Update: B-Cells in Rheumatic Disease
Volume 7 | July 1, 2007 - September 30, 2007
Return to B-Cell Literature Review Index
Highest Rated Articles
One of the leading lupus B-cell immunobiology group describes rituximab-induced altered patterns in blood and tonsillar B-cell subset distribution, which they assert may correlate with clinical response status. These studies were performed after long-term follow-up of patients from a previously reported small phase I/II trial in patients with SLE who received three different regimens of rituximab infusions. After disregarding several patients from further analysis due to atypical baseline B-cell subset profiles or for inadequate rituximab treatment, the authors contend that they found evidence that persistent delays in recovery of pre-treatment levels of B-cell memory populations (ie, CD27+ and others) in blood and tonsillar biopsies correlates with (or is a biomarker for) prolonged clinical response. These hopeful analyses of a very limited number of patients (with likely bias in patient selection) are interpreted as evidence that anti-CD20 therapy may at times reset the balance within the B-cell compartment to an earlier pre-disease state. This hypothesis and the state-of-the-art analytic approach will no doubt be tested in larger randomized trials.
Dass S, Vital EM, Emery P. Development of psoriasis after B cell depletion with rituximab. Arthritis Rheum 2007;56(8):2715-8.
This retrospective anecdotal case series describes three very different rheumatic patients who received standard doses of rituximab along with IV cyclophosphamide that newly developed biopsy-proven psoraiform lesions at the time of maximal B-cell depletion. This limited report raises the question of whether there are functional contributions of B cells, or their antibody products, that aid homeostasis to prevent the initiation phase of cutaneous psoriasis in some predisposed individuals. While neither B cells nor local immunoglobulin deposition are common components of these cutaneous lesions, synovial B-cell infiltrates are often seen in psoriatic arthritis. This report may therefore herald that current trials in psoriatic arthritis will show a dissociation of clinical responses to rituximab for skin and joint disease activity.
Ng KP, Cambridge G, Leandro MJ, Edwards JC, Ehrenstein M, Isenberg DA. B cell depletion therapy in systemic lupus erythematosus: long-term follow-up and predictors of response. Ann Rheum Dis 2007;66(9):1259-62.
Long-term follow-up (3-78 months) is described for the largest reported open trial of refractory SLE patients, who received treatments with a total dose of 1 gm rituximab. Most also received “Euro” doses of IV cyclophosphamide (dose?), along with different regimens of substantial corticosteroid regimens. While all of the 30/32 evaluable patients had some level of beneficial clinical responses, five patients flared in less than 6 months, nine flared in 6 to 12 months, and four flared in 12 to 28 months; the remaining 12 patients had sustained clinical benefits for 9 to 73 months after a single course of therapy. A baseline positive test for Extractable Nuclear Antigens (ie, Ro, La, RNP or Sm) and low C3 significantly correlate with earlier disease flare. Four serious adverse effects were seen in these generally very challenging patients, which suggested an attractive safety profile in light of their refractory clinical histories. While clinical response rates were impressive, these co-treatment regimens differ from reported phase I/II American trials, as well as with randomized controlled trials now in progress.
