CLL-264: CLL Patients with Identical IGHV Genes

Abstract

Background Studies over the last 20 years demonstrate a significant IGHV repertoire narrowing in CLL. For this disease, the existence of more than 200 subsets of tumor IGHV antigen-binding sites, so called stereotypical antigen receptors (SAR), has been shown among unrelated cases. Most common subsets (19 SARs) are responsible for more than 12% of all cases of CLL. Methods We assessed nucleotide sequences and CDR3 composition in 1038 CLL patients diagnosed and followed up from 2008 to 2020. Results 132 patients had one of major 19 SARs. Among all patients with SAR, three pairs of patients were identified whose CDR3 amino acid sequences matched 100%. In the first pair (with CLL#1), the IGHV complete nucleotide sequences were differed significantly. One patient had 100% homology with IGHV1-3*01 gene, the other had 99.7% similarity with IGHV1-2*02 gene. There were 34 differences in their nucleotide sequences; 4 were in the CDR3 region. In a pair of patients with CLL#2 SAR, both expressed IGHV3-21*01 gene with homology 96.6% and 97.2%. As a result, the complete nucleotide sequences of these patients were differed in 14 positions; 1 was in the CDR3 region. The most interesting case was the third pair, with the expression of CLL#28A. Their nucleotide sequences were composed from IGHV1-2*06 (100% homology), IGHD1-26*01 and IGHJ6*02 and were almost identical, differing by 1 nucleotide in the CDR3 region only. Conclusions These findings support additional arguments in favour of the significant role of antigen stimulation in the pathogenesis of CLL. Studies over the last 20 years demonstrate a significant IGHV repertoire narrowing in CLL. For this disease, the existence of more than 200 subsets of tumor IGHV antigen-binding sites, so called stereotypical antigen receptors (SAR), has been shown among unrelated cases. Most common subsets (19 SARs) are responsible for more than 12% of all cases of CLL. We assessed nucleotide sequences and CDR3 composition in 1038 CLL patients diagnosed and followed up from 2008 to 2020. 132 patients had one of major 19 SARs. Among all patients with SAR, three pairs of patients were identified whose CDR3 amino acid sequences matched 100%. In the first pair (with CLL#1), the IGHV complete nucleotide sequences were differed significantly. One patient had 100% homology with IGHV1-3*01 gene, the other had 99.7% similarity with IGHV1-2*02 gene. There were 34 differences in their nucleotide sequences; 4 were in the CDR3 region. In a pair of patients with CLL#2 SAR, both expressed IGHV3-21*01 gene with homology 96.6% and 97.2%. As a result, the complete nucleotide sequences of these patients were differed in 14 positions; 1 was in the CDR3 region. The most interesting case was the third pair, with the expression of CLL#28A. Their nucleotide sequences were composed from IGHV1-2*06 (100% homology), IGHD1-26*01 and IGHJ6*02 and were almost identical, differing by 1 nucleotide in the CDR3 region only. These findings support additional arguments in favour of the significant role of antigen stimulation in the pathogenesis of CLL.