In the present study, B-lymphocyte counts in peripheral blood were recovered in all patients after end of follow-up, and possible mechanisms for sustained clinical responses are not obvious. Pilot immunophenotyping analyses of B-cell subsets (naïve versus memory versus transitional versus plasmablasts) after B-cell regeneration (i.e. at 36-40-44 months follow-up) are in progress, aiming to investigate possible differences between sustained responders, patients with partial or complete relapse, and non-responders.
The relationships between rituximab treatment, B-cell depletion, B-cell subsets and clinical responses have been studied in rheumatoid arthritis (RA) [
16]. An increased fraction of memory cells was detected in those with early relapses [
17]. In B-cell depletion naïve RA-patients, low levels of CD27+ memory B-cells may predict later response to rituximab treatment [
18]. Rituximab targets short-lived autoreactive plasma cells more consistently than the more long-lived protective plasma cells [
19,
20]. In systemic lupus (SLE), B-cell clones producing autoantibodies had a more rapid turnover than B-cells producing protective antibodies [
21], making autoreactive B-cells more vulnerable to rituximab treatment.