June 2007
Cardiolipin
Antibodies to this antigen, which occur in both autoimmune disorders and infectious disease, may require it to associate with a plasma protein for binding. Can you guess what it is?
Phospholipids are esters of fatty acids and phosphate with an alcohol. There are two major classes, depending on the alcohol: glycerophospholipids (glycerol) and sphingophospholipids (sphingosine). Anti-phospholipid antibodies are important autoantibodies that can contribute to fetal loss as well as initiate a devastating systemic thrombotic disorder in some patients. Often found in patients with systemic lupus erythematosus (SLE), they may also occur in other settings. Although they may react with a variety of glycerophospholipids, the most commonly used antigen is cardiolipin, which is an unusual phospholipids in that glycerol is surrounded on either side by a phosphatidyl group. Primarily a mitochondrial membrane phospholipid, cardiolipin is released in a variety of types of tissue injury and short-lived autoantibodies may develop. This is the basis for the rapid plasma reagin (RPR) test for syphilis. (SLE patients often have a "biological false-positive" RPR.) Binding of the autoantibody to cardiolipin requires the presence of a plasma protein, beta-2-glycoprotein 1, and autoantibodies against this protein may also develop.
May 2007
Anti-Centromere
Bees target the yellow disk of the daisy but which autoantibodies target the center of these chromosomes?
Systemic sclerosis (or scleroderma) is a multi-system disease that presents in two major ways. Most patients have what is now called "limited cutaneous systemic sclerosis". This is different from localized scleroderma, which affects only the skin. In limited systemic sclerosis, other organs may be affected but not to the degree seen is what is now called "diffuse cutaneous systemic sclerosis". In the diffuse form of the disease, renal and lung involvement is common and the lung involvement is typically severe (with interstitial fibrosis). Almost all patients with systemic sclerosis have a positive anti-nuclear antibody (ANA) and the specific pattern (usually verified by specific immunoassay) can help differentiate the two major forms of the disorder. The limited form (sometimes referred to using the acronym "CREST" because of the presence of calcinosis, Raynaud phenomenon, esophageal involvement, sclerodactyly and telangiectasia) is usually positive for anti-centromere antibody while the diffuse form is not. Anti-centromere produces a characteristic speckled pattern using indirect immunofluorescence and immunoassays for these antibodies are also now available.
April 2007
Atypical p-ANCA
Instead of an Easter egg hunt, here's an ANCA hunt. Which of these ANCAs is associated with inflammatory bowel disease?
Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies against components of peripheral blood neutrophils which are characteristic of certain relatively rare small vessel vasculitic disorders often called "pauci-immune" because direct immunofluorescence seldom reveals any significant amount of immune complexes. In Wegener's granulomatosis, the autoantibody target is a proteinase. In other types, the autoantibody targets include myeloperoxidase and other granular enzymes. Besides using specific immunoassays, the two types of reactivity may be differentiated using indirect immunofluorescence. Ethanol fixation disrupts the granules. Proteinase remains within the cytoplasm, producing the "c-ANCA" pattern (left) but myeloperoxidase (and, perhaps, other enzymes) relocate to the neri-nuclear region, producing the "p-ANCA" pattern (middle). Specimens from patients with inflammatory bowel disease show a so-called "atypical" p-ANCA pattern (with a fine rim-like pattern). To learn more, look up the review article by Drs. Terjung and Worman in the 2002 Immunotes.
March 2007
Desmoglein
Autoantibodies to this molecule (which holds skin cells together) can cause this immunofluorescence pattern. Can you guess what it is?
Pemphigus is a group of disorders in which the skin (and mucous membranes) form blisters. Especially if it involves large surface areas of the skin, it can be fatal. The cause is an autoantibody against desmoglein, a "cadherin" or protein that holds cells together. Antibodies bound to these intracellular proteins in the skin produce the characteristic immunofluorescence pattern shown, both in lesional skin biopsies as well as in indirect immunofluorescence assays. There are different types of pemphigus clinically and some of these may be identified by finding antibodies to specific types of desmogleins (using ELISA). Monitoring patients is a useful tool because it appears that antibody levels rise before the onset of a new episode, allowing for preventive administration of glucorticoids and other immunosuppressive agents.
February 2007
Oxidized Phospholipid
Autoantibodies may develop to the antigen on the right and they may worsen cardiovascular disease. Can you guess what it is?
Phospholipids released from LDL cholesterol deposited in atherosclerotic plaque may become oxidized if the area contains a significant amount of inflammation. Oxygen free radicals formed by inflammatory cells react with fatty acids and induce lipid peroxidation. Further degradation produces reactive aldehydes and ketones that can then modify amino acid residues in the apolipoprotein. Oxidized LDL is the general term used to refer to this mix of modified lipid and protein and measuring plasma levels of these is an interesting area of research. Autoantibodies may develop to these molecules as well; however, there is less clarity about the role that these autoantibodies may play in exacerbating atherosclerosis.
January 2007
Deoxyribonucleoprotein ("LE cell")
Autoantibodies may develop to the antigen on the right and they may worsen cardiovascular disease. Can you guess what it is?
An antigen containing both DNA and histone protein is responsible for the production of the "LE cell". This was the first "anti-nuclear antibody" test. Whole blood from the patient would be drawn into a tube containing glass beads and rotated. As some white cells died, their nuclei would interact with anti-DNP and fix complement. This caused the nuclear material to round-up (and, when stained, have a lighter purplish hue). Other white cells would phagocytize these "hematoxylin bodies", producing a cell that was characteristic of systemic lupus erythematosus. The test has essentially been completely replaced by either indirect immunofluorescence or ELISA but it's unclear whether this particular antibody specificity is similarly detected by these methods.