IMMUNOPARESIS CORRELATES WITH MGUS RISK - APPLICATION OF POLYCLONAL IMMUNOGLOBULIN AND HEAVY/LIGHT CHAIN LEVELS ASSESSMENT

Sborník

Backround. Monoclonal gammopathy of undetermined significance (MGUS) indicates an asymptomatic and potentially malignant state characterised by benign clonal proliferation of plasma cells secerning monoclonal immunoglobulin (MIG, M-protein) in the absence of malignant lymphocyte proliferation. It has been observed that in some patients, MGUS transforms into one of the malignant forms of monoclonal gammopathy. The well-known factors determining the risk degree of progression include in particular the quantity, M-protein type and the ratio of immunoglobulin free light chains (FLC) allowing the efficient stratification of MGUS patients. In addition, several authors consider the present suppression of polyclonal immunoglobulin levels to be a potential factor of progression. Aims. The study aimed at conducting a analysis of polyclonal immunoglobulin and heavy/light chain pair (HLC) levels in a group of MGUS patients. The polyclonal immunoglobulin levels and the levels of HLC alternative pairs were to be compared with a view to verify the degree of immune paresis depending on the MGUS risk degree. Methods. The analysed set comprised 130 serum samples of MGUS patients (102 IgG, 28 IgA) who were stratified into 4 risk groups (low, low-intermediate, high-intermediate, and high risk of transformation) according to the levels, M-protein type and FLC index values. FLC levels, polyclonal immunoglobulin levels, and HLC levels were determined by means of the SPA Plus turbidimeter platform. In the statistical analysis, Mann-Whitney U Test with Bonferroni correction was applied. Results. Comparison of the suppression degree of polyclonal immunoglobulin levels in individual risk classes in the IgG MGUS group brought significantly higher levels of IgA immunoglobulin in patients with low or low-intermediate risk as opposed to the group with high-intermediate risk (p = 0. 0001 and p = 0. 047 respectively). When analysing the MGUS group with IgA isotype, notably higher levels of IgM immunoglobulin were evident in the group with low-intermediate risk than in patients with high-intermediate or high risk (p = 0. 035 and p = 0. 017 respectively). In addition, the levels of alternative isotype pairs were compared among the individual risk groups of the IgG MGUS group. Patients with dominant IgGκ secretion showed significantly higher levels of the IgGλ alternative pair in the group of low and low-intermediate risk than in the group of high-intermediate risk (p = 0. 003 and p = 0. 006 respectively). In case of dominant IgGλ secretion, considerably higher IgGκ levels were detected in patients with low or low-intermediate risk than in the group of high-intermediate risk (p = 0. 0006 and p = 0. 009 respectively). Conclusions. The discovered connection between the degree of immune suppression depending on the MGUS risk level and especially the clearly visible benefit of determining the alternative HLC pairs contributes with another aspect to understanding the links between the biology, behaviour, and the potential malignant evolution of MGUS with the advantage of obtaining a well-measurable parameter.

Supported by NT 12451/5, NS 10387 and The Binding Site, Czech Republic.

Haematologica, 2012; 97(s1):  589