Identification of Patients With Early Rheumatoid Arthritis: Challenges and Future Directions

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis that affects the adult population. Early diagnosis and treatment are the cornerstones to prevent joint damage and avoid long-term costs and disability. This article reviews the limitations of the currently available tools for the evaluation of patients with early arthritis, including clinical assessment, serologic markers and imaging modalities. It also discusses gene expression analysis, a newer and potentially promising approach to the early diagnosis of RA

Serologic Evidence of H1 Swine Influenza Virus Infection in Swine Farm Residents and Employees

We evaluated seropositivity to swine and human H1 influenza viruses in 74 swine farm owners, employees, their family members, and veterinarians in rural south-central Wisconsin, compared with 114 urban Milwaukee, Wisconsin, residents. The number of swine farm participants with positive serum hemagglutination-inhibition (HI) antibody titers >40 to swine influenza viruses (17/74) was significantly higher (p<0.001) than the number of seropositive urban control samples (1/114). The geometric mean serum HI antibody titers to swine influenza viruses were also significantly higher (p<0.001) among the farm participants. Swine virus seropositivity was significantly (p<0.05) associated with being a farm owner or a farm family member, living on a farm, or entering the swine barn >4 days/week. Because pigs can play a role in generating genetically novel influenza viruses, swine farmers may represent an important sentinel population to evaluate the emergence of new pandemic influenza viruses

Prediction of Disease Severity in Patients with Early Rheumatoid Arthritis by Gene Expression Profiling

In order to test the ability of peripheral blood gene expression profiles to predict future disease severity in patients with early rheumatoid arthritis (RA), a group of 17 patients (1 ± 0.2 years disease duration) was evaluated at baseline for gene expression profiles. Disease status was evaluated after a mean of 5 years using an index combining pain, global and recoded MHAQ scores. Unsupervised and supervised algorithms identified “predictor genes” whose combined expression levels correlated with follow-up disease severity scores. Unsupervised clustering algorithms separated patients into two branches. The only significant difference between these two groups was the disease severity score; demographic variables and medication usage were not different. Supervised T-Test analysis identified 19 “predictor genes” of future disease severity. Results were validated in an independent cohort of subjects of established RA with using Support Vector Machines and K-Nearest-Neighbor Classification. Our study demonstrates that peripheral blood gene expression profiles may be a useful tool to predict future disease severity in patients with early and established RA

IgG and IgM Autoantibody Differences in Discoid and Systemic Lupus Patients

Systemic lupus erythematosus (SLE) patients with discoid lupus erythematosus (DLE) were reported to have milder disease. To test this observation, we used sandwich arrays containing 98 autoantigens to compare autoantibody profiles of SLE subjects without DLE (DLE-SLE+) (N=9), SLE subjects with DLE (DLE+SLE+) (N=10), DLE subjects without SLE (DLE+SLE-) (N=11), and healthy controls (N=11). We validated differentially expressed autoantibodies using immunoassays in DLE-SLE+ (N=18), DLE+SLE+ (N=17), DLE+SLE- (N=23), and healthy subjects (N=22). Arrays showed 15 IgG autoantibodies (10 against nuclear antigens) and 4 IgM autoantibodies that were differentially expressed (q-value<0.05). DLE-SLE+ subjects had higher IgG autoantibodies against double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), double-stranded RNA (dsRNA), histone H2A and H2B, and SS-A (52kDa) compared with all other groups including DLE+SLE+ subjects (P<0.05). Immunoassays measuring anti-dsDNA, -ssDNA, and -SS-A (52kDa) IgG autoantibodies showed similar trends (P<0.05). Healthy and DLE+SLE- subjects expressed higher IgM autoantibodies against alpha beta crystallin, lipopolysaccharide, heat-shock cognate 70, and desmoglein-3 compared with DLE+SLE+ and DLE-SLE+ subjects. IgG:IgM ratios of autoantibodies against nuclear antigens progressively rose from healthy to DLE-SLE+ subjects. In conclusion, lower IgG autoantibodies against nuclear antigens in DLE+SLE+ versus DLE-SLE+ subjects suggest that DLE indicates lower disease severity. Higher IgM autoantibodies against selected antigens in healthy and DLE+SLE- subjects may be nonpathogenic

Using gene expression data to identify certain gastro-intestinal diseases

BACKGROUND: Inflammatory bowel diseases, ulcerative colitis and Crohn’s disease are considered to be of autoimmune origin, but the etiology of irritable bowel syndrome remains elusive. Furthermore, classifying patients into irritable bowel syndrome and inflammatory bowel diseases can be difficult without invasive testing and holds important treatment implications. Our aim was to assess the ability of gene expression profiling in blood to differentiate among these subject groups. METHODS: Transcript levels of a total of 45 genes in blood were determined by quantitative real-time polymerase chain reaction (RT-PCR). We applied three separate analytic approaches; one utilized a scoring system derived from combinations of ratios of expression levels of two genes and two different support vector machines. RESULTS: All methods discriminated different subject cohorts, irritable bowel syndrome from control, inflammatory bowel disease from control, irritable bowel syndrome from inflammatory bowel disease, and ulcerative colitis from Crohn’s disease, with high degrees of sensitivity and specificity. CONCLUSIONS: These results suggest these approaches may provide clinically useful prediction of the presence of these gastro-intestinal diseases and syndromes

Clinical and Immunologic Profiles in Incomplete Lupus Erythematosus and Improvement with Hydroxychloroquine Treatment

Objective. The study goals were to evaluate performance of SLE classification criteria, to define patients with incomplete lupus erythematosus (ILE), and to probe for features in these patients that might be useful as indicators of disease status and hydroxychloroquine response. Methods. Patients with ILE (N=70) and SLE (N=32) defined by the 1997 American College of Rheumatology criteria were reclassified using the 2012 Systemic Lupus International Collaborating Clinics criteria. Disease activity, patient reported outcomes, and levels of Type I interferon- (IFN-) inducible genes, autoantibodies, and cytokines were measured. Subgroups treated with hydroxychloroquine (HCQ) were compared to patients not on this drug. Results. The classification sets were correlated (R2=0.87). ILE patients were older (P=0.0043) with lower disease activity scores (P<0.001) and greater dissatisfaction with health status (P=0.034) than SLE patients. ILE was associated with lower levels of macrophage-derived cytokines and levels of expressed Type I IFN-inducible genes. Treatment of ILE with HCQ was associated with better self-reported health status scores and lower expression levels of Type I IFN-inducible genes than ILE patients not on HCQ. Conclusion. The 2012 SLICC SLE classification criteria will be useful to define ILE in trials. Patients with ILE have better health status and immune profiles when treated with HCQ