HLA and Disease

Microsatellite protocol Ankylosing Spondylitis (AS) Insulin Dependent Diabetes Mellitus (IDDM) Celiac Disease Narcolepsy Rheumatoid Arthritis

Erik Thorsby, Chair (erik.thorsby@labmed.uio.no) Background It is well established that susceptibility and/or resistance to certain diseases is primarily associated with genes encoding peptide-presenting HLA molecules. Type I diabetes, narcolepsy, coeliac disease (CD), ankylosing spondylitis (AS) and rheumatoid arthritis (RA) have each been clearly associated with specific class I or class II HLA genes. Several groups have reported disease associations to other HLA linked genes such as LMP, TAP, DM and TNF and more recently studies utilizing polymorphic microsatellite markers have suggested that there may be other HLA-linked genes influencing disease susceptibility and/or resistance. These genes are also likely to be under the influence of linkage disequilibrium with the classical HLA genes. A broad based population analysis comparing these associations in different racial and ethnic groups should be especially informative as demonstrated in previous workshops which have defined more clearly these genetic interactions. Goal To determine if there are any contributions to HLA-associated disease and/or resistance by other HLA linked genes other than those encoding peptide presenting molecules. Objectives/Plans Disease Projects. The following HLA associated diseases will be studied. Each project will have a separate subcommittee and subcommittee chair.

	Subcommittee	Chair	Co-Chair
	Type I Diabetes	Sophie Caillat-Zucman Laboratoire d"Immunologie et INSERM U25 Hopital Necker 161 Rue de Sevres 75014 Paris, France 33-44-49-53-74 (phone) 33-44-49-52-21 (fax) caillat@ceylan.necker.fr	Alberto Pugliese Diabetes Research Institute University of Miami 1450 NW 10th Avenue Miami, FL 33136- USA 1-305-243-4404 (phone) 1-305-243-5348 (fax) apuglies@med.miami.edu
	Narcolepsy	Emanuel Mignot Stanford University Medical Center 701 Welch Road, Suite 2226 Palo Alto, CA 94304, USA 1-415-725-6517 (phone) 1-650-498-7761 (fax) mignot@leland.stanford.edu
	Celiac Disease	Cristina Mazzilli Dipartimento di Medicina Sperimentale Universita La Sapienza Viale Regina Elena, 324 00161 rome, Italy 39-06-4451286 (phone) 39-06-4454820 (fax) cmazzilli@uniroma1.it	Alessio Fasano Div. Pediatric GI & Nutrition Center for Celiac Research Univ.Maryland School of Medicine 22 S. Greene St. P.O. Box 140 Baltimore, MD 21201 U.S.A. 1-410-328-0812 (phone) 1-410-328-1072 (fax) afasano@umaryland.edu
	Rheumatoid Arthritis	Lee Nelson Fred Hutchinson Cancer Center 1100 Fairview Ave. North, D2-100 Seattle, WA 98109-1024, USA 1-206-667-5149 (phone) 1-206-667-6969 (fax) lnelson@fred.fhcrc.org	Jean-Francois Eliaou Laboratorie d'Immunologie Hopital Saint-Eloi, CHU Montpellier 34295 Montpellier, Cedex 5, France 33-4-67-33-74-56 (phone) 33-4-67-33-71-29 (fax) eliaou@infobiogen.fr
	Ankylosing Spondylitis	Antoine Toubert Laboratoire de Biologie Moleculaire Service du Professeur D. Charron Hopital Saint Louis 1 Ave Claude Vellefaux F-75475 Paris, Cedex 10, France 33-1-42-49-49-49 (phone) 33-1-42-49-48-89 (fax) toubert@neptune.chu-stlouis.fr

Each disease subcommittee will 1) recruit patients and normal controls matched for the primary disease associated HLA allele(s)(for example, DR and DQ matched controls for patients with type I diabetes); 2) recruit families to identify a parent who is homozygous for the primary disease associated allele(s). Patients and controls will be typed for selected microsatellite polymorphisms spanning the HLA complex centromeric to the class II region through the class III region and telomeric to class I. These markers will provide preliminary evidence that might assist in identifying additional disease-specific genes. Additional approaches including sequencing of selected regions will be developed to achieve high-resolution analysis of selected regions of the HLA complex to search for sequence homology preferentially shared by patients. Other studies appropriate for each disease subcommittee will be included. This information is available by contacting each of the Disease Section Chairs listed above.