , Inflamación/etiología , Inflamación/virología , Mordeduras y Picaduras de Insectos/epidemiología , Mordeduras y Picaduras de Insectos/virología , Células Asesinas Naturales/inmunología , Neoplasias/epidemiología , Neoplasias/etiología , Neoplasias/virologíaRESUMEN
Results of long-term immunological monitoring of liquidators of consequences of the Chernobyl accident and the revealed regularities are presented. Earlier the unknown phenomenon of the activating influence of radiation at small doses on the T-cellular link of the immune status (IS), mainly on T-lymphocytes/helper was for the first time established. This phenomenon came to light among participants of LPA working in an extreme situation of 1986 in the zones of the CN PP and further was confirmed by inspection of the personnel of a 30-km zone of the CNPP in 1990; the personnel at radiation dangerous nuclear power plants and the population living near these objects, the population polluted by radionuclides on the territories of the Bryansk region. This effect in the presence of clinical symptoms which can be caused by influence of a radiation factor was most expressed. Prognostic value of the changes in the development of IS immune insufficiency (ID), cellular and humoral link in the near future after taking part in clean-up workers are established. These laws have a theoretical value for immunology and radiobiology, and practical health care as well, as the formation of a phenotype of IS defines approaches to immunoprophylactics and immunocorrection, as in extreme situations, and in the following years. During the delayed periods development of an imbalance, immune in- sufficiency in T-lymphocytes and natural killer cells is revealed. By the end of the 3rd - the beginning of the 4th fifth anniversary after the accident the high frequency of clinical manifestations of immune dysfunction and chronic somatic diseases was defined. The immunological characteristic of an immunoproliferative syn- drome that allowed one to reveal predictors of early diagnostics of malignant new growths in immune status is for the first time established. Clinical-immunological signs of early aging of liquidators and features of changes in liquidators in the lipidic status depending on the age and risk factors of Chernobyl accident are revealed. Features of antiviral protection of an organism ofliquidators that is defined by changes in the cluster of genes of cytokines (IL28A, IL28B and IL29) localized on the 19th chromosome (19ql3) of the person are established. Establishment of genotypes can be associated with a positive effect of treatment, steady and long remission of GVI.
Asunto(s)
Accidente Nuclear de Chernóbil , Trastornos Inmunoproliferativos/inmunología , Monitorización Inmunológica/métodos , Traumatismos por Radiación/inmunología , Humanos , Inmunidad/inmunología , Inmunidad/efectos de la radiación , Trastornos Inmunoproliferativos/epidemiología , Trastornos Inmunoproliferativos/etiología , Trastornos Inmunoproliferativos/fisiopatología , Interferones , Interleucinas/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/efectos de la radiación , Masculino , Exposición Profesional , Dosis de Radiación , Traumatismos por Radiación/epidemiología , Traumatismos por Radiación/fisiopatología , Factores de Riesgo , Linfocitos T/inmunología , Linfocitos T/efectos de la radiaciónRESUMEN
Cirrhosis and hepatocellular carcinoma are the prototypic complications of chronic hepatitis C virus infection in the liver. However, hepatitis C virus also affects a variety of other organs that may lead to significant morbidity and mortality. Extrahepatic manifestations of hepatitis C infection include a multitude of disease processes affecting the small vessels, skin, kidneys, salivary gland, eyes, thyroid, and immunologic system. The majority of these conditions are thought to be immune mediated. The most documented of these entities is mixed cryoglobulinemia. Morphologically, immune complex depositions can be identified in small vessels and glomerular capillary walls, leading to leukoclastic vasculitis in the skin and membranoproliferative glomerulonephritis in the kidney. Other HCV-associated entities include porphyria cutanea tarda, lichen planus, necrolytic acral erythema, membranous glomerulonephritis, diabetic nephropathy, B-cell non-Hodgkin lymphomas, insulin resistance, sialadenitis, sicca syndrome, and autoimmune thyroiditis. This paper highlights the histomorphologic features of these processes, which are typically characterized by chronic inflammation, immune complex deposition, and immunoproliferative disease in the affected organ.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Hepatitis C/complicaciones , Hepatitis C/inmunología , Enfermedades del Complejo Inmune/inmunología , Trastornos Inmunoproliferativos/inmunología , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/patología , Crioglobulinemia/complicaciones , Crioglobulinemia/inmunología , Crioglobulinemia/patología , Glomerulonefritis Membranoproliferativa/etiología , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/patología , Hepacivirus/inmunología , Hepatitis C/patología , Humanos , Enfermedades del Complejo Inmune/etiología , Enfermedades del Complejo Inmune/mortalidad , Trastornos Inmunoproliferativos/etiología , Trastornos Inmunoproliferativos/patología , Vasculitis/etiología , Vasculitis/inmunologíaRESUMEN
The acturial probability of malignant transformation was analyzed in a series of 263 patients with monoclonal gammopathy of undetermined significance (MGUS) over a 15-year period and followed from 5 to 20 years. At a median follow-up of 11.5 years, 157 patients (59.7%) had died of causes unrelated to MGUS, 47 (17.9%) were still alive and presented no increase in monoclonal component, 11 (4.1%) presented an increase in monoclonal component without evidence of malignant immunoproliferative disease, and 48 (18.3%) had developed a malignant transformation of MGUS. In particular, MGUS evolved into 35 cases of multiple myeloma, two of solitary plasmacytoma of the bone, four of macroglobulinemia, three of malignant lymphoma, two of amyloidosis, one of chronic lymphocytic leukemia, and one of plasma cell leukemia. The cumulative incidence of malignant transformation was 18.3%; and the actuarial risk of malignant transformation was 6.1, 15.4, and 31.3% at 5, 10 and 20 years, respectively. The multivariate regression analysis according to Cox's proportional hazard model selected among 22 different variables established at initial diagnosis of MGUS only age as the factor significantly (P < 0.011) and negatively (b = -1.104) related to the risk of developing a malignant immunoproliferative disease. Therefore, patients with MGUS present an increased risk of developing a malignant lymphoproliferative or plasma cell proliferative disease, and MGUS could be considered a pre-neoplastic condition. Since no clinical or laboratory features are able to identify in advance the patients at high risk of disease progression, each patient must be followed up periodically and over an indefinite period.
Asunto(s)
Trastornos Inmunoproliferativos/epidemiología , Paraproteinemias/patología , Análisis Actuarial , Anciano , Transformación Celular Neoplásica , Femenino , Estudios de Seguimiento , Humanos , Trastornos Inmunoproliferativos/etiología , Persona de Mediana Edad , Análisis Multivariante , Paraproteinemias/complicaciones , Factores de RiesgoAsunto(s)
Trastornos Inmunoproliferativos/etiología , Linfocitos B/citología , Secuencia de Bases , Diferenciación Celular , Femenino , Reordenamiento Génico , Humanos , Inmunoglobulinas/clasificación , Inmunoglobulinas/genética , Masculino , Datos de Secuencia Molecular , Paraproteinemias/etiologíaRESUMEN
OBJECTIVE: To review data that postulate a role for cytokines and oncogenes in the pathogenesis of monoclonal gammopathies. DESIGN: Published studies that provide evidence of the clinical progression of normal B cells to monoclonal gammopathy of undetermined significance (MGUS) to active myeloma are discussed. RESULTS: On the basis of mouse plasmacytoma models, increased expression of c-myc in B lymphocytes may be the initial oncogenic event that leads to MGUS in humans. Over time, this monoclonal subpopulation may acquire additional genetic abnormalities, such as aberrant interleukin (IL) 1 beta expression. Because IL 1 beta has potent osteoclast activating factor activity, increased production of IL 1 beta by monoclonal plasma cells may be the genetic event responsible for the progression of MGUS to myeloma. The in vivo plasma cell labeling index (proliferative rate) is the most powerful prognostic factor in patients with myeloma. The proliferative compartment observed in myeloma may parallel normal B-cell development because cytoplasmic immunoglobulin-positive cells with the ability to proliferate exist normally. With continued progression of disease, the ratio of proliferating monoclonal plasmablasts to nonproliferating monoclonal plasma cells may increase under the influence of cytokines such as IL 6. CONCLUSION: A more complete understanding of the basic biologic features of myeloma should lead to innovative therapies in the future.
Asunto(s)
Citocinas , Trastornos Inmunoproliferativos/inmunología , Animales , Citocinas/genética , Citocinas/inmunología , Humanos , Trastornos Inmunoproliferativos/etiología , Trastornos Inmunoproliferativos/genética , Gammopatía Monoclonal de Relevancia Indeterminada/etiología , Gammopatía Monoclonal de Relevancia Indeterminada/genética , Gammopatía Monoclonal de Relevancia Indeterminada/inmunología , Mieloma Múltiple/etiología , Mieloma Múltiple/genética , Mieloma Múltiple/inmunologíaRESUMEN
This report has attempted to review the pathology of immunoblastic proliferations, to indicate their similarities and differences, and hopefully to offer some guidelines in the approach to their diagnosis. Their pathology, immunology, and clinical features overlap, making it necessary to evaluate all possible parameters in reaching definite diagnoses. Methods to identify predominant B- or T-cell populations in order to distinguish the neoplasms from the reactive or prelymphomatous lesions can be readily employed using immunohistochemical techniques on either snap-frozen or paraffin-embedded sections. Flow cytometry can be employed to identify major cell populations and evaluate DNA ploidy. DNA probe techniques and cytogenetic evaluation further define the possible clonality of immunoblastic proliferations. Common sense is a basic index for the initial approach to the problem. The abnormal immune lesions present firm challenges in histological diagnosis and in dealing with the concepts of the disease. The immunoblastic sarcomas must be recognized for their status as high-grade lymphomas and separated from the benign reversible reactions and problematic, potentially fatal abnormal immune processes.
Asunto(s)
Linfadenopatía Inmunoblástica/patología , Linfoma/patología , Lesiones Precancerosas/patología , Humanos , Linfadenopatía Inmunoblástica/etiología , Trastornos Inmunoproliferativos/etiología , Trastornos Inmunoproliferativos/patología , Linfoma/etiologíaRESUMEN
The neuropathologic findings of brains and spinal cords removed at autopsy from 26 infants and children with AIDS is described; in two cases, only the spinal cords were available. The most common finding in the brains was dystrophic calcification of blood vessels of all calibers in the basal ganglia and deep cerebral white matter (21 og 24 cases). The next most frequent finding was subacute encephalitis (SE) (15 of 24 cases) with microglial nodules and multinulceated giant cells. Immunocytochemical and in situ hybridization studies showed HIV antigen or genetic sequences only in the brains of cases with SE. Multinucleated giants cells (MGC) were the most frequent cells with reaction products. MGC were labeled with ricinus lectin (RCA), but not with leukocyte common antigen (LCA) or glial fibrillary acidic protein. Many cells in microglial nodules were labeled with RCA, but not LCA; cells in the perivascular compartment were labeled with LCA, but not RCA. Corticospinal tract degeneration was noted in 15 of 20 spinal cords. In six cases tract degeneration was consistent with delayed myelination, and the remaining cases had axonal injury consistent with Wallerian degeneration. Opportunistic infections were rare (three cases). Central nervous system lymphoma occurred in three children and was the most common mass lesion. In two cases lymphoma occurred in the setting of a systemic polyclonal immunoproliferation possibly related to Epstein-Barr virus infection. Cerebrovascular accidents were noted in seven cases. Two cases had hemorrhage associated with immune thrombocytopenia; one hemorrhage was catastrophic. Two children had large vessel arteriopathy with multiple encephalomalacias. Two children had a necrotizing encephalopathy with encephalomalacia and vascular changes suggestive of a mitochondrial cytopathy.(ABSTRACT TRUNCATED AT 250 WORDS)