Biomarker Commons

Spectral effects of UV on psoriasis.

Photochem Photobiol Sci. 2013 Jan;12(1):47-53

Authors: Weatherhead SC, Farr PM, Reynolds NJ

Abstract
Ultraviolet B (UVB) is a highly effective, relatively safe, affordable and widely used therapeutic option for moderate psoriasis. Several types of UVB lamp are available to treat psoriasis, both broadband and narrowband, allowing a choice of spectral emission. However despite years of clinical use, the mechanism of action of UVB in clearing psoriasis remained incompletely understood. Moreover, there has been little insight into how the relative effectiveness of different UVB wavelengths linked to the mechanism of action, although it is known that the action spectrum for clearance of psoriasis differs from the action spectrum of erythema. This paper examines the existing literature from which our current treatments have evolved, and offers new insight into the use of keratinocyte apoptosis as a biomarker which may help to optimise UV treatment in the future. When combined with a systems biology approach, this potential biomarker may provide insight into which wavelengths of UV are the most effective in clearing psoriasis, allowing a more rational and potentially an individually tailored approach to optimising phototherapy for psoriasis.

PMID: 23023652 [PubMed - indexed for MEDLINE]

Single administration of lesion-limited high-dose (TURBO) ultraviolet B using the excimer laser: clinical clearing in association with apoptosis of epidermal and dermal T cell subsets in psoriasis.

Photodermatol Photoimmunol Photomed. 2012 Dec;28(6):293-8

Authors: Kagen M, Cao LY, Oyetakin-White P, Tacastacas JD, Yan C, McCormick TS, Cooper KD

Abstract
BACKGROUND/PURPOSE: Development of effective therapy for psoriasis is confounded by numerous factors contributing to disease pathogenesis, including pathogenic immunocytes which appear to drive epidermal keratinocyte hyperproliferation. Our objective was to study clinical and biomarker effects of a single dose of TURBO laser UVB (308 nm) applied directly to psoriatic plaques.
METHODS: Eighteen patients with chronic plaque psoriasis received a single dose of 10 minimal erythema dose (MED) UVB and were followed for 8 weeks. Keratome and punch biopsies were assessed for T cell depletion and apoptosis following a single 308-nm dose of UVB.
RESULTS: Patients demonstrated clinical improvement as indicated by decreased global Psoriasis Area and Severity Index scores and reduced numbers of pathogenic memory/effector T cells infiltrating lesional epidermis and dermis. Consistent with apoptosis induction, caspase activation increased in lesional T cells after treatment.
CONCLUSION: We conclude that a single 10 MED dose of TURBO UVB is effective at reducing the severity and extent of psoriatic lesions. We hypothesize that the reason a single treatment is sufficient to clear a psoriatic plaque is that the 10 MED dose is able to deliver sufficient photons to a microanatomic area of the lesion where susceptible pathogenic T cell mechanisms are operative.

PMID: 23126290 [PubMed - indexed for MEDLINE]

Markers of inflammation and bone remodelling associated with improvement in clinical response measures in psoriatic arthritis patients treated with golimumab.

Ann Rheum Dis. 2013 Jan;72(1):83-8

Authors: Wagner CL, Visvanathan S, Elashoff M, McInnes IB, Mease PJ, Krueger GG, Murphy FT, Papp K, Gomez-Reino JJ, Mack M, Beutler A, Gladman D, Kavanaugh A

Abstract
OBJECTIVE: To determine serum biomarker associations with clinical response to golimumab treatment in patients with psoriatic arthritis (PsA).
METHODS: GO-REVEAL was a randomised, placebo-controlled study of golimumab in patients with active PsA. Samples were collected from 100 patients at baseline, week 4 and week 14, and analysed for serum-based biomarkers and protein profiling (total 92 markers); data were correlated with clinical measures at week 14.
RESULTS: Serum levels of a subset of proteins (apolipoprotein C III, ENRAGE, IL-16, myeloperoxidase, vascular endothelial growth factor, pyridinoline, matrix metalloproteinase 3, C-reactive protein (CRP), carcinoembryonic antigen, intercellular adhesion molecule 1 and macrophage inflammatory protein 1α) at baseline or week 4 were strongly associated with American College of Rheumatology 20% improvement (ACR20) response and/or disease activity score in 28 joints (DAS28) at week 14. A smaller subset of proteins was significantly associated with a 75% improvement in the psoriasis area and severity index score (PASI75) at week 14, (adiponectin, apolipoprotein CIII, serum glutamic oxaloacetic transaminase, and tumour necrosis factor α). Subsets of proteins were identified as potentially predictive of clinical response for each of the clinical measures, and the power of these biomarker panels to predict clinical response to golimumab treatment was stronger than for CRP alone.
CONCLUSIONS: This analysis provides insight into several panels of markers that may have utility in identifying PsA patients likely to have ACR20, DAS28, or PASI75 responses following golimumab treatment.

PMID: 22975755 [PubMed - indexed for MEDLINE]

Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling.

Eur J Pharm Biopharm. 2012 Aug;81(3):635-41

Authors: Bodenlenz M, Höfferer C, Magnes C, Schaller-Ammann R, Schaupp L, Feichtner F, Ratzer M, Pickl K, Sinner F, Wutte A, Korsatko S, Köhler G, Legat FJ, Benfeldt EM, Wright AM, Neddermann D, Jung T, Pieber TR

Abstract
BACKGROUND: Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic patients over 25h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps.
METHODS: Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.5% cream) on a lesional and a non-lesional application site once daily for 8 days. Multiple dOFM sampling was performed for 25 h from each site on day 1 and day 8. Patients were mobile as dOFM probes were operated by a novel light-weight push-pull pump. Ultrasound was used to verify intradermal probe placement, cap-LC-MS/MS for BCT194 and ELISA for TNFα analysis.
RESULTS: dOFM was well tolerated and demonstrated significant drug concentrations in lesional as well as non-lesional skin after 8 days, but did not show significant differences between tissues. On day 8, TNFα release following probe insertion was significantly reduced compared to day 1.
CONCLUSIONS: Novel membrane-free probes and wearable multi-channel pumps allowed prolonged intradermal PK/PD profiling of a lipophilic topical drug in psoriatic patients. This initial study shows that dOFM overcomes limitations of microdialysis sampling methodology, and it demonstrates the potential for PK/PD studies of topical products and formulations in a clinical setting.

PMID: 22554768 [PubMed - indexed for MEDLINE]