Background/Purpose: To investigate the utility of serum free light chains (FLC), antiphospholipid antibodies (APL), and cytokines in the evaluation of patients with biopsy-proven giant cell arteritis (GCA).

Methods: We conducted a cross-sectional study of 75 patients with biopsy-proven GCA. Sera were evaluated for the presence and quantity of the following biomarkers: serum FLC [kappa, lambda], anticardiolipin antibodies (ACL; IgM/IgG) , beta-2 glycoprotein antibodies (β2GP; IgM/IgG), antiphosphytidylserine-prothrombin antibodies (PS-PT; IgM/IgG), and 20 circulating cytokines (GCSF, GMCSF, IFNγ, IL-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, MCP-1, TNFα, TNFβ and VEGF). Quantification of serum FLC was obtained by nephelometric assay. ACL, β2GP, and PS-PT antibody levels were determined via enzyme-linked immunosorbent assay. Cytokines were measured with a fluorescent microsphere-based assay. Rank sum test was used to compare biomarker levels between patients with active and inactive GCA, patients with and without large vessel vasculitis (LVV), patients with and without visual ischemia. Associations between biomarker levels and ESR/CRP were examined using Spearman correlation methods.

Results: The study included 60 (80%) women and 15 (20%) men. Mean age at inclusion was 75.0±7.3 years. Clinically active disease was present in 28 (37%) and 47 (63%) were clinically inactive at time of sera collection. LVV was identified radiographically in 29 (39%) and visual ischemia occurred in 19 (25%). At time of sera collection, no significant difference in prednisone dose was observed between the evaluated groups. APL were infrequently detected: 13 ACL IgM weak(+); 1 ACL IgM(+); 6 ACL IgG weak(+); 1 β2GP IgM(+); 3 β2GP IgG weak(+); 5 PS-PT IgM(+); 2 PS-PT IgG(+). No significant differences between the presence and the level of APL were observed between the evaluated groups. Elevated kappa FLC levels were present in 35 (74%), elevated lambda in 4 (5%), and elevated kappa/lambda ratios in 14 (19%). There was no difference between serum FLC or kappa/lambda ratios between comparison groups. Serum FLC and APL had weak to moderate correlation with ESR/CRP.

Cytokine levels of IL-6, IL-8, and VEGF were significantly higher in active patients compared to inactive patients (p<0.05). No differences between APL, serum FLC, or cytokines were observed between patients with and without LVV. Patients with visual ischemia had significantly higher cytokine levels of GCSF, GMCSF, IFNγ, IL-10, IL-12p70, IL-13, IL-1b, IL-2, IL-4, IL-5, IL-6, TNFα compared to those without visual ischemia. The highest correlations (r_s) among individual cytokines with ESR/CRP were observed with IL-6 (0.42), IL-7 (0.42), IL-8 (0.46), and IL-17 (0.43).

Conclusion:: In this study, APL and serum FLC were not useful in determining the level of disease activity or differentiating between patients with or without LVV or visual ischemia. A distinct cytokine profile was observed in patients with visual ischemia compared to those without. Prospective studies are needed to determine the role of these cytokines as biomarkers of visual ischemic complications in patients with GCA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/utility-of-serum-free-light-chains-antiphospholipid-antibodies-and-cytokines-in-giant-cell-arteritis/