Fig. 2

Mediation analyses showing that inflammation is in the causal pathways of anti-citrullinated protein antibodies (ACPA). Schematic overview of the causal paths that were studied using mediation models as described by Baron and Kenny. The diagram illustrates the two causal paths that can lead to the outcome; a direct path from the independent to the outcome (C) and an indirect path from the mediator to the outcome (B). Finally, there is a path between the independent variable and the mediator (A). According to the description of Baron and Kenny, to test for mediation the following three regression analyses need to be performed [16]: (1) regress the mediator on the independent variable (A) - the independent variable should significantly affect the mediator; (2) regress the dependent (outcome) variable on the independent variable (C) - also here the independent variable should significantly affect the outcome; (3) regress the dependent variable on both the mediator and the independent variable (B and C′ in one model); in the case of mediation the mediator is significantly associated with the outcome and the effect of the independent variable on the outcome is less than in step 2 (partial mediation) or there is no effect at all (full mediation). In this study, the hypothesis was tested whether severity of local inflammation detected with magnetic resonance imaging (MRI) acts as a mediator in the causal path of the presence of anti-citrullinated protein antibodies (ACPA) on the erosion score. The data revealed that inflammation mediated the effect of ACPA on bone erosions. The mediator could account for more than half of the total effect: (A*B)/(A*B + C′) = 0.57