Background Patients with systemic lupus erythematosus (SLE) have autoantibodies against the L1-encoded open-reading frame 1 protein (ORF1p). Here, we report (i) which immune cells ORF1p emanates from, (ii) which L1 loci are transcriptionally active, (iii) whether the cells express L1-dependent interferon and interferon-stimulated genes, and (iv) the effect of inhibition of L1 ORF2p by reverse transcriptase inhibitors. Results L1 ORF1p was detected by flow cytometry primarily in SLE CD66b+CD15+ regular and low-density granulocytes, but much less in other immune cell lineages. The amount of ORF1p was higher in neutrophils from patients with SLE disease activity index (SLEDAI) > 6 (p = 0.011) compared to patients with inactive disease, SLEDAI < 4. Patient neutrophils transcribed seven to twelve human-specific L1 loci (L1Hs), but only 3 that are full-length and with an intact ORF1. Besides serving as a source of detectable ORF1p, the most abundant transcript encoded a truncated ORF2p reverse transcriptase predicted to remain cytosolic, while the two other encoded an intact full-length ORF2p. A number of genes encoding proteins that influence L1 transcription positively or negatively were altered in patients, particularly those with active disease, compared to healthy controls. Components of nucleic acid sensing and interferon induction were also altered. SLE neutrophils also expressed type I interferon-inducible genes and interferon β, which were substantially reduced after treatment of the cells with drugs known to inhibit ORF2p reverse transcriptase activity. Conclusions We identified L1Hs loci that are transcriptionally active in SLE neutrophils, and a reduction in the epigenetic silencing mechanisms that normally counteract L1 transcription. SLE neutrophils contained L1-encoded ORF1p protein, as well as activation of the type I interferon system, which was inhibited by treatment with reverse transcriptase inhibitors. Our findings will enable a deeper analysis of L1 dysregulation and its potential role in SLE pathogenesis.

Many patients suffering from autoimmune diseases have autoantibodies against proteins encoded by genomic retroelements, suggesting that normal epigenetic silencing is insufficient to prevent the production of the encoded proteins for which immune tolerance appears to be limited. One such protein is the transmembrane envelope (Env) protein encoded by human endogenous retrovirus K (HERV-K). We reported recently that patients with rheumatoid arthritis (RA) have IgG autoantibodies that recognize Env. Here, we use RNA sequencing of RA neutrophils to analyze HERV-K expression and find that only two loci with an intact open-reading frame for Env, HERV-K102, and K108 are expressed, but only the former is increased in RA. In contrast, other immune cells express more K108 than K102. Patient autoantibodies recognized endogenously expressed Env in breast cancer cells and in RA neutrophils but not healthy controls. A monoclonal anti-Env antibody also detected Env on the surface of RA neutrophils but very little on the surface of other immune cells. We conclude that HERV-K102 is the locus that produces Env detectable on the surface of neutrophils in RA. The low levels of HERV-K108 transcripts may contribute only marginally to cell surface Env on neutrophils or other immune cells in some patients.

Objective The study objective was to assess sociodemographic disparities in telehealth use among patients in an urban adult rheumatology clinic during the coronavirus disease 2019 (COVID‐19) pandemic. Methods In this retrospective cohort study, patient‐level sociodemographic data associated with all rheumatology visits in the following two periods were reviewed: pre‐COVID‐19 (March 1, 2019 to February 28, 2020) and COVID‐19 (April 1, 2020 to March 31, 2021). Data were extracted from the electronic health record. Multivariable logistic regression analyses were performed to determine sociodemographic factors associated with video visits during the COVID‐19 period. Results In the pre‐COVID‐19 period, 1503 patients completed 3837 visits (100% in person). In the COVID‐19 period, 1442 patients completed 3406 visits: 41% in person, 30% video, and 29% telephone only. Several factors were associated with decreased video use: preference for Spanish language (adjusted odds ratio [aOR] 0.27, 95% confidence interval [CI] 0.15‐0.47) or other non‐English languages (aOR 0.34, 95% CI 0.21‐0.55), Black or African American race/ethnicity (aOR 0.50, 95% CI 0.35‐0.73), Medicaid payer, and increasing age. Conclusion Decreased video visit use among rheumatology patients was associated with non‐English language preference, minority race/ethnicity, increasing age, and indicators of low income. Rapid deployment and expansion of telehealth during the COVID‐19 pandemic likely has improved access for some but widened preexisting disparities for others. As medical care evolves toward ongoing digital care delivery, clarifying and addressing causes of telehealth disparities is essential for delivering equitable health care.

ObjectiveTo expand in an unbiased manner our knowledge of autoantigens and autoantibodies in patients with systemic lupus erythematosus (SLE) and evaluate their associations with serological and clinical parameters.MethodsHuman proteome arrays (>21,000 proteins) were screened with serum from SLE patients (n=12) and healthy controls (n=6) for IgG and IgA binding. Top hits were validated with two cohorts of SLE patients (n=49, n=46) and other rheumatic diseases by ELISA. Clinical associations of the autoantibodies were tested.ResultsRo60 was the top hit in the screen and the 10 following proteins included 2 additional known lupus autoantigens, plus 8 novel autoantigens involved in microRNA processing (AGO1, AGO2, and AGO3), ribosomes (RPLP2, OTUD5), RNA transport by the vault (MVP), and the immune proteasome (PSME3). Patient serum contained IgG reactive with these proteins and IgA against the Argonaute proteins. Using the 95th percentile of healthy donor reactivity, 5 to 43 % were positive for the novel antigens with OTUD5 and AGO1 showing the highest percentages of positivity. Autoantibodies against AGO1 proteins were more prevalent in patients with oral ulcers in a statistically significant manner. IgG autoantibodies against Argonaute proteins were also seen in other rheumatic diseases.ConclusionWe discovered new autoantigens existing in cytosolic macromolecular protein assemblies containing RNA (except the proteasome) in cells. A more comprehensive list of autoantigens will allow for a better analysis of how proteins are targeted by the autoimmune response. Future research will also reveal whether specific autoantibodies have utility in the diagnosis or management of SLE.