Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells.

Objectives: Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL.

Correlation of Professional Antigen-Presenting TbetCD11c B Cells With Bone Destruction in Untreated Rheumatoid Arthritis.

Objective: Subsets of CD21 memory B cells (MBCs), including double-negative (DN, CD27IgD) and TbetCD11c cells, are expanded in chronic inflammatory diseases. In rheumatoid arthritis (RA), CD21 MBCs correlate with joint destruction. However, whether this is due to the TbetCD11c subset, its function and pathogenic contribution to RA are unknown.

Sex differences in cytokines and adipokines in obese patients with PsA and controls undergoing a weight loss intervention.

Objective: In this post hoc analysis of a previously published study, we compared cytokines and adipokine levels in women and men with psoriatic arthritis (PsA) at baseline (BL) and 6 months (M6) following a weight loss intervention.

Methods: Patients with PsA (n=41) between 25 and 75 years of age, with body mass index (BMI)≥33 kg/m were included in a weight loss intervention with a very low energy diet (VLED) for 12 or 16 weeks depending on BL BMI<40 or ≥40 kg/m. As controls (n=39), obese individuals, already planned for VLED treatment were recruited and matched for sex, age and weight to the patients with PsA.

Rheumatoid arthritis chondrocytes produce increased levels of pro-inflammatory proteins.

Objective: To investigate whether articular chondrocytes from rheumatoid arthritis (RA) patients have acquired a proinflammatory phenotype.

Method: Articular cartilage explants from RA patients and healthy controls (HC) were cultured with or without interleukin (IL)-1β for two weeks. Protein levels of cytokines and metalloproteinases (MMPs) in the supernatant were measured by LUMINEX, mRNA with qPCR and nitrogen oxide (NO) levels with Griess assay.

Early Increase of Circulating Transitional B Cells and Autoantibodies to Joint-Related Proteins in Patients With Metastatic Melanoma Developing Checkpoint Inhibitor-Induced Inflammatory Arthritis.

Objective: To investigate potential associations between B cell-related immunologic changes and development of inflammatory arthritis (IA) after treatment with immune checkpoint inhibitors (ICIs).

Methods: Patients who developed ICI-induced IA (ICI-IA) and patients who did not develop immune-related adverse events (non-IRAE) after receiving ICIs to treat metastatic melanoma were consecutively recruited. Blood samples were collected at the time of ICI-IA occurrence and at different time points during treatment.

A close-up on the expanding landscape of CD21-/low B cells in humans.

Memory B cells (MBCs) are an essential part of our immunological memory. They respond fast upon re-encountering pathogens and can differentiate into plasma cells that secrete protective antibodies. The focus of this review is on MBCs that lack, or express low levels of, CD21, hereafter referred to as CD21-/low.

Data describing expression of formyl peptide receptor 2 in human articular chondrocytes.

The formyl peptide receptor 2 (FPR2) belongs to the family of seven-transmembrane G protein-coupled receptors (GPCR) and are expressed by many different cells but mainly studied in immune cells. FPR2 is involved in host defense against bacterial infections and clearance of damaged cells through the oxidative burst and chemotaxis of neutrophils. In addition, FPR2 has also been implicated as an immunomodulator in sterile inflammations, e.

CD21 B cells associate with joint damage in rheumatoid arthritis patients.

Depletion of B cells is beneficial in rheumatoid arthritis (RA) patients with autoantibodies to citrullinated proteins (ACPA) and/or the Fc portion of immunoglobulins (rheumatoid factor [RF]), suggesting a role for B cells in disease pathogenesis. To date, however, the identity of specifically pathogenic B cell subsets has not been discovered. One candidate population is identified by the low expression or absence of complement receptor 2 (CD21 B cells).

The Fate of a Hapten - From the Skin to Modification of Macrophage Migration Inhibitory Factor (MIF) in Lymph Nodes.

Skin (contact) allergy, the most prevalent form of immunotoxicity in humans, is caused by low molecular weight chemicals (haptens) that penetrate stratum corneum and modify endogenous proteins. The fate of haptens after cutaneous absorption, especially what protein(s) they react with, is largely unknown. In this study the fluorescent hapten tetramethylrhodamine isothiocyanate (TRITC) was used to identify hapten-protein conjugates in the local lymph nodes after topical application, as they play a key role in activation of the adaptive immune system.

In vivo study of an instantly formed lipid-water cubic phase formulation for efficient topical delivery of aminolevulinic acid and methyl-aminolevulinate.

We demonstrate a rapidly formed cubic liquid crystalline phase, i.e. typically 1g cubic phase in less than 1 min confirmed by X-ray diffraction, consisting of an ether lipid, 1-glyceryl monooleyl ether (GME), an aprotic solvent (propylene glycol or pentane-1,5-diol) and water.

The pilosebaceous unit--a phthalate-induced pathway to skin sensitization.

Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.

Modification and expulsion of keratins by human epidermal keratinocytes upon hapten exposure in vitro.

Allergic contact dermatitis is the most prevalent form of human immunotoxicity. It is caused by reactive low molecular weight chemicals, that is, haptens, coming in contact with the skin where hapten-peptide complexes are formed, activating the immune system. By using sensitizing fluorescent thiol-reactive haptens, that is, bromobimanes, we show how keratinocytes respond to hapten exposure in vitro and reveal, for the first time in a living system, an exact site of haptenation.

A study of the enhanced sensitizing capacity of a contact allergen in lipid vesicle formulations.

The growing focus on nanotechnology and the increased use of nano-sized structures, e.g. vesicles, in topical formulations has led to safety concerns.

Caged fluorescent haptens reveal the generation of cryptic epitopes in allergic contact dermatitis.

Allergic contact dermatitis (ACD) is the most prevalent form of human immunotoxicity. It is caused by skin exposure to haptens, i.e.

Diphenylthiourea, a common rubber chemical, is bioactivated to potent skin sensitizers.

Diphenylthiourea (DPTU) is a known skin sensitizer commonly used as a vulcanization accelerator in the production of synthetic rubber, for example, neoprene. The versatile usage of neoprene is due to the multifaceted properties of the material; for example, it is stretchable, waterproof, and chemical- and abrasion-resistant. The wide application of neoprene has resulted in numerous case reports of dermatitis patients allergic to DPTU.

DNA adducts in normal colonic mucosa from healthy controls and patients with colon polyps and colorectal carcinomas.

Colon cancer is a multistage process where adenomatous polyps developing in a normal mucosa may further progress to neoplasia. DNA adducts are biomarkers linked to exposure to carcinogenic compounds, tumour formation and clinically observed cancer. Such DNA adducts have been detected in the mucosa of colon cancer patients.

Reduced sensitizing capacity of epoxy resin systems: a structure-activity relationship study.

Epoxy resins can be prepared from numerous chemical compositions. Until recently, alternatives to epoxy resins based on diglycidyl ethers of bisphenol A (DGEBA) or bisphenol F (DGEBF) monomers have not received commercial interest, but are presently doing so, as epoxy resins with various properties are desired. Epoxy resin systems are known to cause allergic contact dermatitis because of contents of uncured monomers, reactive diluents, and hardeners.

Accumulation of FITC near stratum corneum-visualizing epidermal distribution of a strong sensitizer using two-photon microscopy.

Background: The allergenic potency of a hapten is related to its skin penetration properties, but little is known about the distribution of haptens in the skin following topical application.

Objectives: The aim of this study was to investigate the diffusion and epidermal distribution using two-photon microscopy (TPM) of two fluorescent compounds.

Methods: Sensitizing capacities of fluorescein isothiocyanate (FITC) and fluorescein were investigated using the local lymph node assay.

Limonene hydroperoxide analogues differ in allergenic activity.

Background: The fragrance terpene R-limonene is a very weak sensitizer but forms allergenic oxidation products upon contact with air. Oxidized (ox.) limonene is a frequent cause of contact allergy in clinical testing.

A skin-like cytochrome P450 cocktail activates prohaptens to contact allergenic metabolites.

Allergic contact dermatitis is a complex syndrome representing immunological responses to cutaneous exposure to protein-reactive chemicals. Although many contact sensitizers directly can elicit this disorder, others (prohaptens) require activation. Knowledge regarding the activating mechanisms remains limited, but one possibility is metabolic activation by cytochrome P450 (CYP) enzymes in the skin.

The impact of a new immunomodulator oxo-quinoline-3-carboxamide on the progression of experimental lupus.

Autoimmune, lupus-prone MRL lpr/lpr mice were treated orally with oxo-quinoline-3-carboxamide (ABR-25757), a newly developed immunomodulator. Treatment was initiated in one set of experiment at the age of 10 weeks, before the onset of clinically apparent disease, and in another set at 15 weeks, after the development of established lupus disease. Beneficial therapeutic effects were obtained even when ABR-25757 was administered at the lowest dose tested (7.

Inhibition of the sensitizing effect of carvone by the addition of non-allergenic compounds.

We have previously reported a reduction of sensitization to carvone in guinea pigs when adding non-allergenic, structurally related compounds simultaneously at induction. This study investigates the criteria needed to obtain a reduction of sensitization in contact allergy. Linalool, a non-sensitizer structurally unrelated to carvone, significantly reduced the sensitizing capacity of carvone in guinea pigs.

Mycophenolic acid inhibits inosine 5'-monophosphate dehydrogenase and suppresses immunoglobulin and cytokine production of B cells.

Mycophenolic acid (MPA) reversibly inhibits inosine 5'-monophosphate dehydrogenase (IMPDH), an enzyme involved in the de novo synthesis of guanine nucleotides. Previously, mycophenolate mofetil (MMF), the pro-drug of MPA, was shown to exert beneficial effects on the systemic lupus erythematosus (SLE)-like disease in MRLlpr/lpr mice. In this study, MPA's immunomodulating effects in vitro on the B cell hybridoma MAR 18.

Mycophenolic acid inhibits inosine 5'-monophosphate dehydrogenase and suppresses production of pro-inflammatory cytokines, nitric oxide, and LDH in macrophages.

Mycophenolic acid (MPA) inhibits reversibly inosine 5(')-monophosphate dehydrogenase, an enzyme involved in the de novo synthesis of guanine nucleotides. Previously, mycophenolate mofetil (MMF), the pro-drug of MPA, was shown to exert beneficial effects on the systemic lupus erythematosus (SLE)-like disease in MRLlpr/lpr mice. In this study MPA's immunomodulating effects in vitro on the murine macrophage cell line IC-21 were investigated.