Association of deficiency for mannan-binding lectin with anti-mannan antibodies in Crohnʼs disease: A family study

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Antibodies against mannan, a component of the yeast Saccharomyces cerevisiae cell wall, are more frequently found in Crohn's disease (CD) patients with low levels of mannan-binding lectin (MBL). MBL concentration depends on genetic polymorphisms. The aim of this study was to evaluate whether low MBL is related to ASCA production in healthy family members of CD patients. ASCA and MBL concentrations in sera from patients (n=52), and their 158 healthy relatives were measured by enzyme-linked immunosorbent assay (ELISA). Genetic MBL variants were determined by DNA sequencing. Thirty-five (67%) patients were ASCA-positive. Twenty-six (74%) of the 35 ASCA-positive patients had low MBL levels (<500 ng/mL), whereas only 4 (24%) of the 17 ASCA-negative patients had low values for MBL (P=0.001). ASCA were found in 38 (24%) family members. Twenty-three (50%) of 46 family members with low values for MBL were ASCA-positive compared to 15 (13%) of 112 family members with normal values for MBL (P<0.0001). ASCA were found in 33 of 104 (32%) family members of ASCA-positive patients and in 5 family members (9%) of ASCA-negative patients (P=0.002). Relatives with mutations leading to MBL deficiency had significantly more frequent ASCA than relatives without these mutations (P=0.018). MBL deficiency is associated with ASCA positivity not only in patients with CD, but also in their relatives. An impaired innate immune system defined by low MBL serum concentrations may lead to an increased reactivity of the specific immune system to mannan antigens, and therefore facilitate the generation of ASCA.