Therapeutic administration of Rituximab, a monoclonal antibody against

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Therapeutic administration of Rituximab, a monoclonal antibody against Powered By Docstoc


Ferraro, A J, Drayson, M T,MacLennan, I C M, Savage, C O S
Birmingham University
Therapeutic administration of Rituximab, a monoclonal antibody against CD20, is increasingly used
in ANCA-associated vasculitis. It usually causes profound depletion of all B cell subsets in
peripheral blood, and induction of remission. Falls in serum IgG-ANCA titre typically follow.
Relapse may be preceded by re-emergence of detectable circulating B cells, by re-elevations in
ANCA titre, or both.
A longitudinal study of patients with ANCA-associated vasculitis who were treated with Rituximab
was therefore undertaken to correlate circulating B cell subsets with disease activity. Twenty
patients, who received 23 treatment cycles, were studied over 310 patient-months. CD19+ B cell
subsets were characterised by flow-cytometry according to expression of surface markers including
IgM, IgD, CD20, CD21, CD23, and CD27. All patients became B cell deplete after Rituximab-
based treatment. Thus far, 8 relapses requiring re-treatment have occurred. In four of these, B cells
had become detectable (>5 cells per µl). In a further 8 patients detectable B cell recovery has begun,
but re-treatment has not been necessary. Amongst most of those with detectable B cells IgM +/IgD+
(naïve) and CD27neg cells predominated, though in three patients (two non-relapsers) IgM-/IgD-
(switched) B cells prevailed. In two of these three, returning B cells were also often CD27pos.
Rituximab-induced remission of disease typically precedes falls in serum levels of ANCA, so
alternative mechanisms of remission induction must be considered. In some animal models of
autoimmunity, B cells are required for T cell activation and subsequent disease. Persistent T cell
activation during conventionally induced remission has been reported in ANCA-associated
vasculitis. Thus in the same patient cohort we also studied the effects of B cell depletion on
circulating T cell subsets (according to expression of CD4 & CD8, HLA-DR, CD28, CD45RO, and
CCR7). No significant changes were seen. This may indicate that T cell subsets, at least as defined
by these markers, are unlikely to drive induction of remission and, by implication, disease activity.
In summary, Rituximab effectively induces remission in ANCA-associated vasculitis and depletes
all circulating B cell subsets. However, relapse may occur in the absence of detectable circulating B
cells, perhaps because emergent B cells located within tissues are sufficient or because additional
pathogenic mechanisms are operating.