Abstract
BACKGROUND AND AIMS: Granulocyte/monocyte adsorption apheresis (GMA) is a nonpharmacological adjuvant therapy for treatment-resistant active ulcerative colitis (UC). Endoscopy is the gold standard for diagnosing and evaluating disease activity and treatment efficacy; however, substitution with blood biomarkers is desirable. We aimed to investigate the correlation between neutrophil/monocyte-associated factors, particularly proteases, and therapeutic responses to GMA in patients with intractable UC. METHODS: In this 2-center prospective study conducted at Juntendo University Hospital (Tokyo, Japan) and Juntendo Urayasu Hospital (Chiba, Japan), we included 10 of 12 recruited patients in the final analysis following 10 GMA sessions. GMA is used as an adjunct to conventional medications. Peripheral blood samples were collected before and post-GMA. RESULTS: One month after 10 GMA sessions, 60% of patients showed remission (Lichtiger Clinical Activity Index [CAI]<4), 20% showed treatment effectiveness, and 20% remained unchanged. The neutrophil-to-lymphocyte ratio decreased in 7 participants compared with that in the initial data but did not correlate with CAI changes. Plasminogen levels decreased, whereas tumor necrosis factor-alpha, plasmin-α2-plasmin inhibitor complex, and matrix metalloproteinase-9 (MMP-9) levels increased transiently when precolumn values were compared pre-GMA and post-GMA. However, plasminogen, plasmin-α2-plasmin inhibitor complex, and tumor necrosis factor-alpha levels did not correlate with UC disease severity. Moreover, 80% of patients showed stable or decreased MMP-9 levels across GMA cycles, and MMP-9 changes positively correlated with CAI changes. Only circulating MMP-9 levels positively correlated with CAI changes pre-GMA and post-GMA. CONCLUSION: Decreased circulating MMP-9 levels predict clinical response to GMA in these patients, possibly serving as a novel and cost-effective biomarker for assessing GMA efficacy and substituting classical clinical parameters.