All patients with systemic lupus erythematosus (SLE) demonstrated two classes of newly synthesized DNA in sucrose density gradients of PHA (phytohemagglutinin)-stimulated lymphocytes: a large-molecular-weight fraction that comigrates with control DNA and an excess low-molecularweight DNA (LMW-DNA) fraction not found in control lymphocytes. Excess LMW-DNA was independent of disease activity or drug therapy. LMW-DNA and serologic abnormalities were studied in a four-generation family in which two first cousins had SLE. Excess LMW-DNA was found in the cousins with SLE, sibling parents of the SLE patients, a common grandparent, four of nine siblings of one patient, and five of seven at risk children. Both males and females had excess LMW-DNA. Male-male transmission was observed. The expression of excess LMW-DNA in stimulated lymphocytes is inherited as an autosomal dominant genetic trait in this family. All unaffected adult family members with the marker had positive antinuclear antibodies (ANAs) except the grandmother. However, none of the five children with excess LMW-DNA showed positive ANAs. Excess LMW-DNA precedes the appearance of ANAs when found in children of adults with excess LMW-DNA, and may be a predisposing factor in the development of the immunologic responses of systemic lupus erythematosus.
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