The microorganism in this lung biopsy has provoked an exaggerated immune response which may be diagnosed by finding high levels of both IgE and IgG antibodies. Can you guess what it is?
Allergic bronchopulmonary aspergillosis (ABPA) refers to a condition characterized by an unusual immunologic reaction to inhaled antigens of Aspergillus species (often in patients with asthma) that results in bronchial wall damage and bronchiectasis. The diagnosis is a clinical one but laboratory testing may offer support for ruling it in or excluding it. Helpful laboratory evidence includes a high level of IgE anti-Aspergillus antibody; a high level of total IgE; and the presence of IgG anti-Aspergillus antibody, detected by either immunodiffusion or immunoassay.
The diagnostic significance of antibodies to this molecule has recently been questioned and this controversy is discussed in the Fall Immunotes CDID newsletter. Can you guess what it is?
Check out the on-line Fall 2008 CDID newsletter to see why some experts believe that antibodies against other phospholipids may be more important in the diagnosis and management of anti-phospholipid antibody syndrome.
The molecule at the bottom, which results from the action of tissue transglutaminase, may be a better target for an assay that measures antibodies in celiac disease. Can you guess what it is?
Deamidated Gliadin Peptide
Celiac disease is an autoimmune disorder of the small intestine in which lymphocytes damage the absorptive villi, causing blunting and malabsorption. The pathogenesis involves presentation of peptides derived from gliadin, a protein found in wheat and other grains. Deamidation of the peptides helps this process to be more effective. Although certain major histocompatibility complex (MHC) proteins are required to properly present these dangerous peptides, other genetic (and possibly environmental) factors are also responsible. Autoantibodies develop against the enzyme which catalyzes the deamidation reaction (tissue transglutaminase) and these are considered very sensitive and specific for the diagnosis. Previously, antibodies to gliadin have not been considered specific as these may develop in patients with malabsorption due to other causes. However, recent studies have shown that antibodies specific for the deamidated peptides may be useful in celiac disease.
This month’s issue of Clinical Chemistry features a reprint of a “classic” report describing an immunoassay for the molecule depicted in red in this cartoon. Can you guess what it is?
Dr. Hugo Katus described the discovery of cardiac-specific troponin T, which anchors the troponin complex to tropomyosin (the cord-like structure pictured in blue). During depolarization, calcium binds to troponin C and troponin I (the yellow structure) moves out of the way, allowing actin (orange) to interact with myosin (pink). This generates contraction of the muscle fiber. The original troponin T assay provided results in 90 minutes; modern advances have allowed manufacturers to create assays for cardiac-specific troponin T (and troponin I) that reduce the turnaround time to 20 minutes or less.
Amgen recently announced the success of a clinical trial of denosumab, a monoclonal antibody directed against the molecule which helps produce the multi-nucleated osteoclast pictured. Can you guess what it is?
New bone formation requires initial bone resorption (similar to digging out loose plaster before respackling dry-wall board). When the balance between resorption and formation is disturbed, osteoporosis results. Current drugs like bisphosphonates try to poison the osteoclast to prevent excessive bone resorption. Amgen’s new monoclonal antibody inhibits the molecule (RANK ligand) which promotes osteoclast development and activates osteoclasts. It binds to the “receptor activator of nuclear factor kappa B”.
The CDID award for best abstract at this year’s AACC meeting will be presented to a group who looked at a new way to measure this molecule complexed to a common tumor marker. Can you guess what it is?
Prostate-specific antigen (PSA) is a serine protease inactivated by serine protease inhibitors. Most of the focus on complexed (or, alternatively, free) PSA has been on its binding to anti-chymotrypsin. Recently, investigators at University of Helsinki looked at PSA bound to alpha-1-protease inhibitor (also known as alpha-1-antitrypsin). They employed proximity ligation assay (immunoassay using oligonucleotides and PCR). At the 2008 Issues in Immunodiagnostics symposium, an award was presented to lead author Lei Zhu.
If you discover this bug on your arm this month, your doctor will order a laboratory test looking for antibodies against a particularly devious spirochete. Can you guess what it is?
Borreliosis (“Lyme disease”) is an infectious disease caused by a spirochete bacterium transferred via the bite of the deer tick (shown is Ixodes dammini, the tick responsible for infections in the eastern part of the U.S.). Identifying antibodies against B. burgdorferi is an important part of the diagnosis and this serology test is an especially challenging one. The test only positive in a minority of patients soon after exposure and then, when either neurological or joint symptoms begin, positive results need to be confirmed by Western blot. Wear long pants while hiking this summer!
This antigen will be coming your way this month and we hope that you don’t have IgE antibodies against it. Can you guess what it is?
Oak Tree Pollen
The vaguely triangular shape and the “warty” granular surface identifies this as the pollen of the oak family of trees. Oak trees are present in most of the U.S. and they shed enormous amounts of pollen, making them an important cause of seasonal allergy. If you know that you are not allergic to tree pollen, watch out for grass (June and July) and weed pollen (September and October) later this year. If you are interested in allergic disease, check out the report of the 2008 meeting of the AAAAI (the major organization in the U.S. of allergists) in the new issue of our on-line CDID newsletter “Immunotes” sometime this month.
Investigators look for antibodies to this enzyme in patients with inflammatory bowel disease in this month’s issue of Clinical Chemistry. Can you guess what it is?
A number of antibodies (both autoantibodies and antibodies to foreign antigens) are associated with inflammatory bowel disease (ulcerative colitis and Crohn’s disease). Two commonly described ones include the autoantibody that produces an “atypical” perinuclear ANCA (anti-neutrophil cytoplasmic antibody) pattern and the antibody against the yeast Saccharomyces cerevisiae (ASCA). Vermeulen et al followed up on recent findings that these patients had antibodies to alpha-enolase (a small enzyme involved in the glycolytic pathway) but their presence in healthy controls and patients with other gastrointestinal disorders precludes use of these antibodies as a diagnostic test (see Clin Chem 2008; 54:534-541.)
Certain versions of this relatively common autoantibody can produce this appearance when serum is chilled. Can you guess what it is?
Cryoprecipitable Rheumatoid Factor
Many patients infected with hepatitis C virus develop an abnormal immune response that includes the presence of rheumatoid factor (autoantibody against IgG) with a peculiar physicochemical property. When the temperature is lowered, it denatures and comes out of solution. The denaturation is reversible (it instantly goes back into solution once the temperature is raised) and concentration-dependent (at higher concentrations, denaturation occurs at higher temperatures). In some patients, the rheumatoid factor response may even become monoclonal.
Like Janus, the two-faced Roman god, a particular anti-nuclear antibody can produce this two-faced appearance, with some cells positive and others negative. Can you guess what it is?
Proliferating Cell Nuclear Antigen (PCNA)
Autoantibodies to PCNA exhibit the speckled immunofluorescence pattern only on some Hep2 cells because the antigen expression occurs during late G1 and early S phase of the cell cycle just before DNA synthesis. Autoantibodies to PCNA are detected in the sera of 3–5% of patients with SLE. Anti-PCNA antibody has not been detected in other autoimmune diseases and is thought to be specific for SLE.