Recent findings from genomewide association studies in AS and other spondyloarthritis (SpA)-related diseases, such as inflammatory bowel disease (IBD) and psoriasis suggest networks of shared and disease specific genes in pathogenesis. In the past few years, axial SpA has emerged as a discrete entity for which specific criteria have been developed This proposal is aimed at further evaluation the spectrum of SpA in first degree relatives (FDRs) of AS patients, particularly of new onset axial SpA, and to assess co-morbidities that could explain the diminishing frequency of HLA-B27 with age. Having developed an instrument through the U.S. National Health and Nutrition Examination Survey (NHANES), and validated it in over 137 FDRs of AS patients for inflammatory low back pain (IBP) and axial SpA, which will be further examined in additional FDRs with the range of other SpA manifestations in order to have a better statistical power for calculation of accuracy of each component (Aim 1). We will administer the instrument to all FDR's of AS patients participating in Project 2 either by mail or by clinical/ serologic evaluation in the Clinical Research Units (CPU's) and serum CRP will be assessed to assess chronic inflammation (from those evaluated in person) or DNA obtained from saliva samples (from those examined by mail) (Aim 2). Genetic analysis of genes known to be associated with AS susceptibility (HLA-B27, ERAPl, IL23R, gene deserts at chromosome 2p15 and 21q22, etc will be carried out comparing affected versus unaffected FDR's (an unaffected FDR defined at having reached the age of 40 years without any signs/symptoms of SpA on questionaire evaluation) with the intent of finding potential biomarkers of disease susceptibility in the FDRs. Based on data from the 2009 NHANES study showing a significantly diminished frequency of HLA-B27 in individuals over the age of 50 years, we will carry out a cross-sectional evaluation in FDRs, by questionnaire or clinical evaluation, for comorbidities potentially associated with SpA, particularly cardiovascular disease (Aim 3) and also hyperiipidemia/ hypercholesterolemia, hypertension, diabetes mellitus, and malignancy.

Public Health Relevance

This project will further validate a questionnaire aimed at screening for ankylosing spondylitis (AS) and other manifestations of spondyloarthritis (SpA) in immediate family members. It will also examine how SpA manifests in family members of AS patients looking at genetic and blood markers, as well as other health problems that may be more frequent in HLA-B27 positive people, such as cardiovascular disease, etc.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
5P01AR052915-07
Application #
8546232
Study Section
Special Emphasis Panel (ZAR1-HL)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
7
Fiscal Year
2013
Total Cost
$63,458
Indirect Cost
$19,741
Name
University of Texas Health Science Center Houston
Department
Type
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Kehl, Amy S; Corr, Maripat; Weisman, Michael H (2016) Review: Enthesitis: New Insights Into Pathogenesis, Diagnostic Modalities, and Treatment. Arthritis Rheumatol 68:312-22
Robinson, Philip C; Claushuis, Theodora A M; Cortes, Adrian et al. (2015) Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis. Arthritis Rheumatol 67:140-51
Cortes, Adrian; Pulit, Sara L; Leo, Paul J et al. (2015) Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. Nat Commun 6:7146
Robinson, Philip C; Costello, Mary-Ellen; Leo, Paul et al. (2015) ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients. Ann Rheum Dis 74:1627-9
Cortes, A; Maksymowych, W P; Wordsworth, B P et al. (2015) Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis. Ann Rheum Dis 74:1387-93
Reveille, John D (2015) Spondyloarthropathies: EULAR recommendations reflect advances in imaging. Nat Rev Rheumatol 11:388-9
Kiltz, U; van der Heijde, D; Boonen, A et al. (2015) Development of a health index in patients with ankylosing spondylitis (ASAS HI): final result of a global initiative based on the ICF guided by ASAS. Ann Rheum Dis 74:830-5
Reveille, John D (2015) Biomarkers for diagnosis, monitoring of progression, and treatment responses in ankylosing spondylitis and axial spondyloarthritis. Clin Rheumatol 34:1009-18
Thom, Nicole; Ritchlin, Christopher T; Zhang, Xiao et al. (2015) Prevalence of chronic axial pain, inflammatory back pain, and spondyloarthritis in diagnosed psoriasis. Arthritis Care Res (Hoboken) 67:829-35
Reveille, John D (2014) An update on the contribution of the MHC to AS susceptibility. Clin Rheumatol 33:749-57

Showing the most recent 10 out of 51 publications