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Agglutination Assays Red cells are incubated with purified specific antigen (eg, thyroglobulin), which is adsorbed to the cell surface. The antigen-coated cells are suspended in the patient's serum, and antibody is detected by red cell agglutination. Antigen-coated latex particles are substituted for red cells in latex fixation tests. Enzyme-Linked Immunosorbent Assay Antibodies to various tissue antigens can be readily detected by these tests. Extracted and purified antigens are fixed to a plastic microtiter well or beads. The patient's serum is added, and excess proteins are removed by washing and centrifugation. Adherent immunoglobulin is then detected when a second antibody coupled to an enzyme (eg, alkaline phosphatase) is added. Finally, the enzyme's substrate is added; color forms and is measured in a spectrophotometer. This test can also be adapted for antigen detection by placing the antibody on the plastic surface. ELISA is very sensitive and less cumbersome than ...

Selective IgA deficiency is the most common primary immunodeficiency disorder and is characterized by the absence of serum IgA with normal levels of IgG and IgM; its prevalence is about 1:500 individuals. Most persons are asymptomatic because of compensatory increases in secreted IgG and IgM. Some affected patients have frequent and recurrent infections such as sinusitis, otitis, and bronchitis. Some cases of IgA deficiency may spontaneously remit. When IgG2 subclass deficiency occurs in combination with IgA deficiency, affected patients are more susceptible to encapsulated bacteria and the degree of immune impairment can be more severe. Patients with a combined IgA and IgG subclass deficiency should be assessed for functional antibody responses to glycoprotein antigen immunization. Atopic disease and autoimmune disorders can be associated with IgA deficiency. Occasionally, a sprue-like syndrome with steatorrhea has been associated with an isolated IgA deficit. Treatment with commercia...

NONALLERGIC RHINITIS Vasomotor Rhinitis Vasomotor rhinitis can be the primary cause of chronic nasal congestion, rhinorrhea or, less commonly, sneezing paroxysms. About one-fifth of patients who seek medical attention at an allergy/immunology subspecialty clinic complaining of chronic rhinitis will actually have nonallergic, vasomotor rhinitis; one-third of patients in whom allergic rhinitis is diagnosed will also have a vasomotor component to the disease. Nonspecific nasal hyperreactivity leads to symptoms triggered by cold temperature, inhaled irritants, strong odors, spicy food, and other nonallergic environmental stimuli. Intranasal corticosteroids (eg, fluticasone), azelastine, and ipratropium, and oral decongestants may be effective as monotherapy or in combination. Nasal Polyposis Compared with the general population, nasal polyps are not found more frequently in patients with allergic rhinitis, but they are associated with aspirin sensitivity syndrome, chronic sinusitis, allerg...

General Considerations Some drugs are clearly more immunogenic than others, and this can be reflected in the incidence of drug hypersensitivity. A partial list of drugs frequently implicated in drug reactions includes -lactam antibiotics, sulfonamides, phenytoin, carbamazepine, allopurinol, muscle relaxants used for general anesthesia, nonsteroidal anti-inflammatory drugs, antisera, and antiarrhythmic agents. Many drugs can be associated with recognizable known toxicities, drug interactions, or idiosyncratic reactions that are not immune-mediated. These must be distinguished from true hypersensitivity reactions because the prognosis and management differ. Some estimate that only 10% or less of adverse reactions to drugs are true hypersensitivity reactions. Patients with multidrug hypersensitivity are quite rare, and those reporting "allergies" to more than three distinct classes of drugs should be carefully evaluated since intolerance to many of these drug classes may not be ...

Biochemical genetics deals not only with enzymatic defects but also with proteins of all functions, including cytoskeletal and extracellular structure, regulation, and receptors. The principal functions of the biochemical genetics laboratory are to determine the presence or absence of proteins, to assess the qualitative characteristics of proteins, and to verify the effectiveness of proteins in vitro. The key elements from the referring clinician's perspective are: (1) to indicate what the suspected clinical diagnoses are and (2) to make certain that the proper specimen is obtained and transported to the laboratory in a timely manner. Indications for Biochemical Investigations Some inborn errors are relatively common in the general population, eg, hemochromatosis, defects of the low-density lipoprotein receptor, and cystic fibrosis (Table 44–3). Others, although rare across the entire population, are common in certain ethnic groups, such as Tay-Sachs disease in Ashkenazic Jews, s...

AUTOIMMUNITY Autoimmune diseases cannot be explained by a solitary cause or mechanism. Small amounts of autoantibodies are normally produced and may have physiologic roles in cellular interactions. Positive serologic findings may be found years before the development of pathogenic autoimmunity or clinical illness, and in some cases, they represent normal immunity or "benign autoimmunity" without disease. The major theories regarding the development of autoimmune disease are (1) release of normally sequestered antigens; (2) escape from anergy or defective apoptosis (programmed cell death) leading to abnormal autoreactive cellular clones; (3) shared antigens between the host and microorganisms, ie, "molecular mimicry"; and (4) defects in helper or suppressor T cell function. A genetic susceptibility is also a likely determinant of autoimmune disease. In nearly all autoimmune diseases, multiple mechanisms of autoimmunity are operative. Cell-Mediated Autoimmunity Certai...

Essentials of Diagnosis Anaphylaxis is a systemic reaction with cutaneous symptoms, associated with dyspnea, visceral edema, and hypotension. Urticaria is characterized by large, irregularly shaped, pruritic, erythematous wheals. Angioedema is painless, deep, subcutaneous swelling, often involving periorbital, circumoral, and facial regions. These disorders may be diagnosed clinically, especially in the context of allergen exposure; detection of specific IgE or elevated serum tryptase can confirm the diagnosis. General Considerations Certain allergens—especially drugs, insect venoms, and foods—may induce an IgE antibody response, causing a generalized release of mediators from mast cells and resulting in systemic anaphylaxis. This potentially fatal condition affects both nonatopic and atopic persons. Isolated urticaria and angioedema are more common cutaneous forms of anaphylaxis with a better prognosis. Food allergies cause an estimated 150 fatalities per year in the United States...

Essentials of Diagnosis Seasonal or perennial occurrence of nasal pruritus, congestion, rhinorrhea, or paroxysms of sneezing, which may be associated with lower respiratory symptoms, eye erythema, pruritus, irritation, tearing, or eczematous dermatitis. Environmental aeroallergen exposure. Presence of specific-IgE antibody to tested aeroallergens. Clinical Findings In addition to the symptoms listed above, up to 40% of patients with allergic rhinitis also manifest lower respiratory symptoms: cough, wheezing, chest tightness, or dyspnea. The physical examination may reveal edematous or inflamed nasal mucosa. In severe cases, the affected mucosa may be pale, boggy, or blue-tinged from vascular engorgement and venous congestion. Nasal symptoms can be nonspecific, however, and the differential diagnosis can include viral rhinitis, bacterial sinusitis, vasomotor rhinitis, nasal polyposis, drug-induced rhinitis, hormonal rhinitis, rhinitis medicamentosa, atrophic rhinitis, gastroesophageal r...