Abstract
A proportion of patients with atopic dermatitis have elevated serum levels of IgG4. In order to investigate further this abnormality of IgG subclass production, atopic patients were immunized with the protein antigen keyhole limpet haemocyanin (KLH), and IgG subclass responses following primary and secondary immunization were analysed. In the primary response, titres of IgG1, 2 and 3 antibodies were lower in the atopic patients than in the controls. In contrast, titres of IgG4 were much higher for the patient group. In both patients and controls, the kinetics of IgG4 antibody production following the initial immunization with KLH showed a slow rise reaching a peak at 30 weeks. This time course indicated that the high IgG4 response was unlikely to be due to previous exposure of the patients to a cross-reacting antigen. A higher proportion of IgG4 was also seen in the atopic patients following secondary immunization; indeed, IgG4 was the major subclass in the secondary response in the patient group. In the controls, but not in the patients, titres of IgG4 anti-KLH correlated with total serum levels of IgG4, and some of the highest IgG4 antibody responses were detected in atopic patients whose serum IgG4 concentration was in the normal range. The results suggest that raised serum levels of IgG4 in atopy may reflect abnormal isotype regulation in response to protein antigens.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aalberse R. C., van der Gaag R., van Leeuwen J. Serologic aspects of IgG4 antibodies. I. Prolonged immunization results in an IgG4-restricted response. J Immunol. 1983 Feb;130(2):722–726. [PubMed] [Google Scholar]
- Bird P., Calvert J. E., Amlot P. L. Distinctive development of IgG4 subclass antibodies in the primary and secondary responses to keyhole limpet haemocyanin in man. Immunology. 1990 Mar;69(3):355–360. [PMC free article] [PubMed] [Google Scholar]
- Bird P., Calvert J. E., Lowe J., Duggan-Keen M., Forouhi N. G., Seppälä I., Ling N. R. ELISA measurement of IgG subclass production in culture supernatants using monoclonal antibodies. J Immunol Methods. 1987 Nov 23;104(1-2):149–158. doi: 10.1016/0022-1759(87)90499-6. [DOI] [PubMed] [Google Scholar]
- Bird P., Lachmann P. J. The regulation of IgG subclass production in man: low serum IgG4 in inherited deficiencies of the classical pathway of C3 activation. Eur J Immunol. 1988 Aug;18(8):1217–1222. doi: 10.1002/eji.1830180811. [DOI] [PubMed] [Google Scholar]
- Brüggemann M., Williams G. T., Bindon C. I., Clark M. R., Walker M. R., Jefferis R., Waldmann H., Neuberger M. S. Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J Exp Med. 1987 Nov 1;166(5):1351–1361. doi: 10.1084/jem.166.5.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burton D. R., Gregory L., Jefferis R. Aspects of the molecular structure of IgG subclasses. Monogr Allergy. 1986;19:7–35. [PubMed] [Google Scholar]
- Devey M. E., Bleasdale-Barr K. M., Bird P., Amlot P. L. Antibodies of different human IgG subclasses show distinct patterns of affinity maturation after immunization with keyhole limpet haemocyanin. Immunology. 1990 Jun;70(2):168–174. [PMC free article] [PubMed] [Google Scholar]
- Devey M. E., Wilson D. V., Wheeler A. W. The IgG subclasses of antibodies to grass pollen allergens produced in hay fever patients during hyposensitization. Clin Allergy. 1976 May;6(3):227–236. doi: 10.1111/j.1365-2222.1976.tb01901.x. [DOI] [PubMed] [Google Scholar]
- Flores-Romo L., Millsum M. J., Gillis S., Stubbs P., Sykes C., Gordon J. Immunoglobulin isotype production by cycling human B lymphocytes in response to recombinant cytokines and anti-IgM. Immunology. 1990 Mar;69(3):342–347. [PMC free article] [PubMed] [Google Scholar]
- French M. Serum IgG subclasses in normal adults. Monogr Allergy. 1986;19:100–107. [PubMed] [Google Scholar]
- Grzych J. M., Dissous C., Capron M., Torres S., Lambert P. H., Capron A. Schistosoma mansoni shares a protective carbohydrate epitope with keyhole limpet hemocyanin. J Exp Med. 1987 Mar 1;165(3):865–878. doi: 10.1084/jem.165.3.865. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jackson P. G., Lessof M. H., Baker R. W., Ferrett J., MacDonald D. M. Intestinal permeability in patients with eczema and food allergy. Lancet. 1981 Jun 13;1(8233):1285–1286. doi: 10.1016/s0140-6736(81)92459-4. [DOI] [PubMed] [Google Scholar]
- Lucisano Valim Y. M., Lachmann P. J. The effect of antibody isotype and antigenic epitope density on the complement-fixing activity of immune complexes: a systematic study using chimaeric anti-NIP antibodies with human Fc regions. Clin Exp Immunol. 1991 Apr;84(1):1–8. doi: 10.1111/j.1365-2249.1991.tb08115.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lundgren M., Persson U., Larsson P., Magnusson C., Smith C. I., Hammarström L., Severinson E. Interleukin 4 induces synthesis of IgE and IgG4 in human B cells. Eur J Immunol. 1989 Jul;19(7):1311–1315. doi: 10.1002/eji.1830190724. [DOI] [PubMed] [Google Scholar]
- Merrett J., Barnetson R. S., Burr M. L., Merrett T. G. Total and specific IgG4 antibody levels in atopic eczema. Clin Exp Immunol. 1984 Jun;56(3):645–652. [PMC free article] [PubMed] [Google Scholar]
- Merrett J., Burr M. L., Merrett T. G. A community survey of IgG4 antibody levels. Clin Allergy. 1983 Sep;13(5):397–407. doi: 10.1111/j.1365-2222.1983.tb02615.x. [DOI] [PubMed] [Google Scholar]
- Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
- O'Hehir R. E., Bal V., Quint D., Moqbel R., Kay A. B., Zanders E. D., Lamb J. R. An in vitro model of allergen-dependent IgE synthesis by human B lymphocytes: comparison of the response of an atopic and a non-atopic individual to Dermatophagoides spp. (house dust mite). Immunology. 1989 Apr;66(4):499–504. [PMC free article] [PubMed] [Google Scholar]
- Paganelli R., Levinsky R. J., Brostoff J., Wraith D. G. Immune complexes containing food proteins in normal and atopic subjects after oral challenge and effect of sodium cromoglycate on antigen absorption. Lancet. 1979 Jun 16;1(8129):1270–1272. doi: 10.1016/s0140-6736(79)92230-x. [DOI] [PubMed] [Google Scholar]
- Rees J., Friedmann P. S., Matthews J. N. Contact sensitivity to dinitrochlorobenzene is impaired in atopic subjects. Controversy revisited. Arch Dermatol. 1990 Sep;126(9):1173–1175. [PubMed] [Google Scholar]
- Romagnani S., Maggi E., Del Prete G. F., Parronchi P., Macchia D., Tiri A., Ricci M. Role of interleukin 4 and gamma interferon in the regulation of human IgE synthesis: possible alterations in atopic patients. Int Arch Allergy Appl Immunol. 1989;88(1-2):111–113. doi: 10.1159/000234758. [DOI] [PubMed] [Google Scholar]
- Rowntree S., Platts-Mills T. A., Cogswell J. J., Mitchell E. B. A subclass IgG4-specific antigen-binding radioimmunoassay (RIA): comparison between IgG and IgG4 antibodies to food and inhaled antigens in adult atopic dermatitis after desensitization treatment and during development of antibody responses in children. J Allergy Clin Immunol. 1987 Oct;80(4):622–630. doi: 10.1016/0091-6749(87)90017-0. [DOI] [PubMed] [Google Scholar]
- Shakib F., McLaughlan P., Stanworth D. R., Smith E., Fairburn E. Elevated serum IgE and IgG4 in patients with atopic dermatitis. Br J Dermatol. 1977 Jul;97(1):59–63. doi: 10.1111/j.1365-2133.1977.tb15428.x. [DOI] [PubMed] [Google Scholar]
- Wierenga E. A., Snoek M., de Groot C., Chrétien I., Bos J. D., Jansen H. M., Kapsenberg M. L. Evidence for compartmentalization of functional subsets of CD2+ T lymphocytes in atopic patients. J Immunol. 1990 Jun 15;144(12):4651–4656. [PubMed] [Google Scholar]