sIgA marker in DRG Pathogen Profile : 95% patients chonically low

The significance of low secretory IgA (SIgA) has always been of great interest to clinicians, but we have never seen such consistently low sIgA reported as we do now with the Diagnostic Research Group (DRG) GI pathogen profile. As a testing service provider we are observing over 95% of patient reports showing chronically low levels of sIgA. This sensitivity is what we are looking for in our testing services to clinicians and we spoke in great length to the CEO of DRG Labs, Tony Hoffman, about why this has now become apparent in the GI pathogen profile. The unstable nature of sIgA in stool samples means that there is a period after which measuring accurate sIgA results becomes difficult due to a time sensitive drop off in the marker. DRG labs sets the drop off point at 4-5 days while other laboratories set it at 9 days. This shorter time between sample collection and accession time of 4 days leads to an increased sensitivity of the sIgA which we have not seen before. This means that we can be sure that every sample is correctly reported in a very short time frame (within 3 days of us receiving your patients sample).

Tony Hoffman has recently released a great small educational piece on sIgA which you can read below:

sIgA consists of two IgA monomers joined by the J-chain and an additional secretory component. It is secreted in plasma cells located in the lamina propia of mucosal membranes. Synthesis of SIgA is independent from the synthesis of serum IgA. This means that lack of serum IgA does not necessarily correlate with a lack of SIgA.

Secretory IgA is the major immunoglobulin in saliva, tears, colostrum, nasal mucous, mother’s milk, tracheobronchial and gastrointestinal secretions. SIgA serves as the first line of defence in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms. Through a process called immune exclusion, SIgA helps in the removal of antigens and pathogenic microorganisms from the intestine by blocking epithelial receptors, entrapment of microorganisms and toxins in mucus, and removal of them by peristaltic and mucociliary activities.(1, 2, 3) In addition, SIgA functions in mucosal immunity and intestinal homeostasis. SIgA has been identified as having the ability to directly quench bacterial virulence factors, influence composition of the intestinal microbiota by Fab-dependent and Fab-independent mechanisms, promote the transport of antigens across the intestinal epithelium to dendritic cells in gut-associated lymphoid tissue, and, finally, SIgA has the ability to down regulate pro-inflammatory responses of highly pathogenic bacteria and potentially allergenic antigens. (4-19)

DRG Laboratory’s SIgA test can determine patients GI immune status. Increased SIgA indicates exposure to pathogenic/potentially pathogenic organisms, enteric toxins or allergens. And low SIgA generally results from low level chronic exposures. However,SIgA deficiency is seen in populations with a maturation defect in B cells. SIgA-deficient patients may be asymptomatic, but do exhibit a tendency to develop gastrointestinal disorders such as celiac disease (CD), and allergies. (20, 21, 22, 23) In both cases removal of the offending organism or allergen will allow for normalization of SIgA. In patients with low SIgA the use of probiotics to increase production of SCFA’s and provide additional colonization resistance may be useful while the SIgA production normalizes.

1. He, B. et al. Intestinal bacteria trigger T cell-independent immunoglobulin A(2)class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity 26, 812–826 (2007).

2. Newberry, R.D. & Lorenz, R.G. Organizing a mucosal defense. Immunol. Rev. 206, 6–21 (2005).

3. Apter, F.M., Lencer, W.I., Finkelstein, R.A., Mekalanos, J.J. & Neutra, M.R. Monoclonal immunoglobulin A antibodies directed against cholera toxin prevent the toxin-induced chloride secretory response and block toxin binding to intestinal epithelial cells in vitro. Infect. Immunol. 61, 5271–5278 (1993).

4. Helander, A., Miller, C.L., Myers, K.S., Neutra, M.R. & Nibert, M.L. Protective immunoglobulin A and G antibodies bind to overlapping intersubunit epitopes in the head domain of type 1 reovirus adhesin sigma1. J. Virol. 78, 10695–10705 (2004).

5. Hutchings, A.B. et al. Secretory immunoglobulin A antibodies against the sigma1 outer capsid protein of reovirus type 1 Lang prevent infection of mouse Peyer’s patches. J. Virol. 78, 947–957 (2004).

6. Uren, T.K. et al. Vaccine-induced protection against gastrointestinal bacterial infections in the absence of secretory antibodies. Eur. J. Immunol. 35, 180–188 (2005).

7. Lycke, N., Erlandsson, L., Ekman, L., Schon, K. & Leanderson, T. Lack of J chain inhibits the transport of gut IgA and abrogates the development of intestinal antitoxic protection. J. Immunol. 163, 913–919 (1999).

8. Apter, F.M. et al. Analysis of the roles of antilipopolysaccharide and anti-cholera toxin immunoglobulin A (IgA) antibodies in protection against Vibrio cholerae and cholera toxin by use of monoclonal IgA antibodies in vivo. Infect. Immunol. 61, 5279–5285 (1993).

9. Silvey, K.J., Hutchings, A.B., Vajdy, M., Petzke, M.M. & Neutra, M.R. Role of immunoglobulinA in protection against reovirus entry into Peyer’s patches. J. Virol. 75, 10870–10879 (2001).

10.Deplancke, B. & Gaskins, H.R. Microbial modulation of innate defense: goblet cells and the intestinal mucus layer. Am. J. Clin. Nutr. 73, 1131S–1141S (2001).

11. Lievin-Le Moal, V. & Servin, A.L. The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: mucins, antimicrobial peptides, and microbiota. Clin. Microbiol. Rev. 19, 315–337 (2006).

12.Boullier, S. et al. Secretory IgA-mediated neutralization of Shigella flexneri prevents intestinal tissue destruction by down-regulating inflammatory circuits. J. Immunol. 183, 5879–5885 (2009).

13. Phalipon, A. et al. Secretory component: a new role in secretory IgA-mediated immune exclusion in vivo. Immunity 17, 107–115 (2002).

14.McGuckin, M.A., Linden, S.K., Sutton, P. & Florin, T.H. Mucin dynamics and enteric pathogens. Nat. Rev. Microbiol. 9, 265–278 (2011).

15.Kraehenbuhl, J.P. & Neutra, M.R. Molecular and cellular basis of immune protection of mucosal surfaces. Physiol. Rev. 72, 853–879 (1992).

16.Dallas, S.D. & Rolfe, R.D. Binding of Clostridium difficile toxin A to human milk secretory component. J. Med. Microbiol. 47, 879–888 (1998).

17.Mantis, N.J., Farrant, S.A. & Mehta, S. Oligosaccharide side chains on human secretory IgA serve as receptors for ricin. J. Immunol. 172, 6838–6845 (2004).

18.Mestecky, J. & Russell, M.W. Specific antibody activity, glycan heterogeneity and polyreactivity contribute to the protective activity of S-IgA at mucosal surfaces. Immunol. Lett. 124, 57–62 (2009).

19. Yel, L. Selective IgA deficiency. J. Clin. Immunol. 30, 10–16 (2010).

20.Meini, A. et al. Prevalence and diagnosis of celiac disease in IgA-deficient children. Ann. Allergy Asthma Immunol. 77, 333–336 (1996).

21. Janzi, M. et al. Selective IgA deficiency in early life: association to infections and allergic diseases during childhood. Clin. Immunol. 133, 78–85 (2009).

22.Brandtzaeg, P. et al. The clinical condition of IgA-deficient patients is related to the proportion of IgD- and IgM-producing cells in their nasal mucosa. Clin. Exp. Immunol. 67, 626–636 (1987).

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