Salivary IgA and Other Secretory Products
Jeffrey W. Terryberry, B.S.
The sublingual, submandibular and parotid glands are salivary exocrine glands which are involved in initial digestive processes as well as in oral host defense against pathogens. The salivary glands are composed of secretory acinar cells, myoepithelial cells and ducts which convey secretions. Secretion is primarily controlled by the autonomic nervous system.1 Acinar cells produce electrolytes which generate an electrochemical gradient involved in secretion. Saliva is involved in soft tissue repair, inhibition of bacterial aggregation and plaque formation, and in digestion. Salivary amylase cleaves 1-4 and 1-6 saccharide branch points on ingested carbohydrates. Mucins are involved in food lubrication; whereas, lipase degrades long-chain triglycerides; the proteases (kallikrein, gelatinase and collagenase) degrade proteins. Salivary lactoperoxidase is involved in blood flow regulation; whereas, salivary lysozyme possesses antimicrobial activity. Other constituents include growth hormones, lactoferrin, albumin and immunoglobulins.1-3 Citrate-stimulated salivary gland flow rates are about 0.5 mL/min/gland; whereas, basal rates are 0.1 mL/min/gland.4 Nicotine reduces salivary lactoferrin and lysozyme secretion; whereas, the anti-gingivitis agent, delmopinol has no effect on salivary lysozyme.5,6
Salivary IgA is an important first-line defense against pathogens and can be used in the diagnosis of infections. Normal salivary IgA secretion rates (~150 mg/min) decrease with stress and aging.7 Specific salivary IgA antibodies can be detected against Candida albicans, Streptococcus mutans, EBV, adenovirus and HIV-1.8-10 Salivary IgG antibodies are also useful in the detection of Helicobacter pylori, CMV, parvovirus B19 and importantly, HIV infections.11-16 Recombinant HIV-1 gp120 vaccine induces both specific salivary IgA and IgG.17 Tonsillectomy reduces total salivary IgG and IgM, but overall antimicrobial defense is unimpaired.18 Salivary autoantibodies to gliadin in celiac disease, thyrotropin receptor in Graves disease, and salivary ductal epithelium cytokeratin in Sjögren syndrome are also described.19-21 The oral pathogens Streptococcus sanguis, S. oralis and S. mitis are able to secrete proteases that specifically degrade salivary IgA.22 Salivary IgA production is reduced by anti-epileptic drugs, anxiety and Papillon-Lefevre syndrome.23-25 Salivary IgA is increased in diabetics; whereas, lysozyme concentrations are decreased.26-28 Other sialochemical analyses are also useful. Periodontal diseases can alter the salivary secretions of cystatin, amylase, a2-macroglobulin, C-reactive protein, cathepsin G, elastase, lysozyme, lactoferrin and lactoperoxidase.29-31 Salivary IgA was used to create a gingival immunologic defense index in the evaluation of risk for periodontal disease.32 Patients with recurrent parotitis demonstrate elevated concentrations of salivary albumin, IgA, lactoferrin, lysozyme and kallikrein; whereas, HIV-infected individuals have raised salivary cortisol.33,34 Both amylase and low molecular weight mucins interact with the oral pathogens Actinobacillus actinomycetemcomitans and Streptococcus gordonii.35,36
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- Lerner A, Rosenthal MA, Liebow C, Lebenthal E. Salivary secretion. In: Yamada T, Alpers DH, Owyang C, Powell DW, Silverstein FE, editors. Textbook of gastroenterology. Philadelphia: J.B. Lippincott Company, 1991;1:218-33.
- Thomas EL, Jefferson MM, Joyner RE, Cook GS, King CC. Leukocyte myeloperoxidase and salivary lactoperoxidase: identification and quantitation in human mixed saliva. J Dent Res 1994;73:544-55.
- Azuma M, Tamatani T, Fukui K, et al. Proteolytic enzymes in salivary extravasation mucoceles. J Oral Pathol Med 1995;24:299-302.
- Jones RE, Ship JA. Major salivary gland flow rates in young and old, generally healthy African Americans and whites. J Natl Med Assoc 1995;87:131-5.
- Gregory RL, Gfell LE. Effect of nicotine on secretory component synthesis by secretory epithelial cells. Clin Diagn Lab Immunol 1996;3:578-83.
- Tenovuo J, Kannuksela S, Lenander-Lumikari M. Effects of delmopinol on antimicrobial peroxidase systems and lysozyme in vitro and in human whole saliva. Eur J Oral Sci 1995;103:247-52.
- Miletic ID, Schiffman SS, Miletic VD, Sattely-Miller EA. Salivary IgA secretion rate in young and elderly persons. Physiol Behav 1996;60:243-8.
- Franco E, Saunders CP, Roberst GJ. Dental disease, caries related microflora and salivary IgA of children with severe congenital cardiac disease: an epidemiological and oral microbial survey. Pediatr Dent 1996;18:228-35.
- Gallo D, George JR, Fitchen JH, Goldstein AS, Hindahl MS. Evaluation of a system using oral mucosal transudate for HIV-1 antibody screening and confirmatory testing. JAMA 1997;277:254-8.
- Sweet SP, Rahman D, Challacombe SJ. IgA subclasses in HIV disease: dichotomy between raised levels in serum and decreased secretion rates in saliva. Immunology 1995;86:556-9.
- Simor AE, Lin E, Saibil F, et al. Evaluation of enzyme immunoassay for detection of salivary antibody to Helicobacter pylori. J Clin Microbiol 1996;34:550-3.
- Christie JML, McNulty CAM, Shepherd NA, Valori RM. Is saliva serology useful for the diagnosis of Helicobacter pylori? Gut 1996;39:27-30.
- Fallone CA, Elizov M, Cleland P, et al. Detection of Helicobacter pylori infection by saliva IgG testing. Am J Gastroenterol 1996;91:1145-9.
- Wang JB, Adler SP. Salivary antibodies to cytomegalovirus (CMV) glycoprotein B accurately predict CMV infections among preschool children. J Clin Microbiol 1996;34:2632-4.
- Tess BH, Granato C, Parry JV, et al. Salivary testing for human immunodeficiency virus type 1 infection in children born to infected mothers in Sao Paulo, Brazil. Pediatr Infect Dis J 1996;15:787-90.
- Rice PS, Cohen BJ. A school outbreak of parvovirus B19 infection investigated using salivary antibody assays. Epidemiol Infect 1996;116:331-8.
- Gorse GJ, Yang EY, Belshe RB, Berman PW. Salivary binding antibodies induced by human immunodeficiency virus type 1 recombinant gp120 vaccine. Clin Diagn Lab Immunol 1996;3:769-73.
- Kirstilä V, Tenovuo J, Ruuskanen O, Suonpää J, Meurman O, Vilja P. Longitudinal analysis of human salivary immunoglobulins, nonimmune antimicrobial agents, and microflora after tonsillectomy. Clin Immunol Immunopathol 1996;80:110-5.
- Rujner J, Socha J, Barra E, et al. Serum and salivary antigliadin antibodies and serum IgA anti-endomysium antibodies as a screening test for coeliac disease. Acta Paediatr 1996;85:814-7.
- Tumilasci OR, Arqueros MC, Ostuni MA, El Tamer E, Houssay AB. Thyrotropin receptor antibodies in parotid saliva. J Endocrinol Invest 1996;19:412-4.
- Atkinson JC, Royce LS, Wellner R, Pillemer SR, Bermudez D, Fox PC. Anti-salivary antibodies in primary Sjögren's syndrome. J Oral Pathol Med 1995;24:206-12.
- Reinholdt J. A method for titration of inhibiting antibodies to bacterial immunoglobulin A1 proteases in human serum and secretions. J Immunol Methods 1996;191:39-48.
- Henskens, YMC, Strooker H, van den Keijbus PAM, et al. Salivary protein composition in epileptic patients on different medications. J Oral Pathol Med 1996;25:360-6.
- Bosch JA, Brand HS, Ligtenberg TJM, et al. Psychological stress as a determinant of protein levels and salivary-induced aggretion of Streptococcus gordonii in human whole saliva. Psychosom Med 1996;58:374-82.
- Lundgren T, Twetman S, Johansson I, et al. Saliva composition in children and young adults with Papillon-Lefevre syndrome. J Clin Periodontol 1996;23:1068-72.
- Pinducciu G, Micheletti L, Piras V, et al. Periodontal disease, oral microbial flora and salivary antibacterial factors in diabetes mellitus type 1 patients. Eur J Epidemiol 1996;12:631-6.
- Yavuzyilmaz E, Yumak O, Akdoganli T, et al. The alterations of whole saliva constituents in patients with diabetes mellitus. Aust Dent J 1996;41:193-7.
- Guven Y, Satman I, Dinccag N, Alptekin S. Salivary peroxidase activity in whole saliva of patients with insulin-dependent (type-1) diabetes mellitus.
- Henskens YM, van der Weijden FA, van den Keijbus PA, et al. Effect of periodontal treatment on the protein composition of whole and parotid saliva. J Periodontol 1996;67:205-12.
- Pederson ED, Stanke SR, Whitener SJ, et al. Salivary levels of alpha 2-macroglobulin, alpha 1-antitrypsin, C-reactive protein, cathepsin G and elastase in humans with or without destructive periodontal disease. Arch Oral Biol 1995;40:1151-5.
- Suomalainen K, Saxen L, Vilja P, Tenovuo J. Peroxidases, lactoferrin and lysozyme in peripheral blood neutrophils, gingival crevicular fluid and whole saliva of patients with localized juvenile periodontitis. Oral Dis 1996;2:129-34.
- de Souza-Gugelmin MC, Ito IY, Maia Campos G. Creation of the gingival immunologic defense index (GIDI) to evaluate the immunological potential of the gingiva and the possible risk for periodontal disease. Braz Dent J 1995;6:1-2.
- Ericson S, Sjoback I. Salivary factors in children with recurrent parotitis. Part 2. Protein, albumin, amylase, IgA, lactoferrin lysozyme and kallikrein concentrations. Swed Dent J 1996;20:199-207.
- Enwonwu CO, Meeks VI, Sawiris PG. Elevated cortisol levels in whole saliva in HIV infected individuals. Eur J Oral Sci 1996;104:322-4.
- Groenink J, Ligtenberg AJM, Veerman ECI, et al. Interaction of the salivary low-molecular-weight mucin (MG2) with Actinobacillus actinomycetemcomitans. Antonie van Leeuwenhoek 1996;70:79-87.
- Scannapeico FA, Torres GI, Levine MJ. Salivary amylase promotes adhesion of oral streptococci to hydroxyapatite. J Dent Res 1995;74:1360-6.