Diagnostic potential of plasma carboxymethyllysine and carboxyethyllysine in multiple sclerosis

Abstract

Background: This study compared the level of advanced glycation end products (AGEs), N-(Carboxymethyl)lysine (CML) and N-(Carboxyethyl)lysine (CEL), in patients with multiple sclerosis (MS) and healthy controls (HCs), correlating these markers with clinical indicators of MS disease severity.

Methods: CML and CEL plasma levels were analyzed in 99 MS patients and 43 HCs by tandem mass spectrometry (LC/MS/MS). Patients were stratified based on drug modifying therapies (DMTs) including interferon beta, glatiramer acetate and natalizumab.

Results: The level of plasma CEL, but not CML, was significantly higher in DMT-naïve MS patients when compared to HCs (P < 0.001). Among MS patients, 91% had higher than mean plasma CEL observed in HCs. DMTs reduced CML and CEL plasma levels by approximately 13% and 40% respectively. CML and CEL plasma levels correlated with the rate of MS clinical relapse.

Conclusion: Our results suggest that AGEs in general and CEL in particular could be useful biomarkers in MS clinical practice. Longitudinal studies are warranted to determine any causal relationship between changes in plasma level of AGEs and MS disease pathology. These studies will pave the way for use of AGE inhibitors and AGE-breaking agents as new therapeutic modalities in MS.

Figure 1

CML and CEL plasma levels in DMT-naïve MS patients and healthy controls: Comparison of plasma levels of CML (A) and CEL (B) in DMT-naïve MS patients and HCs, stratified by gender. The results are means ± SEM. P value ≤ 0.05 is statistically significant. Abbreviations as in Table 1 and DMT:disease modifying therapy.

Figure 2

CML and CEL plasma levels in DMT-naïve MS patients and MS patients treated with DMTs. Comparison of Plasma levels of CML (A) and CEL (B) in DMT-naïve MS patients and patients on DMTs, stratified by gender. The results are means ± SEM. P value ≤ 0.05 is statistically significant. Abbreviations as in Table 1, and DMT:disease modifying therapy.

Figure 3

Plasma CML and CEL levels in DMT-naïve MS patients at various disease stages. Plasma CML (A) and CEL (B) at various disease stages, in DMT-naïve, clinically stable MS patients. Results are means ± SEM for 4 CIS patients, 28 RRMS patients, 8 SPMS patients and 7 PPMS patients. Abbreviations as in Table 1.