B cell primary immunodeficiencies

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From the 07-02-14 Immunology and Disease lecture.
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Flashcards by sophietevans, updated more than 1 year ago
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Question Answer
Which genetic event is involved in the aetiology of x-linked agammaglobulinaemia? A mutation in Bruton's tyrosine kinase (BTK) gene.
What effect does the genetic event in x-linked agammaglobulinaemia have on B cells? The BTK mutation results in pre-B cells failing to differentiate into mature B cells.
What is the inheritance pattern of XLA? It is X-linked recessive, so it is predominately seen in males as they only have 1 copy of the X chromosome and therefore cannot use X-inactivation as females can. This pattern is used in the diagnostic differentiation between XLA, CVID, and Hyper IgM syndrome.
How does XLA present clinically? As frequent and recurrent infections (otitis, sinusitis, pneumonia) - noticed in the first 5 years of life as the condition is genetic.
How is XLA diagnosed? Blood screening identifying low serum IgG, IgA, and IgM (2 or more S.D. below the normal value for the individual's age) and low (<2%) CD19+ B cells in the peripheral blood is diagnostic of XLA, along with the inheritance pattern and infection history.
How is XLA treated? Lifelong immunoglobulin replacement therapy (IRT), antibiotic courses for infections (potentially long term), and no vaccinations as IgG and IgM responses cannot be developed against the pathogens.
What genetic event results in common variable immunodeficiency (CVID)? Mutations in the TACI alleles - the variations in the mutations result in the varied phenotypes seen, as there are 30-40 conditions under the CVID 'umbrella'.
What does the genetic event causing CVID do to B cells? Mature B cells fail to differentiate into plasma cells and class switch.
How does CVID present clinically? Frequent and recurrent viral/bacterial/fungal/protozoal infections, especially upper respiratory tract infections, and autoimmunity and allergies develop in ~20% of patients. This can include gastrointestinal disorders such as irritable bowel disease.
How is CVID diagnosed? Blood screening reveals low serum IgG, IgM, and IgA, and there is a familial history of the disease affecting both males and females, unless the mutation is spontaneous.
How is CVID treated? Lifelong immunoglobulin replacement therapy and antibiotic courses when necessary.
What is the cause of IgA deficiency? The aetiology is unknown, but the result is that mature IgA B cells are unable to differentiate into plasma cells and secrete IgA.
How does IgA deficiency present clinically? As frequent and recurrent urogenital, respiratory, and gastrointestinal infections, chronic diarrhoea, allergies and autoimmunity. The autoimmunity usually results in circulating levels of auto-organ antibodies being high, resulting in type 3 hypersensitivity reactions. Further, anti-IgA may be produced, resulting in transfusion reactions on receipt of blood products. Some patients may be asymptomatic as IgM 'compensates' for IgA.
How is IgA deficiency diagnosed? Blood screens reveal low serum IgA (<7mg/dL) but normal levels of other immunoglobulins.
How is IgA deficiency treated? There is no IgA replacement therapy available so long term courses of antibiotics are prescribed to treat the recurrent + frequent infections.
What mutation(s) result in Hyper IgM Syndrome? Hyper IgM Syndrome can result from either a mutation in the B cell activation-induced cytidine-deaminase enzyme which occurs in both males and females, or from a mutation in the CD40 ligand on B cells, which is X-linked and thus predominately occurs in males.
What effect do the mutations in Hyper IgM Syndrome have on B cells? Mature B cells are unable to class switch so only IgM is produced.
How does Hyper IgM Syndrome present clinically? As recurrent sinopulmonary infections, and pneumonia caused by Pneumocystis carnii. Associated abnormalities include neutropenia and aplastic anaemia.
How is Hyper IgM Syndrome diagnosed? Blood screens reveal low IgG/IgA/IgE but >200mg/dL IgM. The ultimate cause of it may be identified by analysing the inheritance pattern within a family.
What is the treatment for Hyper IgM Syndrome? Lifelong immunoglobulin replacement therapy and antibiotic courses whenever these are necessary.
Why might XLA be masked for the first 6 months of life? Because maternal antibodies delivered through the placenta protect the baby for this length of time.
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