Clinical exome sequencing data from patients with inborn errors of immunity: Cohort level diagnostic yield and the benefit of systematic reanalysis.

While next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use and re-use of exome sequencing is still emerging. We revisited clinical exome data from 1300 IEI patients using an updated in silico IEI gene panel. Variants were classified and curated through expert review.

Breathomics to monitor interstitial lung disease associated with systemic sclerosis.

https://bit.ly/4aKMYif.

High Prevalence of Myositis-Specific and Associated Antibodies in Patients with Pulmonary Hypertension.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSAs/MAAs) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies may be underestimated.

Immunogenicity of COVID-19 booster vaccination in IEI patients and their one year clinical follow-up after start of the COVID-19 vaccination program.

Purpose: Previous studies have demonstrated that the majority of patients with an inborn error of immunity (IEI) develop a spike (S)-specific IgG antibody and T-cell response after two doses of the mRNA-1273 COVID-19 vaccine, but little is known about the response to a booster vaccination. We studied the immune responses 8 weeks after booster vaccination with mRNA-based COVID-19 vaccines in 171 IEI patients. Moreover, we evaluated the clinical outcomes in these patients one year after the start of the Dutch COVID-19 vaccination campaign.

The intrinsic coagulation pathway plays a dominant role in driving hypercoagulability in ANCA-associated vasculitis.

The risk of a venous thrombotic event (VTE) is increased in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV); however, a detailed understanding of the underlying mechanisms of hypercoagulability is limited. We assessed prospectively different coagulation parameters in 71 patients with active AAV at baseline and after 6 months of follow-up. D-dimers and fibrinogen were increased in most patients at presentation and remained elevated in half of the patients.

Plasma Dephosphorylated-Uncarboxylated Matrix Gla-Protein in Systemic Sclerosis Patients: Biomarker Potential for Vascular Calcification and Inflammation.

Background: Systemic sclerosis (SSc) patients face an elevated risk of cardiovascular disease (CVD), even when classic cardiovascular risk factors are considered. Plasma dephosphorylated-uncarboxylated Matrix Gla-protein (dp-ucMGP), an inactive form of MGP, is associated with increased CVD risk. Smooth muscle cells, implicated in SSc's development, are the primary dp-ucMGP producers.

Immune Responses 6 Months After mRNA-1273 COVID-19 Vaccination and the Effect of a Third Vaccination in Patients with Inborn Errors of Immunity.

Purpose: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective long-term protection against COVID-19 is therefore of great importance in these patients, but little is known about the decay of the immune response after primary vaccination. We studied the immune responses 6 months after two mRNA-1273 COVID-19 vaccines in 473 IEI patients and subsequently the response to a third mRNA COVID-19 vaccine in 50 patients with common variable immunodeficiency (CVID).

Assessment of longitudinal serum neutrophil extracellular trap-inducing activity in anti-neutrophil cytoplasmic antibody-associated vasculitis and glomerulonephritis in a prospective cohort using a novel bio-impedance technique.

Neutrophil extracellular traps (NET) have been implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Here, we developed a novel, label-free, high-throughput bio-impedance technique to effectively measure serum NET-inducing activity. Using this technique, NET-inducing activity of serum derived from patients with AAV was assessed in a prospective cohort of 62 patients presenting with active AAV with major organ involvement.

[Chronic anemia and unexplained inflammation: think of VEXAS syndrome].

Background: VEXAS-syndrome is an X-linked acquired multisystemic autoinflammatory disease caused by a somatic mutation in UBA1.

Case Description: In this manuscript we describe a 79-year-old male suffering from skin lesions, macrocytic anemia and lab results showing inflammation in which, based on finding a mutation in UBA1, VEXAS was diagnosed. He was treated with a combination of high dose corticosteroids and anti-IL-6 with good response.

Immunogenicity of the mRNA-1273 COVID-19 vaccine in adult patients with inborn errors of immunity.

Background: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore of great importance in this group, but little is known about the immunogenicity of COVID-19 vaccines in these patients.

Objectives: We sought to study humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult patients with IEI.

Autoantibodies in the disease criteria for systemic sclerosis: The need for specification for optimal application.

The ACR/EULAR classification criteria for systemic sclerosis (SSc) entail three autoantibodies: anti-centromere antibodies (ACA), anti-topoisomerase I antibodies (ATA), and anti-RNA-polymerase III antibodies (ARA). The importance of ACA and ATA in the classification criteria is evidence based, but the diagnostic value is overestimated by clinicians. Fortunately, these autoantibodies are characterized by good agreement between different immuno-assays.

Vascular Remodeling in Pulmonary Arterial Hypertension: The Potential Involvement of Innate and Adaptive Immunity.

Pulmonary arterial hypertension (PAH) is a severe disease with high morbidity and mortality. Current therapies are mainly focused on vasodilative agents to improve prognosis. However, recent literature has shown the important interaction between immune cells and stromal vascular cells in the pathogenic modifications of the pulmonary vasculature.

Evidence and consensus-based recommendations for non-pharmacological treatment of fatigue, hand function loss, Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis.

Objective: SSc is a complex CTD affecting mental and physical health. Fatigue, hand function loss, and RP are the most prevalent disease-specific symptoms of systemic sclerosis. This study aimed to develop consensus and evidence-based recommendations for non-pharmacological treatment of these symptoms.

Breathomics to diagnose systemic sclerosis using thermal desorption and comprehensive two-dimensional gas chromatography high-resolution time-of-flight mass spectrometry.

Systemic sclerosis is a rare autoimmune disease associated with rapidly evolving interstitial lung disease, responsible for the disease severity and mortality. Specific biomarkers enabling the early diagnosis and prognosis associated with the disease progression are highly needed. Volatile organic compounds in exhaled breath are widely available and non-invasive and have the potential to reflect metabolic processes occurring within the body.

Urinary Soluble CD163 and Disease Activity in Biopsy-Proven ANCA-Associated Glomerulonephritis.

Background And Objectives: ANCA-associated GN is a common cause of rapidly progressive GN, with high relapse rates. The early recognition of an ANCA-associated GN relapse is of importance to prevent loss of kidney function. Urinary soluble CD163 has been identified as a promising marker of active ANCA-associated GN.

How do patients with systemic sclerosis experience currently provided healthcare and how should we measure its quality?

Objectives: To gain insight into SSc patients' perspective on quality of care and to survey their preferred quality indicators.

Methods: An online questionnaire about healthcare setting, perceived quality of care (CQ index) and quality indicators, was sent to 2093 patients from 13 Dutch hospitals.

Results: Six hundred and fifty patients (mean age 59 years, 75% women, 32% limited cutaneous SSc, 20% diffuse cutaneous SSc) completed the questionnaire.

Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies.

Background: Diagnosis of primary immunodeficiencies (PIDs) is complex and cumbersome yet important for the clinical management of the disease. Exome sequencing may provide a genetic diagnosis in a significant number of patients in a single genetic test.

Methods: In May 2013, we implemented exome sequencing in routine diagnostics for patients suffering from PIDs.

C5b9 Formation on Endothelial Cells Reflects Complement Defects among Patients with Renal Thrombotic Microangiopathy and Severe Hypertension.

Severe hypertension can induce thrombotic microangiopathy (TMA) in the renal vasculature, the occurrence of which has been linked to mechanical stress to the endothelium. Complement defects may be the culprit of disease in patients who present with severe renal disease and often progress to ESRD, despite BP control. We studied a well defined cohort of 17 patients with hypertension-associated TMA to define the prevalence of complement defects by a specific serum-based microvascular endothelial cell assay.

Necrotizing vasculitis in immediate response to a shoulder dislocation.

The shoulder is one of the most commonly dislocated joints in the human body. Complications usually represent local damage. However, it is unclear whether joint dislocations can have systemic sequellae as wSell.

Disseminated Mycobacterium genavense infection in a patient with a novel partial interleukin-12/23 receptor β1 deficiency.

A patient presented with late onset disseminated nontuberculous mycobacterium (NTM) infection due to a novel interleukin-12/interleukin-23 receptor β1 (IL-12/IL-23Rβ1) mutation, r.1561C>G, leading to the amino acid substitution R521G. This is the second patient reported with a partial IL-12/IL-23Rβ1 defect.