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.
Highlights
Immunologic sensitivity to dietary gluten from wheat and related cereals is most extensively studied and best understood in the context of celiac disease and wheat allergy [1]
The data from this study indicate that, compared with unaffected controls, neither antibodies to native gliadin, nor the more specific and sensitive markers of celiac disease, i.e., antibodies to transglutaminase 2 (TG2) and deamidated gliadin, are significantly elevated in patients with IgA nephropathy (IgAN)
The observed incidence of unequivocal positivity for anti-TG2 and antiendomysial antibodies points to a frequency of celiac disease in the IgAN and unaffected control groups that is similar to that reported for the general population [27,28,29]
Summary
Immunologic sensitivity to dietary gluten (comprised of gliadin and glutenin proteins) from wheat and related cereals is most extensively studied and best understood in the context of celiac disease and wheat allergy [1]. The ensuing innate and adaptive immune responses to ingested gluten lead to inflammation and villous atrophy in the small intestine, the condition is known to have a number of extra-intestinal manifestations [2]. IgA anti-TG2 (or anti-endomysial) autoantibody is considered to be the most specific and sensitive serologic marker of the condition, being used widely to aid diagnosis [5]. Despite lacking the required serologic, histologic, or genetic markers of celiac disease and wheat allergy, experience intestinal or extra-intestinal symptoms in response to ingestion of wheat, sometimes in conjunction with elevated antibody reactivity to native gliadin [6]. The term ‘‘non-celiac gluten sensitivity’’ has been proposed to refer to the spectrum of symptoms reported by these patients [1], a role for gluten as the specific culprit has not been well established [6]
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