a b s t r a c t In this work an innovative and low cost surface plasmon resonance (SPR) biosensor, based on the uti-lization of plastic optical fibers (POF), is presented and experimentally tested for the diagnosis and/or follow-up of celiac disease. In particular, the POF-based sensor was used to monitor the formation of the transglutaminase/anti-transglutaminase antibodies formation, a new hallmark for the diagnosis of celiac disease. In particular, on the gold layer surface of the POF sensor, the guinea pig transglutaminase was immobilized. The ability of the POF-sensor to detect the binding of anti-transglutaminase antibodies to the immobilized transglutaminase was studied. The obtained results showed that the POF-sensor is able to sense the transglutaminase/anti-transglutaminase complex in the range of concentrations between 30 nM and 3000 nM. Importantly, the proposed sensing method could be easily expanded to different target compounds.