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Title: Treatment of diffuse cutaneous systemic sclerosis with hyperimmune caprine serum
Author: Quillinan, N. P.
ISNI:       0000 0004 8503 6239
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Systemic sclerosis (SSc) is a multisystem autoimmune rheumatic disorder with high morbidity and the highest case specific mortality of the rheumatic diseases. There is no currently approved unequivocally effective treatment for SSc and therefore there is a huge unmet medical need for novel and effective therapies. Hyperimmune caprine serum (HCS) is a goat serum extract derivative produced from goats vaccinated with a detergent-inactivated HIV viral lysate. It contains caprine immunoglobulins and small molecular weight proteins as well as a CRH, α-2 macroglobulin (α-2M) and lipoprotein-related peptide-1 complex. In this thesis we explore the hypothesis that hyperimmune caprine serum improves skin and other measures of disease severity in established dcSSc by modulating immunological function that determines persistence of clinical disease. This hypothesis is explored through 1) a prospective clinical trial, 2) long-term clinical use and 3) detailed assessment of serum growth factors and cytokines, as well as established and exploratory markers of disease. The primary objective of the clinical trial was to explore safety and tolerability of HCS in established diffuse cutaneous systemic sclerosis (dcSSc). Secondary objectives included assessment of potential efficacy and biological activity and exploration of candidate biomarkers. There were no safety concerns and frequency of adverse events was not different between HCS and placebo group. MRSS improved in the HCS group and worsened in the placebo group, with more responders in the HCS group at 26 weeks. Neuropathic pain improved in the HCS group compared to placebo. There was a trend to benefit for lung function indices. Cluster analysis revealed changes in a number of cytokines in the HCS group compared to placebo, in parallel with the skin changes. In particular, α-MSH and ACTH were significantly increased in the HCS group leading use to hypothesise that improvement in MRSS may have been mediated through the melanocortin system.
Supervisor: Denton, C. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available