Systemic Lupus Erythematosus (SLE)

Cutaneous lesions are among the earliest and most frequent features of SLE, with over 70% of patients developing mucocutaneous involvement during their disease course. The presence and severity of cutaneous manifestations have been associated with specific autoantibodies, such as anti-Ro/SSA and anti-dsDNA, which may reflect underlying genetic susceptibility. Recent studies have also implicated gene polymorphisms in IRF5, STAT4, TREX1, and TNFA in the pathogenesis of cutaneous SLE phenotypes. Defective TREX1 exonuclease activity, leading to intracellular accumulation of DNA, may trigger type I interferon activation-a key mechanism in lupus pathophysiology. Despite the extensive global literature, data from Egyptian patients remain limited, especially regarding the relationship between TREX1 gene variants and cutaneous lupus phenotypes. Understanding how autoantibody profiles and gene polymorphisms relate to clinical features and disease activity could enhance early diagnosis, predict flares, and improve personalized therapy.

Subject Enrollment This study will consent and enroll 20 subjects total. • For Arm 1, 10 subjects with Idiopathic Pulmonary Arterial Hypertension (IPAH) will be consented and enrolled. For Arm 2, 10 subjects with Connective Tissue Disease Associated Pulmonary Arterial Hypertension (PAH-CTD) will be consented and enrolled. Study Design This study will be observational. Subjects in both arms of the trial will undergo a 129Xe MRI/MRS at timepoints of baseline, 3 months, 6 months, and 12 months. In addition to the this, data from standard of care assessments, such as labs, echocardiography, and six-minute walk distance (6MWD), will also collected at these timepoints. Primary Study Endpoints The primary endpoint for this trial will be the change in defect + low percentage of RBC signal on hyperpolarized 129Xe MRI from baseline to 12 months Secondary Study Endpoints There will be several secondary endpoints for this trial: * Change in regional and global RBC Oscillation Amplitudes on hyperpolarized 129Xe MR spectroscopy from baseline to 12 months * Change in 6MWD from baseline to 12 months * Change in NTproBNP from baseline to 12 months * Change in WHO FC from baseline to 12 months Primary Safety Endpoints There will be several primary safety endpoints for this trial: * Frequency of Adverse Events (AE) and/or Serious Adverse Events (SAE) * Withdrawals due to adverse event or death * Incidence of Adverse Events of Significant Interest (AESI): * Electrocardiogram and any findings * Physical examination and vital signs

Litifilimab is a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting blood dendritic cell antigen 2. It is an inhibitory receptor expressed on the surface of human plasmacytoid dendritic cell (pDCs) and is being investigated for the potential treatment of systemic lupus erythematosus and cutaneous lupus erythematosus. The primary objectives of the study are to evaluate the efficacy of litifilimab compared with placebo in reducing skin disease activity measured by the CLA-IGA-R score \[Parts A\] and the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score \[Part B\] in participants with active SCLE and/or CCLE with or without systemic manifestations and refractory and/or intolerant to antimalarials. The secondary objectives of the study are to evaluate the efficacy of litifilimab in reducing SCLE and/or CCLE disease activity by CLA-IGA-R, CLASI-A; to evaluate additional efficacy parameters of litifilimab in reducing SCLE and/or CCLE disease activity; safety; tolerability; and immunogenicity of litifilimab \[Parts A and B\].

The most clinically meaningful way to discover new targets of T cells in autoimmune diseases is to study the tissues of patients with active autoimmune disease mediated organ inflammation. These tissues contain both cytotoxic and helper T cells that are driving their disease, and these T cells are being guided by TCRs that recognize tissue-specific targets. By collecting tissue when a patient has active inflammation, it is possible to determine which T cells are activated and undergoing clonal expansion in the patient's diseased organ. TScan has developed a genome-wide, high-throughput technology to determine the natural, physiological target of any TCR (Kula, 2019). The goal of this study is to isolate T cells from inflamed tissues and matched blood samples and/or matched normal tissues (for patients with inflammatory bowel diseases). T cell clones that are expanded in diseased tissues relative to blood or normal tissues will be selected and the targets of their TCRs will be defined using TScan's genome-wide, high-throughput target ID technology. The goal of this study is to discover a collection of peptide targets, along with their associated TCRs to be developed as new tolerogenic therapies for patients with autoimmune diseases.

The study was divided into dose increasing stage and dose expanding stage.dose escalation phaseThree dose levels are tentatively determined for dose escalation: 3.0 × 108, 4.5 × 108 and 6.0 × 108 car-cd19/CD20+T cells. It is estimated that the target toxicity probability of the maximum tolerated dose is 30%, and about 12 participants are planned to be enrolled, and the number of enrolled patients in each dose group is subject to the actual situation. During the test, the researchers and partners will jointly negotiate whether to increase or decrease the dose, whether to increase to the set maximum dose group or produce the maximum available cell volume, and whether to increase the exploration of new dose level within the explored dose range (allowed to be conducted when the dose is increased or decreased) according to the participants' cell metabolism characteristics, safety, tolerance and preliminary effectiveness data, so as to determine the possible recommended therapeutic dose (RD).The DLT observation period is 28 days after the first infusion. If the treatment needs to be withdrawn before 28 days after the infusion due to disease progression or other reasons, no obvious car-t cell expansion is detected or car-t treatment is invalid, and the DLT related AE events determined by the researcher may not be related to the product, the DLT observation period can be completed before. During each dose increase, if there is a safety risk that needs to be discussed, the researchers and partners can make a dose increase/stability/decrease decision according to the safety and tolerance of participants and the metabolic kinetics of ct1192 cells. In the same dose group, the first participant had no significant safety risk 14 days after the completion of cell infusion, and subsequent participants could only carry out cell infusion.dose expansion phaseOne or more dose groups may be selected for dose expansion according to the results of the dose increasing stage to further explore the efficacy and safety in SLE patients. Each dose group and each queue plan to include up to 9 cases, and the specific number of patients in the group is subject to the actual number. DLT will not be observed in the dose expansion phase, and other research processes are the same as the dose increment phase. Researchers and collaborators will continue to monitor the safety data of the whole dose expansion phase and make decisions on admission and exit when necessary.

A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19 CAR NK cells (KN5501) in patients with relapsed/refractory B-cell related autoimmune diseases.15 patients are planned to be enrolled in the dose-escalation trial (6×10\^9 cells, 9×10\^9 cells). The primary objective of the study is to evaluation of the safety and feasibility of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases. The secondary objective is to evaluate the effectiveness of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases. The exploratory objective is to evaluate expansion, persistence and ability to deplete CD19 positive B cells of KN5501 in patients with relapsed/refractory B-cell related autoimmune diseases.

The prognosis of patients with active systemic lupus erythematosus (SLE) remains poor, due to two major therapeutic obstacles: (1) current treatment strategies including glucocorticoids, immunosuppressive agents, biological agents, are still difficult to achieve disease control, making the disease condition of some patients continue to be active or even worse; (2) some patients are unable to wean themselves off glucocorticoid and face the risk of numerous adverse effects caused by long-term glucocorticoid dependence, such as glucocorticoid-related diabetes, femoral head necrosis, hypertension, stress ulcers, and infection, etc. Therefore, there is a strong unmet clinical need for more effective treatment for patients suffering from active SLE. Several preclinical studies have shown the efficacy of CAR-T cell treatment in SLE. The aim of this study is to investigate the safety, tolerability, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of CD19 CAR-T cell therapy in active SLE. Patients with active SLE will be invited to participate in the study, to receive CD19 CAR-T intravenous infusion and follow-up visits of up to 2 years after enrollment.

The prognosis of patients with active systemic lupus erythematosus (SLE) remains poor, due to two major therapeutic obstacles: (1) current treatment strategies including glucocorticoids, immunosuppressive agents, biological agents, are still difficult to achieve disease control, making the disease condition of some patients continue to be active or even worse; (2) some patients are unable to wean themselves off glucocorticoid and face the risk of numerous adverse effects caused by long-term glucocorticoid dependence, such as glucocorticoid-related diabetes, femoral head necrosis, hypertension, stress ulcers, and infection, etc. Therefore, there is a strong unmet clinical need for more effective treatment for patients suffering from active SLE. Several preclinical studies have shown the efficacy of CAR-T cell treatment in SLE. The aim of this study is to investigate the safety, tolerability, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of CD19 Universal CAR-γδT cells therapy in active SLE. Patients with active SLE will be invited to participate in the study, to receive CD19 Universal CAR-γδT cells intravenous infusion and follow-up visits of up to 2 years after enrollment.

This study is a single-arm, open-label clinical study designed to evaluate the safety and tolerability of QT-019B in subjects with refractory SLE and to determine the RD. The study has two phases: dose escalation and dose expansion, with a planned enrollment of 18-24 subjects.

This study looks at a study medicine called MK-1045 in people with lupus and rheumatoid arthritis (RA). The main goal of the study is to learn about the safety of MK-1045 and if people tolerate it when they receive it at different dose levels (amounts).