Publications by authors named "Jens Y Humrich"

Background: High-density lipoproteins (HDL) affect endothelial functions such as the expression of endothelial cell adhesion molecules and exert anti-apoptotic/-thrombotic functionalities. Therefore, profound analysis of lipoproteins may unveil biomarkers for (micro-)vasculopathy in systemic sclerosis (SSc) and mortality determining disease manifestations like interstitial lung disease (SSc-ILD). Because nuclear magnetic resonance (NMR) spectroscopy provides a wide range of lipoprotein parameters beyond the capabilities of classical analyses it has been used herein to examine lipoprotein profiles in SSc.

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Introduction: Progressive loss of regulatory T cell (Treg)-mediated control over autoreactive effector T cells contributes to the development of systemic lupus erythematosus (SLE). Accordingly, we hypothesized that Treg may also have the capacity to suppress the activation of autoreactive CD4 T cells that are considered to drive autoimmunity.

Methods: To investigate whether Treg are involved in the control of autoreactive CD4 T cells, we depleted CD25 Treg cells either or , or combined both approaches before antigen-specific stimulation with the SLE-associated autoantigen SmD1(83-119) in the NZB/W F1 mouse model either after immunization against SmD1(83-119) or during spontaneous disease development.

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Article Synopsis
  • The study investigates the role of autoantibodies (aAbs) against the CXCR3 receptor in cardiovascular disease, suggesting a link between chronic inflammation, autoimmunity, and increased cardiovascular risk.* -
  • In a sample of 4195 participants, higher levels of anti-CXCR3 aAbs were associated with thicker arterial walls, increased heart mass, and a higher risk of all-cause mortality, particularly from cardiac causes.* -
  • The findings indicate that elevated anti-CXCR3 aAbs may predict serious cardiac events and contribute to heart failure, highlighting their potential significance in cardiovascular health assessments.*
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Systemic sclerosis (SSc) is a chronic, multisystem connective tissue, and autoimmune disease with the highest case-specific mortality and complications among rheumatic diseases. It is characterized by complex and variable features such as autoimmunity and inflammation, vasculopathy, and fibrosis, which pose challenges in understanding the pathogenesis of the disease. Among the large variety of autoantibodies (Abs) present in the sera of patients suffering from SSc, functionally active Abs against G protein-coupled receptors (GPCRs), the most abundant integral membrane proteins, have drawn much attention over the last decades.

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Purpose Of Review: Low-dose interleukin-2 (IL-2) therapy is increasingly recognized as a promising novel therapeutic concept in inflammatory and autoimmune diseases, in particular in systemic lupus erythematosus (SLE). As IL-2 is indispensable for the growth and survival of regulatory T cells (Treg), deficiency of this regulatory cytokine plays a significant role in immune dysregulation and breach of tolerance in SLE. Recovery of Treg activity by low-dose IL-2 therapy directly interferes with the immune pathology in SLE and thus can be considered a targeted treatment approach with a unique and physiological mode of action.

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Approximately 5% of the world-wide population is affected by autoimmune diseases. Overall, autoimmune diseases are still difficult to treat, impose a high burden on patients, and have a significant economic impact. Like other complex diseases, e.

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In the normal immune system, T cell activation is tightly regulated and controlled at several levels to ensure that activation occurs in the right context to prevent the development of pathologic conditions such as autoimmunity or other harmful immune responses. CD4FoxP3 regulatory T cells (Treg) are crucial for the regulation of T cell responses in the peripheral lymphatic organs and thus for the prevention and control of autoimmunity. In systemic lupus erythematosus (SLE), a prototypic systemic autoimmune disease with complex etiology, a disbalance between Treg and pathogenic effector/memory CD4 T cells develops during disease progression indicating that gradual loss of control over T cell activation is an important event in the immune pathogenesis.

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Objectives: A regulatory T cell (Treg) insufficiency due to shortage of interleukin-2 (IL-2) is central to the pathophysiology of systemic lupus erythematosus (SLE). We performed a multicentre, double-blinded, randomised, placebo-controlled phase II proof-of-concept trial to evaluate the efficacy of low-dose IL-2 therapy in patients with SLE having moderate-to-severe disease activity while receiving standard treatment.

Methods: We randomly assigned 100 patients in a 1:1 ratio to receive either 1.

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Article Synopsis
  • COVID-19 is linked to the production of autoantibodies, similar to systemic autoimmune diseases, indicating their role in the disease's severity.
  • A study of 246 individuals revealed that higher levels of autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules correlate with more severe cases of COVID-19.
  • Specific autoantibodies, particularly against the receptors CXCR3 and AGTR1, were identified as having the strongest association with the severity of the disease, suggesting that changes in their levels and patterns could potentially predict COVID-19 outcomes.
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Regulatory T cells (Treg) are crucial for the maintenance of peripheral tolerance and for the control of ongoing inflammation and autoimmunity. The cytokine interleukin-2 (IL-2) is essentially required for the growth and survival of Treg in the peripheral lymphatic tissues and thus plays a vital role in the biology of Treg. Most autoimmune and rheumatic diseases exhibit disturbances in Treg biology either at a numerical or functional level resulting in an imbalance between protective and pathogenic immune cells.

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Immunophenotyping on the molecular and cellular level is a central aspect for characterization of patients with inflammatory diseases, both to better understand disease etiopathogenesis and based on this to develop diagnostic and prognostic biomarkers which allow patient stratification and tailor-made treatment strategies. Technology-driven developments have considerably expanded the range of analysis tools. Especially the analysis of adaptive immune responses, often regarded as central though mostly poorly characterized disease drivers, is a major focus of personalized medicine.

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In the search for anti-renal autoreactivity in human lupus nephritis, we stimulated blood-derived CD4 T cells from patients with systemic lupus erythematosus with various kidney lysates. Although only minor responses were detectable, these experiments led to the development of a search algorithm that combined autoantibody association with human lupus nephritis and target gene expression in inflamed kidneys. Applying this algorithm, five potential T cell antigens were identified.

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Systemic lupus erythematosus is a systemic and chronic autoimmune disease characterized by loss of tolerance towards nuclear antigens with autoreactive CD4 T cells implicated in disease pathogenesis. However, very little is known about their receptor specificity since the detection of human autoantigen specific CD4 T cells has been extremely challenging. Here we present an analysis of CD4 T cells reactive to nuclear antigens using two complementary methods: T cell libraries and antigen-reactive T cell enrichment.

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An acquired deficiency of interleukin-2 (IL-2) and related disturbances in regulatory T cell (Treg) homeostasis play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Low-dose IL-2 therapy was shown to restore Treg homeostasis in patients with active SLE and its clinical efficacy is currently evaluated in clinical trials. Lupus nephritis (LN), a challenging organ manifestation in SLE, is characterized by the infiltration of pathogenic CD4+ T cells into the inflamed kidney.

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Background: An acquired deficiency of interleukin-2 (IL-2) and related defects in regulatory T cell homeostasis are thought to play a crucial role in the pathogenesis of systemic lupus erythematosus. We hypothesised that reconstitution of regulatory T-cell homoeostasis with low doses of IL-2 would be beneficial to patients with systemic lupus erythematosus.

Methods: In this uncontrolled, phase 1 and 2a trial done in the Department of Rheumatology and Clinical Immunology at Charité-University Medicine Berlin (Berlin, Germany), we assessed the safety and tolerability of low-dose recombinant human IL-2 (aldesleukin) and its effects on regulatory T cells.

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Purpose Of Review: To provide an overview behind the concept and recent advances of low-dose interleukin-2 (IL-2) therapy in systemic lupus erythematosus (SLE).

Recent Findings: A disruption of regulatory T cell homeostasis caused by an acquired deficiency of IL-2 is a crucial event in the pathogenesis of SLE. Here, we highlight the key rationales for the clinical translation of low-dose IL-2 therapy in SLE and summarize the main findings from two independent, early phase uncontrolled clinical studies that investigated the immunological and clinical responses to low-dose IL-2 therapy in patients with active SLE.

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Autoantibodies have been associated with autoimmune diseases. However, studies have identified autoantibodies in healthy donors (HD) who do not develop autoimmune disorders. Here we provide evidence of a network of immunoglobulin G (IgG) autoantibodies targeting G protein-coupled receptors (GPCR) in HD compared to patients with systemic sclerosis, Alzheimer's disease, and ovarian cancer.

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Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV.

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