2009 Antibody Targets of the Month

December 2009

This molecule is often used to treat a disorder associated with chronic renal failure but autoantibodies against it can make the disorder worse. Recently, an unrelated agonist has been shown to help patients with this complication. Can you guess what it is?

CDID December 2009

Erythropoietin
Recombinant human erythropoietin usually successfully treats the anemia associated with chronic renal failure. Rarely, however, autoantibodies may develop against erythropoietin and these can produce red-cell aplasia, a serious condition. European investigators recently reported that a synthetic peptide was able to interact with the receptor for erythropoietin and stimulate red blood cell production in such patients. The peptide is able to stimulate the receptor but is different enough from erythropoietin that it is not recognized by the anti-erythropoietin autoantibodies.


November 2009

This type of display of antibody binding was discussed during the CDID session at the annual CLAS meeting, featured in the new Fall Immunotes on-line now. Can you guess what it is?

CDID November 2009

Microarray Heatmap
In a technique analogous to the use of differently colored cDNA (made from either test sample or reference mRNA) hybridization to a DNA microarray, antibody binding to multiple antigens can be studied. This is a portion of an array of antigens (a different antigen is in each row) interacted with sera from different animals (a different animal is in each column). The color represents the amount of antibody (using fluorescent-labelled anti-immunoglobulin). The rows and columns are ordered by hierarchical cluster analysis to reveal patterns in the data. Wild type (WT) differs from mutant for a number of antibodies, and tree branches show relationships among samples and antigens.


October 2009

This month’s Clinical Chemistry includes a description of an immunoassay for this protein, which is crucial for B cell survival. Can you guess what it is?

BAFF (B cell-activating factor of the TNF family)
This molecule is a member of the tumor necrosis factor (TNF) family of cytokines and it regulates the growth and survival of B cells. There have been conflicting reports regarding whether levels of this cytokine are elevated in autoimmune disorders and the report in last month’s Clinical Chemistry (by Le Pottier et al) describes how the discrepancies are likely to be do to variability in the way in which different immunoassay antibodies recognize differently glycosylated forms of the protein.


 

  September 2009

The autoantibody producing this ANA pattern was missed by ELISA and delayed the diagnosis in the case which opened our 2009 “Issues in Immunodiagnostics”. Can you guess what it is?

Anti-sp100
Dr. Donald Bloch (a rheumatologist at Massachusetts General Hospital in Boston) argued that the ANA is not a test to establish the diagnosis of a particular autoimmune disease but, rather, a screen for the possibility of autoimmune disease. He was critical of immunoassays that only include some specific antigens, and presented a case in which the ELISA ANA was negative but the immunofluorescent ANA (finally obtained after the patient saw several different rheumatologists) was positive because of this relatively unusual pattern. The nuclear dots are seen because of antibodies to sp100, one of several proteins associated with these nuclear structures, whose exact function is still not known. These autoantibodies may be seen in patients with primary biliary cirrhosis (the diagnosis in the case presented) and may be helpful when the test for anti-mitochondrial antibody is negative (which may occur in a minority of PBC patients). To be fair, Dr. Bloch did not mention whether the anti-mitochondrial antibody test had been performed. Also, this pattern is not specific for PBC. But the case was certainly food for thought about using immunoassay screens for “ANA” in place of indirect immunofluorescence.


August 2009

This molecule was first identified using an antibody but we now know that it functions as a primitive antigen recognition protein. Can you guess what it is?

Toll-like receptor
Toll-like receptors (TLRs) are an evolutionarily ancient family of pattern recognition molecules which play a major role in innate immunity. They recognize bacterial lipoproteins on the surface of the cell and bacterial nucleic acid inside of lysosomes. Shown is the leucine-rich portion that appears on the membrane. This is connected to a cytoplasmic domain that can initiate signaling to activate the cell. In the case of a macrophage, this will allow the cell to produce inflammatory cytokines.


July 2009

The accuracy of immunoassays using antibodies against this molecule is investigated using tandem mass spectrometry in this month’s issue of Clinical Chemistry. Can you guess what it is?

July Antibody Target

(Free) Thyroxine
Investigators at Georgetown University and Children’s National Medical Cenetr in Washington DC reported in last month’s issue that free T4 determinations by LC/MSMS (after ultrafiltration) correlated better with TSH than did immunoassay free T4 results. They looked at samples from several different populations including pregnant women, a group in which free T4 results have been controversial.


June 2009

Everyone’s been talking about this organism and wondering if there is time to develop a vaccine to stimulate antibodies against it. Can you guess what it is?

 


H1N1 subtype of influenza A virus
The world’s attention has been on the outbreak of so-called “Swine flu”, recently declared a pandemic by World Health Organization – the first in 40 years. The Swiss pharmaceutical company Novartis AG recently announced that it had successfully manufactured a vaccine, making it likely that there will be supplies ready by the fall – in time for the start of the new flu season.


May 2009

This enzyme, once the target of a popular antibody-based test for prostate cancer eventually replaced by PSA, is now part of a modern immunotherapy approach to treating prostate cancer. Can you guess what it is?

 

Prostatic acid phosphatase (PAP)
This enzyme was the original tumor marker for prostate adenocarcinoma. Although enzymatic activity continued to be the method of choice, immunoassays for PAP were once commercially available. Both types of assays for PAP have all but been replaced by prostate-specific antigen (PSA). A new approach to therapy of prostate cancer is the use of autologous antigen-presenting cells pulsed ex vivo with a recombinant fusion protein consisting of granulocyte-monocyte colony stimulating factor and PAP. This new commercially available product (Provenge) is the first immunotherapy regimen to receive approval from the Food and Drug Administration.


April 2009

At last month’s AAAAI meeting, a study showed that administration of very small amounts of this protein over time helped children with severe allergy. Can you guess what it is?

April 2009 

Cupin (Peanut allergen)
The “cupins” are a superfamily of proteins with a beta-barrel core domain (shown in red). They include two types of proteins (vicilins and legumins) which represent the common allergens in peanuts. Investigators at Duke University recently reported that children enrolled in an open-label trial of oral immunotherapy using such peanut proteins have shown significantly decreased levels of IgE specific anti-peanut antibody.


March 2009

This month’s Clinical Chemistry includes a study looking at antibodies against larger aggregates of this hormone, secreted exclusively by fat cells. Can you guess what it is?


Adiponectin
Pictured is the simplest form of this hormone made by adipose cells, consisting of three peptide monomers. Adiponectin is a “good” cytokine (analogous to HDL as the “good” lipoprotein particle) because it appears to counteract the effects of pro-inflammatory cytokines found in patients with insulin resistance and the “metabolic syndrome”. Measuring adiponectin may have a future role in cardiovascular risk modification and the report by Liu et al in the March Clinical Chemistry seemed to support the use of commercially available ELISAs. However, more work must be done to analyze the way in which more complicated aggregates of the protein (including “high molecular weight” adiponectin) may affect these assays.


February 2009

Lack of antibody production against the organism growing around the beta-hemolytic Staphylococcus on this plate has resulted in the potential return of a disease long thought conquered. Can you guess what it is?

Hemophilus influenzae
Five children were sickened in Minnesota last month by H. influenzae, type B (Hib) and one died. Three of the children (including the one who died) had not received any vaccinations, raising concerns about the recent tendency for parents to decline vaccination. There is also currently a shortage of Hib vaccine. One of the characteristics of Hib is its requirement for certain nutrients released from blood agar by other bacteria, hence its growth around the “staph streak” on this plate.
 


January 2009 

This molecule is the target of an antibody that causes a common thyroid disorder but measurement of its activity in the clinical laboratory is controversial, as shown by a report in the January issue of Clinical Chemistry. Can you guess what it is?

   

TSH receptor
Graves disease is caused by an autoantibody to the receptor on thyroid cells for thyrotropin (or thyroid stimulating hormone, TSH). When the antibody binds to the receptor, it mimics the action of TSH, producing increased production and release of thyroid hormone. Anti-TSH receptor may be detected by the ability of antibodies in the patient’s serum to block the ability of labeled TSH bind to bind to receptors in vitro (so-called “blocking” antibodies) or by the ability of antibodies in the patient’s serum to stimulate cultured thyroid cells (so-called “stimulating” antibodies). Catherine Massart and her colleagues looked at several commercially available assays for blocking antibody in the January issue of Clinical Chemistry (55:183-186, 2009) and they found poor precision and significant variability.  

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