The Diagnostic Value of CD1d Expression in a Large Cohort of Patients With B-Cell Chronic Lymphoproliferative Disorders

Abstract

Immunophenotyping is indispensable in the differential diagnosis of B-cell chronic lymphoproliferative disorders (B-CLPDs). However, B-CLPDs often show overlapping immunophenotypic profiles and may be diagnostically challenging. CD1d is an HLA class I-like molecule that presents glycolipids to invariant natural killer T cells. Normal mature B cells constitutively express CD1d, but with the exception of some conflicting data, its expression in B-CLPDs is unknown. We demonstrate that in 222 B-CLPD cases, CD1d expression of less than 45% is strongly predictive of CLL (likelihood ratio, 32.3; specificity, 97.4%; sensitivity, 84.1%). In addition, CD1d showed significantly higher staining intensity in splenic marginal zone lymphoma compared with atypical hairy cell leukemia, lymphoplasmacytic lymphoma, and mantle cell lymphoma, thus allowing the discrimination of the former from the latter immunophenotypically overlapping B-CLPDs. It is important to note that in a given patient, CD1d expression on malignant B cells was similar between tissues and remained unaffected by disease stage and treatment status. Our findings strongly argue for the incorporation of CD1d into routine lymphoma panels.

Functional invariant natural killer T-cell and CD1d axis in chronic lymphocytic leukemia: implications for immunotherapy

“…37 This study confirms that CLL cells express surface CD1d, but at a level modestly lower than on normal B cells. 38 Despite this, we found that α-GalCer-treated CLL cells were able to elicit iNKT cell proliferation, confirming a previous finding.…”

The significance of CD1d expression in diagnosis of chronic lymphocytic leukemia and its value as a prognostic marker

“…The present study showed lower CD1d expression in CLL patients compared with healthy controls. Consistent with our results Kotsianidis et al [13] reported higher surface expression of CD1d in healthy controls than in CLL patients. A recent study reported that measuring CD1d by flow cytometer and quantitative reverse transcriptase PCR showed lower CD1d molecule and CD1d mRNA expression in B-cells of CLL patients than of healthy controls [14] .…”

“…Previous few studies demonstrated an association between CD1d expression and the adverse immunophenotypic feature, namely CD38 expression in CLL patients [13,24] . By contrast, another research group detected no significant differences between Zap-70 positive and negative, CD38 positive and negative CLL sub groups [25] .…”

“…Using ROC curve analysis CD1d cut off value <38% was able to diagnose CLL and to differentiate between cases of CLL and MCL with high sensitivity and specificity. The mechanism of CD1d down-regulation in CLL B-lymphocytes is unknown; however, upregulation of the nuclear protein lymphoid enhancer-binding factor-1 (LEF-1) may be at least partially responsible for the low CD1d expression in CLL [13] . It has been demonstrated that the expression of gene encoding the human CD1d (CD1D) is regulated by LEF-1 that acts as a transcriptional repressor of the CD1D gene [16] .…”

“…Over the past decade, several prognostic markers of CLL B cells have been added to the original staging systems of Rai and Binet [8] . CD38 was the first marker to be discovered and widely used [13,20] , high CD38 expression has been identified as an adverse prognostic marker [21] . Immunoglobulin heavy chain variable (IgVH) mutational status also confers an adverse prognosis [22] , and the presence of chromosomal deletions of 11q or 17p are predictive not only of an aggressive clinical course, but also of resistance to specific chemotherapy [23] , however, both tests are costly, relatively laborious and not available in all hematology departments [13] .…”