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ObjectivesPatients with rheumatoid arthritis (RA) can test either positive or negative for anti-citrullinated protein antibodies (ACPA), and are thereby ACPA-positive (ACPA+) or ACPA-negative (ACPA–), respectively. Through comprehensive profiling of autoantibodies in serum, we aimed to identify autoantibodies that are differentially abundant between patients with ACPA+ RA and ACPA– RA, and also those that are significantly associated with clinical disease activity.MethodsSerum was collected from patients with ACPA+ RA (n= 32), ACPA– RA (n= 30), and healthy controls (n= 30). Sengenics Immunome™protein microarray was used to screen for over 1,600 IgG autoantibodies against native, unmodified human proteins from each serum sample. Autoantibody profiles were compared between each RA subgroup and controls to identify differentially abundant autoantibodies (P< 0.05, Mann–WhitneyUtest; |Cliff’s delta (d)| > 0.33). Additionally, the relationship between RA patients’ autoantibody abundances and Clinical Disease Activity Index (CDAI) was examined for correlations between serum autoantibodies and disease activity (|Spearman’sρ| > 0.4 andP< 0.01).ResultsWe identified differences in serum autoantibodies between patients with ACPA+ RA and ACPA– RA compared with healthy controls. Specifically, we found 22 and 19 autoantibodies higher in ACPA+ RA patients and ACPA– RA patients, respectively. Among these two sets of autoantibodies, only one autoantibody (anti-GTF2A2) was common in both comparisons. On the other hand, we found 30 and 25 autoantibodies lower in ACPA+ RA and ACPA– RA, respectively, of which eight autoantibodies were common in both comparisons. Functional enrichment analysis of the protein antigens targeted by these autoantibodies showed an over-representation of a range of essential biological processes, including programmed cell death, metabolism, and signal transduction. Lastly, we found that autoantibodies correlate with CDAI, but associate differently depending on the presence or absence of ACPA.ConclusionsACPA status in patients with RA determines not only the composition of the serum autoantibody repertoire, but also the correlative relationships between autoantibodies and disease activity. Notably, many of the autoantibodies identified herein were reported for the first time. Our findings warrant further investigation into the immunological differences between these two RA subgroups, and shed new light on the possible need for different treatment approaches.

ObjectiveTo assess trends in the incidence of heart failure (HF) in patients with incident rheumatoid arthritis (RA) from 1980 to 2009 and to compare different HF definitions in RA.MethodsThe study population comprised Olmsted County, Minnesota residents with incident RA (age ≥ 18 yrs, 1987 American College of Rheumatology criteria met in 1980-2009). All subjects were followed until death, migration, or April 30, 2019. Incident HF events were defined as follows: (1) meeting the Framingham criteria for HF, (2) diagnosis of HF (outpatient or inpatient) by a physician, or (3) International Classification of Diseases, 9th revision (ICD-9), or ICD, 10th revision (ICD-10), codes for HF. Patients with HF prior to the RA incidence/index date were excluded. Cox proportional hazards models were used to compare incident HF events by decade, adjusting for age, sex, and cardiovascular risk factors. HF definitions 2 and 3 were compared to the Framingham criteria.ResultsThe study included 905 patients with RA (mean age 55.9 years; 68.6% female; median follow-up 13.4 years). The 10-year cumulative incidence of HF events by any chart-reviewed method in the RA cohort in the 1980s was 11.66% (95% CI 7.86-17.29), in the 1990s it was 12.64% (95% CI 9.31-17.17), and in the 2000s it was 7.67% (95% CI 5.36-10.97). The incidence of HF did not change across the decades of RA incidence using any of the HF definitions. Physician diagnosis of HF and ICD-9/10 code-based definitions of HF performed well compared to the Framingham criteria, showing moderate to high sensitivity and specificity.ConclusionThe incidence of HF in patients with incident RA in the 2000s vs the 1980s was not statistically significantly different. Physician diagnosis of HF and ICD-9/10 codes for HF performed well against the Framingham criteria.

A 49-year-old woman with no relevant medical history presented to an external neurology clinic with progressive hand and foot paresthesia and gait instability for over 6 months. Initially, she reported tingling and shooting electrical-type sensations involving her feet. Within several weeks of the onset of paresthesia, she noted a burning pain sensation involving the left hand. Sensory symptoms continued to worsen and she felt pressure-like sensation around the neck and scalp region. This was shortly followed by right hand numbness and loss of dexterity. Over the next month, she developed progressive gait imbalance and transitioned to a cane for ambulation.