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Abstracts Food Allergy and Nephritis
Do food antigens play a role in some cases of human glomerulonephritis?
Author van der Woude FJ; Hoedemaeker PJ; van der Giessen M; de Graeff PA; de Monchy J; The TH; van der Hem GKSource Clin Exp Immunol, 1983 Mar, 51:3, 587-94
Abstract Circulating immune complexes after a test meal were measured with three methods (PEG precipitation, Clq-ELISA and the indirect granulocyte phagocytosis test) in 10 controls, two symptomless persons with selective IgA deficiency and 14 patients with various types of glomerulonephritis, of which two patients (with idiopathic membranous glomerulopathy and local focal glomerulonephritis) also had selective IgA deficiency. The PEG and Clq-ELISA test did not show significant differences between the groups. In the two symptomless persons with selective IgA deficiency and in the patient with local focal glomerulonephritis and selective IgA deficiency the indirect granulocyte phagocytosis test (IGFT) showed a reproducible increase in IgG, IgM and complement containing immune complexes. In the last patient multiple food antigens were probably responsible for this phenomenon, a rapid amelioration of kidney function could be induced three times by giving an antigen free diet.
Food antigens, IgA-immune complexes and IgA mesangial nephropathy.
Author Fornasieri A; Sinico RA; Maldifassi P; Paterna L; Benuzzi S; Colasanti G; D'Amico G; Source Nephrol Dial Transplant, 1988, 3:6, 738-43
Abstract To investigate whether patients with IgA nephropathy have an exaggerated serum IgA response to ubiquitous food antigens we measured serum IgA antibodies to gliadin, ovalbumin, bovine serum albumin (BSA), beta-lactoglobulin and casein in 120 patients and 53 normal controls, using ELISA. No significant differences were observed between patients and controls in serum IgA antibodies against each of the antigens tested. Moreover, no correlation was found between serum IgA antibodies and IgA-immune complexes (IgA CIC). However, nine patients but no controls had an association of two or more IgA antibodies to dietary antigens. Sixty-six per cent of these patients (vs 24% in the remaining population) had IgA CIC, suggesting a possible involvement of these antibodies in the constitution of IgA CIC. Analysis of sera by HPLC revealed that both monomeric and higher molecular forms of IgA antibodies were present, the latter being coincident with the peak of IgA CIC. Preincubation of sera with serial concentrations of the specific antigen decreased significantly IgA CIC, suggesting that in this subgroup of patients IgA antibodies to food antigens (mainly BSA) are involved in the formation of IgA CIC. BSA-containing IgA CIC were in fact demonstrated by ELISA using rabbit IgG anti-BSA coated plates and peroxidase-conjugated anti-human IgA. The role of these CIC in the pathogenesis of IgA nephropathy needs to be further elucidated.
Estimation of circulating immune complexes following oral challenge with cow's milk in patients with IgA nephropathy.
Author Sato M; Takayama K; Wakasa M; Koshikawa S. Source Nephron, 1987, 47:1, 43-8
Abstract We recently reported on an experimentally induced model of IgA nephropathy in mice by long-term oral immunization under the reticuloendothelial dysfunction, which was found to be effectively inhibited by the administration of the antiallergic agent sodium cromoglycate (SCG). On the basis of these findings, we investigated the participation of food antigens in patients with IgA nephropathy. We studied 24 patients with IgA nephropathy, 11 patients with primary glomerulonephritis (PGN) except IgA nephropathy and 11 healthy controls. Serum levels of immunoglobulins (IgG, IgA, IgE) and circulating immune complexes containing IgG (IgG-CIC) or IgA (IgA-CIC) were measured in the fasting state and 30, 60, 120 or 180 min after oral challenging with cow's milk (400 ml). After the oral challenge IgA-CIC levels remained within the normal range in healthy controls and in patients with PGN, while 3 out of the 24 patients with IgA nephropathy showed a transient elevation and 2 cases showed a significant rise of IgA-CIC levels. The levels of IgG, IgA, IgE and IgG-CIC remained uninfluenced by the challenge test in all subjects. In addition, we carried out the same challenge test under SCG administration. These cases indicating an oral-challenge-induced IgA-CIC elevation demonstrated an inhibition of this elevation, and in 3 out 7 patients who showed hyper-IgA-CIC-emia before and after oral challenge IgA-CIC levels returned to the normal range through SCG administration. These results suggest that food antigens participate strongly in the pathogenesis of some patients with IgA nephropathy, and that SCG is an effective agent for such patients.
Immune complexes in IgA nephropathy:
Author Sancho J; Egido J; Rivera F; Hernando L; Source Clin Exp Immunol, 1983 Oct, 54:1, 194-202
Abstract Several features suggest that IgA nephropathy is an immune complex (IC)-mediated disease. The source of antigen(s) is unknown but the predominant involvement of IgA suggest that it is associated in some way with the gut or respiratory tract. Taking into account the specific hepatobiliary transport by polymeric IgA of circulating antigens entering through the mucosal surfaces we examined the possible involvement of antibodies against food antigens in the circulating IC and the existence of a defect in their blood clearance in patients with IgA nephropathy. A rise in multimeric IgA-IC (Raji assay) occurred in three of seven control subjects with a peak at 2-4 h after food ingestion. The amount of multimeric IgA-IC present at fasting in four out of six patients, diminished 2-4 h after food challenge, reaching a new peak around 6 h. At fasting, three out of six patients had IC containing antibodies against diet antigens (e.g. ovalbumin). These IC paralleled, both in patients and controls, the levels of multimeric IgA-IC. In patients small multimeric IgA-IC predominated at fasting and 24 h after food ingestion, while larger IC were detected at 2-4 h of food challenge. The specific polymeric IgA-IC showed in controls a maximal peak with similar distribution to that of multimeric IgA-IC, but with a quicker disappearance from the circulation. By contrast, polymeric IgA-IC remained elevated 24 h after food ingestion in most patients. These results suggest that antibodies against common antigens are within circulating IC and that a defect in the hepatic clearance of circulating polymeric IgA-IC exists in patients with IgA nephropathy.
Low doses of drugs able to alter intestinal mucosal permeability to food antigens (5-aminosalicylic acid and sodium cromoglycate) do not reduce proteinuria in patients with IgA nephropathy: a preliminary noncontrolled trial.
Author Bazzi C; Sinico RA; Petrini C; Rizza V; Torpia R; Arrigo G; Ragni A; D'Amico G; Source Nephron, 1992, 61:2, 192-5
Abstract In an uncontrolled trial, patients with IgA nephropathy (IgAN) were treated with drugs that can alter the intestinal mucosal permeability to food antigens. These drugs are known to ameliorate urinary abnormalities and histological lesions of IgAN associated with ulcerative colitis or Crohn's disease [5-aminosalicylic acid (5-ASA)] or to prevent, in mice, the induction of IgAN-like disease by oral immunization [disodium cromoglycate (SCG)]. Nine patients [serum creatinine (s-Cr) less than 2 mg/dl; 24-hour proteinuria higher than 1.5 g, but not nephrotic) were treated with 5-ASA (2.4 g/day for 6 months); 9 similar patients were treated with SCG (400 mg/day for 6 months); the follow-up extended to 6 months after stopping therapy. The 5-ASA group showed a slight but not significant decrease in s-Cr, 24-hour/proteinuria, IgA circulating immune complexes (IgA-CIC) and IgA rheumatoid factor (IgA-RF); serum beta 2-microglobulin and serum IgA were unchanged; 2 of 9 treated patients showed, after 6 months of therapy, a reduction in proteinuria of more than 50% that lasted for the subsequent 18 months. The SCG-treated group showed a slight but not significant increase in 24-hour proteinuria and a significant decrease in serum IgA; unchanged were s-Cr, IgA-CIC, IgA-RF, serum beta 2-microglobulin; no patient treated with SCG showed a reduction in proteinuria of more than 50%. At the dosages and for the periods used, 5-ASA and SCG did not show a significant influence on clinical and laboratory parameters of disease in IgAN; other trials with increased dosages are warranted to definitely ascertain the possible therapeutic role of these drugs in IgAN.
Circulating immune complexes following food: delayed clearance in idiopathic glomerulonephritis.
Author Cairns SA; London A; Mallick NP; Source J Clin Lab Immunol, 1981 Sep, 6:2, 121-6
Abstract Following a meal containing a variety of animal and vegetable proteins circulating immune complexes (CIC) have been found in sera from eight normal subjects. Levels of CIC rose to significantly higher levels in ten patients with idiopathic immune complex glomerulonephritis and return to fasting levels was significantly delayed. The type of CIC detected bore no relation to those in renal biopsy material. The CIC which accumulated in GN were small (MW similar to or approximately 350,000), and plasma exchange did not influence the extent or duration of CIC rise following the meal. An immunological defect manifested by impaired clearance of frequently encountered antigens may exist in subjects who develop GN. The CIC detected in the serum of these patients may be markers of this state and cannot be assumed to be the pathogenic agents in the disease.
Immune complex glomerulopathy in a child with food hypersensitivity.
Author McCrory WW; Becker CG; Cunningham-Rundles C; Klein RF; Mouradian J; Reisman L
Source Kidney Int, 1986 Oct, 30:4, 592-8
Abstract This report describes the occurrence of immune complex glomerulonephritis in a patient with eosinophilic gastroenteritis and food hypersensitivity. A coincident allergen injection may have been a contributing factor in the sudden development of the nephrotic syndrome. Markedly elevated levels of circulating immune complexes (greater than 6400 mg/dl) were found containing kappa-casein and bovine serum albumin (BSA), the latter predominating. Markedly elevated serum BSA hemagglutinating titers were also present (1:40,960). Cross-reacting precipitating antibodies to BSA, beef, and pork were demonstrated, but not to flounder or ovalbumin. Renal biopsy revealed immune complex glomerulonephritis with BSA, immunoglobulins M and G and complement deposited focally in the glomerular basement membrane. With strict dietary limitation of identified causative antigens and prednisone therapy, CIC levels decreased to 16,000 micrograms/dl and serum BSA antibody hemagglutinating titer fell 32-fold over a period of 15 months. There was prompt symptomatic relief and amelioration of signs of nephritis. The patient was able to consume a diet normal in protein and caloric content, and statural catch-up growth occurred. Recognition of food antigens to which the patient was hypersensitive provided a rationale for the relief of the gastrointestinal disturbance, growth stunting, and renal disease.
IgA-containing immune complexes after challenge with food antigens in patients with IgA nephropathy.
Author Jackson S; Moldoveanu Z; Kirk KA; Julian BA; Patterson TF; Mullins AL; Jilling T; Mestecky J; Galla JH
Source Clin Exp Immunol, 1992 Aug, 89:2, 315-20
Abstract The possibility that patients with IgA nephropathy (IgAN) might have abnormal IgA immune responses to immunogens commonly encountered at mucosal surfaces, resulting in the formation of circulating immune complexes (CIC), was examined. Since it is generally held that such increased IgA responses are characterized by detectable aberrancies in handling of IgA-containing CIC, IgAN patients and controls were given a large volume of bovine milk (after dietary deprivation of bovine antigens) and immune complex levels were measured over a period of 12 h. An assay based on binding of CIC containing C3 to solid-phase anti-C3 and subsequent development with isotype-specific antibody revealed no differences in responses of patients and controls with respect to IgG- and IgM-containing CIC. Although IgAN patients tended to have higher levels of IgA-containing CIC, there were no differences in response patterns when IgA CIC levels after ingestion of the milk stimulus were related to baseline levels. Polymorphonuclear leucocytes (PMNC), which bear surface receptors for IgA, were isolated from some subjects at the same times as the samples for CIC levels and examined by two-colour immunofluorescence for the coincident presence of IgA and milk antigens. In contrast to the data obtained in the CIC assays, these experiments revealed the simultaneous presence of IgA and two of three milk proteins in PMNC of IgAN patients but not controls. Follow-up experiments designed to assess more quantitatively the coincidental presence of IgA and milk antigens indicated no significant differences between patients and controls. However, milk proteins seemed to be more commonly associated with IgA in PMNC of IgAN patients, suggesting the presence of non-complement-fixing IgA/antigen CIC after mucosal challenge of some IgAN patients.
Mucosal immunity in primary glomerulonephritis: II. Study of the serum IgA subclass repertoire to food and airborne antigens.
Author Rostoker G; Petit-Phar M; Delprato S; Terzidis H; Lang P; Dubert JM; Weil B; Lagrue G; Source Nephron, 1991, 59:4, 561-6
Abstract IgA specific for 7 food and 6 airborne antigens were sought in the serum of 30 adult patients with IgA mesangial nephropathy (IgA GN), 23 with membranous nephropathy (MGN), 20 with idiopathic nephrotic syndrome (INS), 11 with membranoproliferative GN (MPGN) and 22 healthy controls by means of an enzyme-linked immunoassay. The IgA subclass was determined using monoclonal antibodies. Increased levels of IgA specific for gliadin, bovine serum albumin (BSA), ovalbumin, lysozyme and alpha-lactalbumin were found in IgA GN, while increased levels of IgA to BSA, ovalbumin, lysozyme and alpha-lactalbumin were observed in MGN; IgA specific for alpha-lactalbumin were increased in INS, and MPGN patients had reduced levels of IgA to BSA and increased levels of IgA to beta-lactoglobulin and alpha-lactalbumin. These specific IgA to food antigens were restricted to the IgA1 subclass. Patients with IgA GN had significantly increased levels of IgA specific for Dermatophagoides pteronyssinus (DP) and Dactil while the MGN group showed increased levels of IgA specific for DP, feathers, Dactil and mold. INS patients had increased levels of IgA specific for DP, feathers, Dactil, mold and dog hairs, while MPGN patients had increased levels of IgA specific for feathers, Dactil, dog hairs and mold. All these specific IgA to airborne antigens were restricted to the IgA1 subclass. Patients with the four types of primary glomerulonephritis had decreased IgA specific for cat hairs which were of both the IgA1 and IgA2 subclasses. We conclude that anomalies of the IgA repertoire to environmental antigens are also encountered in primary glomerulonephritis other than IgA GN.
IgA antibodies to dietary antigens and lectin-binding IgA in sera from Italian, Australian, and Japanese IgA nephropathy patients.
Author Coppo R; Amore A; Roccatello D; Gianoglio B; Molino A; Piccoli G; Clarkson AR; Woodroffe AJ; Sakai H; Tomino Y; Source Am J Kidney Dis, 1991 Apr, 17:4, 480-7
Abstract We studied serum IgA as antibodies to dietary antigens (Ag), as lectin-binding molecules, and as conglutinin-binding immune complexes (IgAIC) in people from geographical areas in which IgA nephropathy (IgAGN) is particularly frequent. Sera from 63 Italian, 21 Australian, and 25 Japanese patients affected by IgAGN and 24 Italian, 20 Australian, and 40 Japanese healthy controls were studied. Increased values of IgAIC were detected in 42.8% of Italian patients, while only in 23.8% and 8% of Australian and Japanese patients, respectively. Mean values were significantly increased only in Italian patients (P less than 0.0001). Positive values of IgA antibodies against dietary Ag had variable prevalences, but again Italian patients showed the highest frequency, from 19% to 28.5% versus 0 to 38% in Australians and 0 to 16% in Japanese. Mean values of these antibodies were not significantly increased in any patient groups in comparison to the corresponding healthy populations. However, patients with elevated values of IgAIC had significantly higher serum concentrations of antibodies to alimentary components and a linear correlation was found between IgAIC and some IgA antibodies to food components. The relationship between these two series of data was particularly evident for Italian and Australian IgAGN patients. Moreover, the patients with positive data tended to have a cluster of increased levels of IgA antibodies against several alimentary Ag at the same time. A linear correlation was evident between values of IgA antibodies to gluten fractions and to heterologous albumins. None of these correlations was evident among healthy controls.
Low-antigen-content diet in the treatment of patients with IgA nephropathy.
Author Ferri C; Puccini R; Longombardo G; Paleologo G; Migliorini P; Moriconi L; Pasero G; Cioni LSource Nephrol Dial Transplant, 1993, 8:11, 1193-8
Abstract Since dietary macromolecular antigens can be involved in the pathogenesis of IgA nephropathy (IgAN), the effect of a low-antigen-content diet was evaluated in 21 patients (10 women, 11 men, mean age 27.7 +/- 10 years) with immunohistochemical findings of active IgAN. The diet was followed for a 14-24-week period (mean 18.8 +/- 6); in all cases the effects of the treatment were evaluated by clinical and serological parameters, and in 11 patients also by repeat renal biopsy. After dietetic therapy a significant reduction of urinary proteins was recorded present in 12 cases during the 6 months preceding the treatment, was markedly reduced or disappeared in 11. At post-treatment control biopsy mesangial and parietal deposits of immunoglobulins, complement C5 fraction and fibrinogen were significantly reduced. The improvement of the objective parameters such as heavy proteinuria, a strong predictor of a poor prognosis, and of immunohistochemical alterations indicate that a low-antigen diet can positively affect patients with IgAN. These results could be ascribed to a reduction of nephritogenic food antigen input and to a putative functional restoration of the mononuclear phagocytic system.
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