Analysis of the novel gene identified using a SEREX method in the senrm of bone marrow failure patients

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To identify novel autoantibodies in acquired aplastic anemia (AA), we screened the sera of patients with AA for the presence of antibodies (Abs) which recognize proteins derived from a normal bone marrow mononuclear cells. Immunoblotting using SEREX method revealed the presence of IgG Abs specific to ZNF292 (also known as IUAA0530, Zn-16) protein. This gene maps on chromosome 6, at 6q15 and contains 8 exons. Complete mRNA is 10610bp long. Northern blot analysis revealed that the gene strongly express in placenta, testis, prostate and thyroid gland, and weak expression is detected in heart, brain, spleen, thymus, adrenal gland, skeletal musde and peripheral lymphocytes. This gene encodes a protein which contains 7 zinc finger, C2H2-type domains. The protein binds to an evolutionarily conserved sequence in the growth hormone gene required for effective Pit-1-dependent activation of this promoter in vivo. The antibody recognized region contained zinc finger motifs which were recognized for the binding for promoter of GH gene. In 7 of 25 AA patients, an immunoglobulin G (IgG) antibody response was detected to ZNF292 gene. Intriguingly, antibody response was detected in 5 out of 9 AA patients with HLA DRB1*1501, and in only 1 out of 11 AA patients without HLA DRB1*1501. We also tried to identify the peptide sequences to activate CD8+ cytotoxic T cells(CIL). We could identify the surrogate peptides which supposed to bind HLA A2402, but we failed to identify the real peptide which had a potential to activate CILs.