In an analysis of a large cohort of subjects with IBD, we found a significant association between symptoms of depression or anxiety and clinical recurrence. Patients with IBD should therefore be screened for clinically relevant levels of depression and anxiety and referred to psychologists or psychiatrists for further evaluation and treatment.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with a poor prognosis and limited therapeutic options. Therefore, the development of novel therapeutic strategies is of high priority. ␣-Fetoprotein (AFP) is overexpressed in the majority of HCCs. Priming of immune responses against AFP results in significant protective antitumoral T cell responses in the mouse model. Little information is available about the hierarchy, breadth, frequency, and peripheral versus intrahepatic distribution of AFP-specific CD8 ؉ T cell responses in patients with HCC. To address these important issues we comprehensively analyzed CD8 ؉ T cell responses against full-length AFP in peripheral blood, tumor liver tissue, and nontumor liver tissue from patients with HCC using overlapping AFP peptides. The AFP-specific CD8 ؉ T cell response was also tested in peripheral blood and liver from patients chronically infected with hepatitis C virus (HCV) and compared to the HCV-specific CD8 ؉ T cell response. The majority of patients with HCC showed AFP-specific responses, with many responses directed against previously unreported epitopes. These responses were primarily detectable in the HCC tissue and mainly targeted the C-terminus of AFP. Interestingly, AFP-specific T cells were not only found in patients with HCC but also in patients with chronic HCV infection, other liver diseases, and less frequently in healthy subjects. Conclusion: In patients with HCC, a high frequency of AFPspecific CD8 ؉ T cells directed against different epitopes suggests that AFP has a strong and broad immunogenicity. Further, CD8 ؉ T cells specific for the self-antigen AFP are present in the normal T cell repertoire and are not centrally or peripherally deleted. Our results provide support for strategies to boost AFP-specific CD8 ؉ T cell responses in patients with HCC but also demonstrate a diversity of immune responses that may be needed for protection. (HEPATOLOGY 2008; 48:1821-1833 H epatocellular carcinoma (HCC) is one of the most common tumors in the world, with a global incidence of 500,000 new cases per year. 1 HCC is up to four times more common in men than in women and 60%-90% of these tumors develop in a cirrhotic liver. If untreated, most patients die within 3-6 months after diagnosis and, even if treated, the 5-year survival rate is low. [1][2][3] Therefore, new strategies to treat patients with HCC have a high clinical priority. Immunotherapy aimed at inducing or activating HCC-specific immune responses is one such concept; its rationale is based on the presence of high numbers of tumor-infiltrating T cells in HCC tissue, 4 the correlation between the density of lymphocytic infiltrates in HCC lesions and prognosis, 5,6 and most importantly, the finding that adoptive immunotherapy with anti-CD3 and interleukin-2 (IL-2) stimulated autologous lymphocytes lowers postsurgical HCC recurrence rates in humans. 7

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In CVID patients with suspected celiac disease typing of the HLA loci DQA1 and DQB1 can help to identify those that have a genetic susceptibility for CD. In CVID patients with a celiac-like phenotype but negative for CD-associated HLA-DQ markers, an autoimmune enteropathy (AIE) as part of an extended autoimmune dysregulation needs to be considered. This has important implications for further diagnostics and therapy of these patients.