Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten

Abstract

IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.

Figure 1. Gel electrophoresis profile of the gliadin preparation used for the anti-gliadin antibody assays.

A) 5 µg of protein loaded; B) 10 µg of protein loaded.

Figure 2. Mean levels of A) IgA and B) IgG antibody to gliadin in IgAN patients and unaffected controls, as well as individuals with celiac disease.

Error bars represent the standard error of the mean. * = p<0.05, *** = p<0.001.

Figure 3. Mean levels of A) IgA anti-human TG2, B) IgA anti-deamidated gliadin, and C) IgG anti-deamidated gliadin in IgAN patients and unaffected controls, as well as individuals with celiac disease.

Error bars represent the standard error of the mean. *** = p<0.001.