cAMP Response Element Modulator α Induces Dual Specificity Protein Phosphatase 4 to Promote Effector T Cells in Juvenile-Onset Lupus.

Effector CD4 T cells with increased IL-17A and reduced IL-2 production contribute to tissue inflammation and organ damage in systemic lupus erythematosus (SLE). Increased expression of the transcription factor cAMP response element modulator (CREM) α promotes altered cytokine expression in SLE. The aim of this study was to investigate CREMα-mediated events favoring effector CD4 T cells in health and disease.

Mast cells enhance sterile inflammation in chronic nonbacterial osteomyelitis.

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease, and patients with active or recurrent bone inflammation at multiple sites are diagnosed with chronic recurrent multifocal osteomyelitis (CRMO). The Chronic multifocal osteomyelitis (CMO) mouse model develops IL-1β-driven sterile bone lesions reminiscent of severe CRMO. The goal of this study was to evaluate the potential involvement of mast cells in CMO/CRMO.

The Role of Epigenetics in Autoimmune/Inflammatory Disease.

Historically, systemic self-inflammatory conditions were classified as either autoinflammatory and caused by the innate immune system or autoimmune and driven by adaptive immune responses. However, it became clear that reality is much more complex and that autoimmune/inflammatory conditions range along an "inflammatory spectrum" with primarily autoinflammatory vs. autoimmune conditions resembling extremes at either end.

Childhood IgA Vasculitis (Henoch Schonlein Purpura)-Advances and Knowledge Gaps.

Immunoglobulin A vasculitis (IgAV; formerly Henoch Schonlein Purpura) is the most common form of childhood vasculitis. It can occur in any age and peaks around 4-6 years old. It demonstrates seasonal variation implicating a role for environmental triggers and geographical variation.

CASP1 variants influence subcellular caspase-1 localization, pyroptosome formation, pro-inflammatory cell death and macrophage deformability.

CASP1 variants result in reduced enzymatic activity of procaspase-1 and impaired IL-1β release. Despite this, affected individuals can develop systemic autoinflammatory disease. These seemingly contradictory observations have only partially been explained by increased NF-κB activation through prolonged interaction of variant procaspase-1 with RIP2.

The role of epigenetics in paediatric rheumatic disease.

Purpose Of Review: Autoimmune/inflammatory disorders can be stratified along a spectrum based on the primary involvement of innate vs. adaptive mechanisms. Stratifying patients based on molecular mechanisms rather than clinical phenotypes may allow for target-directed and individualized treatment.

Immunoglobulin replacement for secondary immunodeficiency after B-cell targeted therapies in autoimmune rheumatic disease: Systematic literature review.

Background: Consensus guidelines are not available for the use of immunoglobulin replacement therapy (IGRT) in patients developing iatrogenic secondary antibody deficiency following B-cell targeted therapy (BCTT) in autoimmune rheumatic disease.

Objectives: To evaluate the role of IGRT to manage hypogammaglobulinemia following BCTT in autoimmune rheumatic disease (AIRD).

Methods: Using an agreed search string we performed a systematic literature search on Medline with Pubmed as vendor.

Childhood Vasculitis.

The term vasculitis covers heterogeneous disorders that share the presence of inflammation of blood vessel walls. Immune cell infiltrates can vary significantly and involve granulocytes or mononuclear cells. Vasculitis can be a symptom of other underlying disorders or the underlying cause of organ specific or systemic disease.

Should Pneumococcal Serotype 3 Be Included in Serotype-Specific Immunoassays?

Since the introduction of the 13-valent pneumococcal conjugate vaccine, a number of studies have demonstrated the limited efficacy of the pneumococcal serotype 3 component of this vaccine. Evidence from seven countries (Denmark, France, Greece, Portugal, Sweden, UK, US) shows limited or no effectiveness of the 13-valent pneumococcal conjugate vaccine against serotype 3 invasive pneumococcal disease and carriage. The serotype 3 capsule has some unique characteristics that may serve to explain this lack of efficacy-capsular polysaccharide is abundantly expressed, leading to a greater thickness of capsule, and free capsular polysaccharide may be released during growth.

Recommendations for the management of secondary hypogammaglobulinaemia due to B cell targeted therapies in autoimmune rheumatic diseases.

Objectives: The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases.

Methods: A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative.

Kawasaki Disease.

Kawasaki disease (KD) is an acute-onset systemic vasculitis of medium-sized vessels that mostly affects infants and toddlers. Globally, it is the most common form of childhood primary vasculitis. Delayed diagnosis and treatment results in coronary artery aneurysms in up to 25% of all affected individuals.

Autoinflammatory mutation in NLRC4 reveals a leucine-rich repeat (LRR)-LRR oligomerization interface.

Background: Monogenic autoinflammatory disorders are characterized by dysregulation of the innate immune system, for example by gain-of-function mutations in inflammasome-forming proteins, such as NOD-like receptor family CARD-containing 4 protein (NLRC4).

Objective: Here we investigate the mechanism by which a novel mutation in the leucine-rich repeat (LRR) domain of NLRC4 (c.G1965C, p.

Juvenile-onset systemic lupus erythematosus (jSLE) - Pathophysiological concepts and treatment options.

The systemic autoimmune/inflammatory condition systemic lupus erythematosus (SLE) manifests before the age of 16 years in 10-20% of all cases. Clinical courses are more severe, and organ complications are more common in patients with juvenile SLE. Varying gender distribution in different age groups and increasing severity with younger age and the presence of monogenic disease in early childhood indicate distinct differences in the pathophysiology of juvenile versus adult-onset SLE.

CD14 monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through increased NLRP3 inflammasome expression.

The pathophysiology of chronic nonbacterial osteomyelitis (CNO) remains incompletely understood. Increased NLRP3 inflammasome activation and IL-1β release in monocytes from CNO patients was suggested to contribute to bone inflammation. Here, we dissect immune cell infiltrates and demonstrate the involvement of monocytes across disease stages.

IL10 promoter haplotypes may contribute to altered cytokine expression and systemic inflammation in celiac disease.

Celiac disease (CD) is an autoimmune/inflammatory condition triggered by dietary gluten intake in genetically predisposed individuals. Though associations with MHC class II HLA-DQ2 or -DQ8 are the primary and necessary genetic predisposition for CD, >97% of genetically predisposed individuals never develop CD. Cytokines were measured in the serum of CD patients and controls.

SLE-Associated Defects Promote Altered T Cell Function.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease linked to profound defects in the function and phenotype of T lymphocytes. Here, we describe abnormal signaling pathways that have been documented in T cells from patients with SLE and discuss how they impact gene expression and immune function, in order to understand how they contribute to disease development and progression.

TCRαβCD3CD4CD8 (double negative) T cells in autoimmunity.

TCRαβCD3CD4CD8 "double negative" (DN) T cells comprise a small subset of mature peripheral T cells. The origin and function of DN T cells are somewhat unclear and discussed controversially. While DN T cells resemble a rare and heterogeneous T cell subpopulation in healthy individuals, numbers of TCRαβ DN T cells are expanded in several inflammatory conditions, where they also exhibit distinct effector phenotypes and infiltrate inflamed tissues.

Mechanistic aspects of epigenetic dysregulation in SLE.

Epigenetic events have been linked with disease expression in individuals genetically predisposed to the development of systemic lupus erythematosus (SLE), a severe systemic autoimmune/inflammatory disease. Altered DNA methylation and hydroxymethylation as well as histone modifications mediate changes in chromatin accessibility and gene expression in immune cells from SLE patients. Defective epigenetic control contributes to uncontrolled expression of inflammatory mediators, including cytokines and co-receptors, resulting in systemic inflammation and tissue damage.

Expression of the B cell differentiation factor BAFF and chemokine CXCL13 in a murine model of Respiratory Syncytial Virus infection.

Innate immune responses are known to influence the subsequent development of adaptive immunity. We have previously shown that RSV infection of human airway epithelial cells results in production of the B cell growth factor, BAFF. To better understand how the airway responds to RSV infection by production of this and other factors to support or enhance local B cell responses to infection, we analysed the lung expression of BAFF and B cell homeostatic chemokines CXCL12, CXCL13, CCL19 and CCL21 in a murine model of RSV infection.

Practice and consensus-based strategies in diagnosing and managing systemic juvenile idiopathic arthritis in Germany.

Background: Systemic juvenile idiopathic arthritis (SJIA) is an autoinflammatory disease associated with chronic arthritis. Early diagnosis and effective therapy of SJIA is desirable, so that complications are avoided. The PRO-KIND initiative of the German Society for Pediatric Rheumatology (GKJR) aims to define consensus-based strategies to harmonize diagnostic and therapeutic approaches in Germany.