B-cell numbers and phenotype at clinical relapse following rituximab therapy differ in SLE patients according to anti-dsDNA antibody levels

Abstract

Objectives. To correlate the kinetics of B-cell repopulation with relapse after B-cell depletion therapy in SLE patients and address whether variation in relapse rate, B-cell numbers and phenotype are related to anti-dsDNA antibody levels.Methods. Sixty-one patients with refractory SLE were treated with a standard rituximab regimen. Clinical and serological measures of disease activity and B-cell numbers were assessed. B-cell phenotype was examined in a subgroup of patients by flow cytometry.Results. Disease relapse was substantially delayed beyond B-cell repopulation, and early relapse was associated with a faster rate of repopulation. At relapse, B-cell numbers were significantly lower than at baseline in patients with high anti-dsDNA antibody levels (>100 IU/ml) but not in patients with low anti-dsDNA antibody levels. Of the patients with high anti-dsDNA antibodies at baseline, levels fell significantly only in those patients who remained in remission after repopulation. Relapse with high anti-dsDNA antibody levels was associated with an increased percentage of IgD−CD27hi plasmablasts, whereas relapse with low anti-dsDNA antibody levels was accompanied by an increased percentage of IgD−CD27− B cells.Conclusion. Anti-dsDNA antibody levels distinguished two patient groups, which differ in their B-cell number and phenotype at relapse following rituximab, and suggest that different B-cell pathologies exist in SLE. The data imply that B-cell numbers should be kept very low for a sustained period in patients with high dsDNA binding, therefore justifying a more aggressive regimen.

Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers

“…Consistent with this, after a single dose of RTX to treat autoimmunity, disease flare and autoantibody production are common after repopulation of the B-cell pool. 42,62,63 Together, our results suggest that additional treatment targeting Tfh may be required to reduce relapse risk following RTX treatment of autoimmune disease or in the setting of antibody incompatible transplantation. For personal use only.…”

Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation

“…Clinical evidence of plasmablast activity has been found in patients with NMO, 60 rheumatoid arthritis 30,61 and systemic lupus erythematosus 37,39,62,63 who receive the B-cell-depleting agent rituximab and are more likely to relapse early if their memory B cells, and more importantly their CD27 high plasmablasts, return earlier. In addition, mRNA from rheumatoid arthritis patients who are non-responsive to rituximab treatment demonstrate increases in mRNA markers of plasmablasts.…”

Assessment of flares in lupus patients enrolled in a phase II/III study of rituximab (EXPLORER)

“…Эти факты можно рассматривать как под-тверждение действия РТМ на аутоиммунный компонент патологического процесса при ИВРЗ. В то же время следу-ет подчеркнуть, что во многих случаях эффективность РТМ не коррелирует со снижением уровня аутоантител [69][70][71] и его эффективность, вероятно, определяется вли-янием препарата на другие компоненты иммунопатогенеза ИВРЗ [72,73]. Действительно, у больных БШ и ССД, не-смотря на хороший клинический эффект, не происходило нормализации уровней специфических для этих болезней аутоантител.…”