Increased Prevalence of Celiac Disease in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis.

Marcell Imrei,Hussain Alizadeh,Dávid Németh,Andrea Párniczky,Piroska Pázmány,Péter Hegyi,Fanni Dembrovszky,Zsolt Szakács,Szabolcs Kiss,Judit Bajor

doi:10.3390/jpm11090859

Marcell Imrei, Hussain Alizadeh + Show 8 more

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https://doi.org/10.3390/jpm11090859

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Abstract

Objectives: Immune regulation seems to be altered in cystic fibrosis (CF), thus potentially predisposing patients to developing autoimmune diseases (AID). In this meta-analysis, we aimed to evaluate the prevalence of celiac disease (CeD) among CF patients as by far the most commonly reported autoimmune disease in this population and, secondly, to review the observations on other, less frequently studied autoimmune diseases. Methods: We conducted a systematic literature search for studies that discussed AIDs among CF patients. Following standard selection and data collection, we calculated pooled raw prevalence with 95% confidence intervals (CI) for biopsy-verified CeD and seropositivity. Results: Out of the 21 eligible studies, 15 reported on CeD. Pooled prevalence of biopsy-verified CeD was 1.8% (CI 1.1–2.7%) according to a homogeneous dataset from six prospective, consecutive screening studies, while it proved to be 2.3% (CI 1.1–4.7%) according to a heterogeneous dataset from the other studies. Tissue transglutaminase IgA positivity was detected in 4.5% of CF cases (CI 2.8–6.9%), while tissue transglutaminase IgA–endomysial antibody IgA double positivity was found in 2.4% of them (CI 1.5–3.9%). Findings on other AIDs were strongly limited. Conclusions: The pooled prevalence of CeD in CF seemed to be more than twice as high compared to the global prevalence; therefore, routine screening of CeD could be considered in CF.

Highlights

Cystic fibrosis (CF; OMIM: 219700) is an autosomal recessive disease caused by the loss-of-function mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding the CFTR protein [1,2]
20 reports were eligible for inclusion [29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48], 15 of which reporting the biopsy-verified prevalence or seroprevalence of celiac disease (CeD) were included in the quantitative synthesis [29,30,31,32,33,34,35,36,37,38,39,40,41,42,43]
As regards biopsy-verified CeD, the six consecutive studies included a total of 1591 CF patients with a pooled prevalence of 1.8% (CI 1.1–2.7%) in a homogeneous dataset

Summary

Introduction

Cystic fibrosis (CF; OMIM: 219700) is an autosomal recessive disease caused by the loss-of-function mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding the CFTR protein [1,2]. In the past 10 years, several case–control studies have been published, reporting a wide range (1.2–2.13%) of proven CeD incidence in European CF patients [12]. This comorbidity could be described as a vicious cycle of chronic intestinal mucosal damage due to pancreas insufficiency, malnutrition, intestinal inflammation, and slow GI motility, resulting in an overload of incompletely or undigested nutrients (e.g., proteins), leading to an immunological response to antigens (e.g., gluten) [13,14,15]. There is a growing interest that can be explained by a set of arguments including the following: (1) CeD is the most common AID with an expected prevalence of approximately 1% in the general population; (2) due to the GI manifestations of CF, it is difficult to decide whom to screen for CeD; and (3) CeD is treatable by prescribing a lifelong gluten-free diet, significantly improving quality of life

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