Mucosal signatures of pathogenic T cells in HLA-B*27+ anterior uveitis and axial spondyloarthritis.

HLA-B*27 was one of the first HLA alleles associated with an autoimmune disease, i.e., axial spondyloarthritis (axSpA) and acute anterior uveitis (B27AAU), which cause joint and eye inflammation, respectively.

Transcriptomic profiling of thymic dysregulation and viral tropism after neonatal roseolovirus infection.

Introduction: Herpesviruses, including the roseoloviruses, have been linked to autoimmune disease. The ubiquitous and chronic nature of these infections have made it difficult to establish a causal relationship between acute infection and subsequent development of autoimmunity. We have shown that murine roseolovirus (MRV), which is highly related to human roseoloviruses, induces thymic atrophy and disruption of central tolerance after neonatal infection.

Aqueous Macrophages Contribute to Conserved CCL2 and CXCL10 Gradients in Uveitis.

Purpose: Uveitis is a heterogenous group of inflammatory eye disease for which current cytokine-targeted immune therapies are effective for only a subset of patients. We hypothesized that despite pathophysiologic nuances that differentiate individual disease states, all forms of eye inflammation might share common mechanisms for immune cell recruitment. Identifying these mechanisms is critical for developing novel, broadly acting therapeutic strategies.

A simple point-of-care assay accurately detects anti-spike antibodies after SARS-CoV-2 vaccination.

Objective: Lateral flow assays (LFA) are sensitive for detecting antibodies to SARS-CoV-2 proteins within weeks after infection. This study tested samples from immunocompetent adults, and those receiving treatments for chronic inflammatory diseases (CID), before and after mRNA SARS-CoV-2 vaccination.

Methods: We compared results obtained with the COVIBLOCK Covid-19 LFA to those obtained by anti-spike (S) ELISA.

Sleep Disturbance and SARS-CoV-2 Vaccinations in Patients With Chronic Inflammatory Disease.

Objective: Immunocompromised patients with chronic inflammatory disease (CID) may have experienced additional psychosocial burden during the COVID-19 pandemic due to their immunocompromised status. This study was undertaken to determine if vaccination would result in improved patient-reported outcomes longitudinally among individuals with CID undergoing SARS-CoV-2 vaccination regardless of baseline anxiety.

Methods: Data are from a cohort of individuals with CID from 2 sites who underwent SARS-CoV-2 vaccination.

Reactogenicity of the Messenger RNA SARS-CoV-2 Vaccines Associated With Immunogenicity in Patients With Autoimmune and Inflammatory Disease.

Objective: Little is known regarding the reactogenicity and related SARS-CoV-2 vaccine response in patients with chronic inflammatory disease (CID). Our objective was to characterize the adverse event profile of CID patients following SARS-CoV-2 vaccination and understand the relationship between reactogenicity and immunogenicity of SARS-CoV-2 vaccines.

Methods: CID patients and healthy controls eligible to receive messenger RNA (mRNA) SARS-CoV-2 vaccines participated in 3 study visits (pre-vaccine, after dose 1, and after dose 2) in which blood and clinical data were collected.

The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells.

The tissue-specific drivers of neurosarcoidosis remain poorly defined. To identify cerebrospinal fluid (CSF) specific, antigen-driven T and B cell responses, we performed single-cell RNA sequencing of CSF and blood cells from neurosarcoid participants coupled to T and B cell receptor sequencing. In contrast to pulmonary sarcoidosis, which is driven by CD4 T cells, we found CD8 T cell clonal expansion enriched in the neurosarcoid CSF.

Vitreous microparticles contain apoptotic signals suggesting a diabetic vitreopathy.

Aim: To evaluate differences in microparticle profiles in vitreous samples between diabetic and non-diabetic eyes undergoing vitrectomy.

Methods: Un-masked cross-sectional series of 34 eyes undergoing vitrectomy. Vitreous specimens were collected and processed to evaluate for membrane integrity (DAPI), apoptosis (Annexin-V), and endothelial-cell origin (V-Cadherin).

Reduced antibody activity against SARS-CoV-2 B.1.617.2 delta virus in serum of mRNA-vaccinated individuals receiving tumor necrosis factor-α inhibitors.

Background: Although vaccines effectively prevent coronavirus disease 2019 (COVID-19) in healthy individuals, they appear to be less immunogenic in individuals with chronic inflammatory disease (CID) or receiving chronic immunosuppression therapy.

Methods: Here we assessed a cohort of 77 individuals with CID treated as monotherapy with chronic immunosuppressive drugs for antibody responses in serum against historical and variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses after immunization with the BNT162b2 mRNA vaccine.

Findings: Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with tumor necrosis factor alpha (TNF-α) inhibitors (TNFi), and this pattern appeared to be worse against the B.

Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 : A Prospective Cohort Study.

Background: Patients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear.

Objective: To determine the immunogenicity of mRNA-based SARS-CoV-2 vaccines in patients with CID.

Tofacitinib for refractory ocular mucous membrane pemphigoid.

Purpose: To report the successful use of tofacitinib in the treatment of refractory ocular mucous membrane pemphigoid (MMP).

Observations: Two patients with ocular MMP presented with refractory disease after failure of multiple therapies. Treatment with tofacitinib led to durable control of conjunctival inflammation within 8 weeks and no apparent progression of sub-conjunctival fibrosis.

Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2.

Background: Individuals with chronic inflammatory diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients on immunosuppression is not well established. Therefore, determining the effectiveness of SARS-CoV-2 vaccines in the setting of immunosuppression is essential to risk-stratify CID patients with impaired protection and provide clinical guidance regarding medication management.

Clinicomolecular Identification of Conserved and Individualized Features of Granulomatous Uveitis.

Objective: To identify molecular features that distinguish individuals with shared clinical features of granulomatous uveitis.

Design: Cross-sectional, observational study.

Participants: Four eyes from patients with active granulomatous uveitis.

Identifying RNA Biomarkers and Molecular Pathways Involved in Multiple Subtypes of Uveitis.

Purpose: Uveitis is a heterogeneous collection of diseases. We tested the hypothesis that despite the diversity of uveitides, there could be common mechanisms shared by multiple subtypes, and that evidence of these common mechanisms may be detected as gene expression profiles in whole blood.

Design: Cohort study.

Inhibitory signaling sustains a distinct early memory CD8 T cell precursor that is resistant to DNA damage.

The developmental origins of memory T cells remain incompletely understood. During the expansion phase of acute viral infection, we identified a distinct subset of virus-specific CD8 T cells that possessed distinct characteristics including expression of CD62L, T cell factor 1 (TCF-1), and Eomesodermin; relative quiescence; expression of activation markers; and features of limited effector differentiation. These cells were a quantitatively minor subpopulation of the TCF-1 pool and exhibited self-renewal, heightened DNA damage surveillance activity, and preferential long-term recall capacity.

Revising the Diagnosis of Idiopathic Uveitis by Peripheral Blood Transcriptomics.

Purpose: To test the hypothesis that idiopathic uveitis can be categorized into subtypes based on gene expression from blood.

Design: Case control study.

Methods: We applied RNA-Seq to peripheral blood from patients with uveitis associated with 1 of 4 systemic diseases, including axial spondyloarthritis (n = 17), sarcoidosis (n = 13), inflammatory bowel disease (n = 12), tubulo-interstitial nephritis with uveitis (n = 10), or idiopathic uveitis (n = 38) as well as 18 healthy control subjects evaluated predominantly at Oregon Health and Science University.

Successful use of rituximab for hydralazine-induced anti-neutrophil cytoplasmic antibodies-associated vasculitis.

Hydralazine is a commonly used anti-hypertensive medication. It can, however, contribute to the development of autoimmunity, in the form of drug-induced lupus and anti-neutrophil cytoplasmic antibodies-associated vasculitis. We report a 45-year-old patient with hypertension managed with hydralazine for four years who presented with rapidly progressive glomerulonephritis (RPGN), requiring hemodialysis, and diffuse alveolar hemorrhage (DAH), requiring mechanical ventilation, and extracorporeal membrane oxygenation.

Tofacitinib for refractory uveitis and scleritis.

Purpose: To report the successful use of tofacitinib in the treatment of refractory uveitis and scleritis.

Observations: Two patients, one with scleritis and another with anterior and intermediate uveitis, presented with refractory disease after failure of multiple steroid-sparing therapies. Treatment with tofacitinib led to durable resolution of uveitis and scleritis.

Viral MHCI inhibition evades tissue-resident memory T cell formation and responses.

Tissue-resident memory CD8 T cells (Ts) confer rapid protection and immunity against viral infections. Many viruses have evolved mechanisms to inhibit MHCI presentation in order to evade CD8 T cells, suggesting that these mechanisms may also apply to T-mediated protection. However, the effects of viral MHCI inhibition on the function and generation of Ts is unclear.

From mechanism to therapies in systemic lupus erythematosus.

Purpose Of Review: Systemic lupus erythematosus (SLE) is a disabling and deadly disease. Development of novel therapies for SLE has historically been limited by incomplete understanding of immune dysregulation. Recent advances in lupus pathogenesis, however, have led to the adoption or development of new therapeutics, including the first Food and Drug Administration-approved drug in 50 years.

Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the Inhibitory Receptor PD-1 Are an Early Driver of CD8(+) T Cell Exhaustion.

Dynamic reprogramming of metabolism is essential for T cell effector function and memory formation. However, the regulation of metabolism in exhausted CD8(+) T (Tex) cells is poorly understood. We found that during the first week of chronic lymphocytic choriomeningitis virus (LCMV) infection, before severe dysfunction develops, virus-specific CD8(+) T cells were already unable to match the bioenergetics of effector T cells generated during acute infection.

Cutting Edge: B Cell-Intrinsic T-bet Expression Is Required To Control Chronic Viral Infection.

The role of Ab and B cells in preventing infection is established. In contrast, the role of B cell responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in humans) can prevent acute infections, and T-bet promotes IgG2a isotype switching.

Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells.

Programmed Death-1 (PD-1) has received considerable attention as a key regulator of CD8(+) T cell exhaustion during chronic infection and cancer because blockade of this pathway partially reverses T cell dysfunction. Although the PD-1 pathway is critical in regulating established "exhausted" CD8(+) T cells (TEX cells), it is unclear whether PD-1 directly causes T cell exhaustion. We show that PD-1 is not required for the induction of exhaustion in mice with chronic lymphocytic choriomeningitis virus (LCMV) infection.