·Evaluate mucosal immunity of specific compartments and fluids: intestinal tract, urinary tract, vaginal, salivary and human milk
·Reduced gut S-lgA is associated with a predisposition to: food
allergies, chronic parasitic infections and malabsorption

Basic Facts
Immunoglobulin A is found in 2 forms. A monomer, [IgA]I is predominant in serum and originates from bone marrow and non-mucosal Iymphoid sites. A dimer, [IgA]2, predominants in human mucosal secretions and originates primarily from local tissue immunocytes especially in the lamina propria of the intestines (1). Following local synthesis of the glycoprotein component (SC) (2), the combination SC-[IgA]2 is then translocated by exocytosis into the mucosal
secretions and is termed secretory IgA, S-IgA.

Additionally, SC can complex with the pentamer, IgM, to promote its secretion into body fluids as secretory IgM, S-IgM. The SC also stabilizes and protects S-IgA against degradation by enzymes and bacteria.

Gut Distribution
S-IgA is the predominant humoral factor in exocrine secretions and is normally abundant in the mucus coat of the entire gastrointestinal tract. The relative abundance of IgA over IgM and IgG producing cells in the gut is demonstrated in Table 1 on the following page(3).

Intestinal Secretory IgA Test (continued) Table 1

Postnatal Gut Protection
The S-IgA found in colostrum and human milk seems to prevent the uptake of food antigens by the immature mucosal barrier of the infant (10) and may affect the appearance of atopic conditions (11).
The maternal S-IgA is also reported to block antigen-stimulated release of histamine by regional IgE-polymerization on the mast cell (31).

Developmental Aspects of S-IgA
Immunoglobulin producing cells are not usually evident in the human intestine before 10 days of age (12). Thereafter, the rate of production of S-IgA is dependent on the nursing habit of the infant. Mother's milk
greatly accelerates the appearance and production of infant S-IgA, making formula-fed infants relatively vulnerable to antigen penetration (Table 2 on next page).

Intestinal Secretory IgA Test (continued) Table 2

	Fecal S-IgA mg/dl
Age	Breast Fed	Formula Fed
At birth	0	0
2 weeks	10 + 4	0
4 weeks	29 + 5	1.5 + 0.5
8 weeks	60 + 5	5.0 + 1

Evaluation of Mucosal Immunity
Dissociation Between Serum & Mucosal IgA Systems
There is a clear dissociation between the predominantly monomeric serum IgA system and its predominantly diameric secretory IgA counter part. Recent studies show that less than 2% of salivary dimeric IgA is derived from circulating IgA(14, 15)and that secretory IgA in milk is nearly all derived from mammary gland immunocytes (16). Other reports indicate that patients can have normal S-IgA levels in spite of serum IgA deficiency (7), and low mucosal levels of S-IgA despite normal serum IgA levels(18).
In the light of these reports, the assessment of humoral IgA production should be done using an appropriate serum sample for circulatory IgA and secretions or body fluid samples for assessing local S-IgA production.

Non Uniformity Within the Mucosal S-IgA System
The mucosal immune system has some common functional features and components where, for example, antigen sensitized IgA immunocytes from the gut can migrate into the circulation and home to distant secretory sites to produce S-lgA (5). However, there is sufficient local differences to make the system non-uniform in its responses.

The gut mucosa is exposed to enormous stimulatory loads of micro-flora, pathogen, food antigens and mitogens. This local stimulus can lead to selective gut stimulation (19-22) with clear differences in
localization, magnitude and persistence of S-IgA production when compared to salivary or mammary responses. For example, the density of IgA-producing immunocytes in the colonic mucosa is at least seven fold greater than that in salivary or mammary glands (6).

Salivary SIgA does not correlate with Gut SIgA
Research suggests that the "relative efficiency of the intestinal mucosal barrier in excluding dietary antigen cannot be predicted by serum or salivary IgA levels". Serum and salivary IgA levels do not correlate with (gut) mucosal permeability because levels of S-IgA in the gut are not adequately reflected in either serum or salivary IgA levels (23).

Salivary SIgA concentrations are best suited for use as biomarkers for the evaluation of stress impact (41) and oral cavity immunity. Salivary SIgA is known to respond to changes in sympathovagal flow following (mental and emotional) psychological states (42), and to the prevailing cortisol levels.

Fecal SIgA as a Marker For Gut IgA
Recent studies indicate that fecal S-IgA (antigen specific) levels correlate well with intestinal production of S-IgA (as high up the tract as the duodenum). The accuracy range is 86-92%, thereby abrogating the need for intestinal aspirates for accessing secretory IgA concentration. Furthermore, fecal S-IgA can be standardized to fecal dry weight, which reduces the effect of variable water content and allows accurate and meaningful comparison of serial and/or follow-up samples.

Clinical Relevance & Application
Enteric Condition
Several pathological conditions seem to involve derangements in intestinal S-lgA production and can be satisfactorily assessed by fecal SlgA measurements.

Malabsorption & Villous Atrophy:
Individuals with S-lgA deficiency usually show varying degrees of nutrient malabsorption and are susceptible to gluten-induced food allergies. Additionally, they suffer from reductions in villous height and absorptive surface area (25).

Food Allergy and Intolerance:
Mucosal SIgA is believed to bind and subsequently prevent the
penetration of large soluble allergens from food. Conditions of low intestinal S-IgA production permit the uptake of excessive amounts of various dietary antigens into the local and hepatic portal circulation
(6, 26), and as a result the absorbed antigens may cause:
·Overabundance of circulating IgA & IgA immune complexes that
are associated with glomerulonephritis, nephropathy autoimmune problems and dermatitis hepetiformis (27-29).
·Triggering of mucosal IgE-primed mast cells, leading to histamine/ seratonin release and increased mucosal permeability which can further enhance antigen penetration.
·Overabundance of IgG-antigen complex formation (in the intestinal wall) can lead to complement activation and subsequent development of severe and extensive tissue inflammation (6).

Predisposition to Parasitic Infections:
Research (30) has shown that 3-6 months after eradication of chronic Giardia infections, the mean values of intestinal S-IgA were one third the normal values in control individuals. Low S-IgA conceivably allows successful adhesion and propagation of intestinal parasites in certain individuals.

Predisposition To Candida Infections:
Three lines of evidence indicate that deranged S-IgA production may predispose to yeast infections:
·In a study of recurrent vaginal Candidiasis, only 2 out of 15 women showed detectable secretory component (SC) which implies undetectable levels of S-IgA and S-IgM in vaginal secretion. This
deficiency may facilitate the successful adherence and propagation of Candida (32).
·Clinical studies indicate high correlation (91%) between Giardia infections and intestinal Candida overgrowth. As mentioned above, Giardia patients seem to consistently have low intestinal secretory immunoglobin production.
·Enteral stimulation by oral food intake and presence of normal microflora are crucial for continued intestinal S-lgA production (33), i.e., without enteral stimulation, S-IgA production is severely
compromised.
The two most cited risk factors for disseminated Candida infections are parenteral nutrition (no oral food intake) and broad spectrum antibiotic use (34). Both risk factors cause reductions in intestinal S-IgA that can lead to local yeast proliferation. Further observations showed that 54% of systemic Candida infected patients show no source or portal of entry (35), thus leaving the S-IgA-deprived gut mucosa of these patients as the major yeast reservoir (33).

Non Enteric Conditions
Low S-IgA and Urinary Tract Infections (UTI):
Recent clinical studies indicate that in the absence of urinary tract malformation low urinary S-IgA excretion rates were associated with recurrent UTI. Low S-IgA excretion rate was found independent of the presence or absence of bacteriuria at the time of assessment. However, since UTI are not a feature of selective IgA deficiencies, it is likely that low S-IgA is not the cause of UTI, but a predictor of recurrent bacteriuria.


Back to Contents Page

Home | Company | Saliva Testing | Tests & Panels | Testimonials | Provider Directory | Search

Diagnos-Techs, Inc.
6620 South 192nd Place, Building J
Kent, Washington 98032
Toll Free (800) 878-3787 Fax: (425) 251-0637 E-mail: Diagnos@diagnostechs.com

Copyright ©2000 Diagnos-Techs, Inc. All rights reserved. Use of and access to the information
on this site are subject to the terms and conditions set out in our Site Policies

Site Designed By Collabris