Clinical significance of matrix metalloproteinase-9 in Fragile X Syndrome

High plasma matrix metalloproteases-9 (MMP-9) levels have been reported in Fragile X Syndrome in a limited number of animal and human studies. Since the results obtained are method-dependent and not directly comparable, the clinical utility of MMP-9 measurement in FXS remains unclear. This study aimed to compare quantitative gel zymography and ELISA and to determine which method better discriminates abnormal MMP-9 levels of individuals with FXS from healthy controls and correlates with the clinical profile. The active and total forms of MMP-9 were quantified respectively, by gel zymography and ELISA in a cohort of FXS (n = 23) and healthy controls (n = 20). The clinical profile was assessed for the FXS group using the Aberrant Behavior Checklist FXS adapted version (ABC-C-FX), Adaptive Behavior Assessment System (ABAS), Social Communication Questionnaire (SCQ), and Anxiety Depression and Mood Scale questionnaires. Method comparison showed a disagreement between gel zymography and ELISA with a constant error of - 0.18 [95% CI: - 0.35 to - 0.02] and a proportional error of 2.31 [95% CI: 1.53 to 3.24]. Plasma level of MMP-9 active form was significantly higher in FXS (n = 12) as compared to their age-sex and BMI matched controls (n = 12) (p = 0.039) and correlated with ABC-C-FX (r(s) = 0.60; p = 0.039) and ADAMS (r(s) = 0.57; p = 0.043) scores. As compared to the plasma total form, the plasma MMP-9 active form better enables the discrimination of individuals with FXS from controls and correlates with the clinical profile. Our results highlight the importance of choosing the appropriate method to quantify plasma MMP-9 in future FXS clinical studies.