Ectopic expression of band 3 anion transport protein in colorectal cancer revealed in an autoimmune hemolytic anemia patient.

Cancer patients occasionally have anemia with high mean corpuscular volume in addition to iron deficiency anemia. Secondary autoimmune hemolytic anemia (AIHA) following cancer is also observed with low frequency. To date, no causal mechanisms for these disease states have been reported. Here, we present the case of an 80-year-old woman with AIHA that was resistant to prednisolone. Further examinations revealed primary adenocarcinoma of the sigmoid colon and primary squamous cell carcinoma in the right lung. After resections of these tumors, her anemia partially improved until a colon cancer-derived metastatic tumor was detected in the left lung. Immunoprecipitation of erythrocyte membrane proteins with an autoantibody followed by mass spectrometry/Western blotting identified band 3 as the target of the autoantibody. Immunohistochemical analysis revealed ectopic expression of band 3 in the colon adenocarcinoma. To our knowledge, this is the first report that identifies the cause in a case of anemia without bleeding in a cancer patient and that defines a mechanism underlying secondary AIHA following cancer progression.

Ectopic expression of CXCL13, BAFF, APRIL and LT-ß is associated with artery tertiary lymphoid organs in giant cell arteritis.

OBJECTIVES: To investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. METHODS: Reverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines. RESULTS: ATLOs were observed in the media layer of 60% of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-ß, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13. CONCLUSIONS: ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised.