Abstract: Rheumatoid arthritis (RA) is a debilitating, chronic, inflammatory, autoimmune disease
associated with cachexia. The substitutive therapy of gut hormone ghrelin has been pointed at as
a potential countermeasure for the management of metabolic and inflammatory complications in
RA. The recent discovery of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous
inverse agonist/antagonist of the ghrelin receptor makes feasible the development of a more rational
pharmacological approach. This work aimed to assess the serum LEAP2 levels, in a cohort of RA
patients, in comparison with healthy individuals and determine its correlation with inflammatory
parameters. LEAP2 levels were determined by a commercial ELISA kit, plasma C-reactive protein
(CRP) levels were evaluated using immunoturbidimetry, and serum levels of inflammatory mediators,
namely IL-6, IL-8, IL-1, MIP1, MCP1, and LCN2, were measured by XMap multiplex assay. LEAP2
serum levels were significantly increased in RA patients (n = 101) compared with control subjects
(n = 26). Furthermore, the LEAP2 levels significantly correlated with CRP and inflammatory cytokines,
but not with BMI. These data reveal LEAP2 as a new potential RA biomarker and indicated the
pharmacological control of LEAP2 levels as a novel approach for the treatment of diseases with
alterations on the ghrelin levels, such as rheumatoid cachexia.