Moderator of 1 Session
Presenter of 4 Presentations
IS005 - TARGET THERAPY IN APS (ID 791)
Abstract
Abstract Body
Antiphospholipid syndrome is an autoimmune disease characterized by thrombosis and pregnancy morbidity occurring in patients persistently positive for aPL. Current therapeutic options remain confined to long-term anticoagulation with vitamin K antagonists. The future holds much promise with the identification of novel potential targets, many of which are currently under investigation. The challenge will be to design prospective randomized controlled clinical trials to provide the evidence necessary to support integration of these therapies into clinical practice.
IS037 - THE COMPLEX INTERACTION BETWEEN SLE AND APS AND THE INVOLVEMENT OF CYTOKINES (ID 898)
Abstract
Abstract Body
Genetic, environmental and hormonal factors act on various elements of the innate and adaptive immune response. The T cell response to antigen is aberrant in terms of early and late signaling events and results in misbalanced production of cytokines including decreased IL-2 and increased IL-17. Distinct molecular events account for the opposite production of these two cytokines. IL-17-producing T cells also through distinct pathways acquire increased ability to invade tissues and contribute to the inflammatory response. IL-23 is crucial for the development of various autoimmune diseases by promoting Th17 cell–mediated tissue inflammation. A human monoclonal antibody that binds to the p40 subunit which is shared by IL-23 and IL-12 in patients with lupus. IL-23 alters the function of kidney resident cells and causes their demise. Most Treg cells develop in the thymus, while some can develop in the periphery from naïve CD4+ T cells. The main factor for differentiation, survival and function of Treg cells is the IL-2. People and mice lacking elements of the control of Treg cell development, i.e. IL-2, IL-2 receptor or FoXP3 invariably develop autoimmune disease. Metabolically Tregcells can switch between fatty acid and pyruvate oxidation or glycolysis. The effect of low-dose IL-2 has extensively studied in SLE. Several studies showed biological (Treg cell induction) as well as clinical response (different scores were used, but mostly significant improvement). Other forms of IL-2 formulations with enhanced or specified receptor-binding capacities such as muteins or complexes are in development. Restoration of immune tolerance by expanding and activating Treg cells is now extensively used as a novel approach for treating autoimmune diseases where IL-2 is the first-in-class molecule. It needs to be identified in bigger trials how IL-2 would add-on the current therapeutic landscape in curbing a pro-inflammatory state, e.g., from monotherapy in mild disease to combination therapies with immunosuppressives in highly active inflammation.
IS042 - DIFFERENTIATING BETWEEN UCTD AND EARLY-STAGE SLE: FROM DEFINITIONS TO CLINICAL APPROACH (ID 920)
Abstract
Abstract Body
Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations that can potentially affect every organ and system. SLE is usually identified on the basis of clinical or serological manifestations; however, some individuals can present with signs and symptoms that are consistent with SLE but are not sufficient for a definite diagnosis. Disease in these individuals can either progress over time to definite SLE or remain stable, in which case their disease is often described as intermediate, possible or probable SLE. Alternatively, such individuals might have undifferentiated connective tissue disease (UCTD). Being able to differentiate between those with stable UCTD and those with SLE at an early stage is important to avoid irreversible target-organ damage from occurring. We will provide insight into existing and evolving perceptions of the early stages of SLE, including clinical and mechanistic considerations, as well as potential paths towards early identification and intervention. Further research into the earliest phases of SLE will be important for the development of targeted diagnostic approaches and biomarkers for the identification of individuals with early disease who are likely to progress to definite SLE.
O003 - ANTIPHOSPHOLIPID ANTIBODIES (APL) ARE PERSISTENTLY POSITIVE AT HIGH TITERS. ADDITIVE VALUE OF PLATELET-BOUND C4D (PC4D) (ID 95)
Abstract
Background and Aims
We tested the hypothesis that antiphospholipid antibodies (aPL) at high titers remain positive over time, while low titers fluctuate. We also evaluated the correlation between two assay platforms and between aPL and platelet-bound C4d (PC4d) as they are both associated with thrombosis in systemic lupus erythematosus.
Methods
Consecutive samples sent to Exagen for aPL testing during a 5-year period were analyzed. Serum anti-cardiolipin (aCL) and anti-beta2 glycoprotein-1 antibodies (b2GP1) were measured by chemiluminescence (QUANTA Flash; Werfen) or ELiA fluorescence enzyme immunoassay (Phadia; ThermoFisher Scientific). Anti-phosphatidylserine/prothrombin complex antibodies (aPS/PT) were measured by ELISA (QUANTA Lite; Werfen). Assays were performed following manufacturers' instructions. PC4d was measured by flow cytometry following Exagen’s standard operating procedures.
Results
Most positive samples with aCL and b2GP1 high titers - but not low titers - were positive at a retest. aPS/PT followed a similar trend. aCL and b2GP1 measured with two different technologies were highly correlated (Table). PC4d and IgG of the 3 aPL were at best moderately correlated even when analysis included only positive samples (coefficient: 0.20-0.27).
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Conclusions
In the large Exagen laboratory dataset, high titers aPL are often persistently positive, allowing an earlier diagnosis and risk assessment at the time of the initial screening. The high correlation between two methodologies suggest that these findings are independent of assay platform. The low to moderate correlation between PC4d and aPL suggests additive value to evaluate association with thrombosis in autoimmune diseases.