Kynurenic acid in blood and bone marrow plasma of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients

Increased levels of kynurenic acid (KYNA) have been detected in patients with neurological, autoimmune and tumor diseases. The aim of this paper was to determine KYNA levels in the blood and bone marrow plasma of MGUS and MM patients and to find out common events which are characteristic for both pathological stages and correlates with diagnostic markers of MGUS and MM. We also examined whether bone marrow stromal cells (BMSCs) and MM cells could produce KYNA. The levels of KYNA present in plasma and in cell culture media were examined by HPLC.An increased level of KYNA was detected in the blood and marrow plasma of MGUS patients and in the blood plasma of the MM group. In the MM group, the blood KYNA level was the highest in patients with monoclonal IgG protein and with free light chains of immunoglobulins and correlated positively with blood levels of creatinine and urea. In the MGUS group, KYNA correlated positively with the C-reactive protein (CRP) level, and in both groups KYNA correlated positively with the β2-microglobulin. We detected KYNA production in BMSCs of control and MM patients and by two myeloma cell lines used in the experiments.The results suggest that the increased KYNA level in MGUS patients was mainly caused by a dysfunction of the immune system, as it correlated positively with CRP and β2-microglobulin levels. In MM patients, the increased KYNA level may have been a result of a dysfunction of the immune system, KYNA production by myeloma cells, and decreased KYNA excretion by kidneys.