Low CD1a-positive putative dendritic cell numbers in human breast cancer has recently been described and may explain the apparent 'poor immunogenicity' previously reported in breast cancer. Little attention has been given to dendritic cell activation within the tumour microenvironment, which is another reason why the in-situ immune response may be severely deficient. We have therefore examined CD1a expression as a marker for dendritic cells, together with CMRF-44 and -56 as markers of dendritic cell activation status, in 40 human breast cancers. The results demonstrate few or no CD1a-positive putative dendritic cells and minimal or no expression of the dendritic cell activation markers. Both dendritic cell number and dendritic cell activation appear substantially deficient in human breast cancers, regardless of tumour histological grade.

To investigate the role of thyroid autoantibodies in the development of thyroid dysfunction among chronic hepatitis C (CHC) patients receiving interferon-alpha (IFN-alpha) plus ribavirin (RBV) combination therapy, 95 Taiwanese naïve patients with baseline euthyroidism were enrolled. They were treated with IFN-alpha2b, 6 million units thrice weekly, plus RBV 1,000-1,200 mg daily for 24 weeks. Thyroid function, anti-thyroglobulin and antiperoxidase autoantibodies were tested at enrollment (M0), at the end-of-treatment (M6) and 6 months after end-of-treatment (M12). The percentages of thyroid autoantibodies were 8.4%, 11.6% and 9.5%, at M0, M6 and M12 respectively. Fourteen (14.7%) patients developed thyroid dysfunction at M6 or M12. Thyroid dysfunction occurred during treatment in five (62.5%) of the eight patients with baseline thyroid autoantibodies, which was significantly higher than nine (10.3%) of 87 patients without baseline thyroid autoantibodies (P = 0.0001). Among 14 patients who developed thyroid dysfunction, four (80.0%) of five patients with baseline thyroid autoantibodies recovered at M12, in contrast to two (25%) of eight without baseline thyroid autoantibodies recovered at M12 (P < 0.05). In conclusion, thyroid autoantibodies, either occurred before or during IFN-alpha plus RBV combination therapy, carry a high prediction of subsequent thyroid dysfunction. There also exists difference in the clinical manifestations of thyroid dysfunction in CHC patients treated with combination therapy.

A 62-year-old white man with a hemochromatosis phenotype was found to be heterozygous for the C282Y mutation of the HFE gene. The H63D and S65C mutations of HFE were not present. As most C282Y heterozygotes do not develop a hemochromatosis phenotype, the coding region of the patient's HFE gene was sequenced and a previously undescribed frameshift mutation was identified in exon 2 (c.del277; G93fs) that resulted in a premature stop-codon. There were no coding region mutations of the ferroportin gene (FPN1). We performed human leukocyte antigen (HLA) typing of the patient and his brother who was heterozygous for the C282Y HFE mutation unassociated with a hemochromatosis phenotype. They shared only C282Y and the HLA haplotype A*03, B*14; hence, the c.del277 mutation was linked to the HLA haplotype A*02, B*44 and therefore not on the same chromosome as the C282Y mutation. Thus, the present patient's only intact HFE protein is C282Y, and this may explain his hemochromatosis phenotype.

An African American male of West Indies descent was diagnosed to have elevated transferrin saturation, hyperferritinemia, severe iron deposition in hepatocytes, and hepatic cirrhosis at age 4. He was treated with serial phlebotomy to maintain a normal serum ferritin concentration thereafter. We evaluated him at age 23 and confirmed that he had normal serum ferritin levels, severe iron deposition in hepatocytes, hepatic cirrhosis, and portal hypertension. He did not have endocrinopathy, cardiomyopathy, or arthropathy. He was homozygous for the novel hemojuvelin (HJV) premature stop-codon mutation R54X (exon 3; c.160A-->T). He did not have either HFE C282Y, H63D, or S65C, or deleterious coding region mutations of SLC40A1, TFR2, or HAMP. His erythrocyte measures and hemoglobin electrophoresis were consistent with alpha-thalassemia trait. We conclude that homozygosity for HJV R54X accounts for his severe, early age-of-onset hemochromatosis; his phenotype was probably modified by serial phlebotomy therapy.