Toll-like receptor 4 and 9 expression in B-chronic lymphocytic leukemia: relationship with infections, autoimmunity and disease progression

Toll-like receptors (TLRs) represent major agents of innate immunity and initiators of adaptive immunity. TLR4 and TLR9 gene expression was related to the occurrence of infections, autoimmunity and disease progression in 95 patients with B-chronic lymphocytic leukemia (B-CLL), grouped according to stage, therapy and known prognostic markers, and followed prospectively (median 33.6 months, range 25-50). A retrospective analysis (median 6.8 years, range 6-26) was also performed. TLR4 gene expression was decreased and TLR9 increased in patients versus controls, the former being more pronounced in advanced and multi-treated disease, and in patients with unmutated immunoglobulin heavy chain variable (IgVH) region and unfavorable cytogenetics. Patients with reduced TLR4 had an increased risk of disease progression and development of autoimmune complications. No relationship was found between reduced TLR4 expression and infectious episodes, which were observed in advanced stages and treated patients. These findings suggest that impaired innate immunity identifies patients with B-CLL with a poor prognosis and reduced ability to silence autoreactive phenomena.