Περίληψη:
Objective. Autoreactive B cells play a key role in tissue injury in
systemic autoimmune disease, and therefore a treatment resulting in B
cell depletion could have benefit. This open-label study was undertaken
to evaluate the efficacy of the anti-CD20 monoclonal antibody rituximab
in the treatment of lupus nephritis.
Methods. Lupus patients with active proliferative nephritis (4 with
focal disease and 6 with diffuse disease) received rituximab (4 weekly
infusions of 375 mg/m(2)) combined with oral prednisolone. Clinical,
laboratory, and immunologic responses, including peripheral lymphocyte
subsets measured by flow cytometry, were prospectively assessed at
monthly intervals for 12 months. Complete remission of nephritis was
defined as normal serum creatinine and albumin levels, inactive urine
sediment, and 24-hour urinary protein <500 mg. Partial remission was
defined as >50% improvement in all renal parameters that were abnormal
at baseline.
Results. B cell depletion lasted from I month to 7 months and was well
tolerated. Partial remission was achieved in 8 of 10 patients within a
median of 2 months (range 1-4 months); in 5 of them, complete remission
was subsequently established (at a median of 3 months from baseline),
and it was sustained at 12 months in 4.As early as I month from
baseline, the expression of the costimulatory molecule CD40 ligand on
CD4+ T cells was decreased by 4-fold, and it was almost blocked when
partial remission was clinically evident. The expression of T cell
activation markers CD69 and HLA-DR was significantly decreased at time
points when partial remission was observed, and was further decreased
during complete remission. In contrast, in patients who did not exhibit
a response or when relapse was detected in patients in whom an initial
remission had been achieved, such decreases were not prominent. Serum
concentrations of double-stranded DNA autoantibodies were decreased in
all patients, regardless of clinical outcome.
Conclusion. Following B cell depletion, clinical remission of lupus
nephritis is associated with a decrease in T helper cell activation,
suggesting an additional role for B cells, independent of autoantibody
production, in promoting disease. A controlled trial to confirm these
promising clinical results is warranted.
Συγγραφείς:
Sfikakis, PP
Boletis, JN
Lionaki, S
Vigklis, V and
Fragiadaki, KG
Iniotaki, A
Moutsopoulos, HM
