Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 344
Filter
1.
Front Oncol ; 12: 869706, 2022.
Article in English | MEDLINE | ID: mdl-35574410

ABSTRACT

Extracellular DNA may serve as marker in liquid biopsies to determine individual diagnosis and prognosis in cancer patients. Cell death or active release from various cell types, including immune cells can result in the release of DNA into the extracellular milieu. Neutrophils are important components of the innate immune system, controlling pathogens through phagocytosis and/or the release of neutrophil extracellular traps (NETs). NETs also promote tumor progression and metastasis, by modulating angiogenesis, anti-tumor immunity, blood clotting and inflammation and providing a supportive niche for metastasizing cancer cells. Besides neutrophils, other immune cells such as eosinophils, dendritic cells, monocytes/macrophages, mast cells, basophils and lymphocytes can also form extracellular traps (ETs) during cancer progression, indicating possible multiple origins of extracellular DNA in cancer. In this review, we summarize the pathomechanisms of ET formation generated by different cell types, and analyze these processes in the context of cancer. We also critically discuss potential ET-inhibiting agents, which may open new therapeutic strategies for cancer prevention and treatment.

2.
Nat Rev Endocrinol ; 2022 May 16.
Article in English | MEDLINE | ID: mdl-35578027

ABSTRACT

The physiological process of biomineralization is complex and deviation from it leads to a variety of diseases. Progress in the past 10 years has enhanced understanding of the genetic, molecular and cellular pathophysiology underlying these disorders; sometimes, this knowledge has both facilitated restoration of health and clarified the very nature of biomineralization as it occurs in humans. In this Review, we consider the principal regulators of mineralization and crystallization, and how dysregulation of these processes can lead to human disease. The knowledge acquired to date and gaps still to be filled are highlighted. The disorders of mineralization discussed comprise a broad spectrum of conditions that encompass bone disorders associated with alterations of mineral quantity and quality, as well as disorders of extraskeletal mineralization (hyperphosphataemic familial tumoural calcinosis). Included are disorders of alkaline phosphatase (hypophosphatasia) and phosphate homeostasis (X-linked hypophosphataemic rickets, fluorosis, rickets and osteomalacia). Furthermore, crystallopathies are covered as well as arterial and renal calcification. This Review discusses the current knowledge of biomineralization derived from basic and clinical research and points to future studies that will lead to new therapeutic approaches for biomineralization disorders.

3.
Nat Rev Nephrol ; 2022 May 06.
Article in English | MEDLINE | ID: mdl-35523957
4.
J Innate Immun ; : 1-17, 2022 Apr 20.
Article in English | MEDLINE | ID: mdl-35443244

ABSTRACT

Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-ß superfamily, has been associated with acute and chronic inflammatory conditions including autoimmune disease, i.e., type I diabetes and rheumatoid arthritis. Still, its role in systemic autoimmune disease remains elusive. Thus, we studied GDF15-deficient animals in Fas-receptor intact (C57BL/6) or deficient (C57BL/6lpr/lpr) backgrounds. Further, lupus nephritis (LN) microdissected kidney biopsy specimens were analyzed to assess the involvement of GDF15 in human disease. GDF15-deficiency in lupus-prone mice promoted lymphoproliferation, T-, B- and plasma cell-expansion, a type I interferon signature, and increased serum levels of anti-DNA autoantibodies. Accelerated systemic inflammation was found in association with a relatively mild renal phenotype. Splenocytes of phenotypically overall-normal Gdf15-/- C57BL/6 and lupus-prone C57BL/6lpr/lpr mice displayed increased in vitro lymphoproliferative responses or interferon-dependent transcription factor induction in response to the toll-like-receptor (TLR)-9 ligand CpG, or the TLR-7 ligand Imiquimod, respectively. In human LN, GDF15 expression was downregulated whereas type I interferon expression was upregulated in glomerular- and tubular-compartments versus living donor controls. These findings demonstrate that GDF15 regulates lupus-like autoimmunity by suppressing lymphocyte-proliferation and -activation. Further, the data indicate a negative regulatory role for GDF15 on TLR-7 and -9 driven type I interferon signaling in effector cells of the innate immune system.

5.
Nephron ; : 1-11, 2022 Mar 23.
Article in English | MEDLINE | ID: mdl-35320807

ABSTRACT

INTRODUCTION: Diabetes is a highly prevalent accelerator or even cause of chronic kidney disease imposing a large unmet medical need at the global scale. Massive research activities continue to be in search of a cure but the yield of the classical bench-to-bedside research approach has been low. We speculated that a significant mismatch in design and quality of animal and clinical studies in this domain is a hurdle for translation. METHODS: We performed a meta-analysis of matched pairs of animal and human studies that tested the efficacy of distinct drug interventions for diabetic kidney disease (DKD). We reviewed study designs and reporting quality of such studies over the last decade according to the standards listed in the CONSORT and ARRIVE recommendations, respectively. RESULTS: We noted a wide diversity in the study designs of animal studies in terms of diabetes induction. Major mismatches with the respective human studies referred to age and sex distribution, comorbidities, stage of the kidney disease, and selection of primary endpoints. Usually, treatment was initiated before onset of kidney disease without any standard of care as a background therapy. The reporting quality of animal studies was poor for randomization procedures, blinding, sample size calculation for a prespecified primary endpoint or the safety analysis. Reporting quality of clinical studies had deficits in trial design-, recruitment-, allocation-, and outcome-related aspects. CONCLUSION: Bench-to-bedside translation in the domain of DKD suffers from major deficits in the design of experimental studies in view of the projected clinical trials as well as from significant deficits in the reporting quality in preclinical and clinical studies.

6.
Blood ; 2022 Mar 18.
Article in English | MEDLINE | ID: mdl-35303071

ABSTRACT

Neutrophils are key players during host defense and sterile inflammation. Neutrophil dysfunction is a characteristic feature of the acquired immunodeficiency during kidney disease. We speculated that the impaired renal clearance of the intrinsic purine metabolite soluble uric acid (sUA) may account for neutrophil dysfunction. Indeed, hyperuricemia (HU, serum UA of 9-12 mg/dL) related or unrelated to kidney dysfunction significantly diminished neutrophil adhesion and extravasation in mice with crystal- and coronavirus-related sterile inflammation using intravital microscopy and an air pouch model. This impaired neutrophil recruitment was partially reversible by depleting UA with rasburicase. We validated these findings in vitro using either neutrophils or serum from patients with kidney dysfunction-related HU with or without UA depletion, which partially normalized the defective migration of neutrophils. Mechanistically, sUA impaired ß2 integrin activity and internalization/recycling by regulating intracellular pH and cytoskeletal dynamics, physiological processes that are known to alter the migratory and phagocytic capability of neutrophils. This effect was fully reversible by blocking intracellular uptake of sUA via urate transporters. In contrast, sUA had no effect on neutrophil extracellular trap formation in neutrophils from healthy subjects or patients with kidney dysfunction. Our results identify an unexpected immunoregulatory role of the intrinsic purine metabolite sUA, which contrasts the well-known immunostimulatory effects of crystalline UA. Specifically targeting UA may help to overcome certain forms of immunodeficiency, for example in kidney dysfunction, but may enhance sterile forms of inflammation.

7.
Pediatr Nephrol ; 2022 Mar 14.
Article in English | MEDLINE | ID: mdl-35286452

ABSTRACT

Chronic kidney disease (CKD) is a global public healthcare concern in the pediatric population, where glomerulopathies represent the second most common cause. Although classification and diagnosis of glomerulopathies still rely mostly on histopathological patterns, patient stratification should complement information supplied by kidney biopsy with clinical data and etiological criteria. Genetic determinants of glomerular injury are particularly relevant in children, with important implications for prognosis and treatment. Targeted therapies addressing the primary cause of the disease are available for a limited number of glomerular diseases. Consequently, in the majority of cases, the treatment of glomerulopathies is actually the treatment of CKD. The efficacy of the currently available strategies is limited, but new prospects evolve. Although the exact mechanisms of action are still under investigation, accumulating data in adults demonstrate the efficacy of sodium-glucose transporter 2 inhibitors (SGLT2i) in slowing the progression of CKD due to diabetic and non-diabetic kidney disease. SGLT2i has proved effective on other comorbidities, such as obesity, glycemic control, and cardiovascular risk that frequently accompany CKD. The use of SGLT2i is not yet approved in children. However, no pathophysiological clues theoretically exclude their application. The hallmark of pediatric CKD is the inevitable imbalance between the metabolic needs of a growing child and the functional capacity of a failing kidney to handle those needs. In this view, developing better strategies to address any modifiable progressor in kidney disease is mandatory, especially considering the long lifespan typical of the pediatric population. By improving the hemodynamic adaptation of the kidney and providing additional beneficial effects on the overall complications of CKD, SGLT2i is a candidate as a potentially innovative drug for the treatment of CKD and glomerular diseases in children.

8.
Nephrol Dial Transplant ; 2022 Mar 04.
Article in English | MEDLINE | ID: mdl-35244174

ABSTRACT

Patients with immune-mediated kidney diseases are at increased risk of severe COVID-19. The international rollout of COVID-19 vaccines has provided varying degrees of protection and enabled the understanding of vaccine efficacy and safety. The immune response to COVID-19 vaccines is lower in most patients with immune-mediated kidney diseases; either related to immunosuppression or to co-morbidities and complications caused by the underlying disease. Humoral vaccine response, measured by the presence of antibodies, is impaired or absent in patients receiving rituximab, mycophenolate mofetil (MMF), higher doses of glucocorticoids and likely other immunosuppressants, such as cyclophosphamide. Timing between the use of these agents and administration of vaccines associate with the level of immune response: with rituximab, vaccine response can only be expected once B cells start to recover and patients with transient discontinuation of MMF mount a humoral response more frequently. The emergence of new COVID-19 variants and waning of vaccine induced immunity highlight the value of booster dose and need to develop mutant proof vaccines. COVID-19 vaccines are safe, exhibiting a very low risk of de novo or relapsing immune-mediated kidney disease. Population-based studies will determine whether this is causal or co-incidental. Such cases respond to standard management, including the use of immunosuppression. The IWG and EUVAS recommend that patients with immune-mediated kidney diseases follow national guidance on vaccination. Booster doses based on antibody measurements could be considered.

9.
Cells ; 11(4)2022 02 11.
Article in English | MEDLINE | ID: mdl-35203277

ABSTRACT

Acute organ injury, such as acute kidney injury (AKI) and disease (AKD), are major causes of morbidity and mortality worldwide. Hyperuricemia (HU) is common in patients with impaired kidney function but the impact of asymptomatic HU on the different phases of AKI/AKD is incompletely understood. We hypothesized that asymptomatic HU would attenuate AKD because soluble, in contrast to crystalline, uric acid (sUA) can attenuate sterile inflammation. In vitro, 10 mg/dL sUA decreased reactive oxygen species and interleukin-6 production in macrophages, while enhancing fatty acid oxidation as compared with a physiological concentration of 5 mg/dL sUA or medium. In transgenic mice, asymptomatic HU of 7-10 mg/dL did not affect post-ischemic AKI/AKD but accelerated the recovery of kidney excretory function on day 14. Improved functional outcome was associated with better tubular integrity, less peritubular inflammation, and interstitial fibrosis. Mechanistic studies suggested that HU shifted macrophage polarization towards an anti-inflammatory M2-like phenotype characterized by expression of anti-oxidative and metabolic genes as compared with post-ischemic AKI-chronic kidney disease transition in mice without HU. Our data imply that asymptomatic HU acts as anti-oxidant on macrophages and tubular epithelial cells, which endorses the recovery of kidney function and structure upon AKI.


Subject(s)
Acute Kidney Injury , Hyperuricemia , Reperfusion Injury , Acute Kidney Injury/metabolism , Animals , Humans , Inflammation/metabolism , Ischemia , Macrophages/metabolism , Mice , Phenotype , Reperfusion Injury/metabolism , Uric Acid
10.
Arch Physiol Biochem ; : 1-12, 2022 Jan 05.
Article in English | MEDLINE | ID: mdl-34986074

ABSTRACT

Diabetes is one of the major cause of chronic kidney disease (CKD), including "diabetic nephropathy," and is an increasingly prevalent accelerator of the progression of non-diabetic forms of CKD. The long non-coding RNAs (lncRNAs) have come into the limelight in the past few years as one of the emerging weapons against CKD in diabetes. Available data over the past few years demonstrate the interaction of lncRNAs with miRNAs and epigenetic machinery. Interestingly, the evolving data suggest that lncRNAs play a vital role in diabetes-associated CKD by regulation of epigenetic enzymes such as DNA methyltransferase, histone deacetylases, and histone methyltransferases. LncRNAs are also engaged in the regulation of several miRNAs in diabetic nephropathy. Hence this review will elaborate on the association between lncRNAs and their interaction with epigenetic regulators involved in different aspects and thus the progression of CKD in diabetes.

11.
J Am Soc Nephrol ; 33(2): 259-278, 2022 02.
Article in English | MEDLINE | ID: mdl-34907031

ABSTRACT

Kidney disease is a known risk factor for poor outcomes of COVID-19 and many other serious infections. Conversely, infection is the second most common cause of death in patients with kidney disease. However, little is known about the underlying secondary immunodeficiency related to kidney disease (SIDKD). In contrast to cardiovascular disease related to kidney disease, which has triggered countless epidemiologic, clinical, and experimental research activities or interventional trials, investments in tracing, understanding, and therapeutically targeting SIDKD have been sparse. As a call for more awareness of SIDKD as an imminent unmet medical need that requires rigorous research activities at all levels, we review the epidemiology of SIDKD and the numerous aspects of the abnormal immunophenotype of patients with kidney disease. We propose a definition of SIDKD and discuss the pathogenic mechanisms of SIDKD known thus far, including more recent insights into the unexpected immunoregulatory roles of elevated levels of FGF23 and hyperuricemia and shifts in the secretome of the intestinal microbiota in kidney disease. As an ultimate goal, we should aim to develop therapeutics that can reduce mortality due to infections in patients with kidney disease by normalizing host defense to pathogens and immune responses to vaccines.


Subject(s)
COVID-19/etiology , Immunologic Deficiency Syndromes/etiology , Renal Insufficiency, Chronic/complications , Adaptive Immunity , Blood Platelets/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Gastrointestinal Microbiome/immunology , Humans , Immunity, Innate , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/prevention & control , Immunophenotyping , Models, Immunological , Pandemics , Renal Insufficiency, Chronic/immunology , Risk Factors , SARS-CoV-2 , Seroconversion
12.
Nephrol Dial Transplant ; 2021 Dec 09.
Article in English | MEDLINE | ID: mdl-34888694

ABSTRACT

In 2019 and 2021, the European League for Rheumatism (EULAR) jointly with the European Renal Association (ERA) and the Kidney Disease Improving Global Outcomes (KDIGO), respectively, released updated guidelines on the management of lupus nephritis. The Immunology Working Group of the ERA reviewed and compared both updates. Recommendations were either consistent or differences were of negligible clinical relevance for: Indication for kidney biopsy, kidney biopsy interpretation, treatment targets, hydroxychloroquine dosing, first line initial immunosuppressive therapy for active class III, IV (±V) LN, pregnancy in LN, LN in paediatric patients, and LN patients with kidney failure. Relevant differences in the recommended management relate to the recognition of lupus podocytopathies, uncertainties in steroid dosing, drug preferences in specific populations and maintenance therapy, treatment of pure class V LN, therapy of recurrent LN, evolving alternative drug options, and diagnostic work-up of thrombotic microangiopathy. Altogether, both documents provide an excellent guidance to the growing complexity of LN management. This article endeavours to prevent confusion by identifying differences and clarifying discrepancies.

13.
Nat Rev Nephrol ; 18(3): 171-183, 2022 03.
Article in English | MEDLINE | ID: mdl-34880459

ABSTRACT

Kidney lifespan is a patient-oriented outcome that provides much needed context for understanding chronic kidney disease (CKD). Nephron endowment, age-associated decline in nephron number, kidney injury history and the intrinsic capacity of nephrons to adapt to haemodynamic and metabolic overload vary widely within the population. Defining percentiles of kidney function might therefore help to predict individual kidney lifespan and distinguish healthy ageing from progressive forms of CKD. In response to nephron loss, the remaining nephrons undergo functional and structural adaptations to meet the ongoing haemodynamic and metabolic demands of the organism. When these changes are no longer sufficient to maintain kidney cell homeostasis, remnant nephron demise occurs and CKD progression ensues. An individual's trajectory of glomerular filtration rate and albuminuria reflects the extent of nephron loss and adaptation of the remaining nephrons. Nephron overload represents the final common pathway of CKD progression and is largely independent of upstream disease mechanisms. Thus, interventions that efficiently attenuate nephron overload in early disease stages can protect remnant kidney cells and nephrons, and delay CKD progression. This Review provides a conceptual framework for individualized diagnosis, monitoring and treatment of CKD with the goal of maximizing kidney lifespan.


Subject(s)
Longevity , Renal Insufficiency, Chronic , Glomerular Filtration Rate , Humans , Kidney , Nephrons
14.
Nephrol Dial Transplant ; 2021 Nov 26.
Article in English | MEDLINE | ID: mdl-34850136

ABSTRACT

Klotho is a transmembrane anti-ageing protein that exists in three forms, i.e., α-Klotho, ß-Klotho, and γ-Klotho with distinct organ-specific expression and functions in the body. Here we focus on α-Klotho (mentioned as 'Klotho' only), abundantly expressed by the distal and proximal convoluted tubules of the kidney. Significant decline in systemic and renal Klotho level is a new hallmark for kidney disease progression. Emerging research portrays Klotho as a promising diagnostic as well as a therapeutic target for diabetic and non-diabetic kidney disease. Even so, the underlying mechanisms of Klotho regulation and the strategies to restore its systemic as well as the renal level are still lacking. Angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs) are the current standard of care for kidney diseases where the molecular mechanisms for their nephroprotective action are still ambiguous. Moreover, endoplasmic reticulum stress (ER stress) also plays a crucial role in kidney disease progression. Few studies have claimed that RAAS has a direct relation with ER stress generation and vice versa in kidney disease. Interestingly, RAAS and ER stress modulation is associated with Klotho regulation in kidney disease. Here we focus on how the RAAS and ER stress connects with Klotho regulation in kidney disease. We also discuss Klotho and ER stress in an alliance with the concept of hemodynamic and metabolic overload in kidney disease. In addition, we highlight novel approaches to implement Klotho as a therapeutic target via RAAS and ER stress modulation for the treatment of diabetic and non-diabetic kidney disease.

16.
Br J Pharmacol ; 2021 Nov 16.
Article in English | MEDLINE | ID: mdl-34786690

ABSTRACT

Chronic kidney disease (CKD) is a major public health concern, affecting approximately 10% of the population worldwide. CKD of glomerular or tubular origin leads to the activation of stress mechanisms, including the renin-angiotensin-aldosterone system and mineralocorticoid receptor (MR) activation. Over the last two decades, blockade of the MR has arisen as a potential therapeutic approach against various forms of kidney disease. In this review, we summarize the experimental studies that have shown a protective effect of MR antagonists (MRAs) in nondiabetic and diabetic CKD animal models. Moreover, we review the main clinical trials that have shown the clinical application of MRAs to reduce albuminuria and, importantly, to slow CKD progression. Recent evidence from the FIDELIO trial showed that the MRA finerenone can reduce hard kidney outcomes when added to the standard of care in CKD associated with type 2 diabetes. Finally, we discuss the effects of MRAs relative to those of SGLT2 inhibitors, as well as the potential benefit of combination therapy to maximize organ protection.

17.
Nephrol Dial Transplant ; 2021 Nov 08.
Article in English | MEDLINE | ID: mdl-34748001

ABSTRACT

In the last decades several important advances have taken place in the understanding of the pathogenesis underlying membranous nephropathy, which have sparked renewed interest in its management. Four landmark trials in membranous nephropathy, and a fifth clinical trial-which was a pilot study-, have been published in the last years. The results from some of these trials have had a significant impact in the recommendations included in the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Guideline for the Management of Glomerular Diseases, which represent a significant step forward compared to the previous guideline in several aspects such as diagnosis, disease monitoring and treatment strategies. However, considering the rapidly evolving advances in the knowledge of membranous nephropathy and the recent publication of the STARMEN and RI-CYCLO trials, several recommendations contained in the guideline warrant updates. This manuscript provides a perspective of the Immunonephrology Working Group of the European Renal Association (ERA) regarding the management of membranous nephropathy in native kidneys of adult patients.

18.
Autoimmun Rev ; 20(12): 102986, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34718165

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) pandemic influenced the management of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A paucity of data exists on outcome of patients with vasculitis following COVID-19, but mortality is higher than in the general population and comparable to patients undergoing haemodialysis or kidney transplant recipients (reported mortality rates of 20-25%). Delays in diagnosis have been reported, which are associated with sequelae such as dialysis-dependency. Management of ANCA-associated vasculitis has not changed with the aim to suppress disease activity and reduce burden of disease. The use of rituximab, an important and widely used agent, is associated with a more severe hospital course of COVID-19 and absence of antibodies following severe acute respiratory syndrome (SARS)-CoV-2 infections, which prone patients to re-infection. Reports on vaccine antibody response are scarce at the moment, but preliminary findings point towards an impaired immune response, especially when patients receive rituximab as part of their treatment. Seropositivity was reported in less than 20% of patients when rituximab was administered within the prior six months, and the antibody response correlated with CD19+ B-cell repopulation. A delay in maintenance doses, if disease activity allows, has been suggested using a CD19+ B-cell guided strategy. Other immunosuppressive measures, which are used in ANCA-associated vasculitis, also impair humoral and cellular vaccine responses. Regular measurements of vaccine response or a healthcare-policy time-based strategy are indicated to provide additional doses ("booster") of COVID-19 vaccines. This review summarizes a recent educational forum and a recent virtual meeting of the European Vasculitis Society (EUVAS) focusing on COVID-19.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , COVID-19 , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/epidemiology , Antibodies, Antineutrophil Cytoplasmic , COVID-19 Vaccines , Humans , Pandemics , Rituximab , SARS-CoV-2
20.
Arthritis Res Ther ; 23(1): 239, 2021 09 14.
Article in English | MEDLINE | ID: mdl-34521462

ABSTRACT

BACKGROUND: There is a need for biomarker to identify patients "at risk" for rheumatoid arthritis (risk-RA) and to better predict the therapeutic response and in this study we tested the hypothesis that novel native and citrullinated heterogeneous nuclear ribonucleoprotein (hnRNP)-DL autoantibodies could be possible biomarkers. METHODS: Using protein macroarray and ELISA, epitope recognition against hnRNP-DL was analysed in sera from different developed RA disease and diagnosed SLE patients. Toll-like receptor (TLR) 7/9 and myeloid differentiation primary response gene 88 (MyD88)-dependency were studied in sera from murine disease models. HnRNP-DL expression in cultivated cells and synovial tissue was analysed by indirect immunofluorescence, immunoblot and immunohistochemistry. RESULTS: HnRNP-DL was highly expressed in stress granules, citrullinated in the rheumatoid joint and targeted by autoantibodies either as native or citrullinated proteins in patient subsets with different developed RA disease. Structural citrullination dependent epitopes (SCEs) of hnRNP-DL were detected in 58% of the SLE patients although 98% of these sera were α-CCP-2-negative. To obtain a specific citrullinated signal value, we subtracted the native antibody value from the citrullinated signal. The citrullinated/native index of autoantibodies against hnRNP-DL (CNDL-Index) was identified as a new value for an "individual window of treatment success" in early RA and for the detection of RF IgM/α-CCP-2 seronegative RA patients (24-46%). Negative CNDL-index was found in SLE patients, risk-RA and early RA cohorts such as EIRA where the majority of these patients are DAS28-responders to methotrexate (MTX) treatment (87%). High positive CNDL-values were associated with more severe RA, shared epitope and parenchymal changes in the lung. Specifically, native α-hnRNP-DL is TLR7/9-dependent, associated with pain and ROC analysis revealed an association to initial MTX or etanercept treatment response, especially in seronegative RA patients. CONCLUSION: CNDL-index defines people at risk to develop RA and the "window of treatment success" thereby closing the sensitivity gap in RA.


Subject(s)
Arthritis, Rheumatoid , Autoantibodies , Animals , Arthritis, Rheumatoid/drug therapy , Citrullination , Epitopes , Heterogeneous-Nuclear Ribonucleoproteins , Humans , Mice , Peptides, Cyclic
SELECTION OF CITATIONS
SEARCH DETAIL