SOLUBLE CD30: A BIOMARKER FOR EVALUATING THE CLINICAL RISK VERSUS BENEFIT OF IFN beta 1A TREATMENT IN MULTIPLE SCLEROSIS PATIENTS

作者：Contasta I; Totaro R; Berghella A M^*; Pellegrini P; Del Beato T; Carolei A; Adorno D

来源：International Journal of Immunopathology and Pharmacology, 2010, 23(1): 213-226.

• CD30
• Th cytokine data-driven modelling approaches
• IFN beta 1a therapy
• risk/benefit biomarkers
• multiple sclerosis
• neuroimmunology

Aberrant redox regulation occurs in immune and neurological pathologies, hence targeting the pathways involved in the regulation of the redox system could provide further insights into these diseases and open up new avenues for therapy. Soluble (s) CD30 is of key clinical importance in this respect, as its levels reflect the functionality of the CD30 receptor (CD30R), the specific lymphocyte receptor for thiol disultide/oxidoreductase thioredoxin 1 (Trx1) which is known to regulate important immune and neurological processes. Increased levels of sCD30 appear to be a common element of oxidative stress, immunological alterations and neurological deficit, therefore these increases could be used as a clinical biomarker and target for therapy. We targeted sCD30 in our study of dendritic cell (DC) regulation of the T helper (Th) cell network in multiple sclerosis (MS) patients, as abnormalities in T regulatory (Treg)/Th1/Th17 pathways contribute to the pathogenesis of this immunological/neurological disease. DC profiles in Treg/Th1/Th2/Th17-types of cytokine production in culture supernatants were used as they determine the type of Th differentiation. Our results show that sCD30 levels increase significantly in MS patients, reflecting the disruption in the regulation of the Treg/Th1/Th17 cell network. A fall in the level of soluble CD30, induced by IFN beta 1a therapy, opposed the increase of neurological deficit through increasing IL10 and TGF beta levels, thus re-establishing network homeostasis but only when this was accompanied by an increase in IL12p70 levels. Since IL12p70 cytokine production is regulated by Trx1, our results indicate that redox system alterations may be the cause of IFN beta 1a therapeutic inefficacy. We conclude that an increase in the level of IL10, TGF beta and IL12p70 and a fall in the level of sCD30 represent a means of evaluating the clinical risk/benefit of IFN beta 1a treatment.

• 出版日期2010-3