Intestinal and circulating antibody-forming cells in IgA-deficient individuals after oral cholera vaccination (original) (raw)
Abstract
In search for a possible explanation for the different susceptibility to mucosal infections in IgA-deficient (IgAd) individuals, the frequency of total immunoglobulin-secreting cells (ISC) and vaccine-specific antibody-secreting cells (ASC) in intestinal mucosa and peripheral blood was determined by the enzyme-linked immunospot (ELISPOT) assay before and after peroral vaccination with a B subunit-whole cell cholera vaccine. Two groups of IgAd individuals, frequently infected and non-infected respectively, and normal controls were studied. Before cholera vaccination there were significantly higher frequencies of total IgM and IgG ISC in the gut, but not in the blood, in the IgAd individuals than in the controls. However, there were no significant differences between healthy and infection-prone IgAd individuals in this respect. In response to oral cholera vaccination, intestinal cholera toxin (CT)-specific IgG and IgM ASC were significantly more abundant among the IgAd individuals with a history of frequent infections than among the healthy IgAd individuals and controls. A similar difference in IgG and IgM ASC, although not significant, was also noted in blood. In IgAd individuals with frequent infections the vaccine induced variable anti-CT IgM ASC responses in the gut, ranging from no increase to a few strikingly high responses. In the controls, the CT-specific responses were dominated by IgA ASC. The data show that oral cholera vaccination evoked strong CT-specific IgG ASC responses, and in some cases also strong IgM ASC responses in the intestinal mucosa of IgAd patients with a history of frequent infections. The healthy IgAd individuals unexpectedly responded with lower numbers of CT-specific IgG ASC and did not show any increase of CT-specific IgM ASC in the intestinal mucosa. Thus, inability to mount a mucosal immune response to an oral antigen cannot in itself explain recurrent infections among many IgAd individuals.
Selected References
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- Ammann A. J., Hong R. Selective IgA deficiency: presentation of 30 cases and a review of the literature. Medicine (Baltimore) 1971 May;50(3):223–236. [PubMed] [Google Scholar]
- Arnold R. R., Cole M. F., Prince S., McGhee J. R. Secretory IgM antibodies to Streptococcus mutans in subjects with selective IgA deficiency. Clin Immunol Immunopathol. 1977 Nov;8(3):475–486. doi: 10.1016/0090-1229(77)90011-3. [DOI] [PubMed] [Google Scholar]
- Brandtzaeg P., Baklien K. Immunohistochemical studies of the formation and epithelial transport of immunoglobulins in normal and diseased human intestinal mucosa. Scand J Gastroenterol Suppl. 1976;36:1–45. [PubMed] [Google Scholar]
- Brandtzaeg P., Halstensen T. S., Kett K., Krajci P., Kvale D., Rognum T. O., Scott H., Sollid L. M. Immunobiology and immunopathology of human gut mucosa: humoral immunity and intraepithelial lymphocytes. Gastroenterology. 1989 Dec;97(6):1562–1584. doi: 10.1016/0016-5085(89)90406-x. [DOI] [PubMed] [Google Scholar]
- Brandtzaeg P. Human secretory immunoglobulins. II. Salivary secretions from individuals with selectively excessive or defective synthesis of serum immunoglobulins. Clin Exp Immunol. 1971 Jan;8(1):69–85. [PMC free article] [PubMed] [Google Scholar]
- Brandtzaeg P. Humoral immune response patterns of human mucosae: induction and relation to bacterial respiratory tract infections. J Infect Dis. 1992 Jun;165 (Suppl 1):S167–S176. doi: 10.1093/infdis/165-supplement_1-s167. [DOI] [PubMed] [Google Scholar]
- Brandtzaeg P., Karlsson G., Hansson G., Petruson B., Björkander J., Hanson L. A. 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. 1987 Mar;67(3):626–636. [PMC free article] [PubMed] [Google Scholar]
- Cardinale F., Friman V., Carlsson B., Björkander J., Armenio L., Hanson L. A. Aberrations in titre and avidity of serum IgM and IgG antibodies to microbial and food antigens in IgA deficiency. Scand J Immunol. 1992 Aug;36(2):279–283. doi: 10.1111/j.1365-3083.1992.tb03100.x. [DOI] [PubMed] [Google Scholar]
- Crabbé P. A., Heremans J. F. Lack of gamma A-immunoglobulin in serum of patients with steatorrhoea. Gut. 1966 Apr;7(2):119–127. doi: 10.1136/gut.7.2.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Czerkinsky C. C., Nilsson L. A., Nygren H., Ouchterlony O., Tarkowski A. A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells. J Immunol Methods. 1983 Dec 16;65(1-2):109–121. doi: 10.1016/0022-1759(83)90308-3. [DOI] [PubMed] [Google Scholar]
- Czerkinsky C., Moldoveanu Z., Mestecky J., Nilsson L. A., Ouchterlony O. A novel two colour ELISPOT assay. I. Simultaneous detection of distinct types of antibody-secreting cells. J Immunol Methods. 1988 Nov 25;115(1):31–37. doi: 10.1016/0022-1759(88)90306-7. [DOI] [PubMed] [Google Scholar]
- Frangakis M. V., Koopman W. J., Kiyono H., Michalek S. M., McGhee J. R. An enzymatic method for preparation of dissociated murine Peyer's patch cells enriched for macrophages. J Immunol Methods. 1982;48(1):33–44. doi: 10.1016/0022-1759(82)90207-1. [DOI] [PubMed] [Google Scholar]
- Hanson L. A., Björkander J., Carlsson B., Roberton D., Söderström T. The heterogeneity of IgA deficiency. J Clin Immunol. 1988 May;8(3):159–162. doi: 10.1007/BF00917561. [DOI] [PubMed] [Google Scholar]
- Hermans P. E., Diaz-Buxo J. A., Stobo J. D. Idiopathic late-onset immunoglobulin deficiency. Clinical observations in 50 patients. Am J Med. 1976 Aug;61(2):221–237. doi: 10.1016/0002-9343(76)90173-x. [DOI] [PubMed] [Google Scholar]
- Holmgren J., Fryklund J., Larsson H. Gamma-interferon-mediated down-regulation of electrolyte secretion by intestinal epithelial cells: a local immune mechanism? Scand J Immunol. 1989 Oct;30(4):499–503. doi: 10.1111/j.1365-3083.1989.tb02456.x. [DOI] [PubMed] [Google Scholar]
- Hörnqvist E., Goldschmidt T. J., Holmdahl R., Lycke N. Host defense against cholera toxin is strongly CD4+ T cell dependent. Infect Immun. 1991 Oct;59(10):3630–3638. doi: 10.1128/iai.59.10.3630-3638.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McLoughlin G. A., Hede J. E., Temple J. G., Bradley J., Chapman D. M., McFarland J. The role of IgA in the prevention of bacterial colonization of the jejunum in the vagotomized subject. Br J Surg. 1978 Jun;65(6):435–437. doi: 10.1002/bjs.1800650619. [DOI] [PubMed] [Google Scholar]
- Mellander L., Björkander J., Carlsson B., Hanson L. A. Secretory antibodies in IgA-deficient and immunosuppressed individuals. J Clin Immunol. 1986 Jul;6(4):284–291. doi: 10.1007/BF00917328. [DOI] [PubMed] [Google Scholar]
- Nilssen D. E., Brandtzaeg P., Frøland S. S., Fausa O. Subclass composition and J-chain expression of the 'compensatory' gastrointestinal IgG cell population in selective IgA deficiency. Clin Exp Immunol. 1992 Feb;87(2):237–245. doi: 10.1111/j.1365-2249.1992.tb02981.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norhagen G., Engström P. E., Hammarström L., Söder P. O., Smith C. I. Immunoglobulin levels in saliva in individuals with selective IgA deficiency: compensatory IgM secretion and its correlation with HLA and susceptibility to infections. J Clin Immunol. 1989 Jul;9(4):279–286. doi: 10.1007/BF00918659. [DOI] [PubMed] [Google Scholar]
- Oxelius V. A. IgG subclass levels in infancy and childhood. Acta Paediatr Scand. 1979 Jan;68(1):23–27. doi: 10.1111/j.1651-2227.1979.tb04424.x. [DOI] [PubMed] [Google Scholar]
- Savilahti E. IgA deficiency in children. Immunoglobulin-containing cells in the intestinal mucosa, immunoglobulins in secretions and serum IgA levels. Clin Exp Immunol. 1973 Mar;13(3):395–406. [PMC free article] [PubMed] [Google Scholar]
- Savilahti E., Klemola T., Carlsson B., Mellander L., Stenvik M., Hovi T. Inadequacy of mucosal IgM antibodies in selective IgA deficiency: excretion of attenuated polio viruses is prolonged. J Clin Immunol. 1988 Mar;8(2):89–94. doi: 10.1007/BF00917895. [DOI] [PubMed] [Google Scholar]
- Savilahti E., Pelkonen P., Verkasalo M., Koskimies S. Selective deficiency of immunoglobulin A in children. Klin Padiatr. 1985 Jul-Aug;197(4):336–340. doi: 10.1055/s-2008-1033999. [DOI] [PubMed] [Google Scholar]
- Sedgwick J. D., Holt P. G. A solid-phase immunoenzymatic technique for the enumeration of specific antibody-secreting cells. J Immunol Methods. 1983 Feb 25;57(1-3):301–309. doi: 10.1016/0022-1759(83)90091-1. [DOI] [PubMed] [Google Scholar]
- Svennerholm A. M., Jertborn M., Gothefors L., Karim A. M., Sack D. A., Holmgren J. Mucosal antitoxic and antibacterial immunity after cholera disease and after immunization with a combined B subunit-whole cell vaccine. J Infect Dis. 1984 Jun;149(6):884–893. doi: 10.1093/infdis/149.6.884. [DOI] [PubMed] [Google Scholar]