Whole-blood culture-derived cytokine combinations for the diagnosis of tuberculosis.

Introduction: The diagnosis of tuberculosis (TB) disease and TB infection (TBI) remains a challenge, and there is a need for non-invasive and blood-based methods to differentiate TB from conditions mimicking TB (CMTB), TBI, and healthy controls (HC). We aimed to determine whether combination of cytokines and established biomarkers could discriminate between 1) TB and CMTB 2) TB and TBI 3) TBI and HC.

Methods: We used hemoglobin, total white blood cell count, neutrophils, monocytes, C-reactive protein, and ten Meso Scale Discovery analyzed cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-ɣ, and tumor necrosis factor (TNF)-α) in TruCulture whole blood tubes stimulated by lipopolysaccharides (LPS), zymosan (ZYM), anti-CD3/28 (CD3), and unstimulated (Null) to develop three index tests able to differentiate TB from CMTB and TBI, and TBI from HC.

Proteome and Dihydrorhodamine Profiling of Bronchoalveolar Lavage in Patients with Chronic Pulmonary Aspergillosis.

Neutrophil and (alveolar) macrophage immunity is considered crucial for eliminating . Data derived from bronchoalveloar lavage (BAL) characterizing the human immuno-pulmonary response to are non-existent. To obtain a comprehensive picture of the immune pathways involved in chronic pulmonary aspergillosis (CPA), we performed proteome analysis on AL of 9 CPA patients and 17 patients with interstitial lung disease (ILD).

Culturing of SARS-CoV-2 from patient samples: Protocol for optimal virus recovery and assessment of infectious viral load.

Optimal sampling, preservation, and culturing of SARS-CoV-2 from COVID-19 patients are critical for successful recovery of virus isolates and to accurately estimate contagiousness of the patient. In this study, we investigated the influence of the type of sampling media, storage time, freezing conditions, sterile filtration, and combinations of these to determine the optimal pre-analytic conditions for virus recovery and estimation of infectious viral load in COVID-19 patients. Further, we investigated the viral shedding kinetics and mucosal antibody response in 38 COVID-19 hospitalized patients.

A Novel CDC42 Variant with Impaired Thymopoiesis, IL-7R Signaling, PAK1 Binding, and TCR Repertoire Diversity.

Genetic variants in cell division cycle 42 (CDC42) can manifest with dysmorphic features, autoinflammation, hemophagocytic lymphohistiocytosis, and thrombocytopenia, whereas defective thymopoiesis is a rare disease manifestation. We report a novel CDC42 missense variant (c.46A > G, p.

The multidisciplinary approach to eosinophilia.

Eosinophilic granulocytes are normally present in low numbers in the bloodstream. Patients with an increased number of eosinophilic granulocytes in the differential count (eosinophilia) are common and can pose a clinical challenge because conditions with eosinophilia occur in all medical specialties. The diagnostic approach must be guided by a thorough medical history, supported by specific tests to guide individualized treatment.

Dominant-negative heterozygous mutations in AIRE confer diverse autoimmune phenotypes.

Autoimmune polyendocrine syndrome type 1 (APS-1) is an autosomal recessive disease characterized by severe and childhood onset organ-specific autoimmunity caused by mutations in the autoimmune regulator () gene. More recently, dominant-negative mutations within the PHD1, PHD2, and SAND domains have been associated with an incompletely penetrant milder phenotype with later onset familial clustering, often masquerading as organ-specific autoimmunity. Patients with immunodeficiencies or autoimmunity where genetic analyses revealed heterozygous mutations were included in the study and the dominant-negative effects of the mutations were functionally assessed .

A retrospective cohort study of patients with eosinophilia referred to a tertiary centre.

Introduction: Patients with eosinophilia (an increased number of eosinophilic granulocytes > 0.5 × 10⁸/l in the blood) are encountered in all medical specialties and frequently need thorough workup to identify the eliciting causes and decide whether treatment is indicated. In Denmark, highly specialised centres for eosinophilic diseases or conditions have been established to provide a foundation for the management of complicated cases.

Prolonged viral shedding of SARS-CoV-2 in two immunocompromised patients, a case report.

Background: The duration of viable Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) shedding in immunocompromised patients is still unknown. This case report describes the duration of viable SARS-CoV-2 in two immunocompromised patients with completely different clinical courses and further addresses the immunological aspects.

Case Presentations: Oropharyngeal swaps were collected continuously during hospitalization for two immunocompromised patients infected with SARS-CoV-2 and sent for analysis to real time reverse transcription polymerase chain reaction (RT-PCR), viral culture assessed by plaque assay and full genome sequencing.

Quantification of anti-A of IgM or IgG isotype using three different methodologies.

Background: Reliability of ABO-antibody measurement is important in the context of supplying low-titer ABO incompatible plasma-containing blood products. This study investigated the correlation of anti-A measurements between three different titer methodologies.

Methods: Thirty-four blood group O individuals were included.

Time-related variation in IgG subclass concentrations in a group of healthy Danish adults.

Introduction: Immunoglobulin G subclass measurements are important for the diagnostic work-up of immunodeficiencies and immunoglobulin G4 (IgG4) related diseases. It is currently unknown whether a single sampling is truly representative for an individual's IgG subclass concentrations. This study aimed to investigate whether IgG and IgG subclass concentrations in healthy individuals are stable over time.

Potential anti-EBV effects associated with elevated interleukin-21 levels: a case report.

Background: Germinal center derived memory B cells and plasma cells constitute, in health and during EBV reactivation, the largest functional EBV reservoir. Hence, by reducing germinal center derived formation of memory B cells and plasma cells, EBV loads may be reduced. Animal and in-vitro models have shown that IL-21 can support memory B and plasma cell formation and thereby potentially contribute to EBV persistence.

STK4 Deficiency Impairs Innate Immunity and Interferon Production Through Negative Regulation of TBK1-IRF3 Signaling.

Background: STK4 deficiency due to homozygous mutations in the STK4 gene encoding the STK4/MST1 kinase was first described in 2012. STK4/MST1 kinase regulates cell proliferation, survival, differentiation, and immune responses through canonical and non-canonical Hippo signaling pathways.

Objective: We describe an 11-year-old girl with a clinical presentation consisting of severe recurrent herpes zoster, chronic warts, and recurrent pneumonias, as well as a somatic phenotype with hypothyroidism and low stature.

Association between neutropenia and IgG antineutrophil antibodies in a case of deficiency due to two novel mutations.

This case suggests a mechanistic rationale for the clinical efficacy of intravenous immunoglobulins (IVIG) in treating CD40 ligand (CD40L) deficiency associated neutropenia as it is the first reported instance of free and cell-bound antineutrophil antibodies in a case of CD40L deficiency, accompanied by a prolonged and clinically severe neutropenia.

Reduced membrane attack complex formation in umbilical cord blood during Eculizumab treatment of the mother: a case report.

Background: Atypical hemolytic uremic syndrome (aHUS) is a disorder of the microvasculature with hemolytic anemia, thrombocytopenia and acute kidney injury. Nowadays, aHUS is successfully treated with eculizumab, a humanized, chimeric IgG2/4 kappa antibody, which binds human complement C5 and blocks generation of C5a and membrane-attack-complex.

Case Presentation: A 25-year-old woman with end stage renal disease due to relapsing atypical hemolytic uremic syndrome had a relapse of the disease during pregnancy.

Impaired immune responses to herpesviruses and microbial ligands in patients with MonoMAC.

MonoMAC is a complex primary immunodeficiency caused by mutations in the myeloid transcription factor GATA2, characterized by multilineage cytopenia with malignant complications and severe infections, including mycobacteria and herpesviruses. We describe the clinical presentation, genetics and antiviral inflammatory responses in a small case series. Two patients presented in childhood with mycobacterial infection and were diagnosed with MonoMAC germline GATA2 variants; their healthy fathers with the same mutations were also studied.

Increased but stable isoagglutinin titers in hemodialysis patients.

Background: Prior to an ABO incompatible kidney transplantation it is important to know the recipient's pre-transplantation anti-A and/or anti-B (isoagglutinin) titer. This study determined if pre-transplantation isoagglutinin titers remained stable, over a period of 1 year, among hemodialysis patients.

Method: Blood was collected four times, every 3 months from 54 hemodialysis patients (hemodialysed trice per week ≥ 6 months), and 56 healthy volunteers.

[Chronic pulmonary aspergillosis].

Chronic pulmonary aspergillosis (CPA) is an overlooked disease category in which delay of diagnosis and treatment is associated with increased mortality. A prerequisite for prognostic optimization of CPA is an increased focus on predisposing factors and patients at risk. Diagnosis of CPA is challenging and requires a systematic approach to assessment and interpretation of findings, both of which are necessary for correct disease classification and selection of targeted antifungal treatment and duration.

Minimal variation in anti-A and -B titers among healthy volunteers over time: Implications for the use of out-of-group blood components.

Background: Using potentially out-of-group blood components, like low titer A plasma and O whole blood, in the resuscitation of trauma patients is becoming increasingly popular. However, very little is known whether the donors' anti-A and/or anti-B titers change over time and whether repeated titer measurements on the same donor are required to ensure that each donation produces a low titer product.

Methods: The anti-A and/or anti-B titers were measured on 56 healthy adult volunteers (47 blood donors; nine blood center personnel) every 3 months for 12 consecutive months using an automated solid phase analyzer.

Evidence of perturbed germinal center dynamics, but preserved antibody diversity, in end-stage renal disease.

Introduction: End-stage renal disease (ESRD) is associated with increased infectious susceptibility and with reduced vaccine responses consistent with compromised humoral immunity. Whether the compromised humoral immunity is due to reduced antibody diversity (reduced somatic hypermutation [SHM]) or altered germinal center (GC) dynamics is not known. The GC-derived chemokine CXCL13 as well as peripheral T follicular helper cells (pTFH) reflect GC dynamics, but have, similar to SHM, never been characterized in relation to ESRD.

A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa.

Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had released neutrophil extracellular traps (undergone NETosis) in vivo. The NETosis was mediated through intracellular signals elicited by binding of sialyl Lewis(X) present on salival mucins to l-selectin on neutrophils.

CD4+ CD31+ recent thymic emigrants in CHD7 haploinsufficiency (CHARGE syndrome): a case.

Lymphocyte counts <2000 cells/μL are associated with early death in infants with CHARGE (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) syndrome and CHD7 haploinsufficiency. Absence of recent thymic emigrants is also accompanied by an Omenn-like syndrome and infant death in CHD7 haploinsufficiency. Studies positively identifying recent thymic emigrants, in relation to CHD7 haploinsufficiency, are non-existent.