Cd19

Marker for: B cells, not expressed on plasma cells.

Structure: Membrane glycoprotein (95 kDa).

Note: CD19 is involved in B cell development, activation and differentiation. CD19 is expressed by all neoplastic B cells.

Application: FACS, IHC (P) (G), IF

Normal values:

• 1st year 500 - 1.500/µl
• in the 2nd - 6th year between 700 - 1.300/µl
• in the 7th - 17th year between 300 - 500/µl
• from the 18th year between 105 - 620/µl

(see also below) Cluster of differentiation

CD19 is a member of the immunoglobulin superfamily of proteins expressed on the surface of B cells at most stages of their development, where it functions as a critical component of the B cell receptor-signaling complex (Depoil D et al 2008). CD19 is an ideal target for CAR-targeted therapies because it is expressed on most malignant B cells (including CLL, B-ALL, and many NHL), is not expressed on hematopoietic stem cells, and elimination of all CD19+ B cells in the body is a manageable on-target treatment effect (Scheuermann RH et al.1995).

A potential disadvantage of CD19 as a target is that its surface expression is not required for maintenance of the tumorigenic phenotype, and escape variants have been noted (Maude SL et al. 2014; Evans AG et al. 2015). Although not the first to be studied, CAR T-cell therapies directed against CD19 are the most mature to date (Kochenderfer JN et al. 2009). Second-generation CAR with are selected CD3ζ- and 4-1BB-stimulating domains, which is produced with a lentiviral transduction system .

Indications for anti-CD19 CAR T-cell therapy include B-cell non-Hodgkin lymphoma (Abramson JS 2020).

It is known that autoreactive B cells play a key role in the development of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. B-cell-depleting monoclonal antibodies such as rituximab have low therapeutic efficacy in autoimmune diseases (persistence of autoreactive B cells in lymphoid organs and inflamed tissues?). CD19 CAR-T cells have been introduced into autoimmune disease therapy in recent years. CD19 CAR-T cells resulted in rapid and sustained depletion of circulating B cells and complete clinical and serological remission of refractory systemic lupus erythematosus and dermatomyositis (Carney EF 2022; Kambayana G et al. 2023; Schett G et al. 2023).

1. Abramson JS (2020) Anti-CD19 CAR T-cell therapy for B-cell non-Hodgkin lymphoma. Transfus Med Rev 34:29-33.
2. Carney EF (2022) Treatment of SLE with anti-CD19 CAR-T cells. Nat Rev Nephrol 18:743.
3. Curran KJ et al (2012) Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions. J Gene Med 14:405-415.
4. Depoil D et al (2008) CD19 is essential for b cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand. Nat Immunol 9:63-72.
5. Evans AG et al (2015) Evolution to plasmablastic lymphoma evades cd19-directed chimeric antigen receptor T cells. Br J Haematol Epub ahead of print.
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8. Hantschke M et al (2016) Immunohistochemical techniques. In: L. Cerroni et al. Histopathology of the skin. Springer Verlag Berlin-Heidelberg pp 26-33.
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10. Kochenderfer JN et al (2009) Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor. J Immunother 32:689-702.
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14. Mougiakakos D et al (2021) CD19-targeted CAR T cells in refractory systemic lupus erythematosus. N Engl J Med. 5;385: 567-569.
15. Schett G et al (2023) CAR T-cell therapy in autoimmune diseases. Lancet: S0140-6736.
16. Scheuermann RH et al (1995) CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk Lymphoma 18:385-397.
17. Yu YD et al (2021) Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Metastatic Prostate Cancer: A Comprehensive Review. Int J Mol Sci 22: 640.