W1320 Natalizumab is Effective in the Treatment of Moderate to Severe Crohn's Disease Unresponsive to Anti-TNFα Agents

[Background & Aims]The granulocytapheresis (GCAP) for ulcerative colitis (UC) has been developed in Japan. GCAP is a non-pharmacological therapy thereby does not have severe adverse effect. The mechanism of GCAP is expected to reduce inflammatory cytokines and the production of L-selectin by absorbing selected active granulocytes. Weakness of GCAP is the difficulty of the anticipation of treatment effect in early treatment stage. In this study, we focused on adhesion molecules which are thought to be associated with the pathophysiology of UC. We examined 5 SNPs in 3 adhesion molecule genes. [Methods] Twenty eight UC patients (M12, F16, averaged age 37.9y.o.) who received GCAP in past 5 years were examined. These patients were 21 pancolitis, 5 left sided colitis and 2 proctitis. DNA was extracted from all patients by colonic biopsy or blood sample and examined about the polymorphisms by PCR-RFLP. Genes and polymorphisms were L-selectin -642C>T and 725C>T, PECAM-1 codon125 V>L, E-selectin 98G>T in exon2 and S128R in exon4. The differences of the clinical activity index (CAI) scores of preand post-treatment of each 1 course (5 times of GCAP performed) or 2 course (10times of GCAP performed) were used for the evaluation of UC activity. Statistical analysis was done by Mann-Whitney U test. [Results] L-selectin-642C>T C carrier tended to be contributed to better treatment results after 2 course. L-selectin 725C>T polymorphism was not associated with treatment effect. PECAM-1 codon125 V>L, L/L or L/V was significantly associated with better treatment effect within 1 course treatment than V/V (p T and S128R polymorphisms showed no effect about GCAP treatment. [Conclusions] In this study, a significant effect of polymorphisms in PECAM-1 was found. Future study will be needed to confirm this result in next step.