Characteristics of RA and SLE patients.

<p>SS: Sjögren’s syndrome, RA: rheumatoid arthritis, SLE: systemic lupus erythematosus, ACPA: anti-citrullinated peptide antibody, dsDNA: double-stranded-DNA, Ro(+)La(−): anti-Ro/SS-A-positive but anti-La/SS-B-negative, Ro(+)La(+): anti-Ro/SS-A- and anti-La/SS-B-positive, Ro(−)La(−): anti-Ro/SS-A- and anti-La/SS-B-negative. Association was tested by Fisher’s exact test using 2×2 contingency tables or Student’s t-test. *Student’s t-test was employed.</p

HLA class II allele frequency in the RA cases without SE alleles.

<p>SE: shared epitope, OR: odds ratio, CI: confidence interval, <i>Pc</i>: corrected <i>P</i> value, NS: not significant. Allele frequencies are shown in parenthesis (%). Associations were established by Fisher’s exact test using 2×2 contingency tables.</p

HLA allele frequencies in Ro(+)La(−) RA patients.

<p>RA: rheumatoid arthritis, Ro(+)La(−)RA: anti-Ro/SS-A-positive but anti-La/SS-B-negative RA, Ro(−)La(−)RA: ani-Ro/SS-A- and anti-La/SS-B-negative RA. OR: odds ratio, CI: confidence interval, <i>P</i>c: corrected <i>P</i> value, NS: not significant. Allele frequencies are shown in parenthesis (%). Associations were established by Fisher’s exact test using 2×2 contingency tables.</p

<i>HLA-DPB1</i> allele frequency in the SLE patients.

<p>SLE: systemic lupus erythematosus, Ro(+)La(−): anti-Ro/SS-A-positive but anti-La/SS-B-negative, Ro(+)La(+): anti-Ro/SS-A- and anti-La/SS-B-positive, Ro(−)La(−): anti-Ro/SS-A- and anti-La/SS-B-negative SLE patients. OR: odds ratio, CI: confidence interval, <i>Pc</i>: corrected <i>P</i> value, NS: not significant. Allele frequencies are shown in parenthesis (%). Associations were established by Fisher’s exact test using 2×2 contingency tables.</p

HLA allele frequencies in Ro(+)La(+) RA patients.

<p>RA: rheumatoid arthritis, Ro(+)La(+)RA: anti-Ro/SS-A- and anti-La/SS-B-positive RA, Ro(−)La(−)RA: anti-Ro/SS-A- and anti-La/SS-B-negative RA. OR: odds ratio, CI: confidence interval, <i>P</i>c: corrected <i>P</i> value, NS: not significant. Allele frequencies are shown in parenthesis (%). Associations were established by Fisher’s exact test using 2×2 contingency tables.</p

HLA class II allele frequencies in RA cases with or without specific class II alleles.

<p>RA: rheumatoid arthritis, Ro(+)La(−)RA: anti-Ro/SS-A-positive but anti-La/SS-B-negative RA, Ro(−)La(−)RA: anti-Ro/SS-A- and anti-La/SS-B-negative RA, Ro(+)La(+)RA: anti-Ro/SS-A- and anti-La/SS-B-positive RA, OR: odds ratio, CI: confidence interval, <i>P</i>c: corrected <i>P</i> value, NS: not significant. Allele frequencies are shown in parenthesis (%). Associations were established by Fisher’s exact test using 2×2 contingency tables.</p

Associations of amino acid residues in DRβ (A), DQβ (B), and DPβ chains (C) with the presence of anti-La/SS-B antibodies.

<p>Corrected <i>P</i> (<i>P</i>c) values were calculated by multiplying the <i>P</i> value by the number of amino acid residues tested. Associations were established by Fisher’s exact test using 2×2 contingency tables.</p

Associations of amino acid residues in DRβ (A), DQβ (B), and DPβ chains (C) with the presence of anti-Ro/SS-A antibodies.

<p>Corrected <i>P</i> (<i>P</i>c) values were calculated by multiplying the <i>P</i> value by the number of amino acid residues tested. Associations were established by Fisher’s exact test using 2×2 contingency tables.</p

Association of Functional Polymorphisms in <i>Interferon Regulatory Factor 2</i> (<i>IRF2</i>) with Susceptibility to Systemic Lupus Erythematosus: A Case-Control Association Study

<div><p>Interferon regulatory factor 2 (IRF2) negatively regulates type I interferon (IFN) responses, while it plays a role in induction of Th1 differentiation. Previous linkage and association studies in European-American populations suggested genetic role of <i>IRF2</i> in systemic lupus erythematosus (SLE); however, this observation has not yet been confirmed. No studies have been reported in the Asian populations. Here we investigated whether <i>IRF2</i> polymorphisms contribute to susceptibility to SLE in a Japanese population. Association study of 46 <i>IRF2</i> tag single nucleotide polymorphisms (SNPs) detected association of an intronic SNP, rs13146124, with SLE. When the association was analyzed in 834 Japanese patients with SLE and 817 healthy controls, rs13146124 T was significantly increased in SLE compared with healthy controls (dominant model, P = 5.4×10⁻⁴, Bonferroni-corrected P [Pc] = 0.026, odds ratio [OR] 1.48, 95% confidence interval [CI] 1.18–1.85). To find causal SNPs, resequencing was performed by next-generation sequencing. Twelve polymorphisms in linkage disequilibrium with rs13146124 (r²: 0.30–1.00) were identified, among which significant association was observed for rs66801661 (allele model, P = 7.7×10⁻⁴, Pc = 0.037, OR 1.53, 95%CI 1.19–1.96) and rs62339994 (dominant model, P = 9.0×10⁻⁴, Pc = 0.043, OR 1.46, 95%CI 1.17–1.82). The haplotype carrying both of the risk alleles (rs66801661A–rs62339994A) was significantly increased in SLE (P = 9.9×10⁻⁴), while the haplotype constituted by both of the non-risk alleles (rs66801661G–rs62339994G) was decreased (P = 0.0020). A reporter assay was carried out to examine the effect of the <i>IRF2</i> haplotypes on the transcriptional activity, and association of the <i>IRF2</i> risk haplotype with higher transcriptional activity was detected in Jurkat T cells under IFNγ stimulation (Tukey's test, P = 1.2×10⁻⁴). In conclusion, our observations supported the association of <i>IRF2</i> with susceptibility to SLE, and the risk haplotype was suggested to be associated with transcriptional activation of <i>IRF2</i>.</p></div

Case-case analysis on the association of rs1063320 with anti-Sm and anti-RNP antibody-positive SLE and antibody-negative SLE.

<p>Case-case analysis on the association of rs1063320 with anti-Sm and anti-RNP antibody-positive SLE and antibody-negative SLE.</p