Proinflammatory Cytokines Profile in Monoclonal Gammopathies Related to Pathogenesis of Bone Disease.
Authors: Gervas Javier , Pocovi Miguel , Giraldo Pilar 
Published: October 2019

Abstract
Abstract 4913
Bone disease is one of the most frequent complications in Multiple Myeloma (MM), and as consequence produce irreversible and invaliding lesions. The pathogenesis of bone disease is not completely known. There are several publications about the influence of different cytokines in the bone remodelling, by break the balance between osteoclastic/osteoblastic activities. Aims of the study: to analyze a cytokine panel in a group of consecutive patients diagnosed as Monoclonal Gammopathy according the International Myeloma Working Group, 2003 criteria and to compare the results between MGUS and MM and patients with an without overt bone disease.

Patients and methods
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.

Results
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.

Comments
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

Disclosures
No relevant conflicts of interest to declare.