Anti-Actin IgA Antibodies Identify Celiac Disease Patients with a Marsh 3 Intestinal Damage among Subjects with Moderate Anti-TG2 Levels

A new diagnostic tool (algorithm-1) for coeliac disease (CD) permitting the diagnosis without performing the duodenal biopsy has been recently proposed by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). It combines symptoms associated with CD, high anti-transglutaminase type 2 antibody (anti-TG2) levels, anti-endomysium-IgA antibodies (EMA), and at-risk HLA. Our aims were (i) to evaluate retrospectively in 227 individuals (149 CD patients and 78 controls) the algorithm-1, (ii) to reduce the number of duodenal biopsies among CD patients for whom algorithm-1 is not applicable through the addition of antiactin IgA antibodies (AAA-IgA), and (iii) to evaluate prospectively algorithm-1 and AAA-IgA in 50 patients with suspected CD. Algorithm-1 identified 70 out of 149 CD patients with Marsh 3 lesions. Adding AAA-IgA to the remaining patients with anti-TG2 levels comprised between 4 and 10 times upper limit of normal (ULN) allowed the detection of further 20 patients with a Marsh 3 damage. In our prospective study, algorithm-1 identified 23 out of 50 patients, whilst further 7 were recognized adding AAA-IgA. We confirm that algorithm-1 may avoid the duodenal biopsy in many CD patients and underscores the usefulness of AAA-IgA in reducing the number of duodenal biopsies in patients with moderate anti-TG2 levels

HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease

Objective. Celiac disease (CD) is a T-lymphocyte-mediated small intestinal enteropathy triggered and maintained by dietary gluten, with a strong genetic component mapping to the HLA genes encoding for the class II DQ(α1*0501, β1*02) molecule. Damage of the small intestine may cause a variety of clinical signs ranging from isolated long-standing iron-deficiency anemia refractory to iron supplementation to forms of severe malnutrition that may become life threatening. However, patients carrying the typical intestinal lesions of CD and presenting no symptoms at all (silent CD) are also a common clinical observation. Since it is commonly assumed that clinical signs and symptoms tend to correlate with the severity of the intestinal damage, the purpose of this study was to investigate whether particular HLA class II genotypes might also influence the extent of intestinal damage and consequently the clinical presentation of the disease. Material and methods. We retrospectively compared histological grading of celiac disease intestinal biopsies with HLA haplotype, age at onset of disease and clinical signs and symptoms. Results. Our findings showed that homozygosis for the DQB1*0201 allele is associated with a higher severity of the histological score (p<0.008). Of note for the clinician, this work also suggests that the same type 3c of intestinal damage causes a different clinical syndrome, depending on the patient's age. Conclusions. The genetic predisposition at the HLA-DQB1 locus influences the severity of the mucosal damage in a dose-dependent manner, but not the clinical presentation, of celiac disease

Decline of lactase activity and C/T-13910 variant in Sardinian childhood

OBJECTIVES: Our study aims to determine the age of onset of adult-type hypolactasia in Sardinians, and to establish the age at which genotyping of the C/T-13910 variant can be used reliably in the diagnosis of lactose malabsorption. PATIENTS AND METHODS: A lactose breath hydrogen test was given to 383 randomly selected patients, from 3 to 19 years old. RESULTS: The C/C-13910 genotype was found in 90% of patients; the frequency of the positive lactose breath hydrogen test increased with age and reached a prevalence of 85% at 9 years. CONCLUSIONS: In Sardinians, adult-type hypolactasia becomes phenotypically evident in all individuals older than 9 years, suggesting that this should be considered the minimum age at which the genetic test for lactase nonpersistence should be applied

Utility of Anti-actin Iga Antibody in Combination with the New ESPGHAN Guidelines for Coeliac Disease Diagnosis

AIM: An option to reduce the number of duodenal biopsies in the diagnosis of coeliac disease (CD) has recently been reported by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. New criteria showed that the duodenal biopsy may be avoided in presence of symptoms, high anti-transglutaminase type 2 antibody (anti-TG2) levels, anti-endomysial antibodies (EMA) and at-risk HLA, whilst biopsy still remains mandatory for individuals with moderate and low anti-TG2 levels. In this study, we considered the addition of serum measurement of anti-actin IgA antibody (AAA-IgA) to the new criteria, with the aim of further reducing the number of duodenal biopsies. METHODS: One hundred and forty consecutive symptomatic CD children and 78 controls were studied. All subjects were classified according to the new criteria with the addition of AAA-IgA levels and results were compared with the outcome of duodenal biopsy. RESULTS: The biopsies from the sixty-four individuals (out of 218) identified by the new criteria, presence of symptoms, anti-TG2 levels >10 times upper limit of normal (ULN), positive EMA and at-risk HLA, showed CD with a Marsh 3 lesion. In the remaining individuals, the addition of AAA-IgA allowed the detection of further 20 CD patients with a Marsh 3 damage when moderate (4 to 10 times ULN) but not low anti-TG2 levels were present. CONCLUSIONS: Our study confirms that the new criteria may avoid the duodenal biopsy in many CD patients. Moreover, although our finding needs to be confirmed, positivity for AAA-IgA may further reduce the number of duodenal biopsies in moderate anti-TG2 levels