Loss of tet methyl cytosine dioxygenase 3 (TET3) enhances cardiac fibrosis via modulating the DNA damage repair response.

Background: Cardiac fibrosis is the hallmark of all forms of chronic heart disease. Activation and proliferation of cardiac fibroblasts are the prime mediators of cardiac fibrosis. Existing studies show that ROS and inflammatory cytokines produced during fibrosis not only signal proliferative stimuli but also contribute to DNA damage.

Relevance of histopathological findings for predictive scoring of short-term treatment response to plasma exchange in severe ANCA-associated renal vasculitides.

Introduction: Rapidly progressive glomerulonephritis (RPGN) is characterized by a rapid loss of kidney function, affecting both renal and overall patient survival. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems including the kidney, and among most frequent causes of RPGN. We here aimed to validate a recently described scoring system for short-term treatment response to therapeutic plasma exchange (PLEX) in a well-characterized and independent cohort of severe renal AAV presenting with RPGN.

Serum Uric Acid Associates with Systemic Complement C3 Activation in Severe ANCA-Associated Renal Vasculitides.

Involvement of the complement system is key to the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis, but immunometabolic implications, especially on serum uric acid (UA) levels, still need to be elucidated. A total of 34 patients with biopsy-proven ANCA-associated renal vasculitis between 2015 and 2020 were retrospectively enrolled. Serum UA levels were correlated with clinical and histopathological characteristics, separated for critically ill (CI, = 19), myeloperoxidase (MPO)-ANCA ( = 21) and proteinase 3 (PR3)-ANCA ( = 13) subgroups.

A Transcriptome Array-Based Approach to Link SGLT-2 and Intrarenal Complement C5 Synthesis in Diabetic Nephropathy.

Diabetic nephropathy is a common microvascular complication of diabetes mellitus. It is characterized by progressive chronic kidney disease (CKD) with decline of kidney function by hyperfiltration. On a mechanistic level, activation of the complement system has been implicated in the pathogenesis of diabetic nephropathy.

Low levels of circulating methylated IRX3 are related to worse outcome after transcatheter aortic valve implantation in patients with severe aortic stenosis.

Background: Aortic stenosis (AS) is one of the most common cardiac diseases and major cause of morbidity and mortality in the elderly. Transcatheter aortic valve implantation (TAVI) is performed in such patients with symptomatic severe AS and reduces mortality for the majority of these patients. However, a significant percentage dies within the first two years after TAVI, such that there is an interest to identify parameters, which predict outcome and could guide pre-TAVI patient selection.

Low hemoglobin levels are associated with Bowman's capsule rupture and peritubular capillaritis in ANCA-associated renal vasculitis: a link of vascular injury to anemia?

Background: Anemia in anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis is a severe complication that predicts renal survival. We here conducted correlative analyses to evaluate correlations of low hemoglobin levels and histopathological characteristics in ANCA-associated renal vasculitis.

Methods: Fifty-two patients with biopsy-proven ANCA-associated renal vasculitis observed between 2015 and 2020 were retrospectively evaluated.

Serum sodium levels associate with recovery of kidney function in immune checkpoint inhibitor nephrotoxicity.

Background: Immune checkpoint inhibitors (ICIs) are novel drugs targeting programmed cell death protein 1-ligand 1 (PD-L1) or its receptor (PD-1). Enhancing the immune system has also been associated with a wide range of immune-related adverse events (irAE). Among them, acute interstitial nephritis (AIN) is a rare but deleterious irAE in the kidney.

A Transcriptome Array-Based Approach Links Proteinuria and Distinct Molecular Signatures to Intrarenal Expression of Type I Interferon in Lupus Nephritis.

In systemic lupus erythematosus (SLE), the relevance of non-hematopoietic sources of type I interferon in human autoimmunity has recently been recognized. Particularly, type I interferon production precedes autoimmunity in early skin lesions related to SLE. However, the relevance of intrarenal type I interferon expression has not been shown in lupus nephritis.

Case Report: High-dose immunoglobulins prior to plasma exchange in severe pulmonary renal syndrome.

Plasma exchange rapidly depletes pathogenic anti-neutrophil cytoplasmic autoantibodies (ANCAs) and is considered for induction therapy in severe ANCA-associated vasculitis. The aim of plasma exchange is to remove putative disease mediators from the circulation, such as toxic macromolecules and pathogenic ANCAs. To our knowledge, we here provide the first report of applying high-dose IVIGs prior to plasma exchange and assessment of ANCA autoantibody elimination in a patient with severe pulmonary renal syndrome due to ANCA-associated vasculitis.

Study protocol: a prospective single-center study for non-invasive biomonitoring of renal complications in cancer patients treated with immune checkpoint inhibitors.

Background: The advent of immune checkpoint inhibitors (ICIs) has powerfully broadened the scope of treatment options for malignancies with an ongoing increase of indications, but immune-related adverse events (irAEs) represent a serious threat to treatment success. Agents directed against programmed cell death protein 1 (PD-1) or its ligand 1 (PD-L1) are known to cause renal complications with an incidence of 3%. In contrast, subclinical renal involvement is estimated to be much higher, up to 29%.

C-Reactive Protein Levels Are Associated with Complement C4 Deposits and Interstitial Arteritis in ANCA-Associated Renal Vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially life-threatening systemic small-vessel vasculitis that is characterized by pauci-immune glomerulonephritis in case of kidney involvement, representing a major denominator of AAV mortality. Innate immunity with complement system activation is increasingly recognized in the pathogenesis of AAV and as an attractive therapeutic target. Although C-reactive protein (CRP) was thought to be a passive, nonspecific marker of inflammation, recent studies indicate that CRP plays a key role in the innate immune system by recognizing pathogens and altered self-determinants.

Association between Loss of Immune Checkpoint Programmed Cell Death Protein 1 and Active ANCA-Associated Renal Vasculitis.

Immune checkpoint inhibitors (ICIs) have made an important contribution to the survival of patients with certain cancers. ICIs interrupt co-inhibitory signaling pathways mediated by programmed cell death protein 1 (PD-1), programmed cell death protein ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen (CTLA-4) that result in the elimination of cancer cells by stimulating the immune system. However, immune-related adverse events have also been described and attributed to an enhanced immune system activation.

Leukocyturia and hematuria enable non-invasive differentiation of Bowman's capsule rupture severity in PR3-ANCA glomerulonephritis.

Background: Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody-(ANCA)-associated vasculitis potentially resulting in pauci-immune necrotizing and crescentic ANCA glomerulonephritis (GN) with rapid deterioration of kidney function, progression to end stage kidney disease or, if left untreated, lethal exitus. Analysis of the urinary sediment routinely supports clinical management of ANCA GN, but histopathological implications of aberrancies in the urinary sediment mostly remain elusive. Therefore, we aimed to systematically assess the correlation of aberrancies in the urinary sediment and clinico-pathologic findings.

Molecular signatures of intrarenal complement receptors and correlate with renal outcome in human lupus nephritis.

Objective: Lupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE). Lupus nephritis is a major cause of kidney failure in patients with SLE, attributed to increased morbidity and mortality. The in situ deposition of intrarenal immune complexes promotes the accumulation of inflammatory cells and causes kidney injury.

Implication of platelets and complement C3 as link between innate immunity and tubulointerstitial injury in renal vasculitis with MPO-ANCA seropositivity.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially life-threatening systemic small-vessel vasculitis that is characterized by pauci-immune glomerulonephritis, depicting in turn a major denominator of AAV mortality. It is well established that AAV patients feature an increased risk of developing thrombotic events, and platelets are activated in AAV patients being triggered by the alternative complement pathway. Platelets guard vessels integrity and initiate thrombus formation in response to endothelial damage, further constituting a triangular interconnection with the activation of neutrophils and the complement system.

Relevance of Complement C4 Deposits Localized to Distinct Vascular Compartments in ANCA-Associated Renal Vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small-vessel vasculitis affecting multiple organ systems, including the kidney. Small vessels in the kidney include small-sized arteries, capillaries, and venules. Intrarenal C4 deposits are now increasingly recognized as a potential marker and pathogenic mechanism of autoantibody-mediated tissue damage in ANCA-associated renal vasculitis.

The SARS-CoV-2 Delta-Omicron Recombinant Lineage (XD) Exhibits Immune-Escape Properties Similar to the Omicron (BA.1) Variant.

Recently, a recombinant SARS-CoV-2 lineage, XD, emerged that harbors a spike gene that is largely derived from the Omicron variant BA.1 in the genetic background of the Delta variant. This finding raised concerns that the recombinant virus might exhibit altered biological properties as compared to the parental viruses and might pose an elevated threat to human health.

Low levels of hemoglobin associate with critical illness and predict disease course in patients with ANCA-associated renal vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis often leading to critical illness by multi-organ failure. Data for patients with specifically ANCA-associated renal vasculitis requiring intensive care unit (ICU) supportive care are limited and have mainly focused on long-term renal and overall outcome. Particularly, data on critical illness during the initial course of disease are scarce and remain poorly determined.

Intrarenal synthesis of complement C3 localized to distinct vascular compartments in ANCA-associated renal vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems, including the kidney. The activation of the complement system contributes essentially to its pathogenesis by autoantibody-antigen recognition directed against host cells in ANCA-associated renal vasculitis. We herein provide evidence for intrarenal synthesis of complement C3 localized to distinct vascular compartments in ANCA-associated renal vasculitis that associated with distinct inflammatory signaling pathways.