Medical Student Research Fellowship for Summer 2007
Mentor: Heidi T Jacobe, MD
Room number: F4.212A
Mail Code: 9069
Phone number: 214-648-2985
Project title: A histological review of morphea subtypes.
Human subjects IRB approved project number (where applicable): 032007-021 - approved
Animal subjects IRB approved project number (where applicable):
Project Type Patient-based research
Project Summary: Morphea is a form of scleroderma isolated to the skin. It is characterized by sclerosis of the papillary and reticular dermis with varied degrees of inflammation and edema depending on the stage of disease. Although incompletely understood, theses changes are at least in part due to the down regulation of the expression and protein levels of matrix metalloproteinases/collagenase I and upregulation of TGF beta. UVA-1 phototherapy has demonstrated efficacy in the treatment of morphea in numerous small trials, but the mechanism by which this effect is mediated is poorly described. In this study, the student will assess the effect of UVA1 phototherapy on skin thickness and fibrosis scores using H and E stained histological sections of skin pre and post therapy with UVA-1 as well as the level of MMP/collagenase I and TGF beta protein in the same tissue sections using previously published protocols for ELISA. These changes will be correlated with cliical improvement scores.
Brief Description of Project: Morphea is currently thought to be the skin only
manifestation of scleroderma, consisting of five subtypes based solely on cutaneous
morphology without reference to associated systemic manifestations, concomitant
or familial predisposition to autoimmunity, HLA type, or autoantibody profile.
This conception is incomplete and misleading. Small, uncontrolled studies challenge
this conception; reporting increased prevalence of auto-antibodies, concomitant
autoimmune disorders, and systemic findings in some morphea patients. The nature
of these associations and their prognostic and therapeutic significance remains
undefined and of little clinical utility. This creates confusion regarding the
true nature of morphea (harmless/limited vs. part of a systemic autoimmune process)
which negatively impacts patient care. We aim to address this deficiency in
the current state of knowledge via a prospective case control study of adults
and children with morphea investigating clinical morphea manifestations (subtype);
presence of concomitant or familial systemic, autoimmune, and rheumatologic
disorders; autoantibody profile; and HLA type. Our central hypothesis is that
although morphea is thought to consist of one disorder composed solely of cutaneous
manifestations, it is actually comprised of distinct syndromes defined by subtype
with characteristic clinical, serological, and genetic traits.
The completion of this study will clarify the risk of systemic disease and autoimmune profiles in morphea through carefully phenotyping subjects and correlating these findings with autoantibody profiles and HLA type, ultimately leading to a more comprehensive classification scheme which will build consensus for appropriate management. Further, the subjects from the case control study will be invited to enroll into the longitudinal cohort which will correlate disease outcomes with the baseline characteristics established during the case control study to establish whether prognostic variables exist. Further, the data from the case control study, the planned longitudinal study, and further genetic studies will be the platform for application for NIH R01 funding.
Student Role: The fellow will be responsible for the measurement of skin thickness, determination of TGF beta and MMP1 levels using ELISA, and the evaluation of this data under the supervision of myself and our consulting dermatopatholoigist Dr. Joseph Susa.