Abstract
Levels of IgA1, IgA2, IgM, and IgG antibodies specific for 10 ubiquitous food and bacterial antigens were examined by radioimmunoassay in the sera of 29 patients with IgA-associated renal diseases and 22 normal individuals. No significant differences were observed between patient and normal groups in the levels of IgA1 antibodies, and IgA2 antibodies were detected in only a few individuals in either group. Minor differences in IgM or IgG antibodies were seen against some antigens. Significant positive correlations between IgA1 and IgG and between IgA1 and IgM antibodies to casein were found in the patient group. Analysis of the molecular form of serum IgA1 antibodies revealed that although the pattern of polymeric and monomeric forms varied between individuals and between antibody specificities, there was no preponderance of one form in either patient or normal groups. Examination of kidney biopsies from 50 patients with IgA-associated renal diseases revealed that IgA1 represented the predominant subclass deposited in the glomerular mesangium; glomeruli from three patients contained both IgA1 and IgA2. Seventy-eight percent of the patients also had deposits of IgM, although IgA and IgM deposits did not always coincide. When IgG was present in glomeruli (45% of patients), the IgG1 subclass predominated. J chain was detectable in glomeruli of only four patients. C3 was detected in glomeruli of 95% of the patients, although the distribution of C3 did not always coincide with that of IgA. Indirect immunofluorescence staining with rabbit antisera to various environmental antigens showed that milk protein antigens could be deposited in association with IgA in the glomerular mesangium.
Similar content being viewed by others
References
Clarkson AR, Woodroffe AJ, Bannister KM, Lomax-Smith JD, Aarons I: The syndrome of IgA nephropathy. Clin Nephrol 21:7–14, 1984
Lowance DC, Mullins JD, McPhaul JJ Jr: IgA-associated glomerulonephritis. Int Rev Exp Pathol 17:143–172, 1977
Helin H, Mustonen J, Reunala T, Pasternak A: IgA nephropathy associated with celiac disease and dermatitis herpetiformis. Arch Pathol Lab Med 107:324–327, 1983
Woodroffe AJ, Clarkson AR, Seymour AE, Lomax-Smith JD: Mesangial IgA nephritis. Springer Semin Immunopathol 5:321–332, 1982
André C, Berthoux FC, André F, Gillon J, Genin C, Sabatier J: Prevalence of IgA2 deposits in IgA nephropathies. N Engl J Med 303:1343–1346, 1980
Conley ME, Cooper MD, Michael AF: Selective deposition of immunoglobulin A1 in immunoglobulin A nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus. J Clin Invest 66:1432–1436, 1980
Tomino Y, Endoh M, Suga T, Miura M, Kaneshige H, Nomoto Y, Sakai, M: Prevalence of IgA1 deposits in Henoch Schoenlein purpura (HSP) nephritis. Tokai J Exp Clin Med 7:527–532, 1982
Lomax-Smith JD, Zabrowarny LA, Howarth GS, Seymour AE, Woodroffe AJ: The immunochemical characterization of mesangial IgA deposits. Am J Pathol 113:359–364, 1983
Tomino Y, Endoh M, Nomoto Y, Sakai M: Immunoglobulin A1 and IgA nephropathy. N Engl J Med 305:1159–1160, 1981
Delacroix DL, Dive C, Rambaud J, Vaerman JP: IgA subclasses in various secretions and serum. Immunology 47:383–385, 1982
Mestecky J, McGhee JR, Crago SS, Jackson S, Kilian M, Kiyono H, Babb JL, Michalek SM: Molecular-cellular interactions in the secretory IgA response. J Reticuloendothiel Soc 28 (Suppl):45S-60S, 1980
Hanson LA, Ahlstedt S, Anderson B, Carlsson B, Cole MF, Cruz JR, Dahlgren U, Ericsson TH, Jalil F, Khan SR, Mellander L, Schneerson R, Svanborg-Eden C, Soderstrom T, Wadsworth C: Mucosal immunity. Ann NY Acad Sci 409:1–21, 1983
Ferguson A, Carswell F: Precipitins to dietary proteins in serum and upper intestinal secretions of coeliac children. Br Med J 1:75–77, 1972
Russell MW, Hammond D, Radl J, Haaijman JJ, Mestecky J: Secretory IgA1 and IgA2 responses to environmental antigens. Prot Biol Fluids 32:77–80, 1985
Sancho J, Egido J, Rivera F, Hernando L: Immune complexes in IgA nephropathy: Presence of antibodies against diet antigens and delayed clearance of specific polymeric IgA immune complexes. Clin Exp Immunol 54:194–202, 1983
Emancipator SN, Gallo GR, Lamm ME: Experimental IgA nephropathy induced by oral immunization. J Exp Med 157:572–582, 1983
Brown TA, Murphy BR, Radl J, Haaijman JJ, Mestecky J: Hemagglutinin-specific IgA antibody response after secondary infection in humans with influenza A virus. Subclass distribution and molecular forms of IgA in sera and nasal secretions. J Clin Microbiol 22:259–264, 1985
Brown TA, Russell MW, Kulhavy R, Mestecky J: IgA-mediated elimination of antigens by the hepatobiliary route. Fed Proc 42:3218–3221, 1983
Russell MW, Bergmeier LA, Zanders ED, Lehner T: Protein antigens ofStreptococcus mutans: Purification and properties of a double antigen and its protease-resistant component. Infect Immun 28:486–493, 1980
Lowry OH, Rosebrough NJ, Farr AF, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951
Valentijn RM, Radl J, Haaijman JJ, Vermeer BJ, Weening JJ, Kauffmann RH, Daha MR, Van Es LA: Circulating and mesangial secretory component-binding IgA-1 in primary IgA nephropathy. Kidney Int 26:760–766, 1984
Hunter WM: Radioimmunoassay.In Handbook of Experimental Immunology, DM Weir (ed). New York, Blackwell Scientific, 1978, pp 14.1–14.40
Marchalonis JJ: An enzymic method for the trace iodination of immunoglobulins and other proteins. Biochem J 113:299–305, 1969
Mestecky J, Schrohenloher RE, Kulhavy R, Wright GP, Tomana M: Site of J chain attachment to human polymeric IgA. Proc Natl Acad Sci USA 71:544–548, 1974
Rodbard D, Lewald JE: Computer analysis of radio-ligand assay and radioimmunoassay data. Acta Endocrinol 64 (Suppl 147):79–103, 1970
Crago SS, Kutteh WH, Moro I, Allansmith MR, Radl J, Haaijman JJ, Mestecky J: Distribution of IgA1-, IgA2- and J chain-containing cells in human tissues. J Immunol 132:16–18, 1984
Crago SS, Mestecky J: Secretory component: Interactions with intracellular and surface immunoglobulins of human lymphoid cells. J Immunol 122:906–911, 1979
Mayumi M, Kuritani T, Kubagawa H, Cooper MD: IgG subclass expression by human B lymphocytes and plasma cells: B lymphocytes precomitted to IgG subclass can be preferentially induced by polyclonal mitogens with T cell help. J Immunol 130:671–677, 1979
Hijmans W, Schuitt HRE, Klein F: An immunofluorescence procedure for the detection of intracellular immunoglobulins. Clin Exp Immunol 4:457–472, 1969
Inman FP, Mestecky J: The J chain of polymeric immunoglobulins. Contemp Topics Mol Immunol 3:111–141, 1974
Doi T, Kanatsu K, Nagai H, Kohragi N, Kuwahara T, Hamashima Y: Immunoelectron microscopic studies of IgA nephropathy. Nephron 36:246–251, 1984
Katz A, Underdown BJ, Minta JO, Lepow IH: Glomerulonephritis with mesangial deposits of IgA unassociated with systemic disease. Can Med Assoc J 114:209–215, 1976
Sissons JG, Woodrow DF, Curtis JR, Evans DJ, Gower PE, Sloper JC, Peters DK: Isolated glomerulonephritis with mesangial IgA deposits. Br Med J 3:611–614, 1975
Stachura I, Singh G, Whiteside TL: Immune abnormalities in IgA nephropathy (Berger's disease). Clin Immunol Immunopathol 20:373–388, 1981
Tomino Y, Sakai H, Endoh M, Kaneshige H, Nomoto Y: Detection of immune complexes in polymorphonuclear leukocytes by double immunofluorescence in patients with IgA nephropathy. Clin Immunol Immunopathol 24:63–71, 1982
Coppo R, Basolo B, Martina G, Rollino C, DeMarchi M, Giacchino F, Mazzucco G, Messina M, Piccoli G: Circulating immune complexes containing IgA, IgG, and IgM in patients with primary IgA nephropathy and with Henoch-Schoenlein nephritis. Correlation with clinical and histological signs of activity. Clin Nephrol 18:230–239, 1982
Doi T, Kanatsu K, Sekita K, Yoshida H, Nagai H, Hamashima Y: Detection of IgA class circulating immune complexes bound to antiC3d antibody in patients with IgA nephropathy. J Immunol Methods 69:95–104, 1984
Egido J, Sancho J, Rivera F, Hernando L: The role of IgA and IgG immune complexes in IgA nephropathy. Nephron 36:52–59, 1984
Hall RP, Stachura I, Cason J, Whiteside TL, Lawley TJ: IgA-containing circulating immune complexes in patients with IgA nephropathy. Am J Med 74:56–63, 1983
Lesavre P, Digeon M, Bach JF: Analysis of circulating IgA and detection of immune complexes in primary IgA nephropathy. Clin Exp Immunol 48:61–69, 1982
Valentijn RM, Kauffmann RH, de la Riviere GB, Daha MR, Van Es LA: Presence of circulating macromolecular IgA in patients with hematuria due to primary IgA nephropathy. Am J Med 74:375–381, 1983
Woodroffe AJ, Gormly AA, McKenzie PE, Wootton AM, Thompson AJ, Seymour AE, Clarkson AR: Immunologic studies in IgA nephropathy. Kidney Int 18:336–374, 1980
Katz SI, Strober W: The pathogenesis of dermatitis herpetiformis. J Invest Dermatol 70:63–75, 1978
Kutteh WH, Moldoveanu Z, Prince SJ, Kulhavy R, Alonso F, Mestecky J: Biosynthesis of J chain in human lymphoid cells producing immunoglobulins of various isotypes. Mol Immunol 20:967–976, 1983
Tomino Y, Sakai H, Miura M, Endoh M, Nomoto Y: Detection of polymeric IgA in glomeruli from patients with IgA nephropathy. Clin Exp Immunol 49:419–425, 1982
Béné MC, Fauré G, Duheille J: IgA nephropathy: Characterization of the polymeric nature of mesangial deposits byin vitro binding of free secretory component. Clin Exp Immunol 47:527–534, 1982
Egido J, Sancho J, Mampaso F, Lopez-Trascasa M, Sanchez-Crespo M, Blasco R, Hernando L: A possible common pathogenesis of the mesangial IgA glomerulonephritis in patients with Berger's disease and Schönlein-Henoch syndrome. Proc Eur Dial Transplant Assoc 17:660–666, 1980
Shakib F, Stanworth DR: Human IgG subclasses in health and disease. II. La Ricerca Clin Lab 10:561–580, 1980
Cunningham-Rundles C, Brandeis WE, Good RA, Day NK: Bovine antigens and the formation of circulating immune complexes in selective immunoglobulin A deficiency. J Clin Invest 64:272–279, 1979
Paganelli R, Atherton DJ, Levinsky R: Differences between normal and milk allergic subjects in their immune responses after milk ingestion. Arch Dis Child 58:201–206, 1983
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Russell, M.W., Mestecky, J., Julian, B.A. et al. IgA-associated renal diseases: Antibodies to environmental antigens in sera and deposition of immunoglobulins and antigens in glomeruli. J Clin Immunol 6, 74–86 (1986). https://doi.org/10.1007/BF00915367
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00915367