Nationwide Laboratory Surveillance of Progressive Multifocal Leukoencephalopathy in Japan: Fiscal Years 2011-2020.

Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis.

Clinical and immunological differences between MOG associated disease and anti AQP4 antibody-positive neuromyelitis optica spectrum disorders: Blood-brain barrier breakdown and peripheral plasmablasts.

Background: Patients with anti-aquaporin-4 (AQP4) water channel antibody-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein (MOG) associated disease (MOGAD) often present with similar clinical symptoms, and some cases are hard to differentiate at the time of onset. In this study, we compared the clinical characteristics, cerebrospinal fluid (CSF) analysis parameters, and peripheral T/B lymphocyte subsets during the active and chronic phases in AQP4-NMOSD and MOGAD.

Methods: A total of 17 MOGAD cases and 24 AQP4-NMOSD cases were studied.

Tacrolimus is effective for neuromyelitis optica spectrum disorders with or without anti-AQP4 antibody.

Background: Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory central nervous system disorders characterized by optic neuritis, transverse myelitis, and anti-aquaporin 4 (AQP4) antibody production. However, it has recently been shown that some cases of typical NMOSD can be anti-AQP4 antibody-negative as well. In this study, we retrospectively investigated the disorder relapse-suppressing effect of tacrolimus (TAC) when combined with prednisolone (PSL) in anti-AQP4 antibody-positive and -negative NMOSD cases.

Differentiation between control subjects and patients with chronic spontaneous urticaria based on the ability of anti-IgE autoantibodies (AAbs) to induce FcεRI crosslinking, as compared to anti-FcεRIα AAbs.

Background: The reported prevalences of IgG autoantibodies (AAbs) to FcεRIα and IgE in sera from patients with chronic spontaneous urticaria (CSU) have varied, and these AAbs are also often observed in healthy control subjects. Regarding the histamine release activity of purified IgG from patients with CSU, the number of examined patients has been small. Thus, we sought to determine the prevalence and FcεRI crosslinking ability of these AAbs in a large number of patients with CSU and non-atopic control (NC) subjects.

Depletion of Epidermal Langerhans Cells in the Skin Lesions of Pellagra Patients.

Pellagra is a nutrient deficiency disease caused by insufficient niacin levels. Recent studies have shown that numbers of epidermal Langerhans cells decreased in other diseases caused by nutritional deficiencies, including necrolytic migratory erythema and acrodermatitis enteropathica. Epidermal Langerhans cells are capable of modulating or even halting the inflammatory reaction.

Stress Tolerance of Antibody-Poly(Amino Acid) Complexes for Improving the Stability of High Concentration Antibody Formulations.

The stabilization of antibodies in aqueous solution against physical stress remains a problematic issue for pharmaceutical applications. Recently, protein-polyelectrolyte complex (PPC) formation using poly(amino acids) was proposed to prepare antibody formulation in a salt-dissociable precipitated state without protein denaturation. Here, we investigated the stabilization effect of PPC of therapeutic antibodies with poly-l-glutamic acid on agitation and thermal stress as forms of mechanical and non-mechanical stress, respectively.

[A case of cerebellar brainstem form of progressive multifocal leukoencephalopathy associated with idiopathic CD4+ lymphocytopenia].

A 77-year-old woman presented with a 6-month history of slowly progressive cerebellar ataxia. T2-weighted MRI showed high signal intensity in the left upper dorsal pons and bilateral middle cerebellar peduncles. JC virus (JCV) DNA was detected in cerebrospinal fluid (CSF).

Protein-poly(amino acid) precipitation stabilizes a therapeutic protein l-asparaginase against physicochemical stress.

Long-term storage in aqueous solution has been demanded for the practical application of therapeutic proteins. Recently, a precipitation-redissolution method was proposed to prepare salt-dissociable protein-polyelectrolyte complex (PPC). To elucidate the utility of the complex for storage of proteins, we investigated the stress tolerance of PPC precipitates containing l-asparaginase (ASNase) and poly-l-lysine (polyK).

Feasibility of antibody-poly(glutamic acid) complexes: preparation of high-concentration antibody formulations and their pharmaceutical properties.

Development of high-concentration antibody formulations for subcutaneous administration remains challenging. Recently, a precipitation-redissolution method was proposed to prepare suspensions or precipitates of salt-dissociable protein-poly(amino acid) complexes. To elucidate the utility of this method for protein therapy, we investigated the feasibility of a precipitation-redissolution method using poly(amino acid) for high-concentration antibody formulation.

Protein-poly(amino acid) complex precipitation for high-concentration protein formulation.

A method for concentration of protein solutions is required for high-dosage protein formulation. Here, we present a precipitation-redissolution method by poly(amino acid) for proteins, including therapeutic enzymes, antibodies, and hormones. The proteins were fully precipitated by the addition of poly-L-lysine or poly-L-glutamic acid at low ionic strength, after which precipitate was dissolved at physiological ionic strength.

Hemophagocyctic lymphohistiocytosis developed in a Japanese boy with Chédiak-Higashi syndrome.

Chédiak-Higashi syndrome (CHS) is one of the primary immunodeficiency syndromes accompanied by oculocutaneous albinism. It is characterized by existence of giant granule of neutrophils, and development of symptoms of hemophagocytic lymphohistiocytosis. CHS is a rare disorder and recognition of the disease is indispensable for its diagnosis.

[A case of neuromyelitis optica spectrum disorder developing a fulminant course with multiple white-matter lesions following fingolimod treatment].

A 49-year-old female neuromyelitis optica spectrum disorder (NMOSD) patient with positive anti-aquaporin 4 (AQP4) antibody was treated with fingolimod (FTY720). Ten days later, she developed acute disturbance of consciousness, aphasia, right hemi-spatial neglect, and right hemiparesis. Brain MRI showed multiple white-matter lesions with slight Gadolinium enhancement.