Progressive waves of IL-1β release by primary human monocytes via sequential activation of vesicular and gasdermin D-mediated secretory pathways.

IL-1β is an essential cytokine, but its release needs to be strictly controlled to avoid severe inflammatory manifestations. Lacking a signal sequence, IL-1β does not follow the endoplasmic reticulum-Golgi route. Several pathways have been proposed to mediate its release.

Transcriptional signature of human pro-inflammatory T17 cells identifies reduced IL10 gene expression in multiple sclerosis.

We have previously reported the molecular signature of murine pathogenic T17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γIL-17 (T1/17) and IFN-γIL-17 (T17) CD4 T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to T17 cells, T1/17 cells have gene signatures with marked similarity to mouse pathogenic T17 cells.

Autoimmune sensorineural hearing loss as presenting manifestation of paediatric Behçet disease responding to adalimumab: a case report.

Background: Autoimmune sensorineural hearing loss, also known as autoimmune inner ear disease (AIED) is a rare clinical entity characterized by progressive and bilateral sensorineural hearing loss often accompanied by vestibular symptoms. Diagnosis is essential as a consistent number of patients show a positive response to steroids alone or in association with other immunosuppressive drugs. AIED is defined as primary when the disease is limited to the ear, whereas in up to a third of cases it is associated to other systemic autoimmune diseases such as Behçet disease (BD).

Consensus classification criteria for paediatric Behçet's disease from a prospective observational cohort: PEDBD.

Background: We aimed to describe the main features of Behçet's disease (BD) in children in the largest prospective cohort to date and to propose a classification.

Methods: An international expert consensus group was formed to define a data set of minimal symptoms for the inclusion of patients. Patients were entered prospectively during 66 months.

Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome.

The life-threatening Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome is a genetically heterogeneous autosomal recessive disorder. Twenty percent of patients cannot be explained by mutations in the known ICF genes DNA methyltransferase 3B or zinc-finger and BTB domain containing 24. Here we report mutations in the cell division cycle associated 7 and the helicase, lymphoid-specific genes in 10 unexplained ICF cases.

From bench to bedside and back again: translational research in autoinflammation.

Translational research approaches brought major changes to the understanding and treatment options of autoinflammatory diseases. Patients with common complex multifactorial diseases such as systemic-onset juvenile idiopathic arthritis (sJIA), and particularly those with rare monogenic autoinflammatory diseases such as cryopyrin-associated periodic syndromes (CAPS) or TNF receptor-associated periodic syndrome (TRAPS), benefited from a deeper understanding of the pathophysiological mechanisms and new treatment options emerging from preclinical studies. The study of IL-1 and IL-6 in this context led to novel therapies by forward translation.

Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases.

Background: Hyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin).

Objective: We sought to characterize the genetic cause and clinical spectrum of Hz/Hc.

Methods: Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome.

A Retrospective Patient Chart Review and Survey in Patients with Cryopyrin-associated Periodic Syndromes Treated with Anakinra.

Cryopyrin-associated periodic syndromes (CAPS) is a group of rare autoinflammatory diseases. Little is known about the burden of disease, patients' views on treatment, and adverse events (AEs) with current therapy. The main study objective was to quantify the patients' burden of disease in terms of flares and resource use and to characterize patient symptomatology and tolerability of treatment with anakinra.

Soluble HLA-G dampens CD94/NKG2A expression and function and differentially modulates chemotaxis and cytokine and chemokine secretion in CD56bright and CD56dim NK cells.

Soluble HLA-G (sHLA-G) inhibits natural killer (NK) cell functions. Here, we investigated sHLA-G-mediated modulation of (1) chemokine receptor and NK receptor expression and function and (2) cytokine and chemokine secretion in CD56bright and CD56dim NK cells. sHLA-G-treated or untreated peripheral blood (PB) and tonsil NK cells were analyzed for chemokine receptor and NK receptor expression by flow cytometry.

HLA-G and HLA-E in patients with juvenile idiopathic arthritis.

Objective: To investigate the expression and release of HLA-G and HLA-E in JIA.

Methods: Soluble (s)HLA-G and HLA-E were measured in sera from 58 JIA patients and 54 healthy donors. Surface expression of HLA-G, HLA-E and immunoglobulin-like transcript (ILT)2 and ILT4, two receptors for HLA-G, was assessed on T, B cells and monocytes from peripheral blood (PB) and SF of 12 JIA patients and from PB of 12 controls.

Disseminated Mycobacterium scrofulaceum infection in a child with interferon-gamma receptor 1 deficiency.

Disseminated disease caused by non-tuberculous, environmental mycobacteria (EM) reflects impaired host immunity. Disseminated disease caused by Mycobacterium scrofulaceum has primarily been reported in patients with AIDS. Moreover, observing M.

Multiple relapses of visceral leishmaniasis in an adolescent with idiopathic CD4+ lymphocytopenia associated with novel immunophenotypic and molecular features.

An adolescent with idiopathic CD4 lymphocytopenia suffered from 4 visceral leishmaniasis relapses despite appropriate treatment. CD8 lymphocytopenia and abnormal expansion of TCRalphabeta, CD4, CD8 cells were consistently detected together with reduced export of mature T cells from thymus. This novel form of idiopathic CD4 lymphocytopenia may predispose to multiple visceral leishmaniasis relapses.

Diagnosis and management of autoinflammatory diseases in childhood.

Introduction: Autoinflammatory diseases are a group monogenic inflammatory conditions characterized by an early onset during childhood.

Discussion: Under the term "periodic fevers" are gathered some monogenic diseases (familial Mediterranean fever, mevalonate kinase deficiency, and tumor necrosis factor receptor-associated syndrome) characterized by periodic or recurrent episodes of systemic inflammation causing fever often associated with rash, serositis (peritonitis, pleuritis), lymphadenopathy, arthritis, and other clinical manifestations. Systemic reactive (AA) amyloidosis may be a severe long-term complication.

T cell mediated immune responses to Toxoplasma gondii in pregnant women with primary toxoplasmosis.

The aim of this study was to investigate T cell immunity to Toxoplasma gondii (Tg) in pregnant women with primary toxoplasmosis. This issue has never been addressed before in humans and available information derives from murine models. Peripheral blood mononuclear cells (PBMC) from pregnant women with primary Tg infection were stimulated with Tg tachyzoites, excretory-secretory antigens (ESA) or recombinant surface antigen-1 (rSAG-1), and tested for proliferation, immunophenotype, cytokine production and antigen specific cytotoxic activity.

Immunogenicity of human neuroblastoma.

Neuroblastoma (NB) is a neuroectodermal tumor that affects children in the first years of life. Half of NB cases present with metastatic disease at diagnosis and have a poor prognosis, in spite of the most advanced chemotherapeutic protocols combined with autologous hematopoietic stem cell transplantation. Among the new avenues for NB treatment that are being explored, immunotherapy has attracted much interest.

Cytokine flexibility of early and differentiated memory T helper cells in juvenile idiopathic arthritis.

Objective: It has been suggested that CD45RO+CD27+ T cells represent recently activated memory cells, whereas CD45RO+CD27- T cells are activated memory T cells in the process of differentiating into effector cells. We investigated (1) CCR7 and CCR5 expression and (2) modulation of cytokine expression in "early" (CD27+) and "differentiated" (CD27-) memory CD4+ T cells from peripheral blood and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA).

Methods: SF CD4+CD45RO+CD27+ and CD27- memory T cells from 6 patients with JIA were tested by flow cytometry for intracellular interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) after in vitro priming with CD3 and CD28 mAb in the presence of IL-4, and subsequent culture with IL-2.

Synovial expression of osteopontin correlates with angiogenesis in juvenile idiopathic arthritis.

Objective: To evaluate the synovial expression of osteopontin (OPN) and its possible correlation with the degree of synovial angiogenesis in human chronic idiopathic arthritis.

Methods: Forty-five patients with active juvenile idiopathic arthritis (JIA) were studied. All patients underwent SF aspiration before steroid injection.

High incidence of childhood type 1 diabetes in Liguria, Italy, from 1989 to 1998.

Objective: Assessing updated incidence of type 1 diabetes in 0- to 14-year-old children in Liguria, a Northwest region of Italy.

Research Design And Methods: Incident cases were recorded prospectively from 1989 to 1998. Incidence rates (IRs) were standardized to the 1999 world population using the direct method.

Levels of soluble CD27 in sera and synovial fluid and its expression on memory T cells in patients with juvenile idiopathic arthritides.

Objective: CD27 is a member of tumour necrosis factor receptor family. Its expression is predominantly confined to mature lymphocytes and is strongly enhanced after cell activation. Shedding of the CD27 from the surface of activated cells is related to their effector phase.

Pyloric atresia: report of two cases (one associated with epidermolysis bullosa and one associated with multiple intestinal atresias).

We describe the US findings in two vomiting newborns affected by different forms of pyloric atresia, a rare congenital anomaly that includes a spectrum of lesions limited to the antro-pyloric region of the stomach and with various inheritance mechanisms and syndromic associations.

Serum and synovial fluid concentration of vascular endothelial growth factor in juvenile idiopathic arthritides.

Objective: To evaluate the role of vascular endothelial growth factor (VEGF) in the pathogenesis of local joint inflammation in juvenile idiopathic arthritis (JIA).

Methods: Sera from 50 patients affected with JIA and 10 age-matched healthy controls were tested with a commercial ELISA for VEGF. Corresponding synovial fluid (SF) concentrations of VEGF and p75 soluble tumour necrosis factor receptor (sTNFR) were evaluated in 20 active JIA patients.

Tumor necrosis factor induced adhesion molecule serum concentrations in Henoch-Schönlein purpura and pediatric systemic lupus erythematosus.

Objective: Animal models of immune complex mediated tissue injury have shown that tumor necrosis factor (TNF) and TNF induced adhesion molecules play an important role in the pathogenesis of tissue damage mediated by IgG, but not in that mediated by IgA, immune complexes. We compared possible differences in the behavior of 2 TNF induced adhesion molecules (VCAM-1 and ICAM-1) in Henoch-Schönlein purpura (HSP), which is characterized by the formation of IgA immune complexes, versus systemic lupus erythematosus (SLE), which is mostly associated with the vascular deposition of IgG immune complexes.

Methods: Serum concentrations of soluble (s)VCAM-1 and ICAM-1 were determined by ELISA methods in 20 patients with pediatric SLE showing variably active disease, 20 active patients with active HSP, and 19 healthy controls.

Recurrent antiphospholipid-related deep vein thrombosis as presenting manifestation of systemic lupus erythematosus.

Unlabelled: Antiphospholipid antibodies (aPL) are frequently associated with thrombotic disorders in the so-called antiphospholipid syndrome. Together with anticardiolipin antibodies (aCL), lupus anticoagulant (LA) is the main diagnostic tool for aPL detection. Since LA determination is based on the finding of prolonged clotting time in vitro, concomitant anticoagulant therapy may significantly interfere with its detection.