Baseline MxA mRNA expression predicts interferon beta response in multiple sclerosis patients.
BACKGROUND
Myxovirus resistance protein A (MxA) is a molecule induced after interferon-beta injection, mostly used to evaluate its bioactivity. There is little available data on clinical utility of baseline MxA mRNA status. The objective of the study is to investigate whether baseline MxA mRNA expression can predict relapse and disease progression in multiple sclerosis patients treated with interferon-beta.


METHODS
Baseline blood samples were obtained before the first interferon-beta dose was administered to evaluate MxA mRNA expression using real-time polymerase chain reaction (PCR). Demographic and clinical variables were prospectively recorded to define treatment responder and non responder groups.


RESULTS
104 patients were included in the study. Baseline MxA mRNA expression was significantly lower in the group of patients who met the definition of responders (1.07 vs 1.95, Student t test, p<0.0001). A threshold of 1.096 was established using Receiver Operating Characteristic analysis to differentiate between responders and non-responders (sensitivity 73.9%, specificity 69.0%). Survival analysis using this threshold showed that time to next relapse (p<0.0001) and to EDSS progression (p = 0.01) were significantly higher in patients with lower MxA titers.


CONCLUSIONS
The results suggest that baseline MxA mRNA levels may be useful for predicting whether multiple sclerosis patients will respond or not to interferon-beta treatment.
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Elisabet
E
Matas
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Laura
L
Bau
Translational Research Laboratory, Institut Català d'Oncologia- IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
María
M
Martínez-Iniesta
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Lucía
L
Romero-Pinel
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Department of Neurology, Joan XXIII University Hospital, Universitat Rovira I Virgili, Tarragona, Spain.
M Alba
MA
Mañé
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Álvaro
Á
Cobo-Calvo
Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Sergio
S
Martínez-Yélamos
D015415:Biomarkers / Q000097:blood*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D011795:Surveys and Questionnaires; D016019:Survival Analysis
D015415:Biomarkers; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D016899:Interferon-beta