Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


BAFF Binding Receptors (BBR) Related To Relapse after Rituximab in Patients with Reumatoid Arthritis (RA).

Torre1,  Inmaculada De la, Valor1,  Lara, Moura2,  Rita, Leandro3,  Maria J., Edwards3,  Jonathan C. W., Cambridge3,  Geraldine

Hospital Gregorio Maranon, Madrid, Spain
Instituto de Biologia Molecular, Lisboa, Portugal
University College London, London, UK

Background:

Coordinated expression of BBR (BAFF-R, TACI, BCMA) control differentiation of B cells into immunoglobulin (Ig) secreting cells. We have previously shown that i) BAFF levels increase after B cell depletion with rituximab (rtx) in patients with RA, remaining raised even after B cell return ii) BAFF-R expression in naïve (NB) and memory B (MB) cells is reduced after rtx and related to clinical relapse independently of circulating BAFF levels or time to relapse after B cell return. iii) Class-switch recombination (CSR) and autoantibody production is also related to clinical relapse after rtx. When B cells differentiate into Ig secreting cells, BAFF-R is lost and BCMA up-regulated. TACI is induced upon B cell activation. Although it can be expressed on activated NB cells (<25%) it is related to CSR and memory-plasma cell differentiation.

Aim:

To investigate BBR expression in relation to B cell maturation and clinical relapse in RA patients after rtx.

Methods:

Phenotypic analysis of BAFF-R, TACI and BCMA expression on PBMC were performed using combinations of CD19, CD27, CD38 and IgD (% and mean fluorescence intensity-MFI) in normal controls (NC) (n: 5) and patients pre (n: 10) and after rtx, classified as concordant ie relapsing at B cell repopulation (C-R, n: 16), or discordant relapsing > 3 months after repopulation (D-R, n: 10) or non-relapsing after B cell return (D-NR, n: 11).

Results:

Mean % of NB cell BAFF-R+ was significantly lower only in patients relapsing (C-R: 65.3%, D-R: 89.7%) when compared to NC (p=0.027,p=0.026). Percentage and MFI of MB cell BAFFR+ was significantly lower in all patients when compared to both NC and pre-rtx (%: p<0.05, MFI: p<0.005). In patients relapsing, % NB cell TACI+ tended to be higher in C-R than D-R (23.4% vs 9.9%). All patients pre and after rtx had significantly lower % of MB cell TACI+ when compared to NC (p<0.05). However % of MB cell TACI+ was significantly higher in D-NR when compared to D-R (p=0.001).

 BAFFR Naïve B cellsBAFFR Memory B cellsTACI Naïve B cellsTACI Memory B cells
 %MFI%MFI%MFI%MFI
NC (n:5)98.512695.43107.616.2206.581.5155.7
Pre (n:10)93.4082.883.579.413.562.1#50.4#65.3#
C-R (n:16)65.3#/*45.3#/*44.6#/*51.7#/*23.460.4#43.6#67.6#
D-R (n:10)89.7#/**60.9#63.2#/*57.5#/*9.973.2#38.9#/*77.2#
D-NR (n:11)92.0347.6#63.8#/*56.7#/*18.171.4#49.8#/***83.5#/***
P < 0.05:
#vs NC
*vs Pre
**vs CR
***vs DR

BAFF-R and BCMA did not always had an inverse correlation in plasma cells population after rtx. Finally, C-R patients had higher % of plasma cells than D-R and D-NR (16.5 vs 2.06 and 1.85; p=0.03 and p=0.06).

Conclusions:

Rises in autoantibody levels have been related to clinical relapse after rtx. Modulation of BBR expression permissive to plasma cell formation in C-R patients with an earlier down regulation of BAFF-R and up regulation of TACI on (presumably activated autoreactive) NB cells may explain clinical relapse closer to B cell return. Normal BAFF-R expression on NB cells from D-NR patients may reduce the chance of becoming Ig-producing cells, allowing a normal maturation process within germinal center reactions. The consequences of disturbed BBR expression on B cell selection and the advancement or inhibition of progression to autoantibody production may explain timing of relapse after rtx.

To cite this abstract, please use the following information:
Torre, Inmaculada De la, Valor, Lara, Moura, Rita, Leandro, Maria J., Edwards, Jonathan C. W., Cambridge, Geraldine; BAFF Binding Receptors (BBR) Related To Relapse after Rituximab in Patients with Reumatoid Arthritis (RA). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :739
DOI: 10.1002/art.28507

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