Shared early autoantibody recognition events in the development of anti-SmB/B ' in human lupus

Many aspects of the immune maturation are uncharted. For ordinary human aut oimmune systems there are no complete descriptions of the progression from an initial antigenic epitope to a maximally complex immune response. In thi s study we have exploited a large serial collection of human sera to invest igate the development of the anti-Sm autoimmune response in systemic lupus ertythematosus (SLE). The results suggest a similar, if not virtually ident ical, stepwise progression in the early humoral immune maturation of anti-S m. The amino acid sequence PPPGMRPP comprises the first epitope in the anti -Sm B/B' response and its close relative, PPPGMRGP, the second. Epitopes ar e subsequently enlarged by the incorporation of neighbouring amino acids. T he third and fourth epitopes are also recognised by an antibody in a nearly identical sequence in different lupus patients. A column absorption with P PPGMRPP demonstrates that the epitope spreading among the first four early epitopes appears to occur by the sequential generation of crossreactive ant ibodies. Unexpectedly, epitope spreading in this system occurs in a predict able fashion by involving essentially the same sequence of antigenic struct ures from person to person. In addition, these data support the lupus anti- Sm antibodies originating against a single antigenic structure and, hence, strongly support a unifying mechanism in the generation of these autoantibo dies.