The hidden link between iron deficiency and celiac disease: a clinical perspective

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals and represents a frequent but underdiagnosed cause of iron deficiency (ID). Screening for CD is recommended in unexplained ID, yet data on its prevalence among patients with absolute ID remain limited. This study aimed to determine the frequency of confirmed CD and Suspected Seronegative CD at Marsh 1 (SSCDM1) and to characterize their clinical, serological, histological, and immunogenetic profiles.

A retrospective study was conducted within the ViaIron cohort including 86 individuals (≥14 years) with absolute ID (ferritin <50 ng/mL), with or without anemia, and no prior CD diagnosis. All underwent serological testing, duodenal biopsy with CD8⁺ intraepithelial lymphocyte staining, and HLA-DQ2/DQ8 genotyping. SSCDM1 was defined by Marsh 1 histology and permissive HLA genotypes in seronegative patients.

Among 86 participants (93% female, median age 41 years), 14% had confirmed CD (Marsh 3) and 39.5% had SSCDM1. Only one-third of confirmed cases were seropositive, and 77% were asymptomatic. SSCDM1 patients closely resembled overt CD, showing low ferritin, hepcidin, and IgA levels but normal inflammatory markers, suggesting a shared malabsorption-driven, non-inflammatory mechanism of iron depletion. Autoimmune comorbidities, particularly autoimmune thyroiditis, and permissive HLA-DQ2/DQ8 haplotypes were highly frequent in both groups.

Nearly half of participants exhibited either overt or seronegative CD, revealing a continuum between both conditions. These findings highlight a frequently under-recognized, seronegative, immune-mediated duodenal injury consistent with possible gluten-sensitive enteropathy, which may escape detection by standard serological screening.