RESEARCH - CD19: a promising B cell target for RA

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Nat Rev Rheumatol. 2009 Oct;5(10):572-7.

CD19: a promising B cell target for rheumatoid arthritis.

Tedder TF.

Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.

B-cell depletion with unconjugated CD20 monoclonal antibody (mAb) is

used to treat rheumatoid arthritis and other autoimmune diseases.

CD20-targeted immunotherapy depletes mature B cells through

monocyte-mediated antibody-dependent cellular cytotoxicity, but does

not effectively deplete pre-B or immature B cells, certain peripheral

B cell subpopulations, most antibody-producing cells, or their

malignant counterparts. As immature B cells expressing autoreactive

antigen receptors are not depleted by anti-CD20 mAb, a new strategy

for eliminating autoantigen-selected B cells and for treating early

lymphoblastic leukemias and/or lymphomas was developed using

CD19-specific mAbs that induce Fcgamma receptor-dependent and

monocyte-dependent B-cell depletion. Preclinical studies using

transgenic mice expressing human CD19 have shown that pre-B cells and

their malignant counterparts, as well as pre-existing

antibody-producing and autoantibody-producing cells, are depleted.

Therefore, CD19-directed immunotherapy is expected to treat diverse

pre-B-cell-related and plasmablast-related malignancies, and humoral

transplant rejection. Moreover, in contrast to CD20-directed

immunotherapies, CD19 mAbs could purge the B cell repertoire of

autoreactive clones and reset the developmental clock to a point that

curtails the extent of emerging self-reactivity, in addition to

reducing autoreactive T-cell activation through the elimination of

mature B cells. Humanized CD19 mAbs are expected to enter clinical

trials in 2009, offering a new approach for the treatment of

autoimmune disease that removes both immature B cells and antibodies

with autoreactive specificities. CD19-directed immunotherapy could,

therefore, offer a new horizon in B-cell depletion for the treatment

of multiple autoimmune diseases.

PMID: 19798033

http://preview.ncbi.nlm.nih.gov/pubmed/19798033

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