Analysis of altered miRNA profiling in the colon of a mouse model with ß-lactoglobulin allergy.

OBJECTIVES: The differences in the expression profiles of colonic miRNAs between ß-lactoglobulin (ß-Lg) allergic mice and normal mice were analyzed to investigate the important role of the miRNA regulation mechanism in the pathogenesis of cow's milk allergy. METHODS: The present study performed Illumina sequencing to characterize the miRNA profile changes in mouse colon responding to ß-Lg challenge. Target genes were predicted by TargetScan 50 and miRanda 3.3a algorithms and assessed by GO and KEGG analysis. The expression levels of selected miRNAs and cytokine production were verified by cell transfection and quantitative RT-PCR. RESULTS: A total of 15 miRNAs were diversely expressed between the colon of the normal and ß-Lg-sensitized mice (P < 0.05, fold change of >1.50 or <0.67), including six up-regulated miRNAs and nine down-regulated miRNAs, among which seven miRNAs were validated using qRT-PCR. GO enrichment and KEGG pathway analyses further revealed that biological process, protein binding, cytoplasm and the pathways of cancer were significantly enriched, which were closely connected to the allergic inflammation development. Additionally, six key functional interaction pairs in ß-Lg allergy were identified in miRNA prediction algorithms and verified using qRT-PCR. CONCLUSIONS: We can conclude that our results suggested that the miRNAs regulation network participated in the pathogenesis of cow's milk allergy.

Modulatory effect of Lactobacillus acidophilus KLDS 1.0738 on intestinal short-chain fatty acids metabolism and GPR41/43 expression in ß-lactoglobulin-sensitized mice.

We investigated the correlation between the beneficial effect of Lactobacillus acidophilus on gut microbiota composition, metabolic activities, and reducing cow's milk protein allergy. Mice sensitized with ß-lactoglobulin (ß-Lg) were treated with different doses of L. acidophilus KLDS 1.0738 for 4 weeks, starting 1 week before allergen induction. The results showed that intake of L. acidophilus significantly suppressed the hypersensitivity responses, together with increased fecal microbiota diversity and short-chain fatty acids (SCFAs) concentration (including propionate, butyrate, isobutyrate, and isovalerate) when compared with the allergic group. Moreover, treatment with L. acidophilus induced the expression of SCFAs receptors, G-protein-coupled receptors 41 (GPR41) and 43 (GPR43), in the spleen and colon of the allergic mice. Further analysis revealed that the GPR41 and GPR43 messenger RNA expression both positively correlated with the serum concentrations of transforming growth factor-ß and IFN-γ (p < .05), but negatively with the serum concentrations of IL-17, IL-4, and IL-6 in the L. acidophilus-treated group compared with the allergic group (p < .05). These results suggested that L. acidophilus protected against the development of allergic inflammation by improving the intestinal flora, as well as upregulating SCFAs and their receptors GPR41/43.

Effect of Lactobacillus acidophilus KLDS 1.0738 on miRNA expression in in vitro and in vivo models of ß-lactoglobulin allergy.

This study aims to investigate the correlation between the ability of L. acidophilus to modulate miRNA expression and prevent Th17-dominated ß-lactoglobulin (ß-Lg) allergy. In vitro immunomodulation was evaluated by measuring splenocyte proliferation, Th17-related immune response and miRNA expression in ß-Lg-sensitized splenocytes cultured with live L. acidophilus. Next, the allergic mouse model was used to evaluate anti-allergy capability of lactobacilli. The ß-Lg challenge led to induction of up-regulation of miR-146a, miR-155, miR-21 and miR-9 expression in both in vivo and in vitro, along with increased Th17-related cytokine levels and mRNA expression of RORγt and IL-17. However, treatment of live L. acidophilus significantly suppressed hypersensitivity responses and Th17 cell differentiation. Moreover, administration of live L. acidophilus reduced expression of four miRNAs, especially miR-146a and miR-155. In addition, the decreased expression of the miRNAs in the spleen of the L. acidophilus-treated group was closely associated with decrease of IL-17 and RORγt mRNA expression.

Oral administration of lipid oil-in-water emulsions performed with synthetic or protein-type emulsifiers differentially affects post-prandial triacylglycerolemia in rats.

In this study, we compared the impact of administration of size-calibrated lipid emulsions prepared with either synthetic or natural emulsifiers on the post-absorptive plasma triacylglycerol responses in rats. We did this using four types of size-calibrated (10 µm diameter) and metastable (3 days) emulsions with 20% of an oleic acid-rich sunflower oil and 1% of either synthetic emulsifiers (Tween 80 or sodium 2-stearoyl-lactylate) or two proteins (ß-lactoglobulin or sodium caseinate). An oral fat tolerance test was performed in fasted rats by oral administration of each of these formulations in continuous or emulsified forms. Kinetic parameters (AUC0-inf., AUC0-6h, Cmax, Tmax, and T1/2) for the description of the plasma triacylglycerol responses were calculated. AUC0-6h and AUC0-inf. calculated for the protein groups were significantly lower than those of the control and the synthetic groups. These lower values were associated with significant decreases in the Cmax, exacerbated by the emulsion form and with marked decreases in the Tmax as compared to the control group. T1/2 values were differentially affected by the lipid administration forms and by the nature of the emulsifiers. As compared with the control group, T1/2 was largely increased in the sodium stearoyl-2-lactylate group, but on the contrary, largely lowered in the casein group. We concluded that the use of proteins as natural emulsifiers in lipid emulsions decreased the magnitude of post-prandial triacylglycerolemia for the same amount of ingested lipids, when the emulsion size is controlled for. Proteins could be a promising alternative to the widespread use of synthetic emulsifiers in the food industry.

Ingestion of partially hydrolyzed whey protein suppresses epicutaneous sensitization to ß-lactoglobulin in mice.

BACKGROUND: Epicutaneous sensitization to food allergens can occur through defective skin barriers. However, the relationship between oral tolerance and epicutaneous sensitization remains to be elucidated. We aimed to determine whether prior oral exposure to whey proteins or their hydrolysates prevents epicutaneous sensitization and subsequent food-allergic reaction to the whey protein, ß-lactoglobulin (ß-LG), and investigated the underlying mechanisms. METHODS: BALB/c mice were given whey protein concentrate (WPC), two kinds of partial whey protein hydrolysate (PWH1 or PWH2), or extensive whey protein hydrolysate (EWH) in drinking water for 21 days. The mice were then epicutaneously sensitized with ß-LG on tape-stripped skin. Sensitization was assessed by basophil activation tests and by measuring the level of serum ß-LG-specific antibodies and cytokines secreted from ß-LG-restimulated spleen and mesenteric lymph node (MLN) cells. Development of an allergic reaction was assessed by monitoring body temperature and by measuring mast cell protease-1 level in plasma after the ß-LG oral challenge. Activated T-cell population among ß-LG-restimulated MLN cells was also analyzed. RESULTS: In mice fed with WPC, PWH1, or PWH2, sensitization and the development of an allergic reaction were totally reduced. The acceleration of cytokine release from the spleen and MLN cells or T-cell activation was not evident after ß-LG restimulation. In EWH-fed mice, a suppressive effect, though milder than that in WPC-, PWH1-, or PWH2-fed mice, was observed during the development of the allergic reaction. CONCLUSIONS: Prior oral exposure to partially hydrolyzed whey protein prevents epicutaneous sensitization and subsequent allergic response to ß-LG in mice.

Allergenicity reduction of bovine milk ß-lactoglobulin by proteolytic activity of lactococcus lactis BMC12C and BMC19H isolated from Iranian dairy products.

Nowadays health benefits of bioactive food constituents, known as probiotic microorganisms, are a growing awareness. Cow's milk is a nutritious food containing probiotic bacteria. However, milk allergenicity is one of the most common food allergies. The milk protein, ß-lactoglobulin (BLG), is in about 80% of all main cases of milk allergies for children and infants. With the aim of screening proteolytic strains of lactic acid bacteria to evaluate their potential for the reduction of allergenicity of the major bovine milk proteins, we isolated new proteolytic strains of cocci lactic acid bacteria from traditional Iranian dairy products. The proteases produced by these strains had strong proteolytic activity against BLG. Proteolysis of BLG, observed after sodium dodecyl sulfate-PAGE, was confirmed by the analysis of the peptide profiles by reversed-phase HPLC. The two isolates were submitted to 16S rDNA sequencing and identified as Lactcoccus lactis subsp. cremoris and Lactcoccus lactis subsp. hordniea. The competitive ELISA experiments confirmed that these isolates, with high proteolytic activity, reduce significantly the allergenicity of BLG. Accordingly, these isolates can reduce the immunoreactivity of bovine milk proteins, which can be helpful for the production of low-allergic dairy products.

[A CASE OF ANAPHYLAXIS IN THE PEDIATRIC PATIENT WITH MILK ALLERGY DUE TO TRACES OF MILK PROTEIN IN THE LACTOSE USED AS AN EXCIPIENT OF INAVIR INHALATION].

The patient was a 6-year-old female with milk allergy and persistent asthma. She experienced anaphylactic reactions just after the inhalation of Inavir (Laninamivir Octanoate Hydrate) to treat flu infection. A skin-prick test showed positive reactions for Inavir inhaler powder and lactose used as an excipient but negative for Laninamivir. Same results were obtained in a drug-stimulated basophil activation test. The lactose excipient in Inavir inhaler powder was supposed to contain milk proteins, which caused anaphylactic reactions. To test this possibility, we examined the contamination of allergic milk proteins in the lactose excipient and found the smear band by silver staining, which was identified as ß-lactoglobulin (ß-LG) by Western blotting using specific monoclonal antibody and patient's sera. The ß-LG in Inavir was supposed to be glycosylated with lactose because the molecular weight was slightly higher than ß-LG standard reference as seen in mobility. In fact, the incubation with lactose in vitro tended to increase molecular weight. Following these results, we herein report that the trace amounts of ß-LG contaminated in the lactose excipient of Inavir could cause immediate allergic reactions. The risk that the lactose-containing dry powder inhalers cause allergic reactions for patients with cow's milk allergy need to be reminded. In particular, the use for flu patients should be paid careful attention because of increased airway hypersensitivity in those patients.

Safety evaluation of chemically modified beta-lactoglobulin administered intravaginally.

Currently, there is no specific antiviral therapy for treatment of HPV infection. Jiang and colleagues previously reported that anhydride-modified proteins have inhibitory activities against multiple viruses including HPV. Here, we evaluated the safety of 3-hydroxyphthalic anhydride-modified bovine beta-lactoglobulin, designated JB01, vaginally applied in women infected by high-risk HPV. After the vaginal application of JB01 in 38 women for 3 months, no serious adverse events were reported, and normalization of the vaginal micro-environment has been observed. It can be concluded that JB01-BD is safe for vaginal use in HPV-infected women, suggesting its potential application for the treatment of HPV infection.

Bifidobacterium longum BBMN68-specific modulated dendritic cells alleviate allergic responses to bovine ß-lactoglobulin in mice.

AIMS: This study was designed to demonstrate the protective effects of Bifidobacterium longum BBMN68-specific modulated dendritic cells (DCs) on allergic inflammation in ß-lactoglobulin (BLG)-sensitized mice. METHODS AND RESULTS: BALB/c mice were sensitized to BLG in accordance with a model of food allergy protocol and given oral BBMN68 daily. BBMN68 was found to significantly reduce BLG-specific hypersensitivity reactions by suppressing the aberrant balance of Th1/Th2 responses with increasing the number of CD4+CD25+Foxp3+ Treg cells in mesenteric lymph nodes (MLN) by 48·1%. The level of CD103+DCs was up-regulated by 136·7 and 56·2% in payer's patches and MLN, respectively, in response to the lower expression levels of cell-surface molecules (CD86 and MHC-II) induced by BBMN68 supplementation. The CD11c+DCs isolated from BBMN68 mice showed 45·6% more Foxp3+ expression in vitro. CONCLUSIONS: These data suggest that BBMN68-specific induction of CD11c+CD103+DCs and semi-mature DCs reduce BLG allergic reactions. SIGNIFICANCE AND IMPACT OF THE STUDY: These data confirm that BBMN68 may be a suitable therapeutic approach to the alleviation of food allergies, and BBMN68-specific induction of CD11c+CD103+DCs and semi-mature DCs are associated with this protection.

Preliminary assessment of potential toxicity of methylated soybean protein and methylated ß-lactoglobulin in male Wistar rats.

Methylated soybean protein (MSP) and methylated ß-lactoglobulin (MLG), previously confirmed for their antibacterial and antiviral activities, were tested for their potential toxicity in Wistar male Albino rats as one single dose (2500, 5000 and 10,000 mg/kg body wt) or as repeated daily dose (500 and 2500 mg/kg body wt/day) over 28 days to assess potential toxicity. Single acute administration of very high doses (2500, 5000 and 10,000 mg/kg body wt) of MSP and MLG did not produce any mortality. Changes in body weight, organ weight, hematological parameters, histo-pathological images of selected organs, serum albumin, globulin and albumin/globulin ratio, cholesterol, triglycerides and electrolytes were all within normal amounts in the rats fed with these two methylated proteins and not significantly different from controls. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine and urea were slightly reduced by the administration of these two modified proteins indicating the absence of any adverse effect on hepatic or renal functions.

Assessment of the respiratory sensitization potential of proteins using an enhanced mouse intranasal test (MINT).

There remains a need for a simple and predictive animal model to identify potential respiratory sensitizers. The mouse intranasal test (MINT) was developed to assess the relative allergic potential of detergent enzymes, however, the experimental endpoints were limited to evaluation of antibody levels. The present study was designed to evaluate additional endpoints (serum and allergic antibody levels, pulmonary inflammation and airway hyperresponsiveness (AHR)) to determine their value in improving the predictive accuracy of the MINT. BDF1 mice were intranasally instilled on days 1, 3, 10, 17 and 24 with subtilisin, ovalbumin, betalactoglobulin, mouse serum albumin or keyhole limpet hemocyanin; challenged with aerosolized methacholine or the sensitizing protein on day 29 to assess AHR, and sacrificed on day 29 or 30. Under the conditions of this study, evaluation of AHR did not improve the predictive power of this experimental model. Allergic antibody responses and IgG isotype characterization proved to be the most sensitive and reliable indicators of the protein allergenic potential with BAL responses providing additional insight. These data highlight that the evaluation of the respiratory sensitization potential of proteins can be best informed when multiple parameters are evaluated and that further improvements and refinements of the assay are necessary.

Acute macrovascular dysfunction in patients with type 2 diabetes induced by ingestion of advanced glycated ß-lactoglobulins.

OBJECTIVE: Recent evidence indicates that heat-enhanced food advanced glycation end products (AGEs) adversely affect vascular function. The aim of this study was to examine the acute effects of an oral load of heat-treated, AGE-modified ß-lactoglobulins (AGE-BLG) compared with heat-treated, nonglycated BLG (C-BLG) on vascular function in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: In a double-blind, controlled, randomized, crossover study, 19 patients with T2DM received, on two different occasions, beverages containing either AGE-BLG or C-BLG. We measured macrovascular [brachial ultrasound of flow-mediated dilatation (FMD)] and microvascular (laser-Doppler measurements of reactive hyperemia in the hand) functions at baseline (T0), 90 (T90), and 180 (T180) min. RESULTS: Following the AGE-BLG, FMD decreased at T90 by 80% from baseline and remained decreased by 42% at T180 (P < 0.05 vs. baseline, P < 0.05 vs. C-BLG at T90). By comparison, following C-BLG, FMD decreased by 27% at T90 and 51% at T180 (P < 0.05 vs. baseline at T180). A significant decrease in nitrite (T180) and nitrate (T90 and T180), as well as a significant increase in N(ε)-carboxymethyllisine, accompanied intake of AGE-BLG. There was no change in microvascular function caused by either beverage. CONCLUSIONS: In patients with T2DM, acute oral administration of a single AGE-modified protein class significantly though transiently impaired macrovascular function in concert with decreased nitric oxide bioavailability. These AGE-related changes were independent of heat treatment.

Low doses of allergen and probiotic supplementation separately or in combination alleviate allergic reactions to cow ß-lactoglobulin in mice.

Probiotic supplementation and oral tolerance induction can reduce certain types of food allergy. The objectives of this study were to investigate the allergy-reducing effects of probiotics (VSL#3) and/or oral tolerance induction via low doses of an allergen supplementation in ß-lactoglobulin (BLG)-sensitized mice. Three-week-old, male BALB/c mice were divided into 6 groups (n = 8/group): sham-sensitized negative control (CTL-), BLG-sensitized positive control (CTL+), oral tolerance-induced and BLG-sensitized group (OT), probiotic-supplemented OT group (OTP), probiotic-supplemented CTL- (PRO), and probiotic-supplemented and BLG-sensitized (PROC) groups. Mice were i.p. sensitized with BLG and alum and then orally challenged with BLG. Immunological responses were assessed by monitoring hypersensitivity scores and measuring levels of BLG-specific serum Igs, total serum IgE and fecal IgA, and cytokines from serum and spleen lysates. Hypersensitivity scores were significantly lower in the PROC (2.00 ± 0.53), OT (0.75 ± 0.46), and OTP mice (1.00 ± 0.53) than in the CTL+ mice (2.63 ± 0.52) as were BLG-specific serum IgE concentrations (34.3 ± 10, 0.442 ± 0.36, 3.54 ± 3.5, and 78.5 ± 8.7 µg/L for PROC, OT, OTP, and CTL+, respectively). Our results suggest that supplementation of VSL#3 suppressed the allergic reaction mainly through increased intestinal secretary IgA (sIgA) in PROC mice, and oral tolerance offered allergen-specific protective effects to BLG-induced allergy, probably through CD4+CD25+ regulatory T cell-mediated active suppression. In OTP mice, probiotics did not induce a further reduction of hypersensitivity score compared with OT mice but may provide additional protection to unforeseen nonspecific challenges through increased intestinal sIgA.

Suppressive effects of oral administration of heat-killed Lactobacillus acidophilus on T helper-17 immune responses in a bovine ß-lactoglobulin-sensitized mice model.

The present study was planned to explore the effect of Lactobacillus (L.) acidophilus on the T helper-17 (Th17) immune response in a mouse model of ß-lactoglobulin (ß-lg) allergy. Bovine ß-lg sensitised BALB/c mice were orally administered with different doses of heat-killed L. acidophilus (low, 5×10(7) colony forming unit (CFU); medium, 5×10(8) CFU; high, 5×10(9) CFU) in 200 µL of phosphate buffered saline (PBS) three times a week, starting from 1 week before ß-lg sensitisation for 4 weeks. After the allergen challenge, the numbers of blood eosinophils and neutrophils were examined by light microscope; the levels of cytokine (interleukin (IL)-12, IL-4, tumor growth factor (TGF)-ß, IL-10, IL-6 and IL-17A), total immunoglobulin E (IgE) and ß-lg-specific IgE contents in the serum were measured with enzyme-linked immunosorbent assay (ELISA); The mRNA expression levels of TGF-ß, IL-17A,CD25, Foxp3, retinoic acid-related orphan receptor γt (RORγt) and IL-10 were analyzed using real-time polymerase chain reaction (PCR). The results showed that oral administration of L. acidophilus suppressed hypersensitivity responses, attenuated the numbers of inflammatory cells and inhibited IgE production. We found up-regulation of TGF-ß and down-regulation of IL-17A in the serum of L. acidophilus-treated group, along with IL-6 levels was significantly decreased than that of the allergy group (p<0.05). Moreover, the mRNA expression levels of CD25, forkhead box P3 and TGF-ß were significantly higher in the spleen of L. acidophilus-treated group, while the mRNA expression levels of IL-17A, RORγt and IL-10 were significantly lower than that in the allergy group (p<0.05). In conclusion, the suppression of major allergic symptoms by oral administration of L.acidophilus was probably due to improve the regulatory T (Treg)/Th17 balance and inhibit the IL-6 production.

Undeclared allergenic ingredients in foods from animal origin: survey of an Italian region's food market, 2007-2009.

Several EC Directives have been promulgated to protect allergic individuals but no rule has been established with regard to allergen cross-contamination caused by shared transport vehicles or common processing equipment. The aim of this research was to quantify, by enzyme-linked immunosorbent assay (ELISA) or real-time polymerase chain reaction, the presence in meat- or fish-based foods of four allergens (milk, egg, crustaceans and molluscs) that was not indicated either in the list of ingredients or in the label alert. In the time frame of 2007-2009, a total of 723 samples were subjected to 1983 analyses. The percentage of samples scoring positive ranged between 1.8% and 6.8% over the 3 years, and the concentrations of undeclared allergens found were 0.3-13.3 mg kg⁻¹ for milk (ß-lactoglobulin) and 0.21-12 mg kg⁻¹ for egg white proteins. On this basis, the possibility of cross-contamination serious enough to raise public health concern cannot be dismissed.

Allergenic and immunogenic potential of cow's milk ß-lactoglobulin and caseins evidenced without adjuvant in germ-free mice.

SCOPE: In most animal models of allergy, the development of an IgE response requires the use of an adjuvant. Germ-free (GF) mice exhibit Th2-polarized antibody responses combined with defective immunosuppressive mechanisms. The sensitizing potential of milk proteins was investigated in GF mice in the absence of adjuvant. METHODS AND RESULTS: ß-lactoglobulin (BLG) and whole casein (CAS) allergenicity was evaluated by means of intraperitoneal injections without adjuvant. Injections of BLG induced significant IgE and IgG1 responses in GF mice, while CAS injections provoked the production of IgG1 toward κ- and αS1-caseins. No significant antibody response was evidenced in conventional (CV) mice. After in vitro BLG-reactivation, IL-4, IL-5, IL-13 and IFN-γ productions by splenocytes were higher in GF mice than in CV mice. Heat-treatment decreased BLG allergenicity as indicated by the absence of IgE production in GF mice. However, heat-treatment increased protein immunogenicity and led to the production of anti-BLG and anti-κ-casein IgG1 in both GF and CV mice. This correlated with enhanced productions of IL-4, IL-5 and IL-13 in BLG-reactivated splenocytes from CV mice. CONCLUSION: Gut colonization by commensal bacteria appeared then to significantly reduce the susceptibility of mice toward the intrinsic allergenic and immunogenic potential of milk proteins.

Recognition and uptake of free and nanoparticle-bound betalactoglobulin--a food allergen--by human monocytes.

SCOPE: To improve our understanding of the interaction of food allergens with cells of the immune system, the endocytosis by human monocytes of bovine ß-lactoglobulin (BLG) and ovomucoid (OM)--two major food allergens--and human serum albumin (HSA) was studied. METHODS AND RESULTS: BLG was covalently conjugated to dextran-coated magnetic nanoparticles (MNPs) without affecting its structure and immunoreactivity. BLG-conjugated MNPs were taken up by human monocytes much more efficiently than non-conjugated MNPs, allowing easy magnetic separation of cells that had adsorbed the allergen. BLG, OM, and HSA were conjugated to MNPs also labeled with a fluorescent probe. The uptake of these materials by human monocytes was monitored through flow cytometry, and compared with fluorescent MNPs and the free fluorescently labeled proteins, confirming higher uptake of the BLG-conjugated MNPs versus non-conjugated MNPs. OM but not HSA conjugation to particles enhanced uptake of the MNPs. Confocal microscopy provided direct evidence of the actual internalization of BLG-MNP conjugates into the cytoplasm. CONCLUSIONS: These results contribute to the current understanding of the interaction between food allergens and antigen-presenting cells, and demonstrate that the BLG is readily endocytosed by monocytes both as the single protein and as a conjugate.

Gastrointestinal sensitivity to soy and milk proteins in patients with IgA nephropathy.

BACKGROUND: sensitivity to food antigens has been postulated as a contributing factor to the pathogenesis of IgA nephropathy (IgAN). METHODS: in this study we used a recently developed mucosal patch technique to evaluate rectal mucosal sensitivity to soy and cow's milk (CM) proteins in IgAN patients (n = 28) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analyzed for IgA and IgG antibodies to alpha-lactalbumin, beta-lactoglobulin, casein and soy. RESULTS: 14 of 28 (14/28) patients experienced a rectal mucosal reaction, measured by increased NO and/or MPO levels, upon rectal challenge with soy and/or cow's milk proteins. The levels of IgG antibodies to alpha-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, whereas the mean serum levels of IgA antibodies were similar. No differences were seen in serum levels of IgA or IgG antibodies to soy. CONCLUSION: it is concluded that approximately half of our IgAN patients have a rectal mucosal sensitivity to soy or CM, and that an immune reactivity against antigens may be involved in the pathogenesis of IgAN in this subgroup of patients.