Because granulocytes isolated from human SLE patients had alterations in neutrophil nuclear morphology that resembled the Pelger-Huet anomaly, and had prominent mis-splicing of mRNA encoding the nuclear membrane protein lamin B receptor (LBR), consistent with their Pelger-Huet-like nuclear morphology, we used a novel mouse model system to test the hypothesis that a disruption in the structure of the nucleus itself also contributes to the development of lupus autoimmunity.
Because granulocytes isolated from human SLE patients had alterations in neutrophil nuclear morphology that resembled the Pelger-Huet anomaly, and had prominent mis-splicing of mRNA encoding the nuclear membrane protein lamin B receptor (LBR), consistent with their Pelger-Huet-like nuclear morphology, we used a novel mouse model system to test the hypothesis that a disruption in the structure of the nucleus itself also contributes to the development of lupus autoimmunity.
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-molecular-weight DNA (LMW-DNA) fraction not found in control lymphocytes.