Studies of the humoral effects of the Prosorba column were conducted in conjunction with the Phase 3 trial of Prosorba versus sham therapy for rheumatoid arthritis (RA). When perfused with normal human plasma in vitro, Prosorba bound predominantly IgG with a maximal capacity of approximately 462 g of Ig per Prosorba column, equal to about 1.5% of circulating IgG. Prosorba treatment did not alter the concentrations of albumin, IgG, IgM, and IgA in 3 RA patients, except for a small dilutional effect. Kinetic studies demonstrated that Prosorba removed IgG > IgM, IgA, and IgM rheumatoid factor (RF) during the initial moments of apheresis and almost exclusively IgM RF after 15 min. No net protein removal occurred at ജ60 min. Mean values of circulating immune complexes (CICs) were not significantly decreased by 12 weekly treatments. Complement was activated by the apheresis system upstream of the Prosorba column without changing C3 or C4 levels. We conclude that the Prosorba mechanism of action in RA is not bulk removal of Ig, but might involve modification of the CIC repertoire and could include, but not be limited to, effects related to complement activation.

Previous studies conclude that the repertoire of B-1a (CD5+ B) cells is highly restricted. Studies here, which use FACS sorting and single-cell PCR methodology to develop an unbiased representation of the IgH repertoires of B-1a, B-1b, and conventional B cells from the peritoneal cavity, demonstrate that the B-1a cell repertoire is more diverse than previously thought. Furthermore, adult B-1a cells have significantly fewer noncoded nucleotide (N) insertions than conventional B cells. However, B-1a cells are not defined by the absence of these regions, since such insertions are present in two-thirds of B-1a cell transcripts. All three B cell populations use a wide spectrum of V(H), D, and J(H) elements and display considerable diversity in complementarity-determining region 3 (CDR3). However, characteristic differences in the repertoires of all three B cell populations also exist, suggesting different selective and/or developmental forces act to shape each repertoire.

Antibodies to human myeloperoxidase and cathepsin G have been detected in the serum of some patients with systemic lupus erythematosus. Therefore, the presence of antibodies to human myeloperoxidase and cathepsin G was examined in glomerular immune deposits. Glomerular basement membrane fragments were prepared from renal tissues obtained at autopsy from 19 patients with systemic lupus erythematosus. IgG was extracted from the glomerular basement membrane fragments and tested with sensitive immunoassays for antibodies to myeloperoxidase and cathepsin G. Antibodies to cathepsin G were not detected in the extracts but antibodies to human myeloperoxidase were found in extracts of one specimen. In the extract with 6M guanidine hydrochloride these antibodies were enriched 103-fold, compared to the initial supernatant of glomeruli, which served as a serum surrogate. The recovered antibodies to myeloperoxidase accounted for 12% of the recovered IgG. These findings add autoantibodies to human myeloperoxidase to the list of antibodies that have been shown to be present in glomerular immune deposits of patients with lupus glomerulonephritis.