Baseline autoantibody profiles predict normalization of complement and anti-dsDNA autoantibody levels following rituximab treatment in systemic lupus erythematosus.

B cells are thought to play a major role in the pathogenesis of systemic lupus erythematosus (SLE). Rituximab (RTX), a chimeric anti-CD20 mAb, effectively depletes CD20( +) peripheral B cells. Recent results from EXPLORER, a placebo-controlled trial of RTX in addition to aggressive prednisone and immunosuppressive therapy, showed similar levels of clinical benefit in patients with active extra-renal SLE despite effective B cell depletion. We performed further data analyses to determine whether significant changes in disease activity biomarkers occurred in the absence of clinical benefit. We found that RTX-treated patients with baseline autoantibodies (autoAbs) had decreased anti-dsDNA and anti-cardiolipin autoAbs and increased complement levels. Patients with anti-dsDNA autoAb who lacked baseline RNA binding protein (RBP) autoAbs showed increased complement and decreased anti-dsDNA autoAb in response to RTX. Other biomarkers, such as baseline BAFF levels or IFN signature status did not predict enhanced effects of RTX therapy on complement or anti-dsDNA autoAb levels. Finally, platelet levels normalized in RTX-treated patients who entered the study with low baseline counts. Together, these findings demonstrate clear biologic activity of RTX in subsets of SLE patients, despite an overall lack of incremental clinical benefit with RTX in the EXPLORER trial.

Subgroups of luteinizing hormone-releasing hormone perikarya defined by computer analyses in the basal forebrain of intact female rats.

The hypothesis that the basal forebrain population of LHRH perikarya is composed of heterogeneous subgroups was examined in this study. We used three-dimensional computerized reconstruction to examine populations of LHRH-immunopositive neurons detected in noncolchicine treated cycling female rats. Perikarya were detected with two antisera capable of detecting LHRH decapeptide within larger mol wt species, i.e. Millar's (RM) 1076 and Arimura's (AA) 419. No immunopositive perikarya were detected with antiserum AA 422, which requires the fully processed decapeptide for binding. A more broadly distributed population of LHRH neurons was detected in females killed on proestrus than in females killed on estrus or the other days of the cycle. These relationships were observed with both antisera, RM 1076 and AA 419. Subgroups of cells were clearly defined when the population of LHRH neurons detected on proestrus was simultaneously displayed with the population detected on estrus. Strikingly similar subgroups were revealed by simultaneous displays of populations of LHRH neurons detected by the antisera RM 1076 and AA 419 in proestrous females. This study revealed a three-dimensional onion skin-like laminar organization of LHRH subgroups expanding from the ventricle outward laterally and from the diagonal band of Broca to the hypothalamus caudally. We propose that these subgroups vary in their metabolic activity of biosynthesis, processing, transport, or release of LHRH in relation to the proestrous preovulatory release of LH.