We constructed miniaturized autoantigen arrays to perform large-scale multiplex characterization of autoantibody responses directed against structurally diverse autoantigens, using submicroliter quantities of clinical samples. Autoantigen microarrays were produced by attaching hundreds of proteins, peptides and other biomolecules to the surface of derivatized glass slides using a robotic arrayer. Arrays were incubated with patient serum, and spectrally resolvable fluorescent labels were used to detect autoantibody binding to specific autoantigens on the array. We describe and characterize arrays containing the major autoantigens in eight distinct human autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. This represents the first report of application of such technology to multiple human disease sera, and will enable validated detection of antibodies recognizing autoantigens including proteins, peptides, enzyme complexes, ribonucleoprotein complexes, DNA and post-translationally modified antigens. Autoantigen microarrays represent a powerful tool to study the specificity and pathogenesis of autoantibody responses, and to identify and define relevant autoantigens in human autoimmune diseases.

Objective. To evaluate whether magnetic resonance imaging (MRI) of the wrists and finger joints and an analysis of serologic autoantibodies are clinically meaningful for the subsequent development of rheumatoid arthritis (RA) in patients with undifferentiated arthritis (UA). Methods. A total of 129 patients with UA, a disease status formally confirmed by a rheumatologist over a period of at least 1 year, were included. Gadolinium-diethylenetriamine-enhanced MRI of both wrists and finger joints and serologic variables were examined upon admission to our Early Arthritis Clinic at Nagasaki University. After a prospective followup of 1 year, a predictive value for the development of RA was determined for each patient. Results. The subjects were evaluated for their positive or negative status with respect to 3 objective measures at study entry: anti-cyclic citrullinated peptide (anti-CCP) antibodies and/or IgM-rheumatoid factor, MRI-proven symmetric synovitis, and MRI-proven bone edema and/or bone erosion. The patients who were positive for at least 2 of these measures progressed to RA at 1 year with a 79.7% positive predictive value (PPV), 63.0% negative predictive value, 75.9% specificity, 68.0% sensitivity, and 71.3% accuracy. Furthermore, in 22 UA patients positive for both anti-CCP antibodies and MRI-proven bone edema who were considered to have progressed to RA at 1 year, the PPV was increased to 100%. A close correlation was found between the present rule and that established in the Leiden Early Arthritis Cohort. Conclusion. MRI-proven early joint damage in conjunction with serologic autoantibodies is efficient in predicting progression from UA to RA. This method can be used to identify patients who would benefit from early treatment with disease-modifying antirheumatic drugs. INTRODUCTIONEarly undifferentiated arthritis (UA) is defined as early arthritis that does not fulfill the classification criteria for a more definitive diagnosis, according to the 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) criteria for rheumatoid arthritis (RA) (1-3). The natural disease course of UA is variable; therefore, to minimize under-and overtreatment of patients with UA, a model was recently constructed by the Leiden Early Arthritis Cohort to estimate the likelihood of progression to RA in individual patients (2,3). Their prediction rule consists of 9 clinical variables: sex, age, localization of symptoms, morning stiffness, tender joint count, ISRCTN: 021008-1.

This is the first study to report, in a single cohort of DM patients, that distinct clinical subsets are distributed in an anti-155/140 Ab-positive group, an anti-140 Ab-positive group, or an anti-ARS Ab-positive group. Our data also confirm previous evidence that anti-155/140 Abs are involved in malignancies and that anti-140 Abs are involved in rapidly progressive ILD.

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Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs) have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8%) compared to the genome-wide SNPs (6.9%). In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1) gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10−9, odds ratio = 1.21). The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05). As AFF1 transcripts were prominently expressed in CD4+ and CD19+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset.