A CD21 low phenotype, with no evidence of autoantibodies to complement proteins, is consistent with a poor prognosis in CLL.

Nichols, Eva-Maria, Jones, Rachael, Pepper, Chris J, Fegan, Chris and Marchbank, Kevin J (2015) A CD21 low phenotype, with no evidence of autoantibodies to complement proteins, is consistent with a poor prognosis in CLL. Oncotarget, 6 (32). pp. 32669-32680. ISSN 1949-2553

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Abstract

B-cell chronic lymphocytic leukemia (CLL) is characterized by differential BCR
signaling and autoimmune complications. Complement modulates B-cell function
via C3d and CD21 cross-linked to the B-cell receptor (BCR). We hypothesized that
CD21 contributes to BCR signaling and participates in the autoimmunity associated
with CLL. We analyzed CD21 expression on 106 CLL patient samples and matched
serum from 50 patients for the presence of soluble CD21 and autoantibodies to CR2,
CR1, MCP and FH. CD21 expression on CLL B-cells was significantly lower than that
expressed on B-cells from age-matched controls (P < 0.0001) and was inversely
correlated with soluble CD21 (r2 = –0.41). We found no evidence of autoantibody to
any complement regulator. Low CD21 expression correlated to prognostic subsets
of CLL patients, i.e. cases with unmutated IGHV genes (P = 0.0006), high CD38
(P = 0.02) and high ZAP70 expression (P = 0.0017). Low CD21 expression was
inversely correlated to the levels of phosphotyrosine induced in CLL cells following
BCR ligation with αIgM (r2=–0.21). Importantly, lower CD21 expression was also
predictive for reduced overall survival (P = 0.005; HR = 2.7). In conclusion, we
showed that reduced expression of CD21 on CLL B-cells appears functionally relevant
and was associated with poor clinical outcomes.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Depositing User: Gemma Hamilton
Date Deposited: 10 Jan 2018 12:06
Last Modified: 10 Jan 2018 12:06
URI: http://sro.sussex.ac.uk/id/eprint/72715

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