Kyotaro Ohno

Bio: Kyotaro Ohno is an academic researcher from Okayama University. The author has contributed to research in topics: Regulatory T cell & Lymphoma. The author has an hindex of 11, co-authored 17 publications receiving 432 citations.

Atypical hyaline vascular-type castleman's disease with thrombocytopenia, anasarca, fever, and systemic lymphadenopathy.

Abstract: Recently, atypical Castleman's disease (CD) was reported in Japan. This disease is considered as TAFRO syndrome or non-idiopathic plasmacytic lymphadenopathy (IPL), a constellation of clinical symptoms, namely, thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly without hyper-γ-globulinemia. Histopathologically, this disease is similar to hyaline vascular (HV)-type CD. Here, we present a 43-year-old Japanese woman meeting the clinical criteria of TAFRO syndrome who was successfully treated with combined corticosteroid therapy. She showed a rapidly progressive course of thrombocytopenia, systemic lymphadenopathy, fever, anasarca, and increase in acute inflammatory proteins without hyper-γ-globulinemia. Lymph node biopsy was performed and revealed HV-type CD without human herpes virus 8 infection, which was clinicopathologically compatible with non-IPL. The association of these atypical features with well-known multicentric Castleman's disease (MCD), namely, HV-type histology with systemic lymphadenopathy, marked thrombocytopenia even with a high level of interleukin-6, and increased acute inflammatory proteins without hyper-γ-globulinemia, suggests that TAFRO syndrome as presented in our case is a novel entity, which may have been diagnosed as MCD in the past. To define this novel entity more clearly and to demonstrate its etiology, further nationwide surveys of this syndrome and MCD are needed.

Ocular adnexal IgG4-producing mucosa-associated lymphoid tissue lymphoma mimicking IgG4-related disease.

Abstract: IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features A chronic inflammatory state with marked fibrosis, which can often be mistaken for malignancy, especially by clinical imaging analyses, unifies these features In the present report, we describe a case of IgG4-producing mucosa-associated lymphoid tissue lymphoma mimicking IgG4-related disease The patient was a 55-year-old male who was being followed for right orbital tumor over 15 years The lesion had recently increased in size, so a biopsy was performed Histologically, the lesion was consistent with IgG4-related disease ; however, IgG4+ plasma cells showed immunoglobulin light-chain restriction and immunoglobulin heavy chain gene rearrangement was detected in the lesion Therefore, the lesion was diagnosed as IgG4-producing mucosa-associated lymphoid tissue lymphoma In conclusion, in histological diagnosis of IgG4-related disease, it is important to examine not only IgG4-immunostain but also immunoglobulin light-chain restriction

IgG4-related disease involving the sclera

Abstract: A 49-year-old female patient previously treated for scleritis and uveitis-induced cataract in the right eye presented with a subretinal white lesion in the same eye. With a preliminary diagnosis of choroidal tumor, enucleation of the eyeball was performed in accordance with the patient's request. Histologic and immunohistologic examinations were consistent with immunoglobulin G4-related disease. The case demonstrates that it is important to consider IgG4-related disease in the differential diagnosis of an intraocular tumor.

De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease

Abstract: Background IgG 4 -related disease (IgG 4 -RD) is a poorly understood, multiorgan, chronic inflammatory disease characterized by tumefactive lesions, storiform fibrosis, obliterative phlebitis, and accumulation of IgG 4 -expressing plasma cells at disease sites. Objective The role of B cells and IgG 4 antibodies in IgG 4 -RD pathogenesis is not well defined. We evaluated patients with IgG 4 -RD for activated B cells in both disease lesions and peripheral blood and investigated their role in disease pathogenesis. Methods B-cell populations from the peripheral blood of 84 patients with active IgG 4 -RD were analyzed by using flow cytometry. The repertoire of B-cell populations was analyzed in a subset of patients by using next-generation sequencing. Fourteen of these patients were longitudinally followed for 9 to 15 months after rituximab therapy. Results Numbers of CD19 + CD27 + CD20 − CD38 hi plasmablasts, which are largely IgG4 + , are increased in patients with active IgG 4 -RD. These expanded plasmablasts are oligoclonal and exhibit extensive somatic hypermutation, and their numbers decrease after rituximab-mediated B-cell depletion therapy; this loss correlates with disease remission. A subset of patients relapse after rituximab therapy, and circulating plasmablasts that re-emerge in these subjects are clonally distinct and exhibit enhanced somatic hypermutation. Cloning and expression of immunoglobulin heavy and light chain genes from expanded plasmablasts at the peak of disease reveals that disease-associated IgG 4 antibodies are self-reactive. Conclusions Clonally expanded CD19 + CD27 + CD20 − CD38 hi plasmablasts are a hallmark of active IgG 4 -RD. Enhanced somatic mutation in activated B cells and plasmablasts and emergence of distinct plasmablast clones on relapse indicate that the disease pathogenesis is linked to de novo recruitment of naive B cells into T cell–dependent responses by CD4 + T cells, likely driving a self-reactive disease process.

IgG4-related disease.

Abstract: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ and is now being recognized with increasing frequency. IgG4-RD is characterized by a lymphoplasmacytic infiltrate composed of IgG4(+) plasma cells, storiform fibrosis, obliterative phlebitis, and mild to moderate eosinophilia. The diagnosis of IgG4-RD unifies many eponymous fibroinflammatory conditions that had previously been thought to be confined to single organs. IgG4-RD lesions are infiltrated by T helper cells, which likely cause progressive fibrosis and organ damage. IgG4 antibodies are generally regarded as noninflammatory. Although autoreactive IgG4 antibodies are observed in IgG4-RD, there is no evidence that they are directly pathogenic. Rituximab-induced B cell depletion in IgG4-RD leads to rapid clinical and histological improvement accompanied by swift declines in serum IgG4 concentrations. Although IgG autoantibodies against various exocrine gland antigens have been described in IgG4-RD, whether they are members of the IgG4 subclass is unknown. The contribution of autoantibodies to IgG4-RD remains unclear.