IgA-Antigliadin Antibodies in Patients with IgA Nephropathy: The Secondary Phenomenon?Ots M.a · Uibo O.b · Metsküla K.c · Uibo R.c · Salupere V.a
Departments of aInternal Medicine, Renal Division, bPaediatrics, and cImmunology, Institute of General and Molecular Pathology, University of Tartu, Estonia
Mai Ots, MD
Department of Internal Medicine
Division of Nephrology, University of Tartu
6 Puusepa Street, Tartu 51014 (Estonia)
Tel. +372 7 448 605, Fax +372 7 448 607, E-Mail firstname.lastname@example.org
Do you have an account?
Circulating IgA-antigliadin antibodies (IgA-AGA) are often found in patients with IgA nephropathy (NP). IgA-AGA are sensitive markers of an abnormal immune system reaction to gluten, seen particularly in patients with celiac disease. However, a lack of IgA-antireticulin and IgA-antiendomysium antibodies and often jejunal mucosal atrophy of patients with IgA NP suggest that most patients do not have latent celiac disease. To examine the relationship between IgA-AGA and clinical data, enzyme-linked immunosorbent assays for IgA-AGA were performed in 28 patients with IgA NP and in 50 healthy persons. The results were calculated in arbitrary units (AU). The cutoff level for a negative or a positive test was found to be 60 AU, calculated according to the AGA test result (mean + 3 SD) in 50 healthy persons. The following clinical data were assessed: age, gender, disease duration, daily proteinuria, blood pressure, serum creatinine, and creatinine clearance. Control sera were negative for IgA-AGA. Positive IgA-AGA tests were observed in 14 of the 28 patients (p < 0.0001 vs. controls) and high levels of IgA-AGA (AU >90) in 6 of the 28 patients (p < 0.001 vs. controls). The mean duration of the disease of the patients with positive IgA-AGA was significantly longer as compared with the patients who had a negative antibody test. IgA-AGA correlated with age (p < 0.05, r = 0.56), disease duration (p < 0.05, r = 0.40), and blood pressure (p < 0.05, r = 0.48). Antireticulin and antiendomysium antibody tests were negative in all patient and control sera. We conclude that IgA-AGA are associated with the progression of IgA NP. Our findings support the current concept about the pathogenesis of IgA NP, where the defective IgA production itself may be the primary and intestinal lesions as well as the production of IgA-AGA the secondary phenomenon.
Berger J, Hinglais N: Les dépôts intercapillaires d’IgA-IgG. J Urol Néphrol 1968;74:694.
- Rekola S, Bergstrand A, Bucht H: IgA nephropathy: A retrospective evaluation of prognostic indices in 176 patients. Scand J Urol Nephrol 1989;23:37–50.
Rekola S, Bergstrand A, Bucht H, Lindberg A: Are beta-haemolytic streptococci involved in the pathogenesis of mesangial IgA nephropathy? Proc Eur Dial Transplant Assoc Eur Renal Assoc 1985;21:698–702.
- Hirabayashi A, Yorioka N, Oda H, Sekiguchi Y, Kuramoto A, Okushin S, Yamakido M: Involvement of bacterial antigens in immunoglobulin A nephropathy. Hiroshima J Med Sci 1996;45:113–117.
- van der Woude FJ, Hoedemaeker PJ, van der Giessen M, de Graeff PA, de Monchy J, The TH, van der Hem GK: Do food antigens play a role in the pathogenesis of some cases of human glomerulonephritis? Clin Exp Immunol 1983;51:587–594.
- Russell MW, Mestecky J, Julian BA, Galla JH: IgA-associated renal diseases: Antibodies to environmental antigens in sera and deposition of immunoglobulins and antigens in glomeruli. J Clin Immunol 1986;6:74–86.
- Coppo R: The pathogenetic potential of environmental antigens in IgA nephropathy. Am J Kidney Dis 1988;12:420–424.
- Emancipator SN, Gallo GR, Lamm ME: Experimental IgA nephropathy induced by oral immunization. J Exp Med 1983;157:572–582.
- Coppo R, Mazzucco G, Martina G, Roccatello D, Amore A, Novara R, Bargoni A, Piccoli G, Sena LM: Gluten-induced experimental IgA glomerulopathy. Lab Invest 1989;60:499–506.
- Laurent J, Branellec A, Heslan JM, Rostoker G, Bruneau C, André C, Intrator L, Lagrue G: An increase in circulating IgA antibodies to gliadin in IgA mesangial glomerulonephritis. Am J Nephrol 1987;7:178–183.
Fornasieri A, Sinico RA, Maldifassi P, Bernasconi P, Vegni M, D’Amico G: IgA-antigliadin antibodies in IgA mesangial nephropathy (Berger’s disease). Br Med J 1987;295:78–80.
- Coppo R, Roccatello D, Amore A, Quattrocchio G, Molino A, Gianoglio B, Amoroso A, Bajardi P, Piccoli G: Effects of a gluten-free diet in primary IgA nephropathy. Clin Nephrol 1990;33:72–86.
- Woodrow G, Innes A, Boyd SM, Burden RP: A case of IgA nephropathy with coeliac disease responding to a gluten-free diet. Nephrol Dial Transplant 1993;8:1382–1383.
Rostoker G, Laurent J, André C, Cholin S, Lagrue G: High levels of IgA antigliadin antibodies in patients who have IgA mesangial glomerulonephritis but not coeliac disease. Lancet 1988;i:356–357.
Uibo O, Metsküla K, Kukk T, Rägo T, Uibo R: Results of coeliac disease screening in Estonia in 1990–1994. Acta Paediatr 1996(suppl 412):39–41.
- Rifai A, Small PA, Teague PO, Ayoub EM: Experimental IgA nephropathy. J Exp Med 1979;150:1161–1173.
- Montinaro V, Gesualdo L, Schena FP: Primary IgA nephropathy: The relevance of experimental models in the understanding of human disease. Nephron 1992;62:373–381.
- Montinaro V, Hevey K, Aventaggiato L, Fadden K, Esparza A, Chen A, Finbloom DS, Rifai A: Extrarenal cytokines modulate the glomerular response to IgA immune complexes. Kidney Int 1992;42:341–352.
- Fornasieri A, Sinico RA, Maldifassi P, Paterna L, Benuzzi S, Colasanti G, D’Amico G: Food antigens, IgA-immune complexes and IgA mesangial nephropathy. Nephrol Dial Transplant 1988;3:738–743.
- Coppo R, Amore A, Roccatello D, Gianoglio B, Molino A, Piccoli G, Clarkson AR, Woodroffe AJ, Sakai H, Tomino Y: IgA antibodies to dietary antigens and lectin-binding IgA in sera from Italian, Australian, and Japanese IgA nephropathy patients. Am J Kidney Dis 1991;17:480–487.
- Ferri C, Puccini R, Longombardo G, Paleologo G, Migliorini P, Moriconi L, Pasero G, Cioni L: Low-antigen-content diet in the treatment of patients with IgA nephropathy. Nephrol Dial Transplant 1993;8:1193–1198.
- Yagame M, Tomino Y, Eguchi K, Miura M, Suga T, Endoh M, Nomoto Y, Sakai H: Levels of circulating IgA immune complexes after gluten-rich diet in patients with IgA nephropathy. Nephron 1988;49:104–110.
Rostoker G, Delprato S, Benmaadi A, Petit PM, André C, Laurent J, Lang P, Weil B, Lagrue G: Significance of IGA antigliadin antibodies during primary glomerulonephritis with mesangial IGA deposits. Ann Méd Interne (Paris) 1989;140:571–574.
- Rostoker G, André C, Branellec A, Bourhala S, Laurent J, Lagrue G: Lack of antireticulin and IgA antiendomysium antibodies in sera of patients with primary IgA nephropathy associated with circulating IgA antibodies to gliadin. Nephron 1988;48:81.
- Sategna GC, Ferfoglia G, Bruno M, Pulitano R, Roccatello D, Amore A, Coppo R: Do IgA antigliadin and IgA antiendomysium antibodies show there is latent coeliac disease in primary IgA nephropathy? Gut 1992;33:476–478.
- Uibo O, Uibo R, Kleimola V, Jogi T, Maki M: Serum IgA anti-gliadin antibodies in an adult population sample: High prevalence without celiac disease. Dig Dis Sci 1993;38:2034–2037.
Risdon RA, Sloper JS, de Vardener HE: Relationship between renal function and histologic changes found in renal biopsy specimens from patients with persistent glomerulonephritis. Lancet 1968;ii:363–366.
- Bohle A, Mackensen HS, von Gise H, Grund KE, Wehrmann M, Batz C, Bogenschutz O, Schmitt H, Nagy J, Muller C, et al: The consequences of tubulointerstitial changes for renal function in glomerulopathies: A morphometric and cytological analysis. Pathol Res Pract 1990;186:135–144.
- Rekola S, Bergstrand A, Bucht H: Deterioration rate in hypertensive IgA nephropathy: Comparison of a converting enzyme inhibitor and beta-blocking agents. Nephron 1991;59:57–60.
- Williams JD, Coles GA: Proteinuria a direct cause of renal morbidity? Kidney Int 1994;45:443–450.
Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G (Modification of Diet in Renal Disease Study Group): The effects of dietary protein restriction and blood pressure control on the progression of chronic renal disease. N Engl J Med 1994;330:887–894.
- Oldrizzi L, Rugiu C, De Biase V, Maschio G: The place of hypertension among risk factors for renal function in chronic renal failure. Am J Kidney Dis 1993;21:119–123.
- Hood SA, Velosa JA, Halley KE, Donadio JV Jr: IgA-IgG nephropathy: Predictive indices of progressive disease. Clin Nephrol 1981;16:55–62.
- Levey AS, Adler S, Greene T, Hunsicker LG, Kusek JW, Rogers NL, Teschan PE: Effects of dietary protein restriction on the progression of moderate renal disease in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol 1996;7:2616–2626.
- Ruilope LM, Miranda B, Morales JM, Rodicio JL, Romero JC, Raij L: Converting enzyme inhibition in chronic renal failure. Am J Kidney Dis 1989;13:120–126.
- Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G (Modification of Diet in Renal Disease Study Group): The effects of dietary protein restriction and blood pressure control on the progression of chronic renal disease (see comments). N Engl J Med 1994;330:877–884.
Tomino Y, Sakai H, Hanzawa S, Ohno J, Kitajima T, Sakai O: Angiotensin converting enzyme inhibition delays the progression of chronic renal failure in hypertensive patients with immunoglobulin A nephropathy. J Hypertens 1989(suppl 7):63–64.
- Maschio G, Cagnoli L, Claroni F, Fusaroli M, Rugiu C, Sanna G, Sasdelli M, Zuccala A, Zucchelli P: ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: A multicentre, randomized, placebo-controlled study. Nephrol Dial Transplant 1994;9:265–269.
- Lai KN, Lai FM, Ho CP, Chan KW: Corticosteroid therapy in IgA nephropathy: A long-term controlled trial. Clin Nephrol 1986;26:174.
- Kobayashi Y, Hiki Y, Kokubo T, Horii A, Tateno S: Steroid therapy during the early stage of progressive IgA nephropathy. Nephron 1996;72:237–242.
- Donadio JVJ, Bergstralh EJ, Offord KP, et al: A controlled trial of fish oil in IgA nephropathy. N Engl J Med 1994;331:1194–1199.
- Sato M, Takayama K, Wakasa M, Koshikawa S: Estimation of circulating immune complexes following oral challenge with cow’s milk in patients with IgA nephropathy. Nephron 1987;47:119–123.
- Kovacs T, Kun L, Schmelczer M, Wagner L, Davin JC, Nagy J: Do intestinal hyperpermeability and the related food antigens play a role in the progression of IgA nephropathy? I. Study of intestinal permeability. Am J Nephrol 1996;16:500–505.
- Kovacs T, Mette H, Per B, Kun L, Schmelczer M, Barta J, Jean CD, Nagy J: Relationship between intestinal permeability and antibodies against food antigens in IgA nephropathy. Orv Hetil 1996;137:65–69.
- Andersen R, Stordahl A, Hoyseth H, Koppers R, Tverdal A, Aase S, Laerum F: Increased intestinal permeability for the isosmolar contrast medium iodixanol during small-bowel ischaemia in rats. Scand J Gastroenterol 1995;30:1082–1088.
Mestecky J, Haskim O, Tomana M: Alterations in the IgA carbohydrate chains influence the cellular distribution of IgA1; in Clarkson AR, Woodroffe AJ (eds): IgA Nephropathy. Contrib Nephrol. Basel, Karger, 1995, vol 111, pp 66–72.
Feehally J: IgA nephropathy – a disorder of IgA production? Q J Med 1997;90:387–390.