Proinflammatory Cytokines Profile in Monoclonal Gammopathies Related to Pathogenesis of Bone Disease.

Between June 2008-June 2009, a total of 87 patients were studied (46.0% females) in Miguel Servet University Hospital; mean age: 71.5 (range: 69.1-73.9), distributed in two groups: a) MGUS: 46; mean age: 72.8 (range: 69.7-75.8); b) MM: 41; mean age: 70.2 (range: 66.3-74.0). According subtypes distribution: a) IgG: 18(39.1%); IgA 16(34.8%), IgM: 9 (19.6%), double MC 3 (6.5%). b) Light Chain: 6 (15.0%) IgG: 21 (52.5%); IgA 11(27.5%), double MC 2 (5.0%); In b group the ISS(1: 9, 22.5%, 2: 21 52.5%, 3: 10 25.0%). Four different degrees of bone disease was established: 0: normal (68.5%); 1 osteopenia (9.6%); 2 osteoporosis (2.7%); 3 Lytic lesions (11.0%); 4 fractures (8.2%). The cytokine assay was performed in serum samples stored at -80°C at diagnosis, using Millipore human cytokines Kit according the established protocol by Luminex®100 platform. The profile cytokine panel used were: IL-4, IL6, IL-7, IL-10, IL-13, MIP-1a, MIP-1b, TNF-a. Previously we had compared the cytokine profile with a group of healthy population matched by age and gender. The results of the cytokine panel were compared between groups MGUS/MM, bone disease, immunochemical subtypes and ISS stage, haemoglobine, b2 microglobuline concentration, free light chain ratio in the MM group. Descriptive analysis and non parametric comparative test was performed using STATA SE v.10.

For the global serie: IL10 concentration showed significant difference between patients with normal vs abnormal bone. The cytokine profile of MGUS vs MM was significant different for IL-4 (p=0.02), MIP-1a(p=0.03) and TNFa(p=0.003). The comparative analysis of profiles according ISS classification showed significant differences for MIP-1a(p=0.04), IL-13(p=0.02) and IL-6(p=0.07) and b2microglobuline vs TNFa (p=0.002). No significant differences were observed for immunochemicals subtypes, free k/l ratio and hemoglobine.

In our experience Luminex®100 technology is a sensible and accurate technique useful to determine cytokine profile in serum. A different significant cytokine profile was observed in patients with MGUS vs MM and different bone affectation, b2microglobuline and ISS. It is necessary to perform more studies with more patients in order to confirm these results.

This work has been partially sponsored by a grant from CIBERER

No relevant conflicts of interest to declare.