Immuno B Cell Immunodeficiency Disease

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The clinical presentation of antibody deficiencies almost always involve recurrent

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sinopulmonary infections including otitis media, sinusitis, bronchitis, and pneumonia

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Occasionally also presents with

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bacterial sepsis with pyogenic, encapsulated bacteria (blood stream infection) is also a problem

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Approximately 60 percent of hypogammaglobulinemics also have
-60% of these are due to
-

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chronic diarrhea
-giardia as well as other GI pathogens

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Although antibody has little to do with stopping a new viral infection....

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-antibody can prevent a second viral infection, this being the reason for vaccination against measles, mumps, and rubella and chickenpox with attenuated virus vaccines.

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Serum antibody may be very important, however, in preventing the

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enteroviruses (polio, Coxsacchie, and Echoviruses) from gaining access from the GI tract to the central nervous system

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what else may be a problem in untreated antibody

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Thus, paralytic polio or enteroviral meningoencephalitis may be a problem in untreated antibody deficient patients.

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Antibody deficient patients may also develop

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25%) lymphoreticular and squamous cell malignancies, likely from overstimulation from infections, and autoimmunity (25%).

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they cant make_____ but they can make_____

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“good” but they can make “bad” antibodies (immune dysregulation)

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Types of Antibody Deficiencies

Antibody deficiencies include those patients with the many forms of

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SCIDs) as usually both T and B cell immunity is affected in these disorders

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Although, the T cell immunodeficiency will be present from birth, the antibody deficiency will not become apparent

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in the term infant until 4 to 6 months after birth because of the placental transfer of IgG antibody from the mothers

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Bruton’s agammaglobulinemia The disorder is
-appearing only
-and is characterized by a genetic deficiency

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sex-linked,
in males,
-of Bruton’s tyrosine kinase encoded on the X chromosome

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This prevents

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the pre-B cell from becoming a mature B cell with mature immunoglobulin

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Severe sinopulmonary and GI infections develop

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at 4-6 months in term infants, or earlier in premature infants, with the disorder

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what clinical manifestations can occur in infants with the disease?
-what may appear later in life?

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Polio, even from the attenuated live virus vaccine, and enteroviral meningoencephalitis may develop in infants with the disease and dermatomyositis, a disorder characterized by muscle inflammation, may occur. Lymphomas may appear later in life.

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what types of b cell are or are not present in pts with this disorder?

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No mature B cells with surface IgG, IgM or IgA are present in the peripheral blood but pre B cells with mu (IgM) heavy chain in their cytoplasm may be detected.

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Treatment is with

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gammaglobulin infusions, which are life-saving.

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The hyper IgM (HIM) syndrome
-is another predominantly ...
-who have a block above
-Thus, the patients have
-but do not
-due to the lack of

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-sex-linked disorder affecting mainly males (80%)
-IgM (and IgD) in the sequence of B cell development (Xq26.3-27).
-IgM and IgM bearing B cells in their blood
-class switch adequately to IgG, IgA and IgE
- a T cell CD40 ligand component which must bind to B cell CD40 to promote class switching

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These patients may suffer severe
-Many also have
-and may develop

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sinopulmonary infections and may develop severe liver cirrhosis if infected with cryptosporidia
-neutropenia
-lymphomas in early adulthood

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tx?

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Bone marrow or stem cell transplant may be curative and most are treated with gammaglobulin

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Twenty percent of patients, including males and females, may develop a similar presentation due to

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inadequate signaling through CD 40 on B cells, an autosomal disorder.

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Immunoglobulin A deficiency
-Total absence of IgA is usually asymptomatic in ___ who may experience ____

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-up to 2/3 of patients, who may experience mild
-respiratory infections or an increase in allergies such as food allergy, eczema, or hayfever due to the lack of immune exclusion provided by IgA at the mucosal barriers

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One third of IgA deficient patients have more serious infections and 20% of these will lack_____, which is encoded in same region as

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IgG2 and IgG4, which is encode in the same area as on chromosome 14 as IgA1 and IgA2.

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Patients with IgG2 deficiency may be treated with
-but people with no IgA may..

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be treated with IgA depleted intravenous immunoglobulin (IVIG), as patients with no IgA may become allergic to IgA in blood or IVIG and suffer anaphylaxis

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Some patients with IgA deficiency

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may develop large nodules in the lymphoid tissue of the GI tract (lymphonodular hyperplasia) or malignancies due to over stimulation by recurrent infection.

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what kind of therapy is available for isolated IgA deficiency. why?

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At present there is no specific therapy for isolated IgA deficiency as IgA is present in low concentrations in gammaglobulin and has a short half-life (2-3 days

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Moreover, administered IgA would

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not function with the patient’s own secretory piece so IgA would never arrive at the mucosal surfaces where it functions.

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Common variable immunodeficiency disease (CVID
-may be related to IgA deficiency by
-Some who inherit the susceptibility gene

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-inheritance through a common susceptibility gene located, most likely, in the class III HLA region.
-get no disease, some have IgA deficiency and some suffer CVID

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This disorder has onset
-and is characterized by
-with onset of recurrent,

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-several years to 90 years plus after birth
-the cessation of good antibody production (IgG, IgA, IgM)
- bacterial sinopulmonary infections and diarrhea.

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The patients have decreasing concentrations of

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-usually more than one class of antibody and poor antibody responses if vaccinated but have the presence of mature immunoglobulin bearing B cells in their blood.

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Some patients develop
-About 50% of patients may also have___ and suffer___
-Patients may have altered
-Those with normal ratios often have a deficiency

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-malignancies including lymphomas (20-25%) and some develop various autoimmune disorders (20-25%).
-T cell disfunction and suffer viral infections such as Herpes zoster (shingles) or enteroviral infections.
-CD4/CD8 ratios with elevated CD8 cells or may have normal ratios. -
-in the production of IL-2, or T cell growth factor, which also causes B cells and NK cells to grow.

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Treatment with

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IL-2 may have some beneficial effect but is not curative.

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Treatment of Antibody Deficiencies

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intravenous or subcutaneous immunoglobulin IVIG in doses of 400 to 750 mg per Kg per 3 to 4 weeks for life, at present

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IVIG has many potential hazards including

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anaphylaxis in IgA deficient patients, infection with viruses, slow virus or prion disease, BP changes, headaches, backaches, flu like syndrome, aseptic meningitis, rashes, strokes, myocardial infarction, and even renal failure.

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To qualify for therapy,all patients must have

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-serious recurrent infections, significantly low IgG or IgG subclasses, and/or deficient antibody responses when immunized.

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Careful attention to
-and prompt treatment of

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-pulmonary therapy, -sinopulmonary and GI infections as well as early detection of malignancies and autoimmunity adds to longevity and quality of life

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Diagnosis of Antibody Deficiency
-as well as ______ electrophoresis to rule out

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based on quantitative determination of IgG, IgM, IgA and IgG subclasses by nephelometry as well as immunofixation electrophoresis to rule out monoclonal gammopathy of unknown significance (MGUS) and myeloma in adults, which can suppress uninvolved immunoglobulins

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what tests after what vaccine can confirm diagnosis

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ELISA and multianalyte flowcytometry assays of pneumococcal, diphtheria, and tetanus antibody one month after vaccination can confirm the inability to make good antibody.

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Flowcytometry can determine the presence of

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-mature immunoglobulin on B cells as well as the ratio of CD4 to CD8 T cells