2007 Antibody Targets of the Month

December 2007

IgE antibodies against this mold may be responsible for serious allergic disease which is exacerbated during winter months because of overheating of air-tight homes. Can you guess what it is? (Answer next month)

December 2007 Antibody Target

Recently, attention has been given to the possibility that fungal growth in indoor environments (especially with water damage) can produce serious disorders in the building’s occupants. The symptoms of so-call “sick building syndrome” vary, but respiratory disorders attributed to allergic reactions predominate. When air samples have been tested, in addition to common indoor fungi such as Penicillium, Cladosporium and Aspergillus, a high percentage of Stachybotrys has been detected. This fungus likes to grow on cellulose and finds warm moist building material particularly attractive. It is not clear to what degree specific IgE-mediated reactivity against fungal antigens contributes as the fungi may also produce mycotoxins capable of causing the same symptoms.

November 2007

Antibodies against the protein shown in yellow (not the more famous proteins shown in red and blue) will see increased use beginning this month. Can you guess what it is?

November 2007 Antibody Target

Influenza Nucleoprotein
Every year the winter months bring cold and snow and respiratory tract infections. Most are viral in nature and most are due to the common cold virus. Influenza A and B viruses cause annual outbreaks of more serious respiratory tract disease, usually associated with systemic symptoms. Commercial “immunochromatographic” enzyme immunoassays, commonly employed to screen nasal washings for influenza A and B virus even though their sensitivity is not exceedingly high, use antibodies specific for nucleoprotein antigens, not the surface antigens hemagglutinin (H; shown in red) and neuraminidase (N; shown in blue). These latter antigens are the primary target of naturally occurring antibodies. Because these may change due to point mutations (antigen “drift”) or, more dramatically, recombination with animal viruses (antigen “shift”), antibodies from prior infection may not be protective this year. We hope you got your flu vaccine!

October 2007

According to a recent study, antibodies to this HLA-related glycoprotein may contribute to allograft loss even when the recipient is well-matched for HLA. Can you guess what it is?

October 2007 Antibody Target

MICA (MHC Class I-related Chain A)
HLA Class I (HLA-A & HLA-B) and Class II (HLA-DR) antigens are the most important to match between donor and recipient but so-called “minor” antigens are also important, especially if they are expressed on the surface of endothelial cells. This is because antibodies to such antigens can cause vascular rejection. Most of the “minor” antigens are red blood cell antigens (such as the ABO system) but a recent study found that some proteins coded within the Major-Histocompatibility-Complex Class I gene complex that resemble Class I proteins may also be important. These proteins do not function as presenters of peptide antigens to lymphocytes. Rather, they are induced by stress and may signal to a natural killer cell that the cell is in trouble. Note that the structure is similar to Class I MHC but that the “light chain” beta-2-microglobulin is missing.

September 2007

Antibodies involved in the most common drug allergy are directed against this structure, not the drug itself. Can you guess what it is?

Penicilloyl Hapten
IgE antibodies to penicillins are not directed against the parent compound, but against haptens that form when the drug binds to protein. There are several sites for this binding to occur. The most common (forming the "major" allergenic determinant) is the carbonyl carbon within the beta-lactam ring (as shown in this diagram). Other sites (forming "minor" allergenic determinants) include the carbonyl carbon and the sulfur atom of the outer thiazolidine ring.

August 2007
Pseudomonas Aeruginosa

The 2007 CDID Best Abstract Award went to authors of a study that showed that measuring IgG antibodies to products of these organisms could help predict a serious consequence of cystic fibrosis. Can you guess what they are?

Cystic fibrosis produces chronic lung changes that result in colonization with this gram-negative rod. Early antibiotic treatment can prevent this. The winners of this year's CDID award for best abstract presented a study at the annual AACC meeting in July showing how levels of IgG antibodies against Psuedomonas antigens could identify this complication, allowing for early intervention. See Leal T et al, Clin Chem 53(S6):A210, 2007. Thanks to Dr. N. Banaei of Stanford University for the image of the mucoid Pseudomonas.

July 2007

We are moving beyond autoantibody targets, beginning with this month's quiz. The laboratory use of antibodies to the green epitopes in this cartoon will be discussed during this month's "Issues in Immunodiagnostics" session at the AACC meeting. Can you guess what they are?

Free Light Chains
The cartoon is the immunoglobulin molecule, with two heavy chains and two light chains (all linked by disulfide bridges). Epitopes on the light chains such as the ones colored green are hidden when the light chains are attached to the heavy chains. When the light chains are free, however, these antibodies are able to detect these proteins. Sensitive nephelometric assays for such free light chains in serum are able to detect imbalances between the two types of light chains (kappa and lambda) that occur in myeloma. Although originally used primarily to monitor disease in patients whose myelomas produced light chains only, these assays are also finding a place in the management of patients with myelomas that produce intact monoclonal immunoglobulins as well.

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