Increased Risk of IgA Nephropathy Among Individuals With Celiac Disease

Welander, Adina; Sundelin, Birgitta; Fored, Michael; Ludvigsson, Jonas F.

doi:10.1097/mcg.0b013e318284792e

Cited by 67 publications

(45 citation statements)

References 39 publications

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“…Inversely, CD patients can develop IgAN that may progress to overt disease. 32,35,36 A recent study showed no increase in IgA AGA levels in a cohort of American IgAN patients receiving immunosuppressive therapy compared with controls. 37 Our cohort includes European patients in whom the measurement of serum IgA AGA was performed in the beginning of the diagnosis, before immunosuppressant treatment, suggesting that environmental and genetic factors could affect the immune reactivity to gluten in IgAN patients, which could further aggravate the disease development.…”

Section: Discussionmentioning

confidence: 96%

Gluten exacerbates IgA nephropathy in humanized mice through gliadin–CD89 interaction

Papista

Lechner

Mkaddem

et al. 2015

Kidney International

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IgA1 complexes containing deglycosylated IgA1, IgG autoantibodies, and a soluble form of the IgA receptor (sCD89), are hallmarks of IgA nephropathy (IgAN). Food antigens, notably gluten, are associated with increased mucosal response and IgAN onset, but their implication in the pathology remains unknown. Here, an IgAN mouse model expressing human IgA1 and CD89 was used to examine the role of gluten in IgAN. Mice were given a gluten-free diet for three generations to produce gluten sensitivity, and then challenged for 30 days with a gluten diet. A gluten-free diet resulted in a decrease of mesangial IgA1 deposits, transferrin 1 receptor, and transglutaminase 2 expression, as well as hematuria. Mice on a gluten-free diet lacked IgA1-sCD89 complexes in serum and kidney eluates. Disease severity depended on gluten and CD89, as shown by reappearance of IgAN features in mice on a gluten diet and by direct binding of the gluten-subcomponent gliadin to sCD89. A gluten diet exacerbated intestinal IgA1 secretion, inflammation, and villous atrophy, and increased serum IgA1 anti-gliadin antibodies, which correlated with proteinuria in mice and patients. Moreover, early treatment of humanized mice with a gluten-free diet prevented mesangial IgA1 deposits and hematuria. Thus, gliadin-CD89 interaction may aggravate IgAN development through induction of IgA1-sCD89 complex formation and a mucosal immune response. Hence, early-stage treatment with a gluten-free diet could be beneficial to prevent disease.

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Section: Discussionmentioning

confidence: 96%

Gluten exacerbates IgA nephropathy in humanized mice through gliadin–CD89 interaction

Papista

Lechner

Mkaddem

et al. 2015

Kidney International

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“…& There is an epidemiologic association between celiac disease and IgAN [42]. Such an association is also suggested with the far less common IgAV.…”

Section: Treatment Diet and Lifestylementioning

confidence: 92%

Management of Vasculitic Glomerulonephritis

Pendergraft

Nachman

2016

Curr Treat Options in Rheum

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“…As evident from AUC from the two ROC analyses, combined performance of six IgAN-specific IgA antibodies was more discriminatory (AUC=1) compared with IgAN-specific IgG antibodies (AUC=0.86) as described previously (13). Of note, anti-T-TG IgA antibody has been used for the diagnosis of celiac disease (23), wherein there appears to be an increased risk of IgAN (24).…”

Section: Prediction Of Igan By Autoantibodiesmentioning

confidence: 98%

Mapping Novel Immunogenic Epitopes in IgA Nephropathy

Woo

Sigdel

Dinh

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives IgA plays a key role in IgA nephropathy (IgAN) by forming immune complexes and depositing in the glomeruli, leading to an inflammatory response. However, the antigenic targets and functional characterization of IgA have been incompletely defined in this disease.Design, setting, participants, & measurements This study was performed in sera from patients who were studied as part of a prospective, observational study of IgAN. These patients (n=22) all had biopsy-proven IgAN within 3 years of study initiation, complete clinical data, annual urinary inulin clearance for GFRs, and at least 5 years of follow-up. Progression was defined as loss of .5 ml/min per 1.73 m 2 per year of inulin clearance measured over at least 5 years. A protein microarray was used for detection of IgAN-specific IgA autoantibodies in blood across approximately 9000 human antigens to specifically identify the most immunogenic protein targets that drive IgA antibodies in IgAN (n=22), healthy controls (n=10), and non-IgAN glomerular diseases (n=17). Results were validated by ELISA assays in sera and by immunohistochemistry in IgAN kidney biopsies. IgA-specific antibodies were correlated with clinical and histologic variables to assess their effect on disease progression and prognosis.Results Fifty-four proteins mounted highly significant IgA antibody responses in patients with IgAN with a false discovery rate (q value) of #10%; 325 antibodies (P#0.05) were increased overall. Antitissue transglutaminase IgA was significantly elevated in IgAN (P,0.001, q value of 0%). IgA antibodies to DDX4 (r=20.55, P=0.01) and ZADH2 (r=20.48, P=0.02) were significantly correlated with the decline of renal function. Specific IgA autoantibodies are elevated in IgAN compared with normal participants and those with other glomerular diseases.

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Increased Risk of IgA Nephropathy Among Individuals With Celiac Disease

Abstract: Individuals with CD suffer a 3-fold increased risk of future IgAN. Our findings warrant awareness of renal function in individuals with CD.

Cited by 67 publications

References 39 publications

Gluten exacerbates IgA nephropathy in humanized mice through gliadin–CD89 interaction

Gluten exacerbates IgA nephropathy in humanized mice through gliadin–CD89 interaction

Management of Vasculitic Glomerulonephritis

Mapping Novel Immunogenic Epitopes in IgA Nephropathy

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