Reconstitution of the T‐cell repertoire following treatment with alemtuzumab (anti‐CD52 monoclonal antibody) in patients with B‐cell chronic lymphocytic leukaemia

Abstract

SummaryIn this pilot study, T-cell receptor B-variable (TCR-BV) gene usage in CD4 and CD8 T cells was assessed, by real-time polymerase chain reaction, as well as complementarity-determining region 3 (CDR3)-length polymorphism, before and after therapy in five patients with B-cell chronic lymphocytic leukaemia who received alemtuzumab (anti-CD52 monoclonal antibody) as first-line therapy. A decline in expression of most BV family genes in both CD4 and CD8 T cells was observed after alemtuzumab treatment, which was followed by a gradual increase in most BV families during long-term followup. After treatment, CDR3-length polymorphism showed an even more restricted pattern in CD4 T cells compared with pretreatment, with a shift towards a monoclonal/oligoclonal pattern. The clonally restricted pattern was significantly reduced in CD4 (P < 0AE01) but not in CD8 T cells. This was followed by a gradual increase in the number of peaks within the CDR3 region of the different TCR-BV families, i.e. a polyclonal repertoire, during long-term follow-up. A restricted CDR3 pattern became even more restricted after treatment, but normalised during unmaintained follow-up. These results indicate that perturbations in the T-cell alterations following alemtuzumab are complex and include not only changes in CD4/CD8 Tcell numbers but also a highly restricted T-cell repertoire especially in CD4 T cells.

Acute sarcoidosis in a multiple sclerosis patient after alemtuzumab treatment

“…Therefore, our case suggests that acute sarcoidosis may not only occur in patients with T-cell lymphoproliferative disorders such as Sézary syndrome receiving high dosages of alemtuzumab (>1000 mg over several months), but also in MS patients receiving a total of 96 mg in two courses 1 year apart. One possible explanation for the development of sarcoidosis after alemtuzumab was described by Rezvany et al: 11 alemtuzumab leads to T-cell alterations with a highly restricted T-cell repertoire and changes in CD4/CD8 T-cell numbers. One might argue that a disturbed reconstitution of the T-cell repertoire may be a trigger of sarcoidosis.…”

The number of circulating recent thymic emigrants is severely reduced 1 year after a single dose of alemtuzumab in renal transplant recipients

“…An important consequence of the reduced T‐cell production by the thymus after AL depletion might be a restriction of the T‐cell repertoire. Interestingly, a highly restricted T‐cell repertoire was in fact observed, especially in CD4+ cells, following treatment with AL in patients with B‐cell chronic lymphocytic leukemia [31]. This may contribute to trigger T‐cell‐mediated autoimmunity.…”

Alemtuzumab to treat refractory autoimmune hemolytic anemia or thrombocytopenia in chronic lymphocytic leukemia

“…However, it should be noted that alemtuzumab has a major impact on T-cell subpopulations and their functions [28,35,36]. Although it may be an effective agent to treat refractory AIHA or ITP, in other patients the immune alterations induced by alemtuzumab may contribute to the development of autoimmune complications; there have been case reports of autoimmune cytopenias occurring during alemtuzumab therapy for CLL [37,38,39•].…”