Q:

1/15/2015
I would like clarification on the differences between IgG precipitins and IgG specific antibodies. I have a patient with asthma, possible ABPA, an increased specific IgG to aspergillus fumigatus, but negative IgG precipitins. Additionally, in a patient with suspected ABPA, how much emphasis needs to be given to the precipitants vs. the specific IgG antibodies?

A:


IgG precipitins refers to a immunologic method used to measure specific-IgG antibody based upon a precipitation reaction which will occur in fluid phase or agarose when antibody and antigen are at equivalence. Visible precipitation is generally performed in agarose gel. Polyvalent antibodies are more effective in precipitation which means IgM is more likely to demonstrate precipitation. Most laboratories no longer utilize precipitation methodology, at least in agarose, as more than one day is required for equivalence and for the precipitation to be visible. Furthermore, the precipitation interpretation is more subjective and less quantitative than other techniques. Fluid phase precipitation is used to measure immunoglobulins and other antigens as the detection is based upon light scatter and the equipment can be automated and results are faster. In general, specific antibody detection by enzyme linked immunoassay (ELISA) is more rapid, more quantitative and readily automated. Thus, most laboratories measure specific-IgG rather than precipitins. The historical literature utilized precipitins in the diagnostic criteria of diseases such as allergic bronchopulmonary aspergillosis. There is also some concern that detection of specific-IgG by ELISA may be too sensitive and complicate the clinical interpretation of the results.

In summary, in my opinion specific-IgG by ELISA or similar solid phase assays may be used interchangeably with IgG precipitins and are generally more commercially available. Your patient has negative precipitins which raises the possibility of a lower level or falsely positive specific-IgG. Clinical application is complicated by the fact that specific-IgG by ELISA is more sensitive than precipitation and falsely positive results may be a problem.

I have shared your question and this response with Dr. Paul Greenberger, an international expert on ABPA. I will provide his response when available.

Dr. Greenberger has responded.
Another difference between measurements of specific-IgG and IgG preciptins is that serum is concentrated for demonstration of precipitins whereas it is diluted for the IgG test. The antigens should be the same. If one has precipitins there are lots of antibodies analogous to ANAs which can precipitate in gel.

References:
Agarwal, Ritesh, et al. "Cut-off values of serum IgE (total and A. fumigatus-specific) and eosinophil count in differentiating allergic bronchopulmonary aspergillosis from asthma." Mycoses 57.11 (2014): 659-663.

Agarwal, Ritesh, et al. "Diagnostic performance of various tests and criteria employed in allergic bronchopulmonary aspergillosis: a latent class analysis." PLoS One 8.4 (2013): e61105.

I hope this information is of help to you and your patient.

All my best.
Dennis K. Ledford, MD, FAAAA

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