Clinical features and new diagnostic criteria for the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis.

Aim: The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is a common inflammatory disease that presents with periodic fever. We aimed to establish more specific diagnostic criteria for PFAPA based on the clinical characteristics of PFAPA patients in our directory.

Method: The clinical, laboratory, genetic, and family history details of 257 Japanese PFAPA patients treated at our and other affiliated hospitals between April 2000 and April 2018 were analyzed along with quantitative measurements of the number of CD64 molecules on neutrophils, and the levels of serum inflammatory cytokines.

Markedly elevated CD64 expression on neutrophils and monocytes as a biomarker for diagnosis and therapy assessment in Kawasaki disease.

Objective: Kawasaki disease (KD) is the most commonly encountered inflammatory disease in children. However, its pathogenesis and diagnostic biomarkers have not been fully investigated. We examined the activation of neutrophils and monocytes in KD.

A neonatal case of chronic granulomatous disease, initially presented with invasive pulmonary aspergillosis.

Chronic granulomatous disease (CGD) often presents with infectious illness, such as repeating bacterial and fungal infections, due to the inability to generate superoxide, which would destroy certain infectious pathogens, and is usually diagnosed in childhood. We describe a CGD case diagnosed in neonatal period, who initially presented with invasive aspergillosis. Neonatal invasive pulmonary aspergillosis is very rare and, to the best of our knowledge, this might be the youngest case in Japan.

Distinct response in maintenance of human naive and memory B cells via IL-21 receptor and TCL1/Akt pathways.

The molecular mechanisms involving in B-cell survival/proliferation are poorly understood. Here we investigated the molecules affecting the survival of human naïve and memory B cells. Without stimulation, naïve B cells survived longer than memory B cells.

Interleukin-21 stimulates B-cell immunoglobulin E synthesis in human beings concomitantly with activation-induced cytidine deaminase expression and differentiation into plasma cells.

Interleukin (IL)-21 downregulates immunoglobulin E (IgE) production in murine systems by inhibiting germline epsilon transcription in IL-4-stimulated B cells. We here sought to clarify the function of IL-21 in human B-cell IgE synthesis. IL-21 dramatically enhanced IgE production by human mononuclear cells, or purified total, naive, or memory B cells in the presence of IL-4 plus anti-CD40 mAb cross-linked with CD32-transfectants, and the production was strengthened with further addition of IL-10.

TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells.

The T cell immunoglobulin mucin (TIM) proteins regulate T cell activation and tolerance. Here we showed that TIM-4 is expressed on human and mouse macrophages and dendritic cells, and both TIM-4 and TIM-1 specifically bound phosphatidylserine (PS) on the surface of apoptotic cells but not any other phospholipid tested. TIM-4(+) peritoneal macrophages, TIM-1(+) kidney cells, and TIM-4- or TIM-1-transfected cells efficiently phagocytosed apoptotic cells, and phagocytosis could be blocked by TIM-4 or TIM-1 monoclonal antibodies.

CD72-mediated suppression of human naive B cell differentiation by down-regulating X-box binding protein 1.

B cells can differentiate into antibody-secreting plasma cells, however the signals that control the entry into this pathway are not clearly understood. We have investigated the role of human CD72 in mature B cell differentiation. Human CD72 is preferentially expressed in naive B cells, but marginal levels of expression can be found in switched memory B cells.

TIM-1 induces T cell activation and inhibits the development of peripheral tolerance.

We have examined the function of TIM-1, encoded by a gene identified as an 'atopy susceptibility gene' (Havcr1*), and demonstrate here that TIM-1 is a molecule that costimulates T cell activation. TIM-1 was expressed on CD4(+) T cells after activation and its expression was sustained preferentially in T helper type 2 (T(H)2) but not T(H)1 cells. In vitro stimulation of CD4(+) T cells with a TIM-1-specific monoclonal antibody and T cell receptor ligation enhanced T cell proliferation; in T(H)2 cells, such costimulation greatly enhanced synthesis of interleukin 4 but not interferon-gamma.

Expansion of clonotype-restricted HLA-identical maternal CD4+ T cells in a patient with severe combined immunodeficiency and a homozygous mutation in the Artemis gene.

We have observed a male infant with severe combined immunodeficiency (SCID) responsible for Artemis gene mutation, in whom marked expansion of the transplacentally grafted maternal CD4(+) T cells was observed in various tissues. His class I and II major histocompatibility antigens (MHC) were identical to his mother's. We analyzed the T-cell populations within target tissues at a molecular level in order to determine whether different T-cell clonotypes are expanded in different types of tissue.

Granulocyte macrophage-colony stimulating factor delays neutrophil apoptosis and primes its function through Ia-type phosphoinositide 3-kinase.

Phosphoinositide 3-kinases (PI3Ks) constitute a family of lipid kinases that regulate an array of fundamental cellular responses by neutrophils [polymorphonuclear leukocytes (PMN)]. p85alpha Gene-disrupted mice were used to help accurately identify the physiological role of the PI3K isoform in PMN activation in the presence of granulocyte macrophage-colony stimulating factor (GM-CSF). PMN from the p85alpha-/- mice showed normal cellular motility, and the quantity of superoxide anion (O(2(-))) produced by PMN upon stimulation with formyl-Met-Leu-Phe did not significantly differ between p85alpha-/- and wild-type mice under controlled conditions.

Familial Mediterranean fever in 2 Japanese families.

We describe 3 Japanese patients in 2 families with familial Mediterranean fever (FMF) as determined by gene analysis. FMF is an ethnically related, genetic disease, occurring commonly in some Mediterranean populations. The FMF gene (MEFV) mutation found in our patients is M694I.

Detection of neutrophil-associated immunoglobulin using flow cytometry in autoimmune neutropenia of infancy.

Background: Autoimmune neutropenia of infancy (ANI) is a common form of chronic childhood neutropenia, which is caused by antineutrophil antibodies. The syndrome is characterized by a severe selective neutropenia accompanied with recurrent bacterial infections.

Methods: We investigated 10 ANI patients in our hospital.

The different process of class switching and somatic hypermutation; a novel analysis by CD27(-) naive B cells.

The relationship between class switch recombination (CSR) and somatic hypermutation has been unclear. By using human CD27(-) naive B cells, we investigated the somatic hypermutation and producibility of immunoglobulins (Igs) that occur after CSR. Although neither adult CD27(-) nor cord blood B cells, which showed the unmutated Ig V-region genes, produced IgG, IgM, or IgA in response to conventional stimuli, they produced IgG and IgM but not IgA in the presence of Staphylococcus aureus Cowan strain (SAC) + interleukin-2 (IL-2) + IL-10 + anti-CD40 mAb + CD32 transfectants (CD40/CD32T).