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Articles by R. S Abraham
Total Records ( 2 ) for R. S Abraham
  F. C Fervenza , R. S Abraham , S. B Erickson , M. V Irazabal , A Eirin , U Specks , P. H Nachman , E. J Bergstralh , N Leung , F. G Cosio , M. C Hogan , J. J Dillon , L. J Hickson , X Li , D. C Cattran and for the Mayo Nephrology Collaborative Group
 

Background and objectives: It was postulated that in patients with membranous nephropathy (MN), four weekly doses of Rituximab (RTX) would result in more effective B cell depletion, a higher remission rate, and maintaining the same safety profile compared with patients treated with RTX dosed at 1 g every 2 weeks. This hypothesis was supported by previous pharmacokinetic (PK) analysis showing that RTX levels in the two-dose regimen were 50% lower compared with nonproteinuric patients, which could potentially result in undertreatment.

Design, setting, participants, & measurements: Twenty patients with MN and proteinuria >5 g/24 h received RTX (375 mg/m2 x 4), with re-treatment at 6 months regardless of proteinuria response. PK analysis was conducted simultaneously with immunological analyses of T and B cells to ascertain the effect of RTX on lymphocyte subpopulations.

Results: Baseline proteinuria of 11.9 g/24 h decreased to 4.2 and 2.0 g/24 h at 12 and 24 months, respectively, whereas creatinine clearance increased from 72.4 ml/min per 1.73 m2 at baseline to 88.4 ml/min per 1.73 m2 at 24 months. Of 18 patients who completed 24-month follow-up, 4 are in complete remission, 12 are in partial remission, 1 has a limited response, and 1 patient relapsed. Serum RTX levels were similar to those obtained with two doses of RTX.

Conclusions: Four doses of RTX resulted in more effective B cell depletion, but proteinuria reduction was similar to RTX at 1 g every 2 weeks. Baseline quantification of lymphocyte subpopulations did not predict response to RTX therapy.

  N. S Zuckerman , K. J McCann , C. H Ottensmeier , M Barak , G Shahaf , H Edelman , D Dunn Walters , R. S Abraham , F. K Stevenson and R. Mehr
 

Follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL) and primary central nervous system lymphoma are B cell malignancies. FL and DLBCL have a germinal center origin. We have applied mutational analyses and a novel algorithm for quantifying shape properties of mutational lineage trees to investigate the nature of the diversification, somatic hypermutation and selection processes that affect B cell clones in these malignancies and reveal whether they differ from normal responses. Lineage tree analysis demonstrated higher diversification and mutations per cell in the lymphoma clones. This was caused solely by the longer diversification times of the malignant clones, as their recent diversification processes were similar to those of normal responses, implying similar mutation frequencies. Since previous analyses of antigen-driven selection were shown to yield false positives, we performed a corrected analysis of replacement and silent mutation patterns, which revealed selection against replacement mutations in the framework regions, responsible for the structural integrity of the B cell receptor, but not for positive selection for replacements in the complementary determining regions. Most replacements, however, were neutral or conservative, suggesting that if at all selection operates in these malignancies it is for structural B cell receptor integrity but not for antigen binding.

 
 
 
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