The Experts below are selected from a list of 1023 Experts worldwide ranked by ideXlab platform
Masao Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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possible involvement of regulatory t cell abnormalities and variational usage of tcr repertoire in children with Autoimmune neutropenia
Clinical and Experimental Immunology, 2021Co-Authors: Satoshi Goda, Hiroshi Kawaguchi, Shuhei Karakawa, Seiichi Hayakawa, Satoshi Okada, Masao KobayashiAbstract:Autoimmune neutropenia (AIN) in childhood is characterized by chronic neutropenia and positivity for anti-neutrophil antibodies, resulting in the excessive destruction of neutrophils. In this study, we investigated the involvement of regulatory T cells (Tregs ) in the pathogenesis of AIN in childhood. Tregs have been classified into three subpopulations based on the expressions of CD45RA and forkhead box protein 3 (FoxP3): resting Tregs , activated Tregs and non-suppressive Tregs . The frequency of activated Tregs (CD4+ CD25+ FoxP3high CD45RA- T cells) as well as that of total Tregs (CD4+ CD25+ FoxP3+ T cells) in peripheral blood was significantly decreased in patients with AIN. Analysis of the T cell receptor (TCR)-Vβ repertoire of CD4+ T cells revealed skewed usages in patients with AIN compared with that observed in age-matched control subjects. Regarding T cell subsets, the use of four of 24 TCR-Vβ families in Tregs and one in conventional T cells were increased in patients with AIN. The number of patients with AIN who showed skewed usages of TCR-Vβ family in conventional and Tregs was significantly higher than that reported in control subjects. When the preference between Tregs and conventional T cells in each TCR-Vβ family was individually compared, different use was prominently observed in the TCR-Vβ 9 family in patients with AIN. These results suggest that the quantitative abnormalities of Tregs and the skew of the TCR-Vβ repertoire in CD4+ T cells, including Tregs and conventional T cells, may be related to autoantibody production through a human neutrophil antigen-reactive T cell clone.
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possible involvement of regulatory t cell abnormalities and variational usage of tcr repertoire in children with Autoimmune neutropenia
Authorea Preprints, 2020Co-Authors: Satoshi Goda, Hiroshi Kawaguchi, Shuhei Karakawa, Seiichi Hayakawa, Satoshi Okada, Masao KobayashiAbstract:Autoimmune neutropenia (AIN) in childhood is characterized by chronic neutropenia and positivity for antineutrophil antibodies, resulting in the excessive destruction of neutrophils. In this study, we investigated the involvement of regulatory T cells (Tregs) in the pathogenesis of AIN in childhood. Tregs have been classified into three subpopulations based on the expressions of CD45RA and FOXP3: resting Tregs, activated Tregs, and non-suppressive Tregs. The frequency of activated Tregs (CD4+CD25+FOXP3highCD45RA− T cells) as well as that of total Tregs (CD4+CD25+FOXP3+ T cells) in peripheral blood was significantly decreased in patients with AIN. Analysis of the T cell receptor (TCR)-Vβ repertoire of CD4+ T cells revealed skewed usages in patients with AIN compared with that observed in age-matched control subjects. Regarding T cell subsets, the use of four of 24 TCR-Vβ families in Tregs and one in conventional T cells were increased in patients with AIN. The number of patients with AIN who showed skewed usages of TCR-Vβ family in conventional and Tregs was significantly higher than that reported in control subjects. When the preference between Tregs and conventional T cells in each TCR-Vβ family was individually compared, different use was prominently observed in the TCR-Vβ 9 family in patients with AIN. These results suggest that the quantitative abnormalities of Tregs and the skew of the TCR-Vβ repertoire in CD4+ T cells, including Tregs and conventional T cells, may be related to autoantibody production through a human neutrophil antigen-reactive T cell clone.
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adult onset primary cyclic Autoimmune neutropenia a case report
Transfusion, 2018Co-Authors: Tomohiro Yabushita, Masao Kobayashi, Nobuhiro Hiramoto, Satoshi Yoshioka, Shuhei Karakawa, Takayuki IshikawaAbstract:BACKGROUND: A few cases of primary Autoimmune neutropenia (AIN) have been reported in adults, but cyclic primary AIN, which is characterized by the periodic oscillation of neutrophils, is uncommon in adults. STUDY DESIGN AND METHODS: Herein, we report a 70-year-old man referred to our hospital with severe neutropenia and thrombocytopenia. He had experienced intermittent episodes of low-extremity purpura for the past 3 months, with cellulitis on the skin of the scalp 1 month previously. RESULTS: The patient presented with severely low neutrophil and platelet (PLT) counts. Myeloid progenitors and megakaryocytes were increased in the marrow, but mature neutrophils were remarkably decreased. Anti-neutrophil antibodies to specific epitopes were detected at neutropenia. Based on these findings, AIN accompanied by Autoimmune thrombocytopenia was diagnosed. The patient experienced synchronous fluctuations of neutrophil and PLT counts three times. Despite no treatment, the neutrophil count fluctuated within the range of 0.06 × 109 to 1.65 × 109 /L, and the PLT count fluctuated from 0.7 × 1010 to 20.5 × 1010 /L. We identified an inverse relationship between neutrophil count and anti-neutrophil antibody titers, establishing the conclusive diagnosis of cyclic AIN. After prednisolone treatment, the neutrophil and PLT counts normalized, and the patient has maintained long-term remission. CONCLUSION: We report a rare case of cyclic AIN diagnosed from the inverse association between periodic oscillation of anti-neutrophil antibody titers and neutrophil counts. This clinical course suggests that in AIN patients, laboratory data and recurrent signs of infection should be monitored regularly, including shortly after neutrophil recovery.
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remission of Autoimmune neutropenia after development of kawasaki disease
Pediatrics International, 2015Co-Authors: Seigo Okada, Kazuhiro Nakamura, Masao Kobayashi, Shunji Hasegawa, Yasuo Suzuki, Takuya Ichimura, Hidenobu Kaneyasu, Maiko Shimomura, Midori Wakabayashitakahara, Shouichi OhgaAbstract:We report the second case of the association of Kawasaki disease (KD) and Autoimmune neutropenia (AIN). A 21-month-old female diagnosed as having AIN of infancy developed a complete KD when severe neutropenia continued. The patient suffered from no coronary artery lesions, and well responded to a single high-dose gamma-globulin therapy. The cytokine profile of the neutropenic infant was representative of the typical KD. Neutrophil counts notably increased during the convalescent phase of KD, and were then normalized forthwith. The prompt resolutions of KD and AIN paralleled the increase of circulating transforming growth factor (TGF)-β1 levels. The clinical course of the patient was contrasted to that of the first reported case of a patient who developed severe and refractory KD after the high dose granulocyte-colony stimulating factor (G-CSF) therapy.
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sustained complete remission for one year following low dose rituximab therapy for chronic Autoimmune neutropenia
The Japanese journal of clinical hematology, 2011Co-Authors: Masao Hagihara, Kikuyo Taniguchi, Jian Hua, Morihiro Inoue, Naohiko Michikawa, Masao KobayashiAbstract:A 78-year-old male with a 5-year history of neutropenia was admitted to our hospital with high fever. Peripheral blood and bone marrow findings showed severe granulocytic hypoplasia. Granulocyte-colony stimulating factor and steroid pulse therapy did not improve the clinical conditions at all, and severe sepsis persisted. After he was diagnosed with Autoimmune neutropenia by detection of anti-neutrophil antibody in sera, low-dose infusion of rituximab was performed. Neutrophil count promptly increased and normalized one month after the start of treatment. He has remained in remission for 1 year. Compared with the standard dose, low-dose rituximab therapy is promising for the treatment of chronic Autoimmune neutropenia because of the lower cost as well as the lower incidence of adverse reactions.
Roshini S Abraham - One of the best experts on this subject based on the ideXlab platform.
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outcomes and treatment strategies for autoimmunity and hyperinflammation in patients with rag deficiency
The Journal of Allergy and Clinical Immunology: In Practice, 2019Co-Authors: Jocelyn R Farmer, Boglarka Ujhazi, Jack J.h. Bleesing, Zsofia Foldvari, Catharina Schuetz, Karin Chen, Suk See De Ravin, Roshini S Abraham, Waleed AlherzAbstract:Background Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. Objective Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. Methods In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent Autoimmune and/or hyperinflammatory pathology. Results Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 Autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median, 1.9, 2.1, and 2.6 years for Autoimmune hemolytic anemia, immune thrombocytopenia, and Autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for Autoimmune hemolytic anemia, immune thrombocytopenia, and Autoimmune neutropenia, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. Conclusions Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management.
Mojtaba Akhtari - One of the best experts on this subject based on the ideXlab platform.
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neutropenias in felty s syndrome and systemic lupus erythematosus
2012Co-Authors: Mojtaba Akhtari, Edmund K WallerAbstract:Autoimmune neutropenia is characterized by the presence of autoantibodies produced by the patient’s immune system against antigens on neutrophils, and it can be divided into primary and secondary forms. Primary Autoimmune neutropenia is not a common condition in the adult population, but secondary Autoimmune neutropenia may be as common as Autoimmune disorders of red blood cells and platelets. Secondary Autoimmune neutropenia often is not diagnosed because symptoms are less overt with no reliable markers for in vivo neutrophil lysis in contrast with hemoglobin in hemolytic anemia.
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Management of Autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus.
Autoimmunity reviews, 2011Co-Authors: Kam A. Newman, Mojtaba AkhtariAbstract:Autoimmune neutropenia, caused by neutrophil-specific autoantibodies is a common phenomenon in Autoimmune disorders such as Felty's syndrome and systemic lupus erythematosus. Felty's syndrome is associated with neutropenia and splenomegaly in seropositive rheumatoid arthritis which can be severe and with recurrent bacterial infections. neutropenia is also common in systemic lupus erythematosus and it is included in the current systemic lupus classification criteria. The pathobiology of the Autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus is complex, and it could be a major cause of morbidity and mortality due to increased risk of sepsis. Treatment should be individualized on the basis of patient's clinical situation, and prevention or treatment of the infection. Recombinant human granulocyte colony-stimulating factor is a safe and effective therapeutic modality in management of Autoimmune neutropenia associated with Felty's syndrome and systemic lupus erythematosus, which stimulates neutrophil production. There is a slight increased risk of exacerbation of the underlying Autoimmune disorder, and recombinant human granulocyte colony-stimulating factor dose and frequency should be adjusted at the lowest effective dose.
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Autoimmune neutropenia in adults
Autoimmunity Reviews, 2009Co-Authors: Mojtaba Akhtari, Brian R Curtis, Edmund K WallerAbstract:Autoimmune neutropenias (AIN) in adults are a heterogeneous group of diseases with clinical manifestations varying from being asymptomatic to having infectious complications with considerable morbidity and mortality. They are characterized by autoantibodies directed against neutrophils, resulting in destruction of neutrophils. AIN can be divided into two forms. In primary AIN, neutropenia is usually the sole hematologic abnormality and it is more common in children. Secondary AIN, which is more prevalent in adults, is associated with underlying Autoimmune diseases, malignancies, infections, particularly viral, neurological diseases or drug exposure. This article is an overview of these conditions with emphasis on secondary AIN; it also discusses the available serological methods for antibody detection and recent therapeutic developments including colony stimulating factors, rituximab and Campath-1H.
Rudi Steffensen - One of the best experts on this subject based on the ideXlab platform.
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association between human leukocyte antigens hlas and human neutrophil antigens hnas and Autoimmune neutropenia of infancy in danish patients
Pediatric Allergy and Immunology, 2021Co-Authors: Kaspar Rene Nielsen, Signe Rolskov Bojsen, Tania Nicole Masmas, Annelouise Fjordside, John Baech, Thure Mors Haunstrup T, Rudi SteffensenAbstract:BACKGROUND Autoimmune neutropenia of infancy (AIN) is a frequent cause of neutropenia in children. The disease is caused by antibodies against epitopes on the immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb). We investigated the possible association of human neutrophil antigens (HNA), human leukocyte antigen (HLA)-DR, and HLA-DQ alleles with AIN and the association of these genotypes with the presence of autoantibodies. METHODS Eighty AIN cases with a median age of 13.5 months were included. Controls were healthy unrelated Danish blood donors. Anti-HNA-1a autoantibodies were detected using a flow cytometric granulocyte immunofluorescence test (Flow-GIFT) with phenotyped donor cells for detection of antibody specificity. Molecular determination of HNA genotypes was determined using real-time polymerase chain reaction (q-PCR). High-resolution HLA-DRB1 and HLA-DQB1 were determined by next-generation sequencing. RESULTS Antibodies against HNA-1a were detected in 51% (n = 41) of AIN patients, and anti-HNA-1b was detected in 3% (n = 2) of cases. In 46% of cases, the antibodies were anti-FcγIIIb-reactive. FCGR3B*01+,*02-,*03- was more common (odds ratio, 6.70; P < .0001), and FCGR3B*01-,*02+,*03- was less common (odds ratio, 0.30; P < .0001) among AIN cases. HNA-1a antibodies were significantly more frequent among AIN cases with the FCGR3B*01+,*02-,*03- genotype (odds ratio, 3.86; P < .007). The HLA-DRB1*14 - HLA-DQB1*05:03 haplotype was significantly more common (odds ratio, 7.44; P < .0001) in AIN patients. CONCLUSION The HLA haplotype HLA-DRB1*14 - DQB1*05:03 is associated with Danish AIN cases. Among Danish AIN patients, anti-HNA-1a is the most common autoantibody, and the antibody is more common in cases with the FCGR3B*01+,*02-,*03- genotype.
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association between human leukocyte antigens hlas and human neutrophil antigens hnas and Autoimmune neutropenia of infancy in danish patients
Authorea Preprints, 2020Co-Authors: Kaspar Rene Nielsen, Signe Rolskov Bojsen, Tania Nicole Masmas, Annelouise Fjordside, John Baech, Thure Mors Haunstrup, Rudi SteffensenAbstract:Autoimmune neutropenia of infancy (AIN) is a relatively frequent cause of neutropenia in children. The disease is caused by antibodies recognizing membrane antigens of neutrophils, mostly located on immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb receptor). In this study, we investigated the possible association of human neutrophil antigens (HNA), human leukocyte antigen (HLA)-DR and HLA-DQ alleles with AIN and the association of these genotypes with the presence of anti-HNA-1a autoantibodies. Eighty AIN cases with a median age of 13.5 months were included in this study. Controls were healthy unrelated Danish blood donors. Anti-HNA-1a autoantibodies were detected using a flow cytometric granulocyte immunofluorescence test (Flow-GIFT). Molecular determination of HNA genotypes was determined using real-time polymerase chain reaction (q-PCR). High-resolution HLA-DR and HLA-DQB1 were determined by next-generation sequencing. Antibodies against HNA-1a were detected in 51% (n=41) of AIN patients, and anti-HNA-1b was detected in 3% (n=2) of cases. FCGR3B*01+,*02-,*03- was more common (odds ratio, 6.70; p < 0.0001), and FCGR3B*01-,*02+,*03- was less common (odds ratio, 0.30; p < 0.0001) among AIN cases. HNA-1a antibodies were significantly more frequent among AIN cases with the FCGR3B*01+,*02-,*03-genotype (odds ratio, 3.86; p < 0.007). The HLA-DR*14 and HLA-DQB1*05:03 alleles were significantly more common (odds ratio, 7.44; p < 0.0001 and odds ratio, 2.50; p < 0.0001, respectively) in AIN patients. In conclusion the HLA haplotype HLA-DR*14- DQB1*05:03 is associated with Danish AIN cases. Among Danish AIN patients, anti-HNA-1a is the most common autoantibody, and the antibody is more common in cases with the FCGR3B*01-,*02+,*03- genotype.
Jacquesolivier Pers - One of the best experts on this subject based on the ideXlab platform.
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diagnostic criteria for Autoimmune neutropenia
Autoimmunity Reviews, 2014Co-Authors: Pierre Youinou, Christophe Jamin, Laetitia Le Pottier, Yves Renaudineau, Sophie Hillion, Jacquesolivier PersAbstract:article i nfo Autoimmune neutropenia denotes that the number of circulating polymorphonuclear neutrophils is below 1.5 × 10 9 /L. This encompasses a wide range of disorders from primary conditions to complications of systemic Autoimmune diseases or hematological neoplasms. Antineutrophil autoantibodies are particularly difficult to detect, and their amount does not correlate with the degree of neutropenia. Granulocyte colony-stimulating factoristhe first-linetherapy,but should be restricted to patients with totalabsence ofneutrophils and/orsevere infections.
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Diagnostic criteria for Autoimmune neutropenia.
Autoimmunity Reviews, 2014Co-Authors: Pierre Youinou, Christophe Jamin, Yves Renaudineau, Sophie Hillion, Laëtitia Le Pottier, Jacquesolivier PersAbstract:: Autoimmune neutropenia denotes that the number of circulating polymorphonuclear neutrophils is below 1.5×10(9)/L. This encompasses a wide range of disorders from primary conditions to complications of systemic Autoimmune diseases or hematological neoplasms. Antineutrophil autoantibodies are particularly difficult to detect, and their amount does not correlate with the degree of neutropenia. Granulocyte colony-stimulating factor is the first-line therapy, but should be restricted to patients with total absence of neutrophils and/or severe infections.
