Cell cycle-associated autoantibodies: markers for autoimmunity and probes for molecular cell biology

Antinuclear autoantibodies are useful diagnostic markers for systemic autoimmune diseases and as probes for the molecular cell biology of nuclear proteins. Here, we review a subset of autoantibodies to nuclear and cytoplasmic proteins involved in the cell cycle. We propose a classification of these autoantibodies into S-phase (DNA Synthesis) and M-phase (Mitosis) autoantibodies. S-phase autoantibodies are represented by autoantibodies to PCNA (Proliferating Cell Nuclear Antigen), the auxiliary protein of DNA polymerase delta. M-phase autoantibodies are represented by autoantibodies to mitotic spindle components viz. centrosomes, condensed chromosomes, centromeres, mitotic spindle proper and intercellular bridge. We have included autoantibodies to nuclear lamins as M-phase autoantibodies as lamins play a key role in reversible breakdown and reformation of nuclear membranes during mitosis. The usefulness of these autoantibodies as diagnostic markers in systemic autoimmune disease is tempered by their presence in patients with "atypical" autoimmune diseases and in normal individuals. However, as molecular probes, they have proven to be unique and invaluable tools for shedding new light on the workings of the cell cycle.