Session Information
Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics
Session Type: Abstract Submissions (ACR)
Background/Purpose: Systemic Sclerosis (SSc) exhibits great clinical and serologic variability in different populations. Herein we determined MHC class I and II alleles and extended haplotypes in a cohort of Mexican SSc patients to evaluate the contribution of these loci to SSc susceptibility, clinical and autoantibody profile, and to determine the prevalence of Amerindian, Caucasian and African haplotypes.
Methods We included 159 SSc patients (ACR or LeRoy-Medsger criteria), with homogeneous ancestry (at least 3 generations). Patients were classified in diffuse cutaneous (dcSSc) and limited cutaneous systemic sclerosis (lcSSc) based on the extent of their skin involvement. They were evaluated to determine presence and severity of organ involvement (Medsger’s severity scale). Peripheral venous blood was obtained to test for ANA, SSc-associated antibodies and sequence based MHC class I and II typing. We included 234 healthy, ethnically matched individuals as controls. Admixture estimations and principal component analysis (PCA) were performed. IRB approval was obtained for this study, which was performed according to the Helsinki Declaration contents; informed consent was obtained for every participant. Differences were evaluated using Student’s t test, X2, Fisher exact test and Bonferroni when appropriate, p values <0.05 were considered significant.
Results: We found female predominance (98% vs 84%; p=0.004) and longer disease duration in lcSSc patients (13 vs 8 years; p=0.001); higher proportion of interstitial lung disease (44 vs 24%, p=0.01) and gastrointestinal involvement (73 vs 57%, p=0.03) in dcSSc patients. Anti-Topoisomerase I antibody predominated in dcSSc patients (p=0.0009), and anticentromere (ACA) in lcSSc patients (p=0.005). HLA allele analysis showed increased frequency of HLA-B*08:01 in SSc (gene frequency (gf) 4%) and in dcSSc (gf=4%) patients when compared to controls (gf=0.6%; p=0.01, OR 7.1, 95%CI 2-31; and p=0.004, OR 7.5, 95%CI 1.6-47, respectively); increased frequency of HLA-DRB1*11:04 in dcSSc patients (gf=7.8%) when compared to controls (gf=1.7%, p=0.01, OR 4.8, 95%CI 1.6-14-5); decreased frequency of HLA-DQB1*03:01 in SSc (gf=14.5%) and in lcSSc patients (gf=12.7%) when compared to controls (gf=24.7%, p=0.008, OR 0.5, 95%CI 0.3-0.7; and p=0.009, OR 0.4, 95%CI 0.2-0.7, respectively). Antibody analysis revealed association of HLA-DRB1*08:02 and HLA-DQB1*0402 alleles with anti-Topoisomerase I antibody (p=0.03, OR 2.2, 95%CI 1.2-4; and p=0.00001, OR 5.3, 95%CI 2.8-10, respectively), and HLA-DQB1*0302 was negatively associated to the presence of this autoantibody (p=0.04, OR 0.34, 95%CI 0.15-0.71). Admixture estimations using HLA-B showed significant increase in the percentage of Caucasian genes (33% in lcSSc vs 23% in dcSSc) and reduced percentage of African genes in lcSSc patients (13% vs 24% in dcSSc)
Conclusion: MHC Class I and II genes contribute to Systemic Sclerosis susceptibility, influence clinical presentation and autoantibody profile. Genetic admixture shows different components in dcSSc and lcSSc subsets and in controls.
Disclosure:
T. S. Rodriguez-Reyna,
None;
J. Zuniga,
None;
J. Granados,
None;
P. Mercado Velazquez,
None;
C. Nunez Alvarez,
None;
N. Yu,
None;
S. Alosco,
None;
A. Cruz Lagunas,
None;
E. Yunis,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mhc-class-i-and-class-ii-genes-influence-systemic-sclerosis-susceptibility-clinical-presentation-and-autoantibody-profile-in-a-mexican-admixed-population/