Síndrome de Hiper-IgM

Descripción General

Epidemiología

• Grupo de enfermedades muy raras
• Prevalencia:
  • El síndrome de hiper-IgM ligado al AL Amyloidosis cromosoma X afecta aproximadamente 2 de cada millón de niños recién nacidos, lo que representa el 70 % de los LOS Neisseria casos de hiper-IgM.
  • Las formas autosómicas recesivas de hiper-IgM afectan a menos de 1 de cada 1 millón de personas.

Fisiopatología

• El ligando CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome se encuentra en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la superficie de las células T y se une a su receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la membrana de las células B, las cuales producen anticuerpos.
• Un CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome defectuoso conduce a una interacción defectuosa entre las células T y las células B y a una respuesta inmune humoral.
• Los LOS Neisseria defectos genéticos impiden que las células B cambien de IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions a otras clases de inmunoglobulinas ( IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions, IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis, IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions). En EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum consecuencia, los LOS Neisseria pacientes:
  • Producen un exceso de anticuerpos IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions
  • Producen una cantidad insuficiente de IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions, IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis e IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions
  • Experimentan una maduración deficiente de la afinidad de los LOS Neisseria anticuerpos
  • Genera vulnerabilidad a las infecciones, en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum particular a las bacterias encapsuladas y las toxinas

Clasificación

Hay varias condiciones que pertenecen al AL Amyloidosis llamado síndrome de hiper-IgM. Debido a la rareza del síndrome, a continuación solo se mencionan las causas más comunes.

Deficiencia del ligando CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome (CD40L)

• Inmunodeficiencia combinada
• Forma más común del síndrome de hiper-IgM
• Herencia ligada al AL Amyloidosis cromosoma X
• Interacción defectuosa entre las células T CD4+ activadas que expresan CD40L y las células que expresan CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome

Deficiencia de citidina deaminasa inducida por activación (AID)

• Inmunodeficiencia humoral
• 2da forma más común de síndrome de hiper-IgM
• Herencia autosómica recesiva

Presentación Clínica

La edad media de aparición del síndrome de hiper-IgM es de aproximadamente 2 años. Los LOS Neisseria pacientes suelen tardar unos años más en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum ser diagnosticados con la enfermedad. Los LOS Neisseria posibles signos y síntomas incluyen:

• Infecciones sinopulmonares recurrentes en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la infancia, causadas principalmente por bacterias encapsuladas ( Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pneumoniae y Haemophilus influenzae Haemophilus Influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through viii. Haemophilus)
• Infecciones oportunistas, especialmente:
  • Neumonía por Pneumocystis jirovecii
  • Infección pulmonar por Histoplasma Histoplasma Histoplasmosis is an infection caused by Histoplasma capsulatum, a dimorphic fungus. The fungus exists as a mold at low temperatures and as yeast at high temperatures. H. capsulatum is the most common endemic fungal infection in the US and is most prevalent in the midwestern and central states along the Ohio and Mississippi River valleys. Histoplasma/Histoplasmosis
  • Gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis por Cryptosporidium Cryptosporidium A genus of coccidian parasites of the family cryptosporidiidae, found in the intestinal epithelium of many vertebrates including humans. Hyper-IgM Syndrome, lo que conduce a enfermedades de las vías biliares, cirrosis y colangiocarcinoma
  • Infección gastrointestinal por Giardia Giardia A genus of flagellate intestinal eukaryotes parasitic in various vertebrates, including humans. Characteristics include the presence of four pairs of flagella arising from a complicated system of axonemes and cysts that are ellipsoidal to ovoidal in shape. Nitroimidazoles lamblia
  • Hepatitis C Hepatitis C Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C Virus
• Enfermedades malignas (hepatocarcinoma, colangiocarcinoma y tumores neuroectodérmicos periféricos del tracto gastrointestinal y el páncreas)
• Neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia
• Trastornos autoinmunes
• Hipotiroidismo
• Artritis
• Encefalopatía (degenerativa)
• Diarrea crónica y retraso del crecimiento

Diagnóstico

Anomalías en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum exámenes de laboratorio

• Niveles bajos de IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis, IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions e IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum suero
• Niveles normales o elevados de IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum suero
• Respuesta de anticuerpos insuficiente o inexistente a ciertos antígenos proteicos (tétanos, difteria y Haemophilus influenzae Haemophilus Influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through viii. Haemophilus) y polisacáridos ( Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pneumoniae)

Pruebas confirmatorias

• Análisis de ADN para confirmar la mutación del CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome
• Citometría de flujo que muestra la ausencia o la disminución de la expresión de la proteína ligando CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la superficie de las células T

Tratamiento y Pronóstico

Tratamiento

• Deficiencia de CD40L y CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome:
  • La terapia de sustitución de inmunoglobulinas → reduce el riesgo de bronquiectasias e infecciones
  • Trasplante alogénico de células hematopoyéticas: enfoque curativo
  • Seguimiento: evaluación periódica de los LOS Neisseria parámetros hepáticos y ecografía
• Deficiencia de AID:
  • La terapia de sustitución de inmunoglobulinas → reduce el riesgo de bronquiectasias e infecciones
  • Trasplante alogénico de células hematopoyéticas: enfoque curativo
  • Seguimiento: valoraciones periódicas para controlar las bronquiectasias y las enfermedades linfoproliferativas

Pronóstico

• Deficiencia de CD40L y CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome:
  • Las causas más comunes de muerte son las infecciones, las enfermedades hepáticas y los LOS Neisseria tumores malignos.
  • La expectativa de vida se ve VE Ventilation: Mechanics of Breathing más afectada por la presencia y gravedad de enfermedades hepáticas.
  • Alrededor del 60% de los LOS Neisseria pacientes viven hasta los LOS Neisseria 20 años de edad.
  • El trasplante de células hematopoyéticas aumenta la supervivencia a 90% a los LOS Neisseria 20 años.
• Deficiencia de AID:
  • Mejor pronóstico que la deficiencia de CD40L y CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome
  • La terapia recurrente de sustitución de inmunoglobulinas y el tratamiento temprano de las infecciones mejoran significativamente el resultado.

Diagnóstico Diferencial

• Agammaglobulinemia o hipogammaglobulinemia: condición con ausencia o niveles extremadamente bajos de inmunoglobulinas. Los LOS Neisseria tres tipos principales que se han descrito son la ligada al AL Amyloidosis cromosoma X, la de inicio temprano y la de inicio tardío. Los LOS Neisseria pacientes presentan infecciones recurrentes y no tienen amígdalas ni adenoides. El diagnóstico se realiza mediante la medición de inmunoglobulinas séricas disminuidas y mediante pruebas genéticas. El tratamiento incluye la sustitución de inmunoglobulinas.
• Inmunodeficiencia común variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables: Una de las enfermedades de inmunodeficiencia primaria más comunes causada por defectos en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la maduración de las células B y la producción de inmunoglobulinas. La causa de la inmunodeficiencia común variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables sigue siendo desconocida en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la mayoría de los LOS Neisseria casos. Los LOS Neisseria pacientes pueden presentar infecciones recurrentes, hiperplasia linfoide, esplenomegalia y neoplasias. El diagnóstico incluye la medición de las inmunoglobulinas séricas y una pobre respuesta a las vacunas.