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Given that an appropriate immune response to a bacteria may be thwarted in an individual, including not producing all of the antibodies which are known to occur in people who have been infected, or producing insufficient amounts of antibodies specific to a bacteria --- Are all serological tests using antibodies as a basis for detection of a systemic infection inherently flawed? In this instance, I'm assuming appropriate application of a test and competent laboratory methodology. But, equally important, what criteria can routinely be used to consider the efficacy of a particular antibody test, across the board.

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  • $\begingroup$ Can you give some example conditions under which the immune response may be "thwarted"? Are you talking about immunocompromised individuals, or something else? $\endgroup$ – MattDMo May 4 '16 at 22:09
  • $\begingroup$ Infections, such as flu, mono, and CMV can temporaCrily, suppress immune function so we don't produce antibodies to new antigens. If these infections are known -- fine. Would be considered when evaluating results from subsequent antibody tests. But, the primary infections I mentioned may be subclinical for symptoms and still effect overall immune function. So, I'm wondering if or how results of antibody tests "adjust" for this factor. Is it a consideration when evaluating antibody tests? This is the flaw I wondered about and still may not be clear enough. $\endgroup$ – Stephanie May 6 '16 at 0:19
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Antibodies used for serological tests are performed in vitro, and are not required to be effective for eliminating the pathogen. For an infected individual, antibodies may play a role in neutralization, opsonization, or activating the complement system (checkout Janeway's Immunobiology for more details). There are a number of reasons why antibodies may be present and not trigger an effective response down these pathways.

For example, E. Coli O157:H7 produces Shiga toxin and there are immunoassays to test for the presence of the toxin in feces (1). Only low amounts of the toxin is needed to cause disease. Antibodies against the toxin have been seen in individuals with the disease, suggesting the toxin is not a strong enough challenge for an immune response Discussion of (2).

You could go case-by-case for each of the immunoassays and see why their targets are difficult to turn into therapeutics.

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  • $\begingroup$ Can you add sources to the first part of your answer? $\endgroup$ – AliceD Jul 28 '18 at 22:42
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Are all serological tests using antibodies as a basis for detection of a systemic infection inherently flawed?

No

Every diagnostic test must be interpreted in the context of the clinical features of an individual and according to the data about that particular test. Tests of serum for antibodies are no different. See Cecil Medicine Chapters 8 and 9 for a discussion of this. A key passage:

Most tests do not provide a definitive answer about diagnosis or prognosis, but instead reduce uncertainty

Except in cases of passive immunization (e.g., transfused IVIG), the presence of a specific antibody in a serum sample indicates both exposure to an antigen and an immune response. What exactly this means depends on the individual and the test. Though not generally the test of choice for diagnosing active or chronic infection, some antibody tests are excellent indicators of infection in many individuals. A good example would be antibody to HIV.

As with any diagnostic test (again, see Cecil), antibody to HIV was evaluated relative to a standard, giving us a sensitivity (how good the test is at finding disease when it is present) and specificity (how good the test is at excluding disease when it is not present). It's not perfect (I've seen one false positive in my career), and it is not useful in the first few weeks after exposure, but, in general, it is an excellent diagnostic test.

Antibody tests are used for many other things, and again, as with any diagnostic test, they are evaluated for that purpose. Sticking with the use of these tests in infectious diseases, Hepatitis B antibody tests are an interesting example, since antibody to different antigens mean different things. Surface antibody, for example, indicates immunity either from exposure and clearance or from immunization. Core antibody indicates exposure to the virus itself, since core antigen is not present in the vaccine. As with most antibody tests, the antibody class can also give you useful information. IgM antibodies typically represent the initial immune response, where IgG antibodies represent a later response, and either clearance or chronic infection.

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Are all serological tests using antibodies as a basis for detection of a systemic infection inherently flawed?

You're thinking theoretically. Serological assays aren't theoretical, they're empirical.

When any assay is being characterized, it will be correlated with a particular outcome. Serological assays are no different. So long as there's a strong correlation with the targeted phenomenon, it doesn't matter if they're theoretically "flawed" (whatever that means); if they tell you what you need to know, then they're functional.

If every time a serological assay reads 40 or higher, an individual can be shown to be infected and every time it's less than 40 the individual isn't protected, then it doesn't matter what theoretical problems there might be with the assay, it can be used to predict infection. For that matter, if every time a ceramic saint wept salt tears it correlated with infection, then the saint test would be perfectly valid in the clinic, no matter how flawed the theory is.

How do you correlate your assay to the presence of infection, or whatever? Typically there are gold-standard tests that are perhaps too time-consuming, or difficult, or expensive to routinely run, and the serological assay will be cross-referenced to that for validation, and then hopefully approved by whatever regulatory body is in charge (in the US, often the FDA).

Don't confuse theoretical reasons with practical considerations.

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