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1.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(11): 830-836, 2019 Nov 07.
Artigo em Chinês | MEDLINE | ID: mdl-31795544

RESUMO

Objective: To study the effect on immune indexes in children with obstructive sleep apnea hypopnea syndrome (OSAHS) before and after resection of adenoid and/or tonsil. Methods: A total of 100 children with OSAHS due to adenoid hypertrophy were enrolled in Department of Otorhinolaryngology Head and Neck Surgery, the Second Hospital of Dalian Medical University from December 2016 to December 2018. Some cases were complicated with tonsil hypertrophy or chronic tonsillitis. 6 ml of fasting peripheral venous blood were collected from all subjects at the 1st day before surgery, 4th day, 1 month, 3 months and 6 months after surgery to detect lymphoid subsets percentage (CD3(+), CD4(+),CD8(+), CD4/CD8, CD19, NK) and level of immunoglobulin (IgG, IgA, IgM). Grouping: group A was a total of 51 cases with adenoid hypertrophy after Adenoid plasma ablation; group B was a total of 27 cases with adenoid hypertrophy and chronic tonsillitis after plasma ablation of adenoid and tonsil; and group C was a total of 22 cases hypertrophy of adenoid and tonsil after plasma ablation of adenoid and tonsil.In the baseline data, age, gender and other variables were analyzed by anova and chi-square test, repeated measurement anova was used for intra-group and inter-group comparison of observation indicators at different time points after operation, and independent sample t-test was used for comparison between the two groups at observation points 3 months after operation. Results: (1) In group A, the percentage of CD19 lymphocytes before surgery was higher than that at 4th day after surgery, and the difference was statistically significant (21.85±6.20 vs.19.18±5.91, P<0.05). The other immune indexes were not statistically different before and after surgery (P>0.05). (2) In group B, the percentage of CD19 lymphocytes, CD3(+)T lymphocytes, CD8(+)T lymphocytes and the level of IgG at 4th day after surgery were significantly different between those before surgery (all P<0.05). At the 1st month after surgery, the percentage of CD3(+)T lymphocytes, CD8(+)T lymphocytes, CD19 lymphocytes and the level of IgG were significantly different between those before surgery (all P<0.05). The other immune indexes were not statistically different before and after operation (P>0.05). (3) In group C, the percentage of CD19 lymphocytes and the CD3(+)T lymphocytes at 4th day after surgery were significantly different between those before surgery (all P<0.05).In the 1st month after surgery, the percentage of CD8(+)T lymphocytes and CD19 lymphocytes were significantly different between those before surgery (all P<0.05). The other immune indexes were not statistically different before and after operation (P>0.05). (4) Among three groups, the percentage of CD4(+)T lymphocytes, the levels of IgG and IgA before surgery between group A and Group B were statistically significant (all P<0.05). At 4th day after surgery, the percentage of CD4(+)T lymphocytes in group B and C were lower than those in group A, and the differences were statistically significant (32.22±6.14, 32.36±6.87 vs. 36.36±5.19, all P<0.05); the other immune indexes were not statistically different among each group before and after surgery (P>0.05). Conclusions: Resection of adenoid has no significant effect on the immune indexes in children with OSAHS. The children with OSAHS complicated with tonsil problems have immune index disorder before surgery. Surgery has a certain effect on the immune indexes of children with OSAHS in a short period of time, and tends to normal level after one month.


Assuntos
Tonsila Faríngea/cirurgia , Antígenos de Diferenciação de Linfócitos T/imunologia , Tonsila Palatina/cirurgia , Apneia Obstrutiva do Sono/imunologia , Apneia Obstrutiva do Sono/cirurgia , Subpopulações de Linfócitos T/imunologia , Adenoidectomia , Tonsila Faríngea/imunologia , Tonsila Faríngea/patologia , Antígenos de Diferenciação de Linfócitos T/sangue , Criança , Humanos , Hipertrofia , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Contagem de Linfócitos , Tonsila Palatina/imunologia , Tonsila Palatina/patologia , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/etiologia , Tonsilectomia
2.
PLoS Pathog ; 15(12): e1008064, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31841557

RESUMO

Broadly neutralizing antibodies (bNAbs) protect against HIV infection in non-human primates and their efficacy may be enhanced through interaction with Fc receptors on immune cells. Antibody isotype is a modulator of this binding with the IgG3 subclass mediating potent Fc effector function and is associated with HIV vaccine efficacy and HIV control. BNAb functions are typically assessed independently of the constant region with which they are naturally expressed. To examine the role of natural isotype in the context of a bNAb lineage we studied CAP256, an HIV-infected individual that mounted a potent V2-specific bNAb response. CAP256 expressed persistently high levels of plasma IgG3 which we found mediated both broad neutralizing activity and potent Fc function. Sequencing of germline DNA and the constant regions of V2-directed bNAbs from this donor revealed the expression of a novel IGHG3 allele as well as IGHG3*17, an allele that produces IgG3 antibodies with increased plasma half-life. Both allelic variants were used to generate CAP256-VRC26.25 and CAP256-VRC26.29 IgG3 bNAbs and these were compared to IgG1 versions. IgG3 variants were shown to have significantly higher phagocytosis and trogocytosis compared to IgG1 versions, which corresponded to increased affinity for FcγRIIa. Neutralization potency was also significantly higher for IgG3 bNAbs, particularly against viruses lacking the N160 glycan. By exchanging hinge regions between subclass variants, we showed that hinge length modulated both neutralization potency and Fc function. This study showed that co-operation between the variable and natural IgG3 constant regions enhanced the polyfunctionality of antibodies, indicating the value of leveraging genetic variation which could be exploited for passive immunity.


Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , Anticorpos Anti-HIV/imunologia , Imunoglobulina G/imunologia , Isotipos de Imunoglobulinas/imunologia , Adulto , Feminino , Infecções por HIV/imunologia , Humanos , Receptores Fc/imunologia
3.
Pak J Pharm Sci ; 32(3 Special): 1441-1445, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31551229

RESUMO

Objective of the present study was to investigate the effects of peripherally inserted central catheter (PICC) parenteral nutrition support on immune function and nutritional support in patients undergoing radical gastrectomy for gastric cancer. 140 patients who underwent radical gastrectomy for gastric cancer were selected as participants and were divided into study group and the control group by random number table, with 70 cases in each group. Patients in the two groups underwent standard gastrectomy under general anesthesia by the same group of doctors. The study group received postoperative PICC catheter parenteral nutrition, and the control group received central venous catheter (CVC) nutrition support. Comparative study was done using t test and Chi-square test. The serum levels of ALB, TFN, PA, Hb, CD4+, CD8+, CD4+/CD8+, IgA, IgG, IgM and CD3+ in the two groups were observed before and after treatment, and the postoperative complications of the two groups were compared. After treatment, the levels of ALB, TFN, PA and Hb in the two groups were significantly increased (P<0.05). Levels of CD3+, CD4+, CD4+/CD8+, IgA, IgG and IgM also amplified significantly after treatment in both the groups, while CD8+ decreased significantly (P<0.05). What's more, the improvement degree of the study group was significantly greater than that of the control group (P<0.05). The time of drawing drainage tube, recovering intestinal function, getting off bed and the length of hospital stay in the study group were significantly shorter than those in the control group (P<0.05). The incidence of postoperative complications in the study group and control group were 8.6% (6/70 cases) and 11.4% (8/70 cases) respectively, and there was no significant difference (P>0.05). PICC catheter parenteral nutrition support and improve the nutritional status of patients, it was proved a safe and effective nutritional support which improve the cellular immune function and accelerated the recovery of gastrointestinal function.


Assuntos
Nutrição Parenteral/métodos , Complicações Pós-Operatórias/prevenção & controle , Neoplasias Gástricas/cirurgia , Dispositivos de Acesso Vascular , Idoso , Antígenos de Diferenciação de Linfócitos T/sangue , Cateteres Venosos Centrais , Feminino , Gastrectomia , Humanos , Isotipos de Imunoglobulinas/sangue , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral/instrumentação , Complicações Pós-Operatórias/dietoterapia , Complicações Pós-Operatórias/imunologia , Resultado do Tratamento
4.
Clin Biochem ; 74: 42-46, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31526775

RESUMO

OBJECTIVES: Clinical decisions in patients with monoclonal gammopathies may be highly imprecise because of variations of parameters used in diagnosis. In this study, we aimed to calculate the variation in M-protein, free light chains (FLCs), and immunoglobulins in respective patients. DESIGN & METHODS: We analyzed the data of clinically stable patients with monoclonal gammopathy (MG), which were monitored for 7-years to determine the biological variations and reference change values (RCV) of serum M-protein, monoclonal serum FLCs and immunoglobulin (Ig) concentrations. Patients that were included in the study had no change in diagnosis and showed <5 g/L change in serum M-protein during the monitoring. From the patients included at least 3 consecutive samples were analyzed within 8 months and 7 years of initial diagnosis. RESULTS: The total coefficient of variations (CV) was calculated for M-protein and involved/uninvolved fractions of FLCs and immunoglobulins. From 38 patients and 456 samples that were included in the study, the total CVs were calculated for serial M-proteins (8.9%), serum involved FLCs (iFLC, 21.4%), involved Ig (i-Ig, 8.7%) and uninvolved Ig (u-Ig, 9.1%). Combining these CVs and the interassay analytical CVs, we calculated the biological CV for the serum M-protein (8.4%), serum iFLC concentration (21.1%), i-Ig (8.6%) and u-Ig (9.0%). A significant correlation was found in multiple myeloma patients between the κ/λ light chain ratio (rFLC) with i-Ig, the difference between i-Ig level and u-Ig level (d-Ig) and ratio Ig (r-Ig) (r = 0.790, 0.703 and 0.711, respectively). These correlations were not found in patients suffering from MG of undetermined significance and smoldering multiple myeloma. CONCLUSIONS: i-Ig determinations may be an alternative to M-protein for MGs. The variations in serum FLC measurements during MG monitoring were greater than those observed in serum M-proteins and therefore need to be more rigorously revised for recommendations.


Assuntos
Isotipos de Imunoglobulinas/sangue , Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Imunoglobulinas/sangue , Gamopatia Monoclonal de Significância Indeterminada/sangue , Mieloma Múltiplo/sangue , Mieloma Múltiplo Latente/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos
5.
Nature ; 574(7776): 122-126, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31554970

RESUMO

B cells are important in the pathogenesis of many, and perhaps all, immune-mediated diseases. Each B cell expresses a single B cell receptor (BCR)1, and the diverse range of BCRs expressed by the total B cell population of an individual is termed the 'BCR repertoire'. Our understanding of the BCR repertoire in the context of immune-mediated diseases is incomplete, and defining this could provide new insights into pathogenesis and therapy. Here, we compared the BCR repertoire in systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Crohn's disease, Behçet's disease, eosinophilic granulomatosis with polyangiitis, and immunoglobulin A (IgA) vasculitis by analysing BCR clonality, use of immunoglobulin heavy-chain variable region (IGHV) genes and-in particular-isotype use. An increase in clonality in systemic lupus erythematosus and Crohn's disease that was dominated by the IgA isotype, together with skewed use of the IGHV genes in these and other diseases, suggested a microbial contribution to pathogenesis. Different immunosuppressive treatments had specific and distinct effects on the repertoire; B cells that persisted after treatment with rituximab were predominately isotype-switched and clonally expanded, whereas the inverse was true for B cells that persisted after treatment with mycophenolate mofetil. Our comparative analysis of the BCR repertoire in immune-mediated disease reveals a complex B cell architecture, providing a platform for understanding pathological mechanisms and designing treatment strategies.


Assuntos
Doenças do Sistema Imunitário/imunologia , Isotipos de Imunoglobulinas/análise , Isotipos de Imunoglobulinas/imunologia , Receptores de Antígenos de Linfócitos B/análise , Receptores de Antígenos de Linfócitos B/imunologia , Adulto , Idoso , Células Clonais/citologia , Células Clonais/imunologia , Humanos , Imunoglobulina A/análise , Imunoglobulina A/imunologia , Switching de Imunoglobulina/imunologia , Imunoglobulina G/análise , Imunoglobulina G/imunologia , Pessoa de Meia-Idade , Adulto Jovem
6.
Int Arch Allergy Immunol ; 180(3): 221-232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509832

RESUMO

BACKGROUND: Immunoglobulin (Ig) therapy is highly effective in reducing the frequency and severity of infections. However, a subset of patients does not respond adequately. OBJECTIVE: To determine in adult patients with primary hypogammaglobulinemia (a) if failure to reconstitute IgG subclass(es) is associated with inadequate clinical response, (b) whether reconstitution of IgG subclasses differs between routes of Ig administration, (c) which subclasses contribute to low total IgG, and (d) what are the most commonly impaired Streptococcus pneumoniae serotypes. METHODS: A retrospective review of the records of patients with primary hypogammaglobulinemia followed up at the Immunology Clinic between 2010 and 2018 was conducted. Demographic, clinical, and laboratory data were collected. RESULTS: Seventy-one patients with primary hypogammaglobulinemia were included. All subclasses were reconstituted in 85% of the patients. IgG3 and IgG4 were most commonly not reconstituted. Reconstitution occurred in 85% of the patients on intravenous Ig (IVIG), 81% of the patients on conventional subcutaneous Ig (SCIG), and 100% of the patients on enzyme-facilitated subcutaneous Ig (fSCIG). The annual infection rate was 0.87 with IVIG, 0.88 with conventional SCIG, and 0.6 with fSCIG. IgG subclasses contributing to low total IgG included IgG1 (61%), IgG2 (49%), IgG3 (23%), and IgG4 (28%). In patients with concomitant specific antibody deficiency (n = 47), the most commonly impaired antibody responses were against pneumococcal serotypes 3, 4, 6b, 12f, and 23f. CONCLUSIONS: Failure to reconstitute subclasses does not correlate with an inadequate clinical response to immunoglobulin therapy in primary hypogammaglobulinemia. Full reconstitution of IgG subclasses was observed with fSCIG. A smaller panel of pneumococcal antibody responses may be used to define specific antibody deficiency.


Assuntos
Agamaglobulinemia/terapia , Isotipos de Imunoglobulinas/biossíntese , Imunoglobulinas Intravenosas/uso terapêutico , Imunoterapia/métodos , Infecções Pneumocócicas/epidemiologia , Streptococcus pneumoniae/fisiologia , Adolescente , Adulto , Agamaglobulinemia/epidemiologia , Agamaglobulinemia/imunologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Autorrenovação Celular , Feminino , Homeostase , Humanos , Infusões Subcutâneas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos , Adulto Jovem
7.
Sensors (Basel) ; 19(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509969

RESUMO

Food intolerance is delayed adverse food reactions which follow consumption of specific foods. The underlying mechanisms are not well understood, but food intolerance is often considered as a type 2 hypersensitivity reaction mediated by immunoglobulin G (IgG) antibody. To understand the causes of food intolerance, it is important to investigate sensitization patterns of food-specific IgGs (sIgG) in relation to dietary patterns and physical conditions. Conventional approaches to measure serological IgGs often require large volumes of serum, thus are not suitable for highly multiplexed assays. To overcome this impracticality, we developed a highly sensitive method to screen the sIgGs and other antibody isotypes against 66 antigens with minimal amount of serums. We prepared a microarray by immobilizing food antigens on activated glass slides. Human sera and their dietary information were obtained from 30 subjects. Aliquots (200 nl) of sera were analyzed against 66 food antigens in parallel. sIgG levels were determined and analyzed in relation to subjects' dietary patterns. The levels of antibody isotypes were also examined to understand the relationship between allergy and food intolerance. The developed microarray showed exceptional performances in antibody screening and demonstrated the potential to be used as an automated assay system.


Assuntos
Antígenos/análise , Alimentos , Isotipos de Imunoglobulinas/sangue , Análise em Microsséries/métodos , Microtecnologia/métodos , Sorologia , Adulto , Dieta , Feminino , Humanos , Pessoa de Meia-Idade
8.
BMC Infect Dis ; 19(1): 694, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387539

RESUMO

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is an underdiagnosed and misdiagnosed disease and now increasingly recognised. However, the diagnosis of CPA remains challenging. In this study, we aimed to investigate the diagnostic values of serum Aspergillus-specific IgG, IgA and IgM antibodies in patients with CPA. METHODS: The prospective study was performed at Chinese People's Liberation Army General Hospital in Beijing, from January 2017 to December 2017. Adult patients with lung lesions presented as cavity, nodule, mass, bronchiectasis or severe fibrotic destruction with at least two lobes in CT imaging were enrolled. One hundred healthy persons were also enrolled as additional controls. The serum levels of Aspergillus-specific IgG, IgA and IgM antibodies and galactomannan (GM) levels were measured simultaneously by plate ELISA kit. RESULTS: A total of 202 patients were enrolled in this study, including 42 CPA patients, 60 non-CPA patients and 100 healthy persons. The most common underlying lung diseases in CPA patients were bronchiectasis (28.6%) and COPD (19.0%). The most common symptoms in the CPA patients were cough (76.2%), sputum (71.4%), and fever (45.2%); chest pain (4.8%) was infrequent. Receiver operating characteristic (ROC) curve analysis revealed that the optimal CPA diagnostic cut-off of Aspergillus-specific IgG, IgA and IgM assays and GM test were 89.3 AU/mL, 8.2 U/mL, 73.3 AU/mL and 0.5µg/L, respectively. The serum levels of Aspergillus-specific IgG and IgA in CPA patients were higher than these in non-CPA patients or healthy persons. The sensitivities and specificities of Aspergillus-specific IgG, IgA, IgM tests and GM test were 78.6 and 94.4%, 64.3 and 89.4%, 50.0 and 53.7% and 71.4 and 58.1%, respectively. CONCLUSIONS: The sensitivity and specificity of serum Aspergillus-specific IgG assay are satisfactory for diagnosing CPA, while the performance of Aspergillus-specific IgA assay is moderate. Aspergillus-specific IgM assay and serum GM test have limited value for CPA diagnosis. TRIAL REGISTRATION: NCT03027089 . Registered 20 January 2017.


Assuntos
Isotipos de Imunoglobulinas/sangue , Aspergilose Pulmonar/diagnóstico , Adulto , Idoso , Anticorpos Antifúngicos/sangue , Aspergillus/imunologia , Doença Crônica , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Aspergilose Pulmonar/sangue , Aspergilose Pulmonar/etiologia , Curva ROC , Sensibilidade e Especificidade
9.
Sci Adv ; 5(7): eaav8152, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31328158

RESUMO

The function of regulatory immune cells in peripheral tissues is crucial to the onset and severity of various diseases. Interleukin-10 (IL-10)-producing regulatory B (IL-10+ Breg) cells are known to suppress various inflammatory diseases. However, evidence for the mechanism by which IL-10+ Breg cells are generated and maintained is still very limited. Here, we found that IL-10+ Breg cells suppress the activation of IL-13-producing type 2 innate lymphoid cells (IL-13+ ILC2s) in an IL-10-dependent manner in mice with oxazolone-induced severe contact hypersensitivity (CHS). Mast cell (MC) IL-5 was important for maintaining the population of IL-10+ Breg cells in peripheral lymphoid tissues. Overall, these results uncover a previously unknown mechanism of MCs as a type of immunoregulatory cell and elucidate the cross-talk among MCs, IL-10+ Breg cells, and IL-13+ ILC2s in CHS.


Assuntos
Linfócitos B Reguladores/imunologia , Linfócitos B Reguladores/metabolismo , Dermatite de Contato/etiologia , Dermatite de Contato/metabolismo , Interleucina-5/metabolismo , Mastócitos/imunologia , Mastócitos/metabolismo , Oxazolona/efeitos adversos , Tolerância Periférica , Animais , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Citocinas/metabolismo , Dermatite de Contato/patologia , Modelos Animais de Doenças , Imunofluorescência , Isotipos de Imunoglobulinas/imunologia , Masculino , Camundongos , Camundongos Knockout
10.
Sci Adv ; 5(7): eaav9732, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31328159

RESUMO

LRH-1 (liver receptor homolog-1/NR5a2) is an orphan nuclear receptor, which regulates glucose and lipid metabolism, as well as intestinal inflammation via the transcriptional control of intestinal glucocorticoid synthesis. Predominantly expressed in epithelial cells, its expression and role in immune cells are presently enigmatic. LRH-1 was found to be induced in immature and mature T lymphocytes upon stimulation. T cell-specific deletion of LRH-1 causes a drastic loss of mature peripheral T cells. LRH-1-depleted CD4+ T cells exert strongly reduced activation-induced proliferation in vitro and in vivo and fail to mount immune responses against model antigens and to induce experimental intestinal inflammation. Similarly, LRH-1-deficient cytotoxic CD8+ T cells fail to control viral infections. This study describes a novel and critical role of LRH-1 in T cell maturation, functions, and immopathologies and proposes LRH-1 as an emerging pharmacological target in the treatment of T cell-mediated inflammatory diseases.


Assuntos
Imunomodulação , Receptores Citoplasmáticos e Nucleares/genética , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Apoptose/genética , Biomarcadores , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Colite/etiologia , Colite/metabolismo , Colite/patologia , Citocinas/metabolismo , Citotoxicidade Imunológica , Suscetibilidade a Doenças , Feminino , Deleção de Genes , Humanos , Isotipos de Imunoglobulinas/imunologia , Masculino , Camundongos , Receptores Citoplasmáticos e Nucleares/metabolismo
11.
Basic Clin Pharmacol Toxicol ; 125(5): 474-483, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31219219

RESUMO

The aim of the present study was to compare concentrations of IgG, IgA, IgM and IgD in both serum and saliva samples from smoking and non-smoking individuals using a protein microarray assay. The findings were also compared to previous studies. Serum and saliva were collected from 48 smoking male individuals and 48 age-matched never-smoker male individuals. The protein microarray assays for detection of human IgG, IgM, IgA and IgD were established and optimized using Ig class-specific affinity-purified goat anti-human Ig-Fc capture antibodies and horseradish peroxidase (HRP)-conjugated goat anti-human Ig-Fc detection antibodies. The Ig class specificity of the microarray assays was verified, and the optimal dilutions of serum and saliva samples were determined for quantification of Ig levels against standard curves. We found that smoking is associated with reduced IgG concentrations and enhanced IgA concentrations in both serum and saliva. By contrast, smoking differentially affected IgM concentrations-causing increased concentrations in serum, but decreased concentrations in saliva. Smoking was associated with decreased IgD concentrations in serum and did not have a significant effect on the very low IgD concentrations in saliva. Thus, cigarette smoking differentially affects the levels of Ig classes systemically and in the oral mucosa. Although there is variation between the results of different published studies, there is a consensus that smokers have significantly reduced levels of IgG in both serum and saliva. A functional antibody deficiency associated with smoking may compromise the body's response to infection and result in a predisposition to the development of autoimmunity.


Assuntos
Autoimunidade , Fumar Cigarros/imunologia , Isotipos de Imunoglobulinas/análise , Saliva/química , Adulto , Fumar Cigarros/sangue , Humanos , Isotipos de Imunoglobulinas/imunologia , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/química , Mucosa Bucal/imunologia , não Fumantes , Análise Serial de Proteínas , Saliva/imunologia , Fumantes , Adulto Jovem
12.
Elife ; 82019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31225793

RESUMO

In mice, memory B (Bmem) cells can be divided into two subpopulations: CD80hi Bmem cells, which preferentially differentiate into plasma cells; and CD80lo Bmem cells, which become germinal center (GC) B cells during a recall response. We demonstrate that these distinct responses can be B-cell-intrinsic and essentially independent of B-cell receptor (BCR) isotypes. Furthermore, we find that the development of CD80hi Bmem cells in the primary immune response requires follicular helper T cells, a relatively strong CD40 signal and a high-affinity BCR on B cells, whereas the development of CD80lo Bmem cells does not. Quantitative differences in CD40 stimulation were enough to recapitulate the distinct B cell fate decisions in an in vitro culture system. The quantity of CD40 signaling appears to be translated into NF-κB activation, followed by BATF upregulation that promotes Bmem cell differentiation from GC B cells.


Assuntos
Linfócitos B/imunologia , Antígenos CD40/imunologia , Memória Imunológica/genética , Receptores de Antígenos de Linfócitos B/genética , Animais , Antígeno B7-1/genética , Antígenos CD40/genética , Diferenciação Celular/genética , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Centro Germinativo/imunologia , Isotipos de Imunoglobulinas , Memória Imunológica/imunologia , Camundongos , NF-kappa B/genética , NF-kappa B/imunologia , Plasmócitos/imunologia , Receptores de Antígenos de Linfócitos B/imunologia , Transdução de Sinais , Linfócitos T Auxiliares-Indutores/imunologia
13.
Clinics (Sao Paulo) ; 74: e631, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31241661

RESUMO

OBJECTIVE: Primary Sjögren's syndrome (pSjS) is a chronic autoimmune disease that causes dry eye and mouth. No laboratory parameters to monitor the activation of this disease have been identified. Therefore, any possible relationships between salivary and blood myxovirus resistance 1 (MX1) and pSjS must be prospectively studied. METHODS: Thirty female patients with pSjS, 30 women with rheumatoid arthritis (RA) without secondary Sjögren's syndrome (SjS) and 28 healthy control women were enrolled in this investigation. Analyses of MX1 by the enzyme-linked immunosorbent assay (ELISA) method, SS-A (Ro) and SS-B (La) tests by the strip immunoblot method, anti-nuclear antibody (ANA) tests by immunofluorescence and the measurement of serum rheumatoid factor (RF), C3, C4, immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) were performed. RESULTS: The serum level of MX1 in patients without Raynaud phenomenon was higher than in those with Raynaud phenomenon (p:0.029, p<0.05, statistically significant). There was a statistically significant positive association between hemoglobin levels and MX1 serum levels. No statistically significant association was found among the other parameters. Low MX1 levels were shown to be associated with both a low disease activity score based on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and hydroxychloroquine use in all patients. CONCLUSION: MX1 levels have a considerable impact on the assessment of the disease activity in SjS. We believe that more-comprehensive studies should be performed on patients with pSjS who do not use hydroxychloroquine to prove this relationship and that MX1 levels should be used as a routine marker for the assessment of pSjS disease activity. Further studies are needed to create awareness of the role that MX1 has in the diagnosis of pSjS, which may help to uncover novel pathways for new therapeutic modalities.


Assuntos
Isotipos de Imunoglobulinas/sangue , Proteínas de Resistência a Myxovirus/imunologia , Saliva/química , Síndrome de Sjogren/metabolismo , Adulto , Anticorpos Antinucleares/sangue , Biomarcadores/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pessoa de Meia-Idade , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia
14.
Immunol Cell Biol ; 97(7): 647-655, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31141205

RESUMO

Tuberculosis (TB) is a serious infectious disease caused by infection with Mycobacterium tuberculosis, and kills more people annually than any other single infectious agent. Although a vaccine is available, it is only moderately effective and an improved vaccine is urgently needed. The ability to develop a more effective vaccine has been thwarted by a lack of understanding of the mechanism of vaccine-induced immune protection. Over recent decades, many novel TB vaccines have been developed and almost all have aimed to generate memory CD4 T cells. In this review, we critically evaluate evidence in the literature that supports the contention that memory CD4 T cells are the prime mediators of vaccine-induced protection against TB. Because of the lack of robust evidence supporting memory CD4 T cells in this role, the potential for B-cell antibody and "trained" innate cells as alternative mediators of protective immunity is explored.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Memória Imunológica , Mycobacterium tuberculosis/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Tuberculose/imunologia , Tuberculose/microbiologia , Imunidade Adaptativa , Animais , Anticorpos Antibacterianos/imunologia , Especificidade de Anticorpos/imunologia , Antígenos de Bactérias/imunologia , Vacina BCG/administração & dosagem , Vacina BCG/efeitos adversos , Vacina BCG/imunologia , Glicosilação , Humanos , Imunidade Inata , Isotipos de Imunoglobulinas/imunologia , Isotipos de Imunoglobulinas/metabolismo , Avaliação de Resultados em Cuidados de Saúde , Subpopulações de Linfócitos T/citologia , Tuberculose/prevenção & controle , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/efeitos adversos , Vacinas contra a Tuberculose/imunologia , Vacinação/efeitos adversos , Vacinação/métodos
15.
Int Arch Allergy Immunol ; 180(1): 52-63, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31117086

RESUMO

BACKGROUND: Hyper-immunoglobulin M (HIGM) syndrome is a rare heterogeneous group of primary immunodeficiency disorders characterized by low or absent serum levels of IgG and IgA along with normal or elevated serum levels of IgM. METHODS: Clinical and immunological data were collected from the 75 patients' medical records diagnosed in Children's Medical Center affiliated to Tehran University Medical Sciences and other Universities of Medical Sciences in Iran. Among 75 selected patients, 48 patients (64%) were analyzed genetically using targeted and whole-exome sequencing. RESULTS: The ratio of male to female was 2.9:1. The median age at the onset of the disease, time of diagnosis, and diagnostic delay were 10.5, 50, and 24 months, respectively. Pneumonia and lower respiratory tract infections (61.3%) were the most common complications. Responsible genes were identified in 35 patients (72.9%) out 48 genetically analyzed patients. Cluster of differentiation 40 ligand gene was the most mutated gene observed in 24 patients (68.5%) followed by activation-induced cytidine deaminase gene in 7 patients, lipopolysaccharide-responsive and beige-like anchor (1 patient), nuclear factor-kappa-B essential modulator (1 patient), phosphoinositide-3-kinase regulatory subunit 1 (1 patient), and nuclear factor kappa B subunit 1 (1 patient) genes. Nineteen (25.3%) patients died during the study period, and pneumonia was the major cause of death occurred in 6 (31.6%) patients. CONCLUSION: Physicians in our country should carefully pay attention to respiratory tract infections and pneumonia, particularly in patients with a positive family history. Further investigations are required for detection of new genes and pathways resulting in HIGM phenotype.


Assuntos
Síndrome de Imunodeficiência com Hiper-IgM/diagnóstico , Síndrome de Imunodeficiência com Hiper-IgM/etiologia , Fenótipo , Adolescente , Adulto , Biomarcadores , Criança , Suscetibilidade a Doenças , Feminino , Testes Genéticos , Humanos , Isotipos de Imunoglobulinas/sangue , Irã (Geográfico) , Contagem de Linfócitos , Masculino , Mutação , Avaliação de Sintomas , Adulto Jovem
16.
Mucosal Immunol ; 12(4): 1013-1024, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31105268

RESUMO

Recurrent and persistent airway infections remain prevalent in patients with primary immunodeficiency (PID), despite restoration of serum immunoglobulin levels by intravenous or subcutaneous plasma-derived IgG. We investigated the effectiveness of different human Ig isotype preparations to protect mice against influenza when delivered directly to the respiratory mucosa. Four polyvalent Ig preparations from pooled plasma were compared: IgG, monomeric IgA (mIgA), polymeric IgA-containing IgM (IgAM) and IgAM associated with the secretory component (SIgAM). To evaluate these preparations, a transgenic mouse expressing human FcαRI/CD89 within the myeloid lineage was created. CD89 was expressed on all myeloid cells in the lung and blood except eosinophils, reflecting human CD89 expression. Intranasal administration of IgA-containing preparations was less effective than IgG in reducing pulmonary viral titres after infection of mice with A/California/7/09 (Cal7) or the antigenically distant A/Puerto Rico/8/34 (PR8) viruses. However, IgA reduced weight loss and inflammatory mediator expression. Both IgG and IgA protected mice from a lethal dose of PR8 virus and for mIgA, this effect was partially CD89 dependent. Our data support the beneficial effect of topically applied Ig purified from pooled human plasma for controlling circulating and non-circulating influenza virus infections. This may be important for reducing morbidity in PID patients.


Assuntos
Antígenos CD/genética , Expressão Gênica , Isotipos de Imunoglobulinas/imunologia , Receptores Fc/genética , Infecções Respiratórias/imunologia , Infecções Respiratórias/prevenção & controle , Animais , Anticorpos Neutralizantes/imunologia , Antígenos CD/imunologia , Citocinas/biossíntese , Modelos Animais de Doenças , Humanos , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Isotipos de Imunoglobulinas/administração & dosagem , Imunofenotipagem , Camundongos , Camundongos Transgênicos , Células Mieloides/imunologia , Células Mieloides/metabolismo , Testes de Neutralização , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Ligação Proteica/imunologia , Receptores Fc/imunologia
17.
PLoS One ; 14(5): e0216940, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31112572

RESUMO

Many adults with IgG subclass deficiency (IgGSD) experience long intervals of frequent/severe respiratory tract infection before IgGSD diagnosis, but reasons for delays in IgGSD diagnoses are incompletely understood. We performed a retrospective study of 300 white adults (ages ≥18 y) with IgGSD including frequency analyses of age at IgGSD diagnosis, duration of frequent/severe respiratory tract infection before IgGSD diagnosis, and age at onset of frequent/severe infection (calculated). We performed multivariable regressions on age at diagnosis, infection duration, and age at infection onset using these variables, as appropriate: sex; age at diagnosis; diabetes; autoimmune condition(s); atopy; allergy; corticosteroid use; body mass index; serum immunoglobulin isotype levels; blood lymphocyte subsets; three IgGSD-associated human leukocyte antigen-A and -B haplotypes; and referring physician specialties. Mean age at diagnosis was 50 ± 12 (standard deviation) y (median 50 y (range 19-79)). There were 247 women (82.3%). Mean infection duration at IgGSD diagnosis was 12 ± 13 y (median 7 y (range 1-66)). Mean age at infection onset was 38 ± 16 y (median 38 y (range 4, 76)). Age at infection onset was ≥18 y in 95.7% of subjects. Regressions on age at diagnosis and infection duration revealed no significant associations. Regression on age at infection onset revealed one positive association: age at diagnosis (p <0.0001). We conclude that the median duration of frequent/severe respiratory tract infection in adults before IgGSD diagnosis was 7 y. Older adults may be diagnosed to have IgGSD after longer intervals of infection than younger adults. Duration of frequent/severe respiratory tract infection before IgGSD diagnosis was not significantly associated with routine clinical and laboratory variables, including referring physician specialties.


Assuntos
Diagnóstico Tardio/estatística & dados numéricos , Deficiência de IgG/diagnóstico , Isotipos de Imunoglobulinas/classificação , Infecções Respiratórias/diagnóstico , Adulto , Fatores Etários , Idade de Início , Idoso , Índice de Massa Corporal , Feminino , Expressão Gênica , Antígenos HLA-A/classificação , Antígenos HLA-A/genética , Antígenos HLA-A/imunologia , Antígenos HLA-B/classificação , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Haplótipos , Humanos , Deficiência de IgG/sangue , Deficiência de IgG/imunologia , Deficiência de IgG/fisiopatologia , Isotipos de Imunoglobulinas/sangue , Subpopulações de Linfócitos/classificação , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/sangue , Infecções Respiratórias/imunologia , Infecções Respiratórias/fisiopatologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Fatores de Tempo
18.
MAbs ; 11(4): 709-724, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30939981

RESUMO

The Old World monkey, Rhesus macaque (Macaca mulatta, Mm), is frequently used as a primate model organism in the study of human disease and to test new vaccines/antibody treatments despite diverging before chimpanzees and orangutans. Mm and humans share 93% genome identity with substantial differences in the genes of the adaptive immune system that lead to different functional IgG subclass characteristics, Fcγ receptors expressed on innate immune cells, and biological interactions. These differences put limitations on Mm use as a primary animal model in the study of human disease and to test new vaccines/antibody treatments. Here, we comprehensively analyzed molecular properties of the Fc domain of the four IgG subclasses of Rhesus macaque to describe potential mechanisms for their interactions with effector cell Fc receptors. Our studies revealed less diversity in the overall structure among the Mm IgG Fc, with MmIgG1 Fc being the most structurally like human IgG3, although its CH2 loops and N297 glycan mobility are comparable to human IgG1. Furthermore, the Fcs of Mm IgG3 and 4 lack the structural properties typical for their human orthologues that determine IgG3's reduced interaction with the neonatal receptor and IgG4's ability for Fab-arm exchange and its weaker Fcγ receptor interactions. Taken together, our data indicate that MmIgG1-4 are less structurally divergent than the human IgGs, with only MmIgG1 matching the molecular properties of human IgG1 and 3, the most active IgGs in terms of Fcγ receptor binding and Fc-mediated functions. PDB accession numbers for deposited structures are 6D4E, 6D4I, 6D4M, and 6D4N for MmIgG1 Fc, MmIgG2 Fc, MmIgG3 Fc, and MmIgG4 Fc, respectively.


Assuntos
Fragmentos Fc das Imunoglobulinas/química , Isotipos de Imunoglobulinas/química , Animais , Evolução Biológica , Cristalização , Cristalografia por Raios X , Humanos , Fragmentos Fc das Imunoglobulinas/metabolismo , Isotipos de Imunoglobulinas/metabolismo , Macaca fascicularis , Macaca mulatta , Ligação Proteica , Conformação Proteica , Receptores de IgG/metabolismo , Relação Estrutura-Atividade
19.
Viruses ; 11(3)2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30875741

RESUMO

Filoviruses cause lethal hemorrhagic fever in humans. The filovirus nucleoprotein (NP) is expressed in high abundance in infected cells and is essential for virus replication. To generate anti-filovirus monoclonal antibodies (mAbs) against the NP, mice were immunized with peptides known as B-cell epitopes corresponding to different filovirus NPs, and hybridomas were screened using FLAG-tagged filovirus NP constructs. Numerous mAbs were identified, isotyped, and characterized. The anti-NP mAbs demonstrated different ranges of binding affinities to various filovirus NPs. Most of the clones specifically detected both recombinant and wild-type NPs from different filoviruses, including Ebola (EBOV), Sudan (SUDV), Bundibugyo (BDBV), Marburg (MARV), Tai Forest (TAFV), and Reston (RESTV) viruses in western blot analysis. The mAbs were also able to detect native NPs within the cytoplasm of infected cells by immunofluorescence confocal microscopy. Thus, this panel of mAbs represents an important set of tools that may be potentially useful for diagnosing filovirus infection, characterizing virus replication, and detecting NP⁻host protein interactions.


Assuntos
Anticorpos Monoclonais/biossíntese , Anticorpos Antivirais/biossíntese , Filoviridae/imunologia , Nucleoproteínas/imunologia , Proteínas Virais/imunologia , Animais , Anticorpos Neutralizantes/biossíntese , Sítios de Ligação de Anticorpos , Ebolavirus/imunologia , Epitopos de Linfócito B/imunologia , Feminino , Infecções por Filoviridae/imunologia , Infecções por Filoviridae/virologia , Imunização , Isotipos de Imunoglobulinas , Marburgvirus/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/imunologia
20.
Adv Immunol ; 141: 105-164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30904131

RESUMO

Class switch recombination (CSR) generates isotype-switched antibodies with distinct effector functions essential for mediating effective humoral immunity. CSR is catalyzed by activation-induced deaminase (AID) that initiates DNA lesions in the evolutionarily conserved switch (S) regions at the immunoglobulin heavy chain (Igh) locus. AID-initiated DNA lesions are subsequently converted into DNA double stranded breaks (DSBs) in the S regions of Igh locus, repaired by non-homologous end-joining to effect CSR in mammalian B lymphocytes. While molecular mechanisms of CSR are well characterized, it remains less well understood how upstream signaling pathways regulate AID expression and CSR. B lymphocytes express multiple receptors including the B cell antigen receptor (BCR) and co-receptors (e.g., CD40). These receptors may share common signaling pathways or may use distinct signaling elements to regulate CSR. Here, we discuss how signals emanating from different receptors positively or negatively regulate AID expression and CSR.


Assuntos
Citidina Desaminase/metabolismo , Switching de Imunoglobulina/genética , Isotipos de Imunoglobulinas/genética , Receptores de Antígenos de Linfócitos B/metabolismo , Animais , Receptor do Fator Ativador de Células B/metabolismo , Linfócitos B/imunologia , Quebras de DNA de Cadeia Dupla , Humanos , Imunidade Humoral/genética , Cadeias Pesadas de Imunoglobulinas/genética , Camundongos , Recombinação Genética , Transdução de Sinais , Receptores Toll-Like/metabolismo , Proteína Transmembrana Ativadora e Interagente do CAML/metabolismo
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