The purpose of the World Vitiligo Symposium is to mobilize research communities, identify common research objectives and to set integrated research directions in the focus areas of vitiligo. Participants include representatives from patients’ communities, government, non-governmental and voluntary organizations, and researchers from such diverse backgrounds as dermatology, clinical therapy, biochemistry, molecular biology, genetics and bio-IT. The Symposium educated participants about each other's research areas, fostered communication and collaboration, and resulted in the creation of a list of defined research priorities. This document is a first product of the World Vitiligo Symposium. VRF recognizes that participants emphasized different approaches to research and to knowledge translation, therefore it represents a generalized consensus list. In addition to this document, educational programs designed to identify barriers to evidence implementation and to develop solutions through multidisciplinary collaboration have emerged that reflect the impact of the World Vitiligo Symposium.

1. World Vitiligo Symposium
Consensus on research directions
The purpose of the World Vitiligo Symposium is to mobilize research communities, identify
common research objectives and to set integrated research directions in the focus areas of
vitiligo.
Participants include representatives from patients’ communities, government, non-governmental
and voluntary organizations, and researchers from such diverse backgrounds as dermatology,
clinical therapy, biochemistry, molecular biology, genetics and bio-IT.
The Symposium educated participants about each other's research areas, fostered communication
and collaboration, and resulted in the creation of a list of defined research priorities.
This document is a first product of the World Vitiligo Symposium. VRF recognizes that
participants emphasized different approaches to research and to knowledge translation, therefore
it represents a generalized consensus list.
In addition to this document, educational programs designed to identify barriers to evidence
implementation and to develop solutions through multidisciplinary collaboration have emerged
that reflect the impact of the World Vitiligo Symposium.
1. Classification of vitiligo
Currently vitiligo classification is based mostly on phenotypical features. Yet results of
numerous studies clearly indicate that molecular alterations within particular vitiligo type are
very divergent. Therefore molecular parameters should be used for vitiligo classification.
Molecular typing of vitiligo will provide an opportunity to develop personalized approach in
vitiligo treatment, on the first stage by gaining data on efficiency of particular treatments for
specific molecular types of vitiligo, with further development of rational treatment strategies
aiming to target specific molecular targets critical for vitiligo development and progression.
Research in the area of development of molecular classification of vitiligo would include: (1)
selection of candidate molecular markers to be taken into account based on meta-analysis of the
available data, (2) collecting data from the patients for the selected molecular markers, (3)
selecting significant markers from the pool of candidate parameters and building vitiligo
molecular classification system, (4) analyzing relation between molecular subtype of vitiligo and
efficiencies of different treatments.
Rare disease classification. Although it seems like never applied for, vitiligo fits “Rare Disease”
designation, as defined by SEC. 526 of the U.S. Federal Food, Drug and Cosmetic Act [21 USC
360bb], (2)(B). Specifically, ”The term ‘‘rare disease or condition’’ means any disease or
condition which (A) affects less than 200,000 persons in the United States, or (B) affects more
than 200,000 in the United States and for which there is no reasonable expectation that the cost
of developing and making available in the United States a drug for such disease or condition
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will be recovered from sales in the United States of such drug.” Such designation may reduce
cost of vitiligo R&D for pharmaceutical companies.
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2. World Vitiligo Symposium. Consensus on research directions.
2. Genetic research
Genetic factors undoubtedly play some role in predisposition to vitiligo, and a number of genetic
determinants associated with vitiligo have been identified to date. At the same time, it is clear
that vitiligo is a multigenic disease, with many genes involved in various combinations. Two
problems are posed in this field. The first one consists from further search for yet unknown
genetic loci associated with vitiligo, with the emphasis to non-familial sporadic form of the
disease. The second should be focused on functional genomics, i.e. associations of identified
genetic features with particular molecular processes and functional alterations caused by the
presence of a vitiligo-associated locus. This would eventually lead to identification of critical
molecular changes for disease onset and progression which would serve as a specific molecular
target for development of novel treatment modalities for vitiligo.
3. Epigenetic research
While genetic determinants undoubtedly play a role in vitiligo, their manifestation does not
always occur. Factors defining their phenotypical manifestation are likely to be of epigenetic
nature. Yet epigenetic alterations accompanying vitiligo has been almost completely overlooked.
Thus studying epigenetic components in vitiligo pathogenesis is an important direction of
research, including alterations in DNA methylation and microRNA expression profiles, both in
cells of immune system and in skin cells.
4. Mechanism of autoimmune response
One of the generally accepted hypotheses of vitiligo pathogenesis is an autoimmune hypothesis.
Yet the precise mechanisms of autoimmune response activation in vitiligo and immune cells
involved remain unknown. Moreover, different changes in cytokine profile in vitiligo patients
has been reported which again points on the diversity of vitiligo at the molecular level (see
Section 1 above). Further characterization of immune cells and cytokines involved in
autoimmune response in vitiligo patients thus become an important task allowing understanding
molecular basis of the disease and pinpointing potential targets for therapeutic intervention.
Importantly, results of these studies can be translated into the field of oncology potentially
contributing to development of improved immunotherapeutic approaches to treat melanoma.
5. Oxidative stress in vitiligo
Oxidative stress is considered as one of the reason for melanocyte loss in vitiligo and
significantly contributes to pathogenesis. Several models of oxidative stress development has
been suggested based on the experimental findings. An important direction of the research is
identification of agents capable to combat oxidative stress thus to stop the disease progression
and create conditions allowing repigmentation.
6. Growth factor imbalance
Melanocyte functions and viability are regulated by the complex network of growth factors and
cytokines. Available data indicate that vitiligo might be related to the distortions in this network.
Detailed picture of growth factor network imbalance will be obtained from the research
described in Section 1 in which growth factor and cytokine level assessment undoubtedly should
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be included. The next step in this area will consist in determining critical factors which
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3. World Vitiligo Symposium. Consensus on research directions.
expression is altered, and in finding the ways to restore correct pattern of these growth
factor/cytokine expression thus to create appropriate niche for melanocyte repopulation (use of
recombinant proteins, gene therapy approaches, etc.). Within this research direction, an attention
should also be paid for growth factors regulating melanocyte differentiation and motility which
are critical for skin repigmentation.
7. Keratinocyte biology in vitiligo
Although vitiligo is caused by melanocyte loss, keratinocytes are also frequently affected in
vitiligo patients. Taken into account existing dependence of melanocytes from keratinocytes,
keratinocyte malfunctions could well contribute to melanocyte loss. This provide a basis for
expanded investigation of primary reasons, nature and consequences of keratinocyte
dysfunctions in vitiligo, as well as for searching for potential ways to normalize keratinocyte
functions.
8. Sources for repigmentation
Vitiligo treatment relies on the repigmentation of lesional skin which unequivocally depends on
repopulation of melanocytes. The major source of melanocytes for repopulation is hair follicles
although repopulation can be driven by melanocytes in adjacent uninvolved skin or to have a
diffuse pattern suggesting existence of melanocyte reservoir in involved skin. One promising
direction of research would cover development of targeted approaches to induce melanocyte
repopulation both in terms of creating suitable niche for melanocytes in lesional skin (see above)
and in terms of inducing melanocyte production and migration. Another area of research would
include studying and characterizing melanocyte reservoirs in vitiligo lesional skin which
ultimately aims to use this source to induce skin repigmentation.
9. Langerhans cell
Data already partially published show that the melanocyte inactivation and/or loss are related to
apparently reversible alterations of Antigen Presenting Cells / Langerhans cells in the vitiligo
skin. Further investigation on the Keratinocyte/Langerhans cell/Melanocyte functional unit in
vitiligo is required and will receive special attention.
10. Animal Models of Vitiligo
Cooperation with Veterinary Medicine focused on the elucidation of the genetic, molecular and
cellular -based ethiopathogenesis and therapeutic outcome of vitiligo in animals will be
promoted by the VRF and will require specialized interdisciplinary investigators' task force.
Source Funding
The VRF Catalyst Grant program provides seed money to support this consensus activity which
represents a first step towards the pursuit of more comprehensive funding opportunities, such as:
• planning and execution of research projects aiming to contribute to vitiligo evidence
base;
• planning and/or development activities of expert teams (multi-disciplinary, trans-
disciplinary, etc.) coming together to address vitiligo research priorities.
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4. World Vitiligo Symposium. Consensus on research directions.
VRF's contribution to the amount available for this initiative is subject to approval by its Board
of Directors.
The VR Foundation encourages researchers to partake in other Grant Awards Programs.
Additional funds might be provided to those researchers who choose to apply for them. For
further details please visit our website www.VRFoundation.org
Roadmap for dialog with genetic research scientists
A member of the VRF Expert Committee, Dr. Igor Korobko (Institute of Gene Biology, Russia)
has developed the current proposal as a first step towards identifying targets for mutually
beneficial collaboration in genetic research.
Perspective agenda for collaboration:
1. GWAS assay of RF population;
2. focused analysis by non-HTS methods for validation of identified associations (discuss
if required at all);
3. focused analysis of identified associations specifically for RF population;
4. mining functional consequences of identified associations (impact of genetic variations
on gene expression, encoded proteins etc);
5. complementing found genetic associations by data from other analysis, i.e. building
integral picture of molecular determinants altered in vitiligo (systemic and local
cytokines/growth factors, DNA methylation, microRNA profile, transcriptome profiling,
biochemical data, histology data, treatment efficiency).
In more detail:
1. GWAS assay of RF population
Will identify sporadic vitiligo genetic susceptibility loci in RF population thus expanding the list
of genes contributing to vitiligo pathogenesis. Genetic association data for patients enrolled in
the study can be complemented by data derived from other types of analysis such as blood and
skin cytokine and growth factor levels thus building far more comprehensive picture of the
disease at the molecular level.
2. Focused analysis for validation of already identified associations
Aiming to reveal impact and significance of already found genetic associations with vitiligo in
RF population. The preferred method of analysis (for example, focused Illumina bead array vs.
pyrosequencing) has to be discussed.
3. Functional consequences of identified genetic associations
Pursuing linking genetic variations associated with vitiligo with alterations in molecular
processes. Requires multidisciplinary research depending on the affected gene/locus (immune
system, antioxidant system, cytokines, extracellular matrix proteins, growth factors etc.). After
initial bioinformatic assessment of potential impact on molecular processes and (possibly)
studying effect of genetic variation on gene expression, the most competent labs in the area
should be enrolled in further study.
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5. World Vitiligo Symposium. Consensus on research directions.
When GWAS data came from RF set of samples, identified molecular consequences of
variations could be checked on real patient samples to prove the hypothesis.
5. Complementing found genetic associations by data from other analysis
This area seems to be the most appropriate and fitting our general strategy. We will use genetic
data from GWAP hopefully obtained by our collaborators and complement them for the same
patients by data for other molecular parameters such as systemic and local cytokines/growth
factors, DNA methylation, microRNA profile, transcriptome profiling, biochemical data,
histology data, treatment efficiency etc, using biopsy samples. The list of particular parameters
assessed should be finalized after thorough and careful analysis based on our current
understanding of molecular pathogenesis of vitiligo, technical feasibility and cost of assays.
Contact Information
Dear Colleagues, please send your questions, comments and suggestions about this initiative and
research objectives to:
Prof. Torello Lotti
Chair of the Scientific Committee
VR Foundation
Telephone: +1-855-966-3555
Address: 1, Penn Plaza, suite #6205, New York, NY 10119 USA
Email: t.lotti@vrfoundation.org
Website: www.VRFoundation.org
Thank you for your participation in this consensus development!
Next few blank pages are attached for your comments and thoughts.
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