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1.
P R Health Sci J ; 43(3): 156-158, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39269768

RESUMO

Mevalonate kinase deficiency is a rare autosomal recessive disease caused by mutations in the mevalonate kinase gene (MVK). Depending on the mutations, a patient with this deficiency can exhibit any one of a spectrum of rare autoinflammatory diseases, such as hypergammaglobulinemia D (hyper-IgD) with periodic fever syndrome and mevalonic aciduria. To date, approximately 300 cases with mutations in the MVK gene have been reported worldwide. Herein, we present a 3-year-old female from Puerto Rico with a history of fever, arthralgia, and skin lesions since her first month of age and who, upon genetic workup, was confirmed to have compound heterozygous mutations in the MVK gene. Given her medical history and the results of her genetic testing, she was diagnosed with hyper-IgD with periodic fever syndrome. She will be treated with canakinumab, an interleukin-1ß antagonist, after receiving the varicella and measles-mumps-rubella (MMR) vaccines.


Assuntos
Deficiência de Mevalonato Quinase , Mutação , Humanos , Porto Rico , Feminino , Pré-Escolar , Deficiência de Mevalonato Quinase/diagnóstico , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Febre/etiologia , Anticorpos Monoclonais Humanizados , Imunoglobulina D
3.
Fish Shellfish Immunol ; 153: 109823, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39122096

RESUMO

The Asian seabass (Lates calcarifer) faces significant disease threats, which are exacerbated by intensive farming practices and environmental changes. Therefore, understanding its immune system is crucial. The current study presents a comprehensive analysis of immune-related genes in Asian seabass peripheral blood leukocytes (PBLs) using Iso-seq technology, identifying 16 key pathways associated with 7857 immune-related genes, comprising 634 unique immune-related genes. The research marks the first comprehensive report on the entire immunoglobulin repertoire in Asian seabass, revealing specific characteristics of immunoglobulin heavy chain constant region transcripts, including IgM (Cµ, ighm), IgT (Cτ, ight), and IgD (Cδ, ighd). The study confirms the presence of membrane-bound form, ighmmb, ightmb, ighdmb of IgM, IgT and IgD and secreted form, ighmsc and ightsc of IgM and IgT, respectively, with similar structural patterns and conserved features in amino acids across immunoglobulin molecules, including cysteine residues crucial for structural integrity observed in other teleost species. In response to bacterial infections by Flavobacterium covae (formerly F. columnare genomovar II) and Streptococcus iniae, both secreted and membrane-bound forms of IgM (ighmmb and ighmsc) and IgT (ightmb and ightsc) show significant expression, indicating their roles in systemic and mucosal immunity. The expression of membrane-bound form IgD gene, ighdmb, predominantly exhibits targeted upregulation in PBLs, suggesting a regulatory role in B cell-mediated immunity. The findings underscore the dynamic and tissue-specific expression of immunoglobulin repertoires, ighmmb, ighmsc, ightmb, ightsc and ighdmb in Asian seabass, indicating a sophisticated immune response to bacterial pathogens. These findings have practical implications for fish aquaculture, and disease control strategies, serving as a valuable resource for advancing research in Asian seabass immunology.


Assuntos
Doenças dos Peixes , Proteínas de Peixes , Infecções por Flavobacteriaceae , Flavobacterium , Imunoglobulina D , Imunoglobulina M , Imunoglobulinas , Infecções Estreptocócicas , Streptococcus iniae , Animais , Doenças dos Peixes/imunologia , Flavobacterium/fisiologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/veterinária , Imunoglobulina M/imunologia , Imunoglobulina M/genética , Infecções por Flavobacteriaceae/imunologia , Infecções por Flavobacteriaceae/veterinária , Infecções por Flavobacteriaceae/genética , Imunoglobulina D/genética , Imunoglobulina D/imunologia , Imunoglobulina D/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Streptococcus iniae/fisiologia , Imunoglobulinas/genética , Imunoglobulinas/imunologia , Imunidade Inata/genética , Bass/imunologia , Bass/genética
4.
Autoimmunity ; 57(1): 2356089, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38770919

RESUMO

Autoimmune hepatitis (AIH) is a chronic, inflammatory liver disease of unknown aetiology which requires lifelong immunosuppression. Most therapeutic and outcome studies of AIH have been conducted predominantly in Caucasian (European Ancestry, EA) cohorts, with the exclusion of African American (AA) patients due to inadequate sample size. It is known that AA patients have a severe phenotype of autoimmune diseases and demonstrate a poor response to conventional medical therapy. Understanding cellular and molecular pathways which determine AIH severity and progression in AA patients is likely to lead to the discovery of novel, personalised and better tolerated therapies. The aim of the study is to determine the distinct effector B cell phenotypes which contribute to disease severity and progression of AIH in AA children as compared to their EA cohorts. PBMCs were isolated from blood samples collected from patients visiting Children's Healthcare of Atlanta (CHOA) and were grouped into AA, (n = 12), EA, (n = 11) and controls (n = 12) and were processed for flow cytometry. Markers of B cell development, maturation and activation were assessed namely CD19, CD21, IgD, CD27, CD38, CD11c, CD24, CD138. AA children with AIH demonstrated an expansion of CD19 + ve, Activated Naïve (aN), (CD19+ IgD-/CD27- Double Negative (DN2) ([CD19+/IgD-/CD27++CD38++) cells. Plasmablasts were significantly higher along with Signalling Lymphocytic activation molecule F7 (SLAMF7). Unswitched memory [CD19+] IgD+CD27+ (USM) B cells were significantly contracted in AA patients with AIH. B cell phenotyping reveals a distinct profile in AA AIH patients with a major skewing towards the expansion of effector pathways which have been previously characterised in severe SLE in AA patients. These results suggest that the quantification and therapeutic target of B cell pathway could contribute substantially to the clinical approach to AIH especially in the AA population.


Assuntos
Linfócitos B , Hepatite Autoimune , Imunoglobulina D , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral , Humanos , Hepatite Autoimune/imunologia , Hepatite Autoimune/sangue , Hepatite Autoimune/patologia , Hepatite Autoimune/diagnóstico , Imunoglobulina D/imunologia , Imunoglobulina D/metabolismo , Criança , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Masculino , Feminino , Adolescente , Linfócitos B/imunologia , Linfócitos B/metabolismo , Pré-Escolar , Imunofenotipagem , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Idade de Início , Biomarcadores
5.
Biochem Med (Zagreb) ; 34(2): 020801, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38665868

RESUMO

Less than 2% of all symptomatic multiple myeloma (MM) has immunoglobulin D (IgD) as monoclonal protein. Biclonal gammopathy is much rarer. At the time of diagnosis, disease is often in advanced stage, including renal failure, anemia, hypercalcemia and lytic bone lesions. Due to the rarity of myeloma itself, but also due to the fact that anti-IgD antisera is not used in routine practice, there are only a few reports of IgD MM described in the literature. This case report describes a patient with IgD lambda MM with anemia and renal failure. Anemia, renal failure, and > 80 percent plasma cells in bone biopsy in our patient with IgD lambda MM meets International Myeloma Working Group criteria for diagnosis of MM. The patient clinical course was similar to other patients with IgD MM. The final result of serum protein immunofixation (s-IFE) showed IgD lambda and free lambda monoclonal bands. To prevent misdiagnosis, it is necessary to use anti-IgD and anti-IgE antisera whenever the serum protein immunofixation with IgA, IgM, IgG, kappa and lambda antiserums shows a kappa or lambda monoclonal band without monoclonal band in heavy chain.


Assuntos
Imunoglobulina D , Cadeias lambda de Imunoglobulina , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Cadeias lambda de Imunoglobulina/sangue , Imunoglobulina D/sangue , Masculino , Pessoa de Meia-Idade
8.
Cell Rep ; 42(6): 112630, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37300833

RESUMO

Although therapeutic B cell depletion dramatically resolves inflammation in many diseases in which antibodies appear not to play a central role, distinct extrafollicular pathogenic B cell subsets that accumulate in disease lesions have hitherto not been identified. The circulating immunoglobulin D (IgD)-CD27-CXCR5-CD11c+ DN2 B cell subset has been previously studied in some autoimmune diseases. A distinct IgD-CD27-CXCR5-CD11c- DN3 B cell subset accumulates in the blood both in IgG4-related disease, an autoimmune disease in which inflammation and fibrosis can be reversed by B cell depletion, and in severe COVID-19. These DN3 B cells prominently accumulate in the end organs of IgG4-related disease and in lung lesions in COVID-19, and double-negative B cells prominently cluster with CD4+ T cells in these lesions. Extrafollicular DN3 B cells may participate in tissue inflammation and fibrosis in autoimmune fibrotic diseases, as well as in COVID-19.


Assuntos
Subpopulações de Linfócitos B , COVID-19 , Doença Relacionada a Imunoglobulina G4 , Humanos , Fibrose , Imunoglobulina D , Inflamação , Receptores CXCR5 , Subpopulações de Linfócitos B/metabolismo , Subpopulações de Linfócitos B/patologia
9.
Acta Med Okayama ; 77(2): 221-225, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37094962

RESUMO

Several previous case reports have shown that patients with immunoglobulin D (IgD) multiple myeloma (MM) can be withdrawn from hemodialysis, however, the characteristics that can predict withdrawal in these patients have not yet been elucidated. A 57-year-old Japanese woman required hemodialysis because of renal dysfunction due to IgD-λ and Bence Jones protein-λ MM. Bortezomib-based chemotherapy nine days after admission led to her withdrawal from hemodialysis on Day 50. In our case-based review, younger age and early initiation of bortezomib-based chemotherapy emerged as possible predictors of successful hemodialysis withdrawal.


Assuntos
Mieloma Múltiplo , Humanos , Feminino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Bortezomib/uso terapêutico , Imunoglobulina D/uso terapêutico , Diálise Renal , Cadeias lambda de Imunoglobulina
10.
Immunol Lett ; 255: 67-76, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36906182

RESUMO

Human B cells can be divided into four main subsets based on differential expression of immunoglobulin (Ig)D and CD27. IgD-CD27- double negative (DN) B cells make up a heterogeneous group of B cells that have first been described in relation to aging and systemic lupus erythematosus but have been mostly disregarded in B cell research. Over the last few years, DN B cells have gained a lot of interest because of their involvement in autoimmune and infectious diseases. DN B cells can be divided into different subsets that originate via different developmental processes and have different functional properties. Further research into the origin and function of different DN subsets is needed to better understand the role of these B cells in normal immune responses and how they could be targeted in specific pathologies. In this review, we give an overview of both phenotypic and functional properties of DN B cells and provide insight into the currently proposed origins of DN B cells. Moreover, their involvement in normal aging and different pathologies is discussed.


Assuntos
Subpopulações de Linfócitos B , Lúpus Eritematoso Sistêmico , Humanos , Linfócitos B , Envelhecimento , Memória Imunológica , Imunoglobulina D/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
11.
Pharmacol Res ; 189: 106686, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36746360

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis as a result of severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Excessive IgD may play a role in T cell activation via IgD Fc receptor (FcδR). Here we aimed to investigate the effects of IgD in T-ALL and demonstrated the potential benefit by targeting IgD/FcδR in T-ALL patients with IgD-Fc-Ig fusion protein. In T-ALL patients' blood samples and cell lines, the level of IgD, the percentage of FcδR expressing cells and the binding affinity were determined by flow cytometry. T cell viability, proliferation and apoptosis were analyzed. A mouse xenograft model was used to evaluate the in vivo effect of IgD-Fc-Ig, an IgD-FcδR blocker. The levels of serum IgD and FcδR were abnormally increased in part of T-ALL patients and IgD could induce over-proliferation and inhibit apoptosis of T-ALL cells in vitro. FcδR was constitutively expressed on T-ALL cells. IgD-Fc-Ig showed similar binding affinity to FcδR and selectively blocked the stimulation effect of IgD on T-ALL cells in vitro. In vivo study exhibited that IgD-Fc-Ig may also have therapeutic benefit. IgD-Fc-Ig administration inhibited human T-ALL growth and extended survival in xenograft T-ALL mice. In conclusion, this work supports the idea of targeting IgD/FcδR in T-ALL patients with excessive IgD. IgD-Fc-Ig fusion protein might be a potential biological drug with high selectivity for T-ALL treatment.


Assuntos
Linfócitos B , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Camundongos , Animais , Imunoglobulina D/fisiologia , Linfócitos T
12.
Front Immunol ; 14: 1096019, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36776874

RESUMO

B cell maturation and immunoglobulin (Ig) repertoire selection are governed by expression of a functional B cell receptor (BCR). Naïve B cells co-express their BCR as IgM and IgD isotype. However, the role of the additionally expressed IgD on naïve B cells is not known. Here we assessed the impact of IgD on naïve B cell maturation and Ig repertoire selection in 8 individuals from 3 different families with heterozygous loss-of-function or loss-of expression mutations in IGHD. Although naïve B cells from these individuals expressed IgM on their surface, the IGHD variant in heterozygous state entailed a chimeric situation by allelic exclusion with almost half of the naïve B cell population lacking surface IgD expression. Flow cytometric analyses revealed a distinct phenotype of IgD-negative naïve B cells with decreased expression of CD19, CD20 and CD21 as well as lower BAFF-R and integrin-ß7 expression. IgD-negative B cells were less responsive in vitro after engaging the IgM-BCR, TLR7/9 or CD40 pathway. Additionally, a selective disadvantage of IgD-negative B cells within the T2 transitional and mature naïve B cell compartment as well as reduced frequencies of IgMlo/- B cells within the mature naïve B cell compartment lacking IgD were evident. RNA-Ig-seq of bulk sorted B cell populations showed an altered selection of distinct VH segments in the IgD-negative mature naïve B cell population. We conclude that IgD expression on human naïve B cells is redundant for generation of naïve B cells in general, but further shapes the naive B cell compartment starting from T2 transitional B cells. Our observations suggest an unexpected role of IgD expression to be critical for selection of distinct Ig VH segments into the pre-immune Ig repertoire and for the survival of IgMlo/- naïve B cells known to be enriched in poly-/autoreactive B cell clones.


Assuntos
Linfócitos B , Imunoglobulina D , Humanos , Imunoglobulina D/metabolismo , Imunoglobulina M , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/metabolismo , Isotipos de Imunoglobulinas/metabolismo
13.
Joint Bone Spine ; 90(1): 105490, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36410683

RESUMO

BACKGROUND: Mevalonate kinase (MVK) plays a role in cholesterol and non-sterol isoprenoid biosynthesis and its deficiency-related diseases are caused by bi-allelic pathogenic mutations in the MVK gene, (MVK), which leads to rare hereditary autoinflammatory diseases. The disease may manifest different clinical phenotypes depending on the degree of the deficiency in the enzyme activity. The complete deficiency of the enzyme activity results in the severe metabolic disease called mevalonic aciduria, while a partial deficiency results in a broad spectrum of clinical presentations called hyper-immunoglobulin D syndrome (HIDS). Serum immunoglobulin (Ig) D and urine mevalonic acid levels may be increased during inflammatory attacks of HIDS. CASE PRESENTATION: Herein, for the first time in the literature, we present a 6-year-old male patient who suffered from recurrent episodes of fever, polyarthritis, skin rash, diarrhea, abdominal pain, and inflammatory bowel disease-like manifestations with elevated levels of serum IgD, and urine mevalonic acid. Eventually we detected compound heterozygous mutations in the phosphomevalonate kinase (PMVK) gene coding the second enzyme after mevalonate kinase in the mevalonate pathway. CONCLUSION: For patients presenting with HIDS-like findings, disease exacerbations and persistent chronic inflammation, and having high urinary mevalonic acid and serum IgD levels, raising suspicion in terms of MVK deficiency (MVKD), it is recommended to study all mevalonate pathway enzymes, even if there is no mutation in the MVK gene. It should be kept in mind that novel mutations might be seen such as PMVK gene.


Assuntos
Doenças Hereditárias Autoinflamatórias , Deficiência de Mevalonato Quinase , Humanos , Masculino , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Imunoglobulina D , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/genética , Ácido Mevalônico , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Criança
16.
Clin Rheumatol ; 42(4): 1069-1076, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36585530

RESUMO

INTRODUCTION: Many studies have shown that serum immunoglobulin D (IgD) is usually increased in autoimmune diseases. The potential role of IgD in systemic lupus erythematosus (SLE) is still unclear. Our study aimed to compare the serum IgD levels of SLE with different population and to evaluate the relationship between serum IgD and SLE. METHODS: Fifty SLE patients, 40 non-SLE chronic kidney disease (CKD) patients, and 50 healthy volunteers were enrolled in this study. Serum IgD levels were analyzed by ELISA assay and compared between groups. The correlation of serum IgD and SLE disease were evaluated. The ability of serum IgD to predict SLE was analyzed by graphing receiver operating characteristic curves. RESULTS: Serum IgD levels were significantly higher in SLE patients compared to non-SLE CKD and healthy controls (7436.1 ± 5862.1 vs. 4517.8 ± 5255.2 vs. 4180.4 ± 4881 ng/mL, p = 0.01, p = 0.002, respectively), and in patients with high SLE Disease Activity Index (SLEDAI) scores compared with those with low scores (8572.9 ± 5968.7 vs. 5020.4 ± 4972.5 ng/mL, p = 0.044). High level of inflammatory cytokines and decreased circulating basophil counts were found in SLE patients (p < 0.05). No correlations was identified between serum IgD levels and SLEDAI scores (p > 0.05). Serum IgD was noninferior to IgG or IgE in discriminating SLE with an area under the curve of 0.672 (95% CI, 0.59-0.75). CONCLUSIONS: Serum IgD levels are significantly elevated in SLE patients with high SLEDAI scores. Simultaneous occurrence of increased inflammatory cytokines and decreased basophil counts highlights the potential role of IgD-targets interaction in SLE pathogenesis. Key points • Total serum IgD levels were elevated in SLE patients. • High IgD levels were significantly higher in SLE patients with high SLEDAI scores. • The ability of serum IgD was equivalent to IgG or IgE in discriminating SLE from CKD and healthy adult.


Assuntos
Lúpus Eritematoso Sistêmico , Insuficiência Renal Crônica , Adulto , Humanos , Citocinas , Imunoglobulina D , Imunoglobulina E , Imunoglobulina G , Biomarcadores
17.
Front Immunol ; 13: 1001145, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248899

RESUMO

Human B cells encompass functionally diverse lineages and phenotypic states that contribute to protective as well as pathogenic responses. Epstein-Barr virus (EBV) provides a unique lens for studying heterogeneous B cell responses, given its adaptation to manipulate intrinsic cell programming. EBV promotes the activation, proliferation, and eventual outgrowth of host B cells as immortalized lymphoblastoid cell lines (LCLs) in vitro, which provide a foundational model of viral latency and lymphomagenesis. Although cellular responses and outcomes of infection can vary significantly within populations, investigations that capture genome-wide perspectives of this variation at single-cell resolution are in nascent stages. We have recently used single-cell approaches to identify EBV-mediated B cell heterogeneity in de novo infection and within LCLs, underscoring the dynamic and complex qualities of latent infection rather than a singular, static infection state. Here, we expand upon these findings with functional characterizations of EBV-induced dynamic phenotypes that mimic B cell immune responses. We found that distinct subpopulations isolated from LCLs could completely reconstitute the full phenotypic spectrum of their parental lines. In conjunction with conserved patterns of cell state diversity identified within scRNA-seq data, these data support a model in which EBV continuously drives recurrent B cell entry, progression through, and egress from the Germinal Center (GC) reaction. This "perpetual GC" also generates tangent cell fate trajectories including terminal plasmablast differentiation, which constitutes a replicative cul-de-sac for EBV from which lytic reactivation provides escape. Furthermore, we found that both established EBV latency and de novo infection support the development of cells with features of atypical memory B cells, which have been broadly associated with autoimmune disorders. Treatment of LCLs with TLR7 agonist or IL-21 was sufficient to generate an increased frequency of IgD-/CD27-/CD23-/CD38+/CD138+ plasmablasts. Separately, de novo EBV infection led to the development of CXCR3+/CD11c+/FCRL4+ B cells within days, providing evidence for possible T cell-independent origins of a recently described EBV-associated neuroinvasive CXCR3+ B cell subset in patients with multiple sclerosis. Collectively, this work reveals unexpected virus-driven complexity across infected cell populations and highlights potential roles of EBV in mediating or priming foundational aspects of virus-associated immune cell dysfunction in disease.


Assuntos
Linfócitos B , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Autoimunidade , Centro Germinativo , Humanos , Imunoglobulina D/genética , Fenótipo , Receptor 7 Toll-Like/genética
18.
Leuk Lymphoma ; 63(14): 3433-3437, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36263946

RESUMO

IgD multiple myeloma is uncommon. Patients generally present at a younger age and have shorter progression free and overall survivals (OSs). Its rarity has inhibited development of a specific risk stratification system or informed best treatment protocols. We present interphase fluorescence in situ hybridization results from a group of 29 cases. These showed evidence of a decreased male to female ratio, decreased OS in patients aged 70 and over, better outcomes in those with kappa light chain restriction, and CD56 positive patients had longer survivals than those lacking CD56. We discuss the biology of IgD multiple myeloma, the need for prospective studies, and challenges for improvements in diagnosis and treatment. We suggest an International Register to accelerate development of best practice guidelines for diagnosis, risk stratification, and treatment.


Assuntos
Mieloma Múltiplo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Imunoglobulina D , Hibridização in Situ Fluorescente , Mieloma Múltiplo/terapia , Estudos Prospectivos
19.
Sci Rep ; 12(1): 16880, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207336

RESUMO

Graves' disease (GD) is an organ-specific autoimmune disease, but there are a few studies that have evaluated how immunophenotypes are related to clinical symptoms and intractable pathology, or the effects of treatment on immunophenotypes. We performed peripheral blood immunophenotyping in GD. We assessed the proportion of functional subsets of T helper cells (such as Th1, Th17, Treg and Tfh cells), B cells (Naïve, IgM memory, Class-switched, IgD-CD27- double negative and Plasmablasts cells), Monocytes, Dendritic cells and NK cells, and evaluated the relationship of immunophenotypes with clinical indices, disease activity, risk of relapse, and changes in immunophenotypes after treatment with antithyroid drugs. The activated Th17 cells, activated T follicular helper (Tfh) cells, and IgD-CD27- double-negative B cells were higher in newly onset GD compared with healthy participants. Th17 cells were associated with thyroid autoantibodies, thyroid function, thyroid enlargement, and Graves' Recurrent Events After Therapy (GREAT) score; while double-negative B cells were associated with thyroid autoantibodies. Treatment with antithyroid drugs decreased the activated Tfh cells in parallel with the improvement in thyroid function. However, activated Th17 cells were not associated with clinical improvement and remained unchanged. Peripheral blood immunophenotyping identified the differential involvement of T and B cell subsets in the pathogenesis of GD. Abnormalities in the differentiation of Th17, Tfh, and double-negative B cells reflected the clinical pathology associated with autoantibody production and excess thyroid hormones. And Th17 cells are significantly associated with the marker for resistance to treatment. These results suggest the involvement of Th17 cell activation in the intractable pathology associated with potential immune abnormalities in GD. Clinical trial registration: #UMIN000017726 (Date: June 1st, 2015).


Assuntos
Doença de Graves , Células Th17 , Antitireóideos , Autoanticorpos , Humanos , Imunoglobulina D , Imunoglobulina M , Imunofenotipagem , Hormônios Tireóideos
20.
Aging Cell ; 21(10): e13705, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36056604

RESUMO

Age-associated B cells (ABC) accumulate with age and are associated with autoimmunity and chronic infection. However, their contributions to acute infection in the aged and their developmental pathways are unclear. We find that the response against influenza A virus infection in aged mice is dominated by a Fas+ GL7- effector B cell population we call infection-induced ABC (iABC). Most iABC express IgM and include antibody-secreting cells in the spleen, lung, and bone marrow. We find that in response to influenza, IgD+ CD21- CD23- ABC are the precursors of iABC and become memory B cells. These IgD+ ABC develop in germ-free mice, so are independent of foreign antigen recognition. The response of ABC to influenza infection, resulting in iABC, is T cell independent and requires both extrinsic TLR7 and TLR9 signals. In response to influenza infection, IgD+ ABC can induce a faster recovery of weight and higher total anti-influenza IgG and IgM titers that can neutralize virus. Immunization with whole inactivated virus also generates iABC in aged mice. Thus, in unimmunized aged mice, whose other B and T cell responses have waned, IgD+ ABC are likely the naive B cells with the potential to become Ab-secreting cells and to provide protection from infection in the aged.


Assuntos
Vacinas contra Influenza , Influenza Humana , Animais , Humanos , Camundongos , Anticorpos Antivirais , Imunoglobulina D , Imunoglobulina G , Imunoglobulina M , Receptor 7 Toll-Like , Receptor Toll-Like 9 , Vacinas de Produtos Inativados , Linfócitos B , Linfócitos T
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