B Laboratory Findings in Objective-C

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B Laboratory Findings
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Diagnosis is confirmed in patients with recurrent infections by demonstration of functional or quantitative defects in antibody production Serum IgG levels are usually less than 250 mg/dL; serum IgA and IgM levels are also subnormal Decreased to absent functional antibody responses to protein antigen immunizations establish the diagnosis The cause of the panhypogammaglobulinemia in the majority of common variable immunodeficiency patients is an intrinsic B cell defect preventing terminal maturation into antibody-secreting plasma cells In a small number, excessive suppressor T cell activity that inhibits B cells or helper T cell activity inadequate to assist B cells to make antibody has been identified The absolute B cell count in the peripheral blood in most patients, despite the underlying cellular defect, is normal A subset of these patients have concomitant T cell immunodeficiency with increased numbers of activated CD8 cells, splenomegaly, and decreased delayed-type hypersensitivity
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COMMON VARIABLE IMMUNODEFICIENCY
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ESSENTIALS OF DIAGNOSIS
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Defect in terminal differentiation of B cells, with absent plasma cells and deficient synthesis of secreted antibody Frequent sinopulmonary infections secondary to humoral immune deficiency Confirmation by evaluation of serum immunoglobulin levels and deficient functional antibody responses
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The most common cause of panhypogammaglobulinemia in adults is common variable immunodeficiency, a heterogeneous immunodeficiency disorder clinically characterized by an increased incidence of recurrent infections, autoimmune phenomena, and neoplastic diseases The onset generally is during adolescence or early adulthood but can occur at any age The prevalence of common variable immunodeficiency is about 1:80,000 in the United States
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Patients may be treated aggressively with antibiotics at the first sign of infection Since antibody deficiency predisposes patients to high-risk pyogenic infections, antibiotic coverage should be sure to cover encapsulated bacteria Only after the development of bronchiectasis or after sinus surgery do patients become significantly affected by more virulent organisms such as Staphylococcus aureus or Pseudomonas aeruginosa Maintenance intravenous immune globulin (IGIV) therapy is indicated, with infusions of 300 500 mg/kg of IGIV given at about monthly intervals Adjustment of dosage or of the infusion interval is made on the basis of clinical responses and steady-state trough serum IgG levels Such therapy is effective in decreasing the incidence of potentially life-threatening infections and increasing quality of life The yearly cost of monthly infusions can be in excess of $20,000 $30,000
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Castigli E et al Molecular basis of common variable immunodeficiency J Allergy Clin Immunol 2006 Apr;117(4):740 6 [PMID: 16630927] Cunningham-Rundles C Immune deficiency: office evaluation and treatment Allergy Asthma Proc 2003 Nov Dec;24(6): 409 15 [PMID: 14763242] Weiler CR et al Common variable immunodeficiency: test indications and interpretations Mayo Clin Proc 2005 Sep;80 (9):1187 200 [PMID: 16178499]
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Clinical Findings
A Symptoms and Signs
The pattern of immunoglobulin isotype deficiency is variable Most patients present with significantly depressed IgG levels, but over time all antibody classes (IgG, IgA, and IgM) may be affected Increased susceptibility to pyogenic infections is the hallmark of the disease Virtually all patients suffer from recurrent sinusitis, with bronchitis, otitis, pharyngitis, and pneumonia also being common infections Infections may be prolonged or associated with unusual complications such as meningitis or sepsis Gastrointestinal disorders are commonly associated with common variable immunodeficiency, and a spruelike syndrome, with diarrhea, steatorrhea, malabsorption, protein-losing enteropathy, and hepatosplenomegaly, may develop in patients Paradoxically, there is an increased incidence of autoimmune disease (20%), although patients may not display the usual serologic markers Autoimmune cytopenias are most common, but autoimmune endocrinopathies, seronegative rheumatic disease, and gastrointestinal disorders are also commonly seen Lymph nodes may be enlarged in these patients, yet biopsies show marked reduction in plasma cells Noncaseating granulomas are
DISEASES OF IMMUNOGLOBULIN OVERPRODUCTION (GAMMOPATHIES)
The monoclonal gammopathies include those diseases in which there is a proliferation of a single clone of immunoglobulin-forming cells that produce a homogeneous heavy chain, light chain, or complete molecule The amino acid
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