Splenic hypofunction and the spectrum of autoimmune and malignant complications in celiac disease

BACKGROUND & AIMS: We investigated the prevalence of functional hyposplenism in autoimmune disorder (AID)-associated and complicated celiac disease (CD). In addition, because the association between hyposplenism and overwhelming infections caused by Streptococcus pneumoniae in patients with CD is well known, we investigated whether immunoglobulin (Ig)M memory B cells, which are responsible for protection against infections by encapsulated bacteria and require the spleen for their generation and/or survival, mirror the reduced splenic function in CD. METHODS: Peripheral blood samples were collected from 73 adult CD patients (27 with AID, 36 without AID, and 10 with CD-related complications including enteropathy-associated T-cell lymphoma, refractory sprue, and ulcerative jejunoileitis). Thirty-four non-CD patients with AID, 35 healthy volunteers, and 29 splenectomized patients also were studied. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function, and flow cytometry was performed to analyze peripheral blood B cells. RESULTS: A significantly higher risk for hyposplenism was found in AID-associated CD (59%) and complicated CD (80%) than in uncomplicated CD without AID (19%). In AID-associated CD, the degree of splenic function did not correlate to the duration of gluten-free diet. In AID-associated and complicated CD, the frequency of circulating IgM memory B cells was significantly lower than in CD patients without AID or healthy subjects. A significant inverse correlation between IgM memory B cells and pitted red cells was found in all 73 CD patients. CONCLUSIONS: The prevalence of splenic hypofunction is increased in CD with AID and in complicated CD, and is not related to the duration of gluten-free diet. IgM memory B cells are reduced in AID-associated and complicated CD. This defect, which is related to the impairment of splenic function, might predispose hyposplenic CD patients to infections by encapsulated bacteria.