As an integrative clinician, I routinely evaluate my patients for gluten sensitivity (GS). A subset of these individuals have celiac disease, which may be diagnosed with reasonable certainty looking at genes and a celiac panel; but today, I am talking about the broader net of reactions termed gluten sensitivity. GS seems to be rampant, and the removal of gluten from many people’s diets can yield significant clinical improvement. A good portion of individuals have extra-intestinal complaints: think psoriatic arthritis, fibromyalgia, migraines, depression, PMS and on. GI issues may be present, but are not always there. I consulted on a case involving occasional, unexplained ataxic episodes. Gluten? There is evidence in the literature. I would certainly not ruled it out. If I receive an update, I will post it here.
My assessment may include looking at genetic predisposition (HLA DQ2 and DQ3), a serum celiac panel including IgA tissue transglutaminase (TTG) and IgA antigliadin antibodies (AGA), along with a total serum IgA. Given the high prevalence of genetic IgA deficiency (about 10% of the population), a total IgA is important. An IgG4 may also be good; but today I am just talking about IgA.
My favorite initial screening test for GS is a stool IgA deaminated AGA. (AGA is not diagnostic of celiac, hence the term “screening”.) Indeed, I like the whole Metametrix profile, because I can –and often do—indentify gluten sensitivity and possible sequelae, including fat malabsorption and pancreatic insufficiency. I may see this even in individuals without major GI complaints. Evidence of microbiota imbalance is also common.
Stool as a specimen appears to be more sensitive for IgA AGA than serum. I prefer it because anecdotally, I see more positive results that correlate with clinical symptomology.
Why is that?
This question became an itch for me that demanded some scratching, and is the focus of my blog. Forgive the long introduction.
Understanding the basics of IgA immunology helped piece together a working hypotheses.
IgA is the dominant antibody in mucosal secretions- it is a first-line responder to exogenous invaders-- including foods to which we might react. IgA has two subclasses: IgA1 and IgA2. Mucosal IgA is primarily a heterodimeric polymer. Polymeric mucosal IgA is linked to a secretory glycoprotein, giving IgA its famous “secretory” or sIgA designation.
Serum IgA is primarily monomeric- very little is GI-derived sIgA. The bulk of serum IgA is produced in the bone marrow.
I believe the different origin of the IgA may in part explain why stool could be more sensitive than serum. Also: serum may become positive only after enough intestinal damage permits entry of the IgA AGA antigen/antibody complex into systemic circulation.
Consider this: The lower GI contains mainly sIgA2; the saliva and upper GI contain about 30-40% sIgA2; the balance being sIgA1. Serum is >85% IgA1 (non-secretory). These differences could impact specimen choice (be they stool, saliva or serum) as well.
Being a first-line responder, then, it stands to reason that stool sIgA2 may rise in response to gluten exposure sooner than humorally- produced IgA1.
How about saliva, could it be different than stool? I believe the answer is “yes”, particularly if there are subclass deficiencies. In such a case, one would choose a profile with enough of the appropriate subclass. I did note (in a cursory search) one paper that found lower salivary sIgA1 in celiac patients as compared to controls and IBD patients. They did not look at sIgA2 in that particular paper.
Regardless of which assay will be determined to be most sensitive for identifying AGA, one this is sure: IgA is fabulous. Indeed, it’s intestinal IgA that builds commensal biofilms to combat opportunistic or pathogenic biofilms. And I’d image these fabulous biofilms protect the mucosa from gluten pathogenesis. Viva la commensal biofilms!
This is a broad and complex topic, as I found out. I have barely touched the surface of what is known. And from what I understand, much still remains unknown about IgA.
Any thoughts?
Dr Fitzgerald is co-author of Case Studies in Integrative and Functional Medicine, and is on faculty for the Institute for Functional Medicine. She has a clinic and consulting practice in Sandy Hook CT. To schedule with Dr. Fitzgerald, or learn more about her work, visit www.drkarafitzgerald.com.
Cass Nelson-Dooley, MS (18)