High Resolution HLA Analysis In Primary and Secondary Sjögren’s Syndrome

Gabriela Hernandez-Molina¹, Jose Manuel Rodriguez-Perez², Nancy Martínez-Rodríguez², Guadualupe Lima³, Gilberto Vargas-Alarcon⁴ and Jorge Sanchez-Guerrero⁵, ¹Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubirán, Mexico City, Mexico, ²Department of Molecular Biology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico, ³Immunology and Rheumatology Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubirán, Mexico City, Mexico, ⁴Molecular Biology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico, ⁵UHN Toronto Western Hospital, Toronto, ON, Canada

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Sjogren's syndrome and major histocompatibility complex (MHC)

Session Information

Title: Sjögren's Syndrome: Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: The Class II HLA-DR and HLA-DQ alleles have been associated with primary Sjögren’s Syndrome (SS) susceptibility. The aim of this study was to explore and compare the distribution of HLA-A, B, DRB1 and DQB1 alleles in patients with primary SS, secondary SS and patients with Connective Tissue Disease (CTD) without (w/o) SS.

Methods: Patients were drawn from a previous study where 50 pSS and 300 CTD patients were randomly selected from our total population of over 5000 patients, and tested for the presence of SS according to the AECG criteria. For the present study we included 28 patients with pSS, 30 patients with sSS and 96 patients with CTD w/o SS with available DNA samples. HLA-A, B, DRB1 and DQB1 were typed by standard PCR-sequencing based typing method. Serum samples were also examined for anti-Ro/SSA and anti-La/SSB antibodies by ELISA. We used the chi-square analysis or the Fisher’s exact test and the software EPIINFO.

Results: Overall the alleles A*68:01 (a.f. 0.086 vs. a.f 0.02) and DRB1*1406 (a.f. 0.10 vs a.f. 0.008) were associated with SS (OR 4.43 95% C.I. 1.35-14.48, p= 0.007 and OR 14 95% C.I. 1.68-116, p=0.001, respectively). Patients with pSS had a significant higher prevalence of DRB1*1406 than sSS and CTD w/o SS patients (a.f 0.11, a.f 0.09 and a.f 0.008, respectively, OR 16 95% C.I. 1.59-390 p=0.001). Patients with sSS had a higher frequency of the allele A*03:36 when compared with CTD w/o SS patients (a.f. 0.067 vs. a.f 0.005, OR 13.64 95% C.I., 1.40-327, p=0.01). Then we analyzed the patients according to the positivity to anti-Ro/SSA or anti-La/SSB positivity regardless of SS status. Anti-Ro/SSA positive patients had more frequently the allele B*51:01 (a.f. 0.100 vs. a.f. 0.011, OR 10.11 95% C.I. 1-09-245.99, p=0.02) and DRB1*03:01 (a.f. 0.10 vs. a.f 0.027, OR 4.26 95% C.I. 1.01-18.89, p=0.029). The DRB1*03:01 allele was also more prevalent among patients with anti-La/SSB antibodies (a.f. 0.13 vs. a.f. 0.03, OR 4.26 95% C.I.0.93-18.70 p=0.043), as well as the A*01:01 allele (a.f. 0.20 vs. a.f. 0.05, OR 4.75 95% C.I. 1.32-16.92, p=0.003). When we analyzed by generic HLA, we also found an association with DQB1*02 (a.f. 0.23 vs a.f. 0.06, OR 4.16 95% CI 1.32-12.93, p=0.003) and DQB1*04 (a.f. 0.43 vs a.f. 0.07, OR 4.04 95% C.I. 1.63-9.99, p=0.005) and the presence of anti-Ro/SSA antibody.

Conclusion: DRB1*1406 identified patients with both SS varieties whereas B*51:01 and DRB1*03:01 patients with anti-Ro/SSA positivity.

Disclosure:

G. Hernandez-Molina,
None;

J. M. Rodriguez-Perez,
None;

N. Martínez-Rodríguez,
None;

G. Lima,
None;

G. Vargas-Alarcon,
None;

J. Sanchez-Guerrero,
None.

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