Multiple nuclear dot antinuclear antibody in patients without primary biliary cirrhosis

Multiple nuclear dot (MND), or pseudocentromere, anti-nuclear antibody (ANA) is an uncommon pattern associated primarily with primary biliary cirrhosis (PBC) and anti-mitochondrial antibody (AMA). A 53 kDa antigen with an apparent molecular mass of 100 kDa as found on sodium dodecyl sulphate-polyacrylamide gel electrophoresis is thought to be responsible for the uncommon pattern. This study analyzes sera from 21 patients without PBC or AMA that produced the uncommon MND ANA immunofluorescence pattern. Diseases present include lupus, rheumatoid arthritis and scleroderma. On immunoblotting nineteen of 21 (91%) bound a 70 kDa protein. Western blot analysis showed that this nuclear antigen was different from pyruvate dehydrogenase, p80 coilin and the antigen responsible for MND ANA in those with PBC. Affinity purified anti-70 kDa reproduced the MND ANA immunofluorescence pattern. Thus, the MND ANA in patients without PBC/AMA is associated with binding to a 70 kDa nuclear protein and not with a 53 kDa antigen (that runs at 100 kDa) found in those with MND and PBC/AMA. The data demonstrate the MND antigen without PBC/AMA is immunologically distinct from the pattern when found with PBC/AMA.