Similar Humoral Immunity Parameters in Chronic Lymphocytic Leukemia Patients Independent of V_H Gene Mutation Status

Abstract

Chronic lymphocytic leukemia (CLL) is a clonal B-cell disorder, which has recently been divided into 2 subtypes based on the somatic hypermutation status of the immunoglobulin heavy chain (IgVH) genes. In patients with unmutated tumor cells the survival time is approximately half of that in mutated cases, but the reason for this difference is poorly understood. Since infections are the major cause of mortality in CLL, we investigated the effect of the mutation status on host immunity and proneness to infections in patients with CLL. As expected, the disease progression seemed to be faster and the disease more advanced (Binet B and C) among unmutated patients than in the mutated ones. Surprisingly, no differences in humoral immunity [immunoglobulin G (IgG), IgM, IgA, IgG subclasses, anti-ABO blood group antibodies and mannan-binding lectin (MBL)] or immune responses (Haemophilus influenzae serotype b conjugate vaccination) were detected between these 2 patient groups. Furthermore, UM-patients were not more prone to infections compared to M-patients, and therapy had no impact on the incidence and pattern of infections in either of the patient groups. The current findings within this patient cohort reveal that the worse outcome in the unmutated subgroup is not caused by more severe defects in immunity and increased susceptibility to infections when compared with the hypermutated group. It is thus conceivable that active immunization procedures such as vaccination can successfully be applied on patients with unmutated IgVH gene and advanced disease stage.

Evaluation of Periodontal Parameters in Patients with Early Stage Chronic Lymphocytic Leukemia

“…Production of immunoglobulin from normal B cells and antibody response to different antigens are significantly reduced in CLL patients (11). All 3 classes (IgG, A and M) are affected, although predominantly IgG3 and IgG4 (12).…”

“…Na antigeni podražaj oboljeli od KLL-a reagiraju smanjenom sekrecijom protutijela jer im je broj zdravih B-limfocita znatno smanjen (11). Smanjena je i sekrecija svih imunoglobulina (IgG, IgA, IgM), a osobito IgG3 i IgG4 (12).…”

Disease-Specific Complications of Chronic Lymphocytic Leukemia

“…12 There does not appear to be any correlation between Ig levels and IgVH mutation status. 13 The primary serum antibody response is also affected early in the disease. Even in successfully treated patients, there is rarely recovery of Ig levels, although a recent study has suggested that use of high doses of rituximab in CLL can improve immune dysfunction and restore, in part, the production of immunoglobulins.…”

Management of Infectious Complications in Patients with Chronic Lymphocytic Leukemia

“…4 The impact of immunoglobulin V H mutation (i.e., unmutated versus mutated) status on humoral immunity and infectious complications has recently been examined. 5,6 In the series of Sinisalo et al, no significant differences in immunoglobulin levels, mannan-binding lectin, or immune responses to Haemophilus influenzae B vaccination were found between two groups of patients that differed in the mutational status of the B-cell clone. 5 Likewise, no difference in infection rate was found among the mutated and unmutated patients in this series.…”

“…5,6 In the series of Sinisalo et al, no significant differences in immunoglobulin levels, mannan-binding lectin, or immune responses to Haemophilus influenzae B vaccination were found between two groups of patients that differed in the mutational status of the B-cell clone. 5 Likewise, no difference in infection rate was found among the mutated and unmutated patients in this series. In a retrospective analysis of 280 patients with CLL, those with an unmutated immunoglobulin V H gene status had a significantly shorter time to first infection and higher infection-related mortality than those patients with immunoglobulin V H gene mutations, despite immunoglobulin levels being comparable among the two groups.…”