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Transplantation
Targeting B Cells with Rituximab – A Novel Therapy for
Renal Disease and Transplantation
a report by
Alan D Salama
Senior Lecturer and Honorary Consultant Physician, Renal Section, Division of Medicine, Imperial College London and Hammersmith Hospital
Targeting specific limbs of the immune response known to be involved rituximab as induction therapy in active (SLE), antineutrophil
in the pathogenesis of autoimmunity or transplant rejection is a logical cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and numerous
means of managing these conditions. For example, using agents such as aspects of transplantation, which over the next few years should
anti-CD25 monoclonal antibodies or calcineurin inhibitors (CNIs) to establish its true benefit.
inhibit the alloreactive effector T cells (expressing the CD25 molecule) in
transplantation, or using antiproliferative agents that target both T and Biology of Rituximab
B lymphocytes implicated in the pathogenesis of systemic lupus Rituximab targets the CD20 antigen expressed on immature and
erythematosus (SLE), has proved to be a highly effective treatment mature B cells, as well as on malignant B cells (hence its original use in
strategy. Recently, the use of rituximab (a chimeric monoclonal the treatment of non-Hodgkin’s lymphoma). It is a chimeric
antibody) in targeting CD20-expressing B cells has gained considerable monoclonal antibody made up of mouse heavy and light chain variable
popularity in the treatment of autoimmune renal disease and in the regions, directed against human CD20, on the backbone of a human
treatment of transplant pre-conditioning and rejection. This is due to immunoglobulin (Ig)G1 constant region (see Figure 1). As CD20
the general tolerability of the drug and the low complication rate engagement mediates B-cell proliferation and differentiation,
following its administration. Interestingly, as a result of using this agent rituximab therapy prevents B-cell expansion and results in B-cell
we are beginning to understand more about the pathogenesis of a
number of these disorders, which in turn should lead to other significant
therapeutic advances. The critical and central role B cells appear to play
Rituximab is generally well tolerated.
in immune-mediated conditions has become more obvious and the
Adverse effects are most commonly
relative contributions of humoral and cellular immune effectors at
different stages of disease have been emphasised. Rituximab has now related to the infusion and are mild.
been used in diverse immunological renal conditions (see Table 1), as
Moreover, these generally disappear
well as in transplantation as a means of de-sensitisation or in the
treatment of an antibody-mediated rejection processes.
with repeated dosing.
In this article I will summarise the biology of this compound, its
potential utility in kidney diseases and its place in our therapeutic depletion through apoptosis and lysis by complement-dependent and
arsenal. It should be emphasised that, to date, no randomised clinical -independent mechanisms. B-cell depletion generally persists for six to
trials of this compound in autoimmune renal disease or transplantation nine months in more than 80% of patients,
1
although the degree of
have been completed and all reports regarding its efficacy in these depletion is highly variable and is in part dependent on FcγR
settings have been from uncontrolled cohort studies. It has now been polymorphisms as well as antibody concentration.
2
This is important as
firmly established that it can be used in these settings as salvage recent data have suggested that in certain proteinuric states the
therapy. However, the trial data are urgently required for us to duration of B-cell depletion may be shortened, perhaps as a result of
understand how best to use it and to compare it with conventional urinary antibody loss (Fervenza F, American Society of Nephrology
induction or maintenance regimens. There are ongoing trials using (ASN), 2006). The ideal dosing schedules for different conditions have
not been established, although data from our own co-operative
studies (in ANCA vasculitis) have suggested that, at least for some
Alan D Salama is a Senior Lecturer at Imperial College and
an Honorary Consultant at Hammersmith Hospital working in
autoimmune diseases, no difference in efficacy exists between the
the West London Renal and Transplant Centre. Previously, he traditional (non-Hodgkin’s lymphoma) protocol and the two-dose
spent time at The Brigham and Women’s Hospital, Harvard
schedule used in SLE and AAV (Jones R, personal communication).
Medical School, completing post-doctoral research. He
continues to participate in research, leading a group
Whether efficacy in proteinuric states is compromised as a result of
investigating the cause and treatment of systemic vasculitis
briefer periods of B-cell depletion remains to be established.
and autoimmune glomerulonephritis. His clinical interests are
pre-dialysis care, transplantation and glomerulonephritis. Dr
Salama’s PhD, on the immunology of antiglomerular basement membrane (GBM) disease, was Adverse Effects
completed at the Royal Postgraduate Medical School at Hammersmith Hospital. He trained in
Rituximab is generally well tolerated. Adverse effects are most commonly
internal medicine and nephrology in London after training in medicine at Oxford University and
the Royal London Hospital, graduating with honours.
related to the infusion and are mild. Moreover, these generally disappear
with repeated dosing. Infections are the next most common problem, but
E: a.salama@imperial.ac.uk
there does not seem to be an increased incidence of tuberculosis (TB),
62 © TOUCH BRIEFINGS 2007
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