Subject(s)
Hemoglobinuria, Paroxysmal/drug therapy , Hemoglobinuria, Paroxysmal/etiology , Amino Acid Sequence , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Bone Marrow Diseases/etiology , Clinical Trials as Topic , Complement System Proteins , HMGA2 Protein/chemistry , HMGA2 Protein/genetics , Hemolysis , Humans , Molecular Sequence Data , Venous Thrombosis/etiologyABSTRACT
OBJECTIVE: To clarify an expansion mechanism of a paroxysmal nocturnal hemoglobinuria (PNH) clone with the Wilms' tumor gene (WT1). MATERIALS AND METHODS: In PNH patients with the HLA-A*2402 allele, frequencies of peripheral blood (PB) WT1 peptide-specific and HLA-A*2402-restricted CD8+ cells and WT1 peptide-stimulated interferon-gamma-producing mononuclear cells (MNCs), cytotoxicity of WT1 peptide-specific and HLA-A*2402-restricted cytotoxic T lymphocyte (CTL) clone (TAK-1) cells on bone marrow (BM) MNCs, and after co-incubation with TAK-1 cells, changes in colony-forming unit granulocyte-macrophage colony formation of CD34+ cells and in CD59 expression in viable CD34+ cells were investigated. RESULTS: The frequencies of PB WT1 peptide-specific and HLA-A*2402-restricted CD8+ cells (p < 0.005) and WT1 peptide-stimulated interferon-gamma-producing MNCs (p < 0.02) were significantly higher in 5 PNH patients than 8 healthy volunteers (HV). In 5 PNH patients or 3 HV, TAK-1 cells significantly killed BMMNCs and suppressed colony formations of CD34+CD59+ and/or CD34+CD59- cells in the absence and presence of a WT1 peptide or only in the presence of the peptide, respectively, in an HLA-restricted manner. After co-incubation with TAK-1 cells, reduction rates of colony formation of CD34+CD59- cells were significantly less than those of CD34+CD59+ cells in 5 PNH patients (p < 0.002) and proportions of viable CD34+CD59- cells from 5 PNH patients significantly increased in the absence (p < 0.01) and presence (p < 0.01) of a WT1 peptide in an HLA-restricted manner. CONCLUSION: WT1 peptide-specific and HLA-restricted CTLs may play an important role in expansion of a PNH clone during immunologic selection and/or in the occurrence of BM failure via interferon-gamma in PNH.
Subject(s)
Genes, Wilms Tumor , Hemoglobinuria, Paroxysmal/immunology , T-Lymphocytes, Cytotoxic/immunology , Adult , Alleles , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Female , HLA-A Antigens/genetics , HLA-A Antigens/immunology , Humans , Immunophenotyping , Male , Middle Aged , Polymerase Chain Reaction , RNA, Messenger/geneticsABSTRACT
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) usually lacks CD5 expression. Herein is described two cases of CD5-positive MALT lymphoma of ocular adnexal origin. The differential diagnosis between CD5-positive MALT lymphoma and mantle cell lymphoma (MCL), notably cyclin D1-negative MCL, was difficult because both cases consisted histologically of small to medium-sized cells with diffuse or vaguely nodular growth pattern, and the neoplastic cells were positive for CD5 and negative for cyclin D1. Somatic mutation analysis of the immunoglobulin heavy chain variable region (VH) gene in case 1 found a relatively higher mutation frequency (5.0%), which was not definitive to rule out MCL. Interphase fluorescence in situ hybridization (FISH) on paraffin-embedded section using IgH/cyclin D1 (CCND1) probe showed that in both cases there was no molecular evidence of t(11;14), finally leading to the diagnosis of CD5-positive MALT lymphoma. Although the present two patients had no recurrence over 34 months after initial diagnosis, careful observation is needed because the clinicopathological significance of MALT lymphoma with this rare phenotype remains obscure.
Subject(s)
CD5 Antigens/metabolism , Eye Neoplasms/diagnosis , Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, Mantle-Cell/diagnosis , Neoplasms, Adnexal and Skin Appendage/diagnosis , Aged , CD5 Antigens/analysis , CD5 Antigens/genetics , Cyclin D1/genetics , Cyclin D1/metabolism , DNA, Neoplasm/genetics , Diagnosis, Differential , Eye Neoplasms/genetics , Eye Neoplasms/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Heavy Chains/metabolism , In Situ Hybridization, Fluorescence , Lymphoma, B-Cell, Marginal Zone/genetics , Lymphoma, B-Cell, Marginal Zone/metabolism , Lymphoma, Mantle-Cell/genetics , Lymphoma, Mantle-Cell/metabolism , Male , Middle Aged , Neoplasms, Adnexal and Skin Appendage/genetics , Neoplasms, Adnexal and Skin Appendage/metabolismABSTRACT
Host-derived Langerhans cells (LCs) are crucial antigen-presenting cells that cause graft-vs.-host disease after allogeneic haematopoietic stem cell transplantation (HSCT). However, chimaerism of LCs after allogeneic HSCT is largely unknown in humans. We here report a case that developed dermatopathic lymphadenitis accompanied by an accumulation of donor-derived LCs in the second month after allogeneic HSCT with reduced-intensity conditioning. This is the first case to show that donor LCs have the ability to migrate into draining lymph nodes and replace host LCs early after HSCT in humans.
