Autoantibodies specific to hnRNP K: a new diagnostic marker for immune pathophysiology in aplastic anemia.

To identify a new diagnostic marker for the immune pathophysiology of aplastic anemia (AA), we screened sera of immune-mediated AA patients for the presence of antibodies (Abs) specific to proteins derived from a leukemia cell line UT-7 using two-dimensional electrophoresis followed by immunoblotting. The target proteins were identified by peptide mass fingerprinting. Heterogeneous nuclear ribonucleoprotein (hnRNP) K was identified as a novel autoantigen. An enzyme-linked immunosorbent assay revealed high titers of anti-hnRNP K Abs in 85 (31%) of 273 patients with AA. Sixty-four patients received antithymocyte globulin and cyclosporine after undergoing screening for anti-hnRNP K Ab, anti-DRS-1 Ab, anti-moesin Ab, and paroxysmal nocturnal hemoglobinuria (PNH)-type cells. Twenty (87%) of 23 patients with the presence of anti-hnRNP K Abs responded to the immunosuppressive therapy (IST), while 19 (46%) of 41 patients without the presence of anti-hnRNP K Abs responded. A multivariate analysis showed only PNH-type cells and anti-hnRNP K Abs to be significant factors for the prediction of a good response to IST. The detection of anti-hnRNP K Abs as well as PNH-type cells may therefore be useful for diagnosing the immune pathophysiology of AA.