[Interpretation of lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation in the 5th edition WHO classification of haematolymphoid tumours].

The fifth edition of the World Health Organization (WHO) classification of lymphohematopoietic system tumors updated the terminology, types of lesions, diagnostic criteria, nomenclature, and other aspects of lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation. The important updates and main changes in this section were briefly introduced, in order to guide the precise classification of lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation, and standardize pathological reports.

LRBA, a BEACH protein mutated in human immune deficiency, is widely expressed in epithelia, exocrine and endocrine glands, and neurons.

Mutations in LRBA, a BEACH domain protein, cause severe immune deficiency in humans. LRBA is expressed in many tissues and organs according to biochemical analysis, but little is known about its cellular and subcellular localization, and its deficiency phenotype outside the immune system. By LacZ histochemistry of Lrba gene-trap mice, we performed a comprehensive survey of LRBA expression in numerous tissues, detecting it in many if not all epithelia, in exocrine and endocrine cells, and in subpopulations of neurons. Immunofluorescence microscopy of the exocrine and endocrine pancreas, salivary glands, and intestinal segments, confirmed these patterns of cellular expression and provided information on the subcellular localizations of the LRBA protein. Immuno-electron microscopy demonstrated that in neurons and endocrine cells, which co-express LRBA and its closest relative, neurobeachin, both proteins display partial association with endomembranes in complementary, rather than overlapping, subcellular distributions. Prominent manifestations of human LRBA deficiency, such as inflammatory bowel disease or endocrinopathies, are believed to be primarily due to immune dysregulation. However, as essentially all affected tissues also express LRBA, it is possible that LRBA deficiency enhances their vulnerability and contributes to the pathogenesis.

Autoimmune and inflammatory manifestations in pediatric patients with primary immunodeficiencies and their importance as a warning sign

INTRODUCTION AND OBJECTIVES: As well as increased susceptibility to infections, autoimmune and inflammatory manifestations also eventuate due to dysregulation of immune system in a substantial proportion of patients with primary immunodeficiency (PID). Autoimmune and inflammatory manifestations can occur prior or after diagnosis of PID. This study aimed to evaluate autoimmune and inflammatory complications among all types of PID patients in childhood and to emphasize the importance of these findings as a warning sign to diagnose PIDs. METHODS: Medical records of 1036 patients with PID, followed up between 2003 and 2019, were retrospectively screened for occurrence of autoimmunity and inflammation. During this time, demographic features, autoimmune/inflammatory findings and initial time, genetic mutations, laboratory and clinical follow up findings, treatment regimens and outcomes were recorded. RESULTS: Autoimmune and inflammatory manifestations were observed in 83 patients (10.1%). The median age of autoimmunity initial time was 61.3 ± 53 months. Sixty-seven (80.7%) patients presented with autoimmune and inflammatory manifestations, and these findings had occurred during 16 patients' (19.3%) follow-up. The most common autoimmune manifestations were autoimmune hematologic (51.8%) and endocrine diseases (26.5%). Fifty patients (60.2%) had a single autoimmune/inflammatory manifestation, however 23 patients (27.7%) had two, eight patients (9.6%) had three and two patients (2.4%) had four different types of autoimmune/inflammatory manifestations. The frequency of autoimmune and inflammatory manifestations in phagocyte defects (56%), combined immune deficiencies (53%) and immune dysregulation diseases (52%) were observed higher than other forms of PIDs. During follow-up 13 (15.7%) patients died. CONCLUSION: Autoimmune/inflammatory manifestations are associated with high morbidity in patients with PIDs and may precede the diagnosis of PID in childhood. Therefore, physicians must be aware of underlying possible immune deficiency and patients with known PIDs should be evaluated for autoimmune and inflammatory complications

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Evaluation of the frequency and diagnostic delay of primary immunodeficiency disorders among suspected patients based on the 10 warning sign criteria: A cross-sectional study in Iran

BACKGROUND: Common Variable Immunodeficiency (CVID) is characterized by an impaired antibody production and a higher susceptibility to encapsulated bacterial infections. Lung disease is considered to be the most important cause of morbidity and mortality. METHODS: We analyzed clinical, radiological and functional characteristics in 80 patients with CVID assisted in the Unidad Inmunologia e Histocompatibilidad at Durand Hospital from 1982 to 2018. RESULTS: Of the 80 patients, 55 showed pathologic lung Computed Tomography (CT). Twenty of them (36.4%) showed bronchiectasis; 26 (47.3%) interstitial involvement associated with nodules and adenopathies called GLILD (granulomatous-lymphocytic interstitial lung disease); and nine patients (16.3%) showed other lesions. Nine percent of patients with lung disease showed CT progression; none of them had spirometry worsening. GLILD patients had normal and restrictive patterns in lung function tests, in equal proportions. Two patients - one with GLILD and the other one with bronchiectasis - had an increase in spirometric pattern severity without CT progression. Lung biopsy was performed in 19% of GLILD patients, all of whom had histopathologic diagnosis of Lymphoid Interstitial Pneumonia (LIP). CONCLUSIONS: GLILD is the major cause of lung disease in CVID. Computed tomography is useful for diagnosis but not necessary in follow-up, in which functional tests should have better correlation with clinical evolution, reducing radiation exposure. Biopsy should be indicated when the clinical diagnosis is unclear. Treatment should be considered whenever there is clear evidence of disease progression

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Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre

PURPOSE: The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID). METHOD: We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID. RESULTS: 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8±10, 14.2±13.1 and 6.1±7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8±7.6 years). The mean age of living patients at the time of study was 23±11.7 years. CONCLUSIONS: Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients

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Current state and future perspectives of the Latin American Society for Immunodeficiencies (LASID)

Primary immunodeficiencies (PID) are genetic diseases that affect the immune system and for the last 20 years, the Latin American Society for Immunodeficiencies (LASID) has been promoting initiatives in awareness, research, diagnosis, and treatment for the affected patients in Latin America. These initiatives have resulted in the development of programmes such as the LASID Registry (with 4900 patients registered as of January 2014), fellowships in basic and clinical research, PID summer schools, biannual meetings, and scientific reports, amongst others. These achievements highlight the critical role that LASID plays as a scientific organisation in promoting science, research and education in this field in Latin America. However, challenges remain in some of these areas and the Society must envision additional strategies to tackle them for the benefit of the patients. In June 2013, a group of experts in the field met to discuss the contributions of LASID to the initiatives of PID in Latin America, and this article summarises the current state and future perspectives of this society and its role in the advance of PIDs in Latin America

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Granulomas cutáneos no infecciosos en inmunodeficiencia común variable / Non-infectious skin granulomas in a common variable immunodeficiency

La inmunodeficiencia variable común es una inmunodeficiencia primaria por hipogamaglobulinemia de IgG e IgA poco frecuente en la población. Clásicamente se presenta durante la juventud y se diagnostica durante la investigación de infecciones respiratorias y gastrointestinales a repetición. Estos pacientes pueden además presentar enfermedades autoinmunes, inflamatorias, neoplásicas, malabsorción y problemas granulomatosos no infecciosos, que afectan el pulmón, ganglios, bazo, hígado, y menos usualmente la piel. Presentamos el caso de una paciente diagnosticada de inmunodeficiencia variable común que se presenta en la consulta dermatológica con múltiples nódulos eritemato-costrosos en miembros, donde se hallaron únicamente granulomas asépticos (AU)

Common variable immunodeficiency is a rare, primary immunodeficiency characterized by hypogammaglobulinemia of IgG and IgA. It classically presents as recurrent respiratory and gastrointestinal infections in young patients, who may also have autoimmune and inflammatory disease, malignancies, malabsorption and non-infectious granulomas, mainly located in the lung, lymph nodes, spleen, liver and, less frequently, in the skin. We report the case of a patient diagnosed with common variable immunodeficiency who presented in the dermatology clinic with multiple, erythematous, crusted nodules on the limbs. Only aseptic granulomas were found (AU)

Distrofia muscular facioescapulohumeral en Chile: presentación de serie en hospital de referencia terciario / Facioscapulohumeral muscular dystrophy: Report of seven patients

Background: Facioscapulohumeral muscular dystrophy is the third most common muscular dystrophy with an estimated prevalence of 1 per 20.000 and a normal life expectancy in the majority of patients. However, approximately 15% of patients become wheelchair bound in the course of their life. It is a hereditary autosomal dominant disease with high (95%) penetrance by the age of 20, but with variable degree of phenotypic expression even in the same family group. Symptoms frequently start in the second decade of life, with facial and scapular weakness. Aim: To report the clinical features of seven patients with the disease, seen at a public hospital. Material and Methods: Analysis of seven patients with genetic study seen in a public Hospital in Santiago. Results: The age of patients fluctuated from 18 to 61 years and four were females. The mean age at onset of symptoms was 29 years and four had a family history of the disease. The usual presenting complaint was arm or shoulder asymmetric weakness. Four patients had bone pain. Facial involvement was present in four. A genetic study was done in five patients, the other two patients were relatives, confirming the contraction or lower number of repetitions in D4Z4 region. After 12 years of follow up only 2 patients older than 60 years cannot work and one female patients is in a semi dependent state at the age of 30. Conclusions: The clinical workup in the diagnosis and the timely indication of genetic studies are highlighted, to avoid unnecessary and invasive procedures. The variability in the phenotypic expression in a similar genetic defect is discussed and the genetic or epigenetic mechanisms of this muscular dystrophy are described.

Las células tipo epidermodisplasia verruciforme como marcador histológico de inmunodepresión: revisión de 229 carcinomas espinocelulares / Epidermodysplasia verruciformis-like cells as histologic markers of immunosuppression: review of 229 squamous cell carcinomas

Introducción. La epidermodisplasia verruciforme (EV) es una enfermedad en la que existe una mayor susceptibilidad genética a la infección por determinados subtipos oncogénicos del virus del papiloma humano (VPH). Entre otros hallazgos histológicos, en la EV suelen observarse unas células claras, grandes, ovaladas o redondeadas (células EV) en la capa granulosa, que según algunos autores se podrían considerar como un marcador histológico de inmunodepresión. Material y métodos. Hemos estudiado 229 carcinomas espinocelulares (CE) para valorar si presentaban células EV y si se relacionaban con inmunodepresión, tanto localizada o cutánea (tumores con signos de intenso daño solar crónico o con una dermatitis de estasis intensa), como sistémica (pacientes inmunodeprimidos o ancianos). Resultados. Observamos células EV en 33 carcinomas. No hemos encontrado relación significativa entre la existencia de células EV e inmunodepresión. Realizamos reacción en cadena de la polimerasa (PCR) en 8 lesiones, pero los resultados no fueron valorables porque el ADN estaba desnaturalizado. Conclusiones. No hemos demostrado relación entre las células EV e inmunodepresión, localizada o sistémica, posiblemente porque la muestra no era adecuada (se podría considerar que prácticamente todos los CE estudiados se asociaban a signos de inmunodepresión, tanto aquellos que presentaban células EV como los que no). Serían necesarios más estudios que comparasen lesiones asociadas a inmunodepresión con otras que no. Es posible que estas células EV sean el resultado de los efectos citopáticos de determinados subtipos de VPH, como el VPH-5 o el VPH-8, aunque sería necesario demostrar esta hipótesis mediante técnicas de PCR o similar (AU)

Associated with greater susceptibility to infection by certain oncogenic subtypes of human papillomavirus (HPV). Among other histologic findings, large, clear, oval or rounded cells (EV cells) are observed in the granular layer in EV, and some authors consider these cells to be markers of immunosuppression. Material and Methods. We analyzed 229 squamous cell carcinomas (SCC) to determine whether EV cells were present and to assess whether their presence was associated either with localized or cutaneous immunosuppression (tumors with signs of severe chronic actinic damage or severe stasis dermatitis) or with systemic immunosuppression (immunocompromised or elderly patients). Results. We observed EV cells in 33 SCC. No statistically significant relationship was observed between the presence of EV cells and immunosuppression. We performed polymerase chain reaction in 8 lesions, but the results were not informative as the DNA was denatured. Conclusions. We found no relationship between the presence of EV cells and localized or systemic immunosuppression, possibly because the sample was inadequate (almost all SCC studied were associated with signs of immunosuppression, irrespective of the presence or absence of EV cells). Further studies will be required to compare lesions associated with immunosuppression with those in which immunosuppression is absent. The presence of EV cells may be the result of cytopathic effects of certain HPV subtypes, such as HPV 5 or 8, but this will need to be demonstrated using techniques such as polymerase chain reaction (AU)

Inmunodeficiencia grave combinada / Severe combined immunodeficiency

Los síndromes de inmunodeficiencia grave combinada tienen un pronóstico grave, originando la muerte en el primer o segundo año de vida si no se hace un diagnóstico precoz. La importancia actual de estas enfermedades es que, a pesar de su rareza, la reconstitución inmunológica puede lograrse mediante trasplante de medula ósea o terapia de reemplazamiento enzimático. Con gran frecuencia, y de ahí el interés de presentar este caso, puede sospecharse por la existencia de diversas manifestaciones cutáneas como dermatitis seborreica o dermatitis atópica más o menos intensas o el hallazgo de una linfopenia en una analítica realizada por cualquier motivo antes de que aparezcan infecciones (AU)

Síndrome de hiper-IgE con infecciones recurrentes. Conceptos generales y alteraciones del sistema estomatológico / Hyper-IgE syndrome with recurrent infections. General concepts and alterations in the stomatological system

Los individuos inmunocomprometidos frecuentemente presentan afección del sistema estomatológico, requiriendo la participación del odontólogo para una atención integral que preserve la cavidad bucal en buenas condiciones, posibilitando una adecuada nutrición y evirtando la diseminación de infecciones desde este sistema. El síndrome de Hiper-IgE (SHIEIR) es una inmunodeficiencia primaria poco frecuente, caracterizada por concentraciones séricas elevadas de IgE, asociadas a la presencia de abscesos recurrentes de tejidos superficiales y profundos debidos especialmente a Staphylococcus aureus. Un análisis reciente de 30 pacientes con SHIEIR y 50 de sus familiares, lo ha caracterizado como un desorden multisistémico que afecta el sistema inmune, la piel, la dentición, el esqueleto y el tejido conjuntivo. Desde el punto de vista odontológico, se ha reportado un retardo en la exfoliación y erupción dentariaas, pero otras manifestaciones en el sistema estomatológico han sido analizadas en detalle y sólo se reportaron superficialmente, como son la presencia de dientes supernumerarios y la candidiasis bucal recurrente. Se plantea la participación del odontólogo en el diagnóstico y tratamiento de las manifestaciones orales de los pacientes con esta inmunodeficiencia, como una parte importante del abordaje integral que tiene gran valor en la evolución de los pacientes con inmunocompromiso

Proceso para el diagnóstico de una inmunodeficiencia primaria / Primary immunodeficiency evaluation procedure

Las inmunodeficiencias primarias son un grupo de entidades patológicas que se caracterizan por presentar errores en los mecanismos de defensa, específicos o inespecíficos, debidos a la imposibilidad para el reconocimiento antigénico, la alteración de las interconexiones entre los elementos del sistema inmunológico o la ausencia de los mecanismos efectos del sistema, ocasionado por alteraciones genéticas. El estudio de un paciente en quien se sospecha una inmunodeficiencia primaria consiste en determinar la fase o etapa de la inmunología y el elemento de ésta que se encuentra afectada. En el presente trabajo se propone, esquemáticamente, un procedimiento para la metodización del estudio de las inmunodeficiencias primarias conducente al diagnóstico precoz y al tratamiento oportuno de estas entidades, a propósito del análisis de la historia clínica de un lactante atendido en el Servicio de Pediatría del Hospital Universitario de Los Andes. Durante su enfermedad febril originada en una eventual infección respiratoria que evolucionó torpidamente, se comprobó la presencia de niveles elevados de IgM e indetectables de IgG e IgA y en el estudio necrópsico ausencia de centros germinales linfáticos e hipertrofia de la pulpa blanca esplénica como ha sido descrito en el Síndrome Hiper IgM

Imunodeficiencia combinada severa / Severe combined immnodeficiency

As imunodeficiencias primarias (ID) sao classificadas em ID humorais, celulares, combinadas (humorais e combinadas), de fagocitos e complemento. A Sindrome de Imunodeficiencia Combinada Severa discutida na presente monografia, e uma doenca rara com comprometimento da imunidade celular e humoral, cuja heranca e auto-somica recessiva ou ligada ao cromossomo X. Sao varios os defeitos descritos que levam a SCID: bloqueio das "stem cells", bloqueio da maturacao das celulas T e anormalidades da membrana celular. As principais manifestacoes clinicas sao os processos infecciosos recorrentes associados alteracoes cutaneas, pulmonares, de trato digestivo, com evolucao grave (meningite, sepsis). Os exames laboratoriais mostram linfopenia (20 por cento), niveis de imonuglobulinas baixos e ausencia de resposta linfoproliferativa "in vitro". A terapeutica de reposicao de imunoglobulinas esta indicada e a correcao definitiva pode ser obtida atraves do transplante de medula ossea ou terapia genica (na deficiencia de Adenosina Deaminase)

Síndrome de imunodeficiência grave combinada SCID: apresentaçäo de um caso; dados clínicos, laboratoriais e anatomopatológicos / Severe combined immunodeficiency syndrom (SCID): presentation of a case; clinical, laboratory and anatomopathologic information

Os autores apresentam um caso de imunodeficiência grave combinada (SCID) em paciente do sexo feminino. Apesar do aleitamento natural, iniciou infecçöes recorrentes a partir do 3§ mês de vida, sendo o diagnóstico confirmado aos sete meses. A linfopenia acentuada, os niveis séricos de imunoglobulinas (G, M e A) baixos ou ausentes, além da falta de resposta in vitro dos linfócitos T `a fito-hemaglutinina, orientaram para o diagnóstico de SCID. As alteraçöes observadas ao exame anatomopatológico confirmaram o diagnóstico do SCID

Distúrbios inmunológicos, inmunodefiencia y sarcoma angioblástico de tipo Kaposi: aspectos lesionales en los ganglios linfáticos / Immunological disorders, immunodeficiency and angioblastic sarcoma of Kaposis type: lesional aspects in the lymph nodes

Se describen los cambios hitológicos en los ganglios linfáticos en pacientes con evidencias de inmunodeficiencia y sarcoma angioblástico de tipo Kaposi, destacando las modificaciones previas y concomitantes a la instalación de la neoplasia y relacionando las mismas con el disturbio inmunológico. Se realizan consideraciones sobre la histogénesis de las células neoplásicas en los angiosarcomas de tipo Kaposi y se concluye que las mismas muestran caracteres hemangiopericitoides y endoteliales combinados (AU)

Distúrbios inmunológicos, inmunodefiencia y sarcoma angioblástico de tipo Kaposi: aspectos lesionales en los ganglios linfáticos / Immunological disorders, immunodeficiency and angioblastic sarcoma of Kaposis' type: lesional aspects in the lymph nodes

Se describen los cambios hitológicos en los ganglios linfáticos en pacientes con evidencias de inmunodeficiencia y sarcoma angioblástico de tipo Kaposi, destacando las modificaciones previas y concomitantes a la instalación de la neoplasia y relacionando las mismas con el disturbio inmunológico. Se realizan consideraciones sobre la histogénesis de las células neoplásicas en los angiosarcomas de tipo Kaposi y se concluye que las mismas muestran caracteres hemangiopericitoides y endoteliales combinados