Deficiência Seletiva de IgA

Epidemiologia e Fisiopatologia

Epidemiologia

• 1 em 100 – 1.000 pessoas têm deficiência seletiva 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 em todo o mundo
• Mais MAIS Androgen Insensitivity Syndrome comum em caucasianos
• Mais MAIS Androgen Insensitivity Syndrome comum em homens do que mulheres
• Mais MAIS Androgen Insensitivity Syndrome comum em doentes com doenças autoimunes, como a doença celíaca e a diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus tipo 1

Etiologia

• A causa exata é desconhecida.
• A maioria dos casos é esporádico, mas os tipos hereditários têm sido associados aos cromossomas 6 e 17 com um padrão de hereditariedade autossómico dominante e recessivo.
• A deficiência 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 também é observada na ataxia-telangiectasia Ataxia-telangiectasia Ataxia-telangiectasia, also known as Louis-Bar syndrome, is a neurocutaneous syndrome, which involves multiple systems but mainly affects the neurological system. Ataxia-telangiectasia is an autosomal recessive genetic disorder caused by a mutation in the ATM gene (ATM serine/threonine kinase or the ataxia-telangiectasia mutated gene). Ataxia-telangiectasia, juntamente com a degeneração cerebelar, problemas de movimento e coordenação e aumento do risco de alguns tipos de neoplasias.
• Alguns casos de deficiência 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 foram associados a agentes indutores:
  • Fármacos:
    • Medicamentos antirreumáticos (e.g., sulfassalazina, D penicilamina, ciclosporina)
    • Medicamentos anticonvulsivantes (e.g., fenitoina, ácido valproico)
    • Tiroxina
    • Captopril Captopril A potent and specific inhibitor of peptidyl-dipeptidase a. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. Hypertension Drugs
    • Levamisol
  • Infeções (causam deficiência transitória 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):
    • Citomegalovírus
    • Rubéola
    • Toxoplasmose
    • Vírus de Epstein Barr

Fisiopatologia

• Associada a um defeito intrínseco de linfócitos B, alterações de células T e comprometimento de redes de citocinas
• As células B não conseguem maturar completamente em plasmócitos secretores 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.
• Foram relatados defeitos nas seguintes citocinas: IL-4, IL-6, IL-7 IL-7 A proinflammatory cytokine produced primarily by T-lymphocytes or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene. Severe Combined Immunodeficiency (SCID), IL-10 e IL-21
• A incapacidade hereditária de produzir imunoglobulina A ( 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) ocorre principalmente nas superfícies mucosas dos tratos respiratório e gastrointestinal (GI), levando a infeções bacterianas frequentes nesses sistemas orgânicos.
• Associada a doenças autoimunes em 5% – 30% dos casos

Apresentação Clínica

Aproximadamente 90% dos casos são assintomáticos.

Doentes sintomáticos podem apresentar uma mistura dos seguintes sintomas:

• Infeções pulmonares recorrentes:
  • A primeira apresentação em 40% – 90% dos doentes sintomáticos
  • Geralmente causada por bactérias encapsuladas extracelulares
    • 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
    • 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
• Condições gastrointestinais:
  • Menos comum do que infeções pulmonares, porque a 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 pode compensar de forma mais MAIS Androgen Insensitivity Syndrome eficaz a ausência 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 no trato GI
  • Giardíase (suscetibilidade aumentada devido a uma barreira mucosa GI defeituosa)
  • Doença de Crohn
  • Hiperplasia linfoide nodular (HLN)
  • Colite ulcerosa
• Alergias:
  • Causadas por níveis elevados de IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions compensatórios
  • Conjuntivite
  • Rinite
  • Urticária
  • Eczema Eczema Atopic dermatitis, also known as eczema, is a chronic, relapsing, pruritic, inflammatory skin disease that occurs more frequently in children, although adults can also be affected. The condition is often associated with elevated serum levels of IgE and a personal or family history of atopy. Skin dryness, erythema, oozing, crusting, and lichenification are present. Atopic Dermatitis (Eczema)
  • Alergia alimentar
• Doenças autoimunes:
  • Doença celíaca
  • Lúpus eritematoso sistémico
  • Artrite reumatoide
  • Tiroidite
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus tipo 1
  • Doença de Graves
  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types hemolítica autoimune
• Maior incidência de neoplasias:
  • Adenocarcinoma gástrico
  • Linfoma de células B
  • Cancro colorretal
  • Cancro do ovário
  • Melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma

Diagnóstico e Tratamento

Diagnóstico

• Confirmado por medição laboratorial 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 < 7 mg/dL com 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 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 séricas normais (em pelo menos 2 medições) num doente > 4 anos de idade
• Devem ser excluídas causas secundárias de hipogamaglobulinemia, com uma resposta normal de anticorpos 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 a todas as vacinações e exclusão de defeitos nas células T.

Tratamento

• Terapêutica sintomática:
  • Fármacos anti-inflamatórios e anti-histamínicos para sintomas de alergia
  • Antibióticos profiláticos e/ou direcionados a infeções recorrentes
• Administração da vacina pneumocócica
• A terapêutica de reposição de imunoglobulina ( IVIG IVIG Dermatomyositis, pela sigla em inglês) não é recomendada devido ao risco de reações anafiláticas!

Diagnóstico Diferencial

As condições a seguir são outras imunodeficiências congénitas de células B que servem como diagnósticos diferenciais na deficiência seletiva 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.

• Agamaglobulinemia ligada ao X: também conhecida como agamaglobulinemia de Bruton. Distúrbio genético recessivo caracterizado pelo desenvolvimento inadequado de células B, de células imaturas para células maduras. Resulta numa ausência completa ou quase completa de todos os anticorpos. Mais MAIS Androgen Insensitivity Syndrome comum em homens do que em mulheres, a agamaglobulinemia ligada ao cromossoma X apresenta-se com infeções bacterianas recorrentes após os primeiros meses de vida.
• Imunodeficiência comum variável (ICV): tipo de imunodeficiência primária caracterizada por níveis séricos reduzidos de imunoglobulinas 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 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. As causas subjacentes são desconhecidas. Doentes com esta condição são propensos a infeções no trato GI e nos tratos respiratórios superior e inferior e têm maior risco de desenvolver doenças autoimunes, granulomatosas e neoplásicas.
• Ataxia-telangiectasia Ataxia-telangiectasia Ataxia-telangiectasia, also known as Louis-Bar syndrome, is a neurocutaneous syndrome, which involves multiple systems but mainly affects the neurological system. Ataxia-telangiectasia is an autosomal recessive genetic disorder caused by a mutation in the ATM gene (ATM serine/threonine kinase or the ataxia-telangiectasia mutated gene). Ataxia-telangiectasia: doença rara, autossómica recessiva, caracterizada pela associação de imunodeficiência combinada severa, desenvolvimento tumoral e alterações neurológicas. Apresenta-se como ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia da marcha, apraxia Apraxia A group of cognitive disorders characterized by the inability to perform previously learned skills that cannot be attributed to deficits of motor or sensory function. The two major subtypes of this condition are ideomotor and ideational apraxia, which refers to loss of the ability to mentally formulate the processes involved with performing an action. For example, dressing apraxia may result from an inability to mentally formulate the act of placing clothes on the body. Apraxias are generally associated with lesions of the dominant parietal lobe and supramarginal gyrus. Cranial Nerve Palsies, movimentos anormais, telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency, infeções pulmonares recorrentes e maior risco de linfoma, leucemia e carcinoma gástrico.
• Imunodeficiência combinada severa ( SCID SCID Severe combined immunodeficiency (SCID), also called “bubble boy disease,” is a rare genetic disorder in which the development of functional B and T cells is disturbed due to several genetic mutations that result in reduced or absent immune function. Severe Combined Immunodeficiency (SCID), pela sigla em inglês): forma mais MAIS Androgen Insensitivity Syndrome grave de imunodeficiência primária. A imunodeficiência combinada severa é um distúrbio genético que resulta numa resposta defeituosa dos anticorpos, devido ao envolvimento direto de linfócitos B ou por ativação inadequada de linfócitos B devido a células T auxiliares não funcionais. Apresenta-se com infeções oportunistas graves e recorrentes e é diagnosticada através de testes Testes Gonadal Hormones quantitativos de reação em cadeia de polimerase ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR), pela sigla em inglês) e citometria de fluxo.
• Síndrome de hiper 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: distúrbio causado por uma mutação ligada ao X no gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics ligante 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, que resulta numa sinalização alterada entre os linfócitos B e T. A apresentação é leve e muitas vezes só se apresenta mais MAIS Androgen Insensitivity Syndrome tarde na vida através infeções oportunistas e desregulação imunológica de eosinófilos IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions, células B, células NK e proliferação e ativação de células T CD8+.