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3 Immune Complex Disease
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In this group of diseases (systemic lupus erythematosus, lupus nephritis, rheumatoid arthritis, some drug-induced hemolytic anemias, and thrombocytopenias), autologous tissues are injured as innocent bystanders Autoantibodies are not directed against cellular components of the target organ but rather against autologous or heterologous antigens in the serum The resultant antigen-antibody complexes bind nonspecifically to autologous membranes (eg, glomerular basement membrane) and fix complement Fixation and subsequent activation of complement
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Autoimmune diseases cannot be explained by a solitary cause or mechanism Small amounts of autoantibodies are normally
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components produce a local inflammatory response resulting in tissue injury
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The diagnosis and treatment of specific autoimmune diseases are described elsewhere in this book Autoantibodies associated with certain autoimmune diseases may not be pathogenetic but are thought to be markers or by-products of the injury (eg, autoimmune thyroiditis and antithyroglobulin antibody) See Table 19 2 for autoantibody patterns in connective tissue diseases
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Arbuckle MR et al Development of autoantibodies before the clinical onset of systemic lupus erythematosus N Engl J Med 2003 Oct 16;349(16):1526 33 [PMID: 14561795] Colglazier CL et al Laboratory testing in rheumatic diseases: a practical review South Med J 2005 Feb;98(2):185 91 [PMID: 15759949]
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In humans, very striking associations are observed between particular HLA antigens and specific diseases Some of these are listed in Table 19 3 In some diseases, the HLA molecule may be implicated in the pathogenesis In others, the specific HLA allele may be linked to a gene determining immune responsiveness to a particular antigen The standard method for detecting HLA-A, -B, and -C antigens is that of lymphocyte microcytotoxicity Lymphocytes isolated from peripheral blood or lymph nodes are added to each well of a typing tray filled with sera containing the appropriate cytotoxic alloantibody When complement is added, cells to which antibody has been specifically bound will have complement activated at the cell surface, resulting in cell death or lysis It is thus possible to type for all of the known HLA-A, -B, and -C specificities An appreciable majority of typing serum samples are obtained from multiparous women since they form antibodies to fetal alloantigens Typing for the class II antigens HLA-DR and -DQ by serologic methods is technically more difficult Antigens of the HLA-D, -DR, -DQ, and -DP series may also be detected by in vitro mixed lymphocyte culture Lymphocytes of one individual (responder cells) will undergo proliferation upon encountering lymphocytes from another individual possessing foreign HLA-DR and -DQ antigens (stimulator cells) Lymphocyte proliferation can be readily measured by DNA incorporation of tritiated thymidine Responders possessing matching -DR and -DQ antigens will remain nonreactive Increasingly, HLA class II typing is being performed by molecular technology The DNA sequences for the HLA genes and their flanking sequences are known Selected primers that amplify the gene of interest using the polymerase chain reaction technique are known as sequence-specific primers HLA typing by PCR provides better resolution than serologic identification because typing is done at the genetic level
Reveille JD et al Spondyloarthritis: update on pathogenesis and management Am J Med 2005 Jun;118(6):592 603 [PMID: 15922688] Turesson C et al Genetics of rheumatoid arthritis Mayo Clin Proc 2006 Jan;81(1):94 101 [PMID: 16438485]
A 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 Antigencoated latex particles are substituted for red cells in latex fixation tests
B 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 radioimmunoassay techniques
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