myelin-basic-protein and Leukemia

Topics: Animals; Antibodies; Antigen-Antibody Complex; Antilymphocyte Serum; Asparaginase; Blood Coagulation; Blood Platelet Disorders; Blood Platelets; Carcinoma, Ehrlich Tumor; Cell Membrane; Cells, Cultured; Electrophoresis; Histocompatibility Antigens; Humans; Immunosuppression Therapy; Lectins; Leukemia; Lymphocytes; Myelin Basic Protein; Neuraminidase; Poly I-C; Radiation Effects; Radiation-Protective Agents; Radiation-Sensitizing Agents; Surface Properties

The immune system plays an important role in the control of cancer development. To investigate possible genetic contribution to childhood leukemia risk in the innate immune system, we performed an association study for the 1214 SNPs in 146 gene regions related to innate immunity using GoldenGate (Illumina) oligonucleotide pool assay (OPA) in 106 case patients and 123 controls. Childhood leukemia risk was estimated as odds ratios and 95% confidence intervals adjusted for age, gender and birth weight. The minP test was used to identify statistically significant association at gene level. Three SNPs (STAT6 rs703817, C1qG rs17433222, and MBP rs3794845) were significantly associated with childhood leukemia risk (p(trend) < 0.001, minP < 0.01). The most significant association with childhood leukemia risk was for STAT6 rs703817 (GA vs GG: 0.48 (0.26-0.87), AA vs GG: 0.21 (0.07-0.61), p(trend) = 0.0003, minP = 0.002). Subgroup analysis showed that Ly96 rs78380171 and MBP rs3794845 were significantly associated with the risk of acute lymphoblastic leukemia (p(trend) < 0.001). Our results suggest that genetic polymorphisms in innate immunity genes might play a role in the genesis of childhood leukemia with limited biologic evidence. Additional, larger studies are needed to identify the mechanism of these genes in childhood leukemia patients.

Topics: Adolescent; Asian People; Birth Weight; Child; Child, Preschool; Complement C1q; Female; Gene Frequency; Genotype; Heterozygote; Homozygote; Humans; Immunity, Innate; Korea; Leukemia; Leukemia, Myeloid, Acute; Lymphocyte Antigen 96; Male; Myelin Basic Protein; Polymorphism, Single Nucleotide; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk; STAT6 Transcription Factor

Autoimmune diseases are characterized by the presence of autoantibodies often restricted to host proteins exhibiting charge rich domains. Charged polypeptides elicit strong immune responses, and cationized bovine serum albumin and other cationic proteins are significantly more immunogenic than their less charged counterparts. These phenomena may involve enhanced protein uptake by macrophages, resulting in greater processing and presentation of antigenic peptide-MHC complexes to T-cells. We compared macrophage cell-surface binding and uptake of native and cationized bovine serum albumin. Specific binding of [125I]cationized bovine serum albumin to THP-1 macrophages in vitro was 11-16 fold greater than for native albumin. Half-maximal inhibition of [125I]cationized albumin binding was observed at 10-7M ligand. The specificity of [125I]cationized bovine serum albumin binding and uptake was further studied in terms of competitive inhibition of proteolysis by proteins of varying charge content. Cationized bovine serum albumin, but not native albumin, inhibited proteolysis of [125I]cBSA. Calf thymus histones also inhibited cBSA degradation. High concentration of myelin basic protein was moderately effective at blocking cBSA degradation, while myoglobin and beta lactalbumin showed no inhibition. These results indicate that specific cell-surface binding sites which occur on macrophages may mediate selective uptake of certain proteins with highly charged domains including some autoantigens.

Topics: Binding, Competitive; Cations; Cell Membrane; Electrochemistry; Endopeptidases; Ferritins; Histones; Humans; Isoelectric Point; Leukemia; Macrophages; Myelin Basic Protein; Serum Albumin, Bovine; Tumor Cells, Cultured

Topics: Animals; Antigens, Neoplasm; Asthma; Cell Migration Inhibition; Diagnostic Errors; Electrophoresis; Female; Guinea Pigs; Humans; Influenza, Human; Leukemia; Lymphocytes; Macrophages; Male; Multiple Sclerosis; Myasthenia Gravis; Myelin Basic Protein; Neoplasm Proteins; Neoplasms; Sarcoidosis