Safety and Efficacy of Ianalumab in Patients With Sjögren's Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study.

Objective: The objective of this study was to report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD).

Methods: Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks until week 24 (treatment period [TP]1). At week 24, patients on 300 mg were rerandomized to continue 300 mg or receive placebo until week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, and patients on 5 and 50 mg directly entered posttreatment safety follow-up.

Safety and efficacy of subcutaneous iscalimab (CFZ533) in two distinct populations of patients with Sjögren's disease (TWINSS): week 24 results of a randomised, double-blind, placebo-controlled, phase 2b dose-ranging study.

Background: Sjögren's disease is a chronic autoimmune disease with an unmet need for targeted therapies. The aim of the TWINSS study is to evaluate the safety and efficacy of iscalimab, a monoclonal antibody against CD40, in patients with active Sjögren's disease.

Methods: This randomised, double-blind, placebo-controlled, phase 2b study, conducted at 71 sites in 23 countries, enrolled patients aged 18 years or older fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) 2016 criteria.

Characteristics associated with patient-reported treatment success in psoriatic arthritis.

Objectives: To determine characteristics associated with patient-reported treatment success in psoriatic arthritis (PsA).

Methods: Rheumatologist-diagnosed PsA patients fulfilling the CASPAR classification were recruited from a single center. PsA outcome measures included: 66/68 swollen/tender joint counts, Leeds/SPARCC dactylitis/enthesitis indices, psoriasis body surface area (BSA), and patient-reported outcomes (PROs) including PROMIS.

Designing an electronic medical record alert to identify hospitalised patients with HIV: successes and challenges.

Objectives: Electronic medical record (EMR) tools can identify specific populations among hospitalised patients, allowing targeted interventions to improve care quality and safety. We created an EMR alert using readily available data elements to identify hospitalised people with HIV (PWH) to facilitate a quality improvement study intended to address two quality/safety concerns (connecting hospitalised PWH to outpatient HIV care and reducing medication errors). Here, we describe the design and implementation of the alert and analyse its accuracy of identifying PWH.

Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial.

Background: Sjögren's syndrome is an autoimmune disease characterised by dry eyes and mouth, systemic features, and reduced quality of life. There are no disease-modifying treatments. A new biologic, ianalumab (VAY736), with two modes of suppressing B cells, has previously shown preliminary efficacy.

Measurement of Minimal Disease Activity in Psoriatic Arthritis Using the Patient-Reported Outcomes Measurement Information System-Physical Function or the Health Assessment Questionnaire Disability Index.

Objective: To assess the interchangeability of the Health Assessment Questionnaire disability index (HAQ DI) with the Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) in the calculation of minimal disease activity (MDA) in psoriatic arthritis (PsA).

Methods: Comprehensive PsA disease activity was collected concomitantly with the HAQ DI and the PROMIS-PF measures in a PsA cohort. The PROMIS-PF-based MDA definitions were built using the existing cross-walk between the scores: HAQ DI ≤0.

Ultrasound-Guided Biopsy of Suspected Salivary Gland Lymphoma in Sjögren's Syndrome.

Objective: To evaluate the safety and utility of core needle biopsy (CNB) for diagnosis of salivary gland lymphoma in Sjögren's syndrome (SS).

Methods: We analyzed data from consecutive SS patients who underwent ultrasound-guided major salivary gland CNB for lymphoma diagnosis and determined whether CNB yielded an actionable diagnosis without need for further intervention.

Results: CNBs were performed in 24 patients to evaluate discrete parotid (n = 6) or submandibular (n = 2) gland masses or diffuse enlargement (n = 16; 15 parotid).

Clinical Characteristics of Hydralazine-induced Lupus.

Introduction The use of hydralazine has been associated with the development of lupus erythematosus and lupus-like syndromes. We performed this retrospective study to identify clinical characteristics of individuals who developed hydralazine-induced lupus. Material and methods We performed a single-center retrospective review of seven individuals who had a diagnosis of hydralazine-induced lupus by International Classification of Diseases, Ninth Revision (ICD9) code and were on hydralazine prior to their diagnosis.

A validated method of labial minor salivary gland biopsy for the diagnosis of Sjögren's syndrome.

Objectives/hypothesis: To validate a technique and outcomes of labial minor salivary gland biopsy (LSGB) used for the diagnosis of Sjögren's syndrome (SS).

Study Design: Prospective cohort study.

Methods: Clinical data were prospectively obtained pre- and postbiopsy using patient-reported questionnaires.

Ocular complications of primary Sjögren syndrome in men.

Purpose: To report the ocular complications of primary Sjögren syndrome (SS) in men.

Design: Retrospective cohort study.

Methods: setting: Tertiary-care SS center.

Ocular and systemic morbidity in a longitudinal cohort of Sjögren's syndrome.

Purpose: To report vision-threatening ocular manifestations of primary Sjögren's syndrome (SS).

Design: Retrospective review.

Participants: Consecutive patients evaluated at an SS center between January 2007 and May 2011.

Antibodies recognising sulfated carbohydrates are prevalent in systemic sclerosis and associated with pulmonary vascular disease.

Background: Glycosylation represents an important modification that regulates biological processes in tissues relevant for disease pathogenesis in systemic sclerosis (SSc), including the endothelium and extracellular matrix. Whether patients with SSc develop antibodies to carbohydrates is not known.

Objectives: To determine the prevalence and clinical phenotype associated with serum IgG antibodies recognising distinct glycans in patients with SSc.

Elevation of intracellular cyclic AMP in alloreactive CD4(+) T Cells induces alloantigen-specific tolerance that can prevent GVHD lethality in vivo.

Cyclic AMP (cAMP) is an important negative regulator of T cell activation, and an increased level of cAMP is associated with T cell hyporesponsiveness in vitro. We sought to determine whether elevating intracellular cAMP levels ex vivo in alloreactive T cells during primary mixed lymphocyte reactions (MLR) is sufficient to induce alloantigen-specific tolerance and prevent graft-versus-host disease (GVHD). Primary MLRs were treated with exogenous (8)Br-cAMP and IBMX, a compound that increases intracellular cAMP levels by inhibition of phosphodiesterases.

Apoptotic splenocytes drive the autoimmune response to poly(ADP-ribose) polymerase 1 in a murine model of lupus.

Although defects in apoptosis have been linked to both human and murine lupus, the exact mechanisms remain unknown. Moreover, it is not clear whether such defects are primary or secondary events in disease pathogenesis. To address these issues, we used an induced model of murine lupus, the parent-into-F(1) model of chronic graft-versus-host disease (cGVHD) in which a lupus-like phenotype highly similar to human systemic lupus erythematosus is reliably induced in normal F(1) mice.

Raynaud's phenomenon in mixed connective tissue disease.

Raynaud's phenomenon affects most patients who have mixed connective tissue disease (MCTD) and frequently represents the initial manifestation of the disease. It is the cutaneous symptom of a systemic vasculopathy that is characterized by intimal fibrosis and blood vessel obliteration that frequently leads to visceral involvement, particularly pulmonary hypertension. An association between Raynaud's phenomenon and the characteristic autoantibody in MCTD, anti-U1-RNP (ribonucleoprotein), is found across the spectrum of rheumatic diseases, including undifferentiated connective tissue disease, scleroderma, and systemic lupus erythematosus.

cAMP inhibits both Ras and Rap1 activation in primary human T lymphocytes, but only Ras inhibition correlates with blockade of cell cycle progression.

Cyclic adenosine monophosphate (cAMP) is a negative regulator of T-cell activation. However, the effects of cAMP on signaling pathways that regulate cytokine production and cell cycle progression remain unclear. Here, using primary human T lymphocytes in which endogenous cAMP was increased by the use of forskolin and 3-isobutyl-1-methylxanthine (IBMX), we show that increase of cAMP resulted in inhibition of T-cell receptor (TCR)/CD3 plus CD28-mediated T-cell activation and cytokine production and blockade of cell cycle progression at the G(1) phase.

Induction of immunologic tolerance for allogeneic hematopoietic cell transplantation.

The ability to achieve complete hematopoietic engraftment in the allogeneic setting without intensive myeloablative chemotherapy will have a profound effect on the practice of allogeneic hematopoietic cell transplantation (HCT). Novel methods to induce antigen-specific T-cell tolerance provide promise to ensure engraftment and reduce GVHD without producing generalized and other toxicities caused by myeloablative conditioning regimens. Compelling experimental evidence indicates that the antigen receptors on T-lymphocytes have dual potential to transmit crucial activation signals for initiating immune responses and to discharge equally potent inactivating signals to abort or inhibit immune responses.

Helper T cell anergy: from biochemistry to cancer pathophysiology and therapeutics.

Tolerance in vivo and its in vitro counterpart, anergy, are defined as the state in which helper T lymphocytes are alive but incapable of producing IL-2 and expanding in response to optimal antigenic stimulation. Anergy is induced when the T cell receptor (TCR) is engaged by antigen in the absence of costimulation or IL-2. This leads to unique intracellular signaling events that stand in contrast to those triggered by coligation of the TCR and costimulatory receptors.