RESUMO
Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients' long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers.
Assuntos
Sequenciamento do Exoma , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Feminino , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/imunologia , Predisposição Genética para Doença , Criança , Pré-Escolar , Mutação/genética , Testes Genéticos/métodos , Lactente , Exoma/genética , AdolescenteRESUMO
A homozygous missense mutation in the transferrin receptor 1 (TfR1), also known as CD71, leads to a rare inborn error of immunity (IEI) characterized by the impaired lymphocyte activation and proliferation due to defective iron uptake of cells. However, only one causative mutation (c.58T > C, p.Y20H) in the TFRC gene coding for TfR1 has been reported so far. We herein identified a new disease-causing homozygous germline mutation in the TFRC gene (c.64C > T, p.R22W) (referred to as TfR1R22W from now on) in a Turkish patient with combined immunodeficiency (CID). TfR1R22W results in impaired TfR1 internalization similar to previously defined TfR1Y20H mutation. We found that TfR1R22W is associated with severely restricted B and T lymphocyte clonal diversity and impaired T cell activation and cytokine production as well as defective mitochondrial oxidative phosphorylation in helper T cells. In addition, circulating NK, Treg, and MAIT cell populations were significantly decreased in the patient. Using whole transcriptome analysis, we found dysregulated immune homeostasis and novel biological processes associated with TfR1R22W. We also identified a considerable expansion of circulating low-density neutrophils (LDNs) in patient's PBMCs. Overall, TfR1R22W mutation expands the current understanding of the IEI associated with TfR1 dysfunction and provides new insights underlying impaired immune function, lymphocyte diversity, and granulocyte homeostasis.
Assuntos
Mutação em Linhagem Germinativa , Doenças da Imunodeficiência Primária , Humanos , Perfilação da Expressão Gênica , FerroRESUMO
Recombination activating genes (RAG)1 and RAG2 deficiency leads to combined T/B-cell deficiency with varying clinical presentations. This study aimed to define the clinical/laboratory spectrum of RAG1 and RAG2 deficiency. We retrospectively reviewed the clinical/laboratory data of 35 patients, grouped them as severe combined immunodeficiency (SCID), Omenn syndrome (OS), and delayed-onset combined immunodeficiency (CID) and reported nine novel mutations. The male/female ratio was 23/12. Median age of clinical manifestations was 1 months (mo) (0.5-2), 2 mo (1.25-5), and 14 mo (3.63-27), age at diagnosis was 4 mo (3-6), 4.5 mo (2.5-9.75), and 27 mo (14.5-70) in SCID (n = 25; 71.4%), OS (n = 5; 14.3%), and CID (n = 5; 14.3%) patients, respectively. Common clinical manifestations were recurrent sinopulmonary infections 82.9%, oral moniliasis 62.9%, diarrhea 51.4%, and eczema/dermatitis 42.9%. Autoimmune features were present in 31.4% of the patients; 80% were in CID patients. Lymphopenia was present in 92% of SCID, 80% of OS, and 80% of CID patients. All SCID and CID patients had low T (CD3, CD4, and CD8), low B, and increased NK cell numbers. Twenty-eight patients underwent hematopoietic stem cell transplantation (HSCT), whereas seven patients died before HSCT. Median age at HSCT was 7 mo (4-13.5). Survival differed in groups; maximum in SCID patients who had an HLA-matched family donor, minimum in OS. Totally 19 (54.3%) patients survived. Early molecular genetic studies will give both individualized therapy options, and a survival advantage because of timely diagnosis and treatment. Further improvement in therapeutic outcomes will be possible if clinicians gain time for HSCT.
Assuntos
Linfopenia , Doenças da Imunodeficiência Primária , Imunodeficiência Combinada Severa , Humanos , Masculino , Feminino , Lactente , Proteínas de Homeodomínio/genética , Estudos Retrospectivos , Imunodeficiência Combinada Severa/genética , Mutação , Proteínas de Ligação a DNA/genética , Proteínas Nucleares/genéticaRESUMO
Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment.
Assuntos
Fatores de Transcrição Box Pareados , Imunodeficiência Combinada Severa , Humanos , Fatores de Transcrição Box Pareados/genética , Fenótipo , Linfócitos T , Timo , Imunodeficiência Combinada Severa/genéticaRESUMO
OBJECTIVE: Wound healing is accelerated when Platelet Rich Plasma is activated and growth factors are released. In this study, it was aimed to stimulate platelets without using chemical stimulants. METHOD: Two types of mechanical platelet activation methods have been proposed in this study. The first one is a microfluidic chip developed with the shear-induced platelet activation approach. The second one is a piezo-based ultrasound-assisted device which provides platelet activation by stimulating with an ultrasonic wave (0.55 and 1.1 MHz). Three different microfluidic chip designs were worked out to determine the optimal shear stress characteristics; 8-nodes (2789 µs, 288 shear pulses, and 98.3 dyne/cm2), 40-nodes (2765 µs, 1440 shear pulses, and 95.5 dyne/cm2) and pillar-shaped (1030 µs, 1656 shear pulses, and 48.1 dyne/cm2). RESULTS: The highest platelet activation rate (72.7%) was obtained from the chips with 8-nodes. In the ultrasound-assisted device, 32.4% activation rate was obtained from ultrasound waves with 0.55 MHz frequency and 10 Vp-p amplitude. These activation rates, determined by CD62P (P-Selectin) expression, are significantly higher than spontaneous activation of intact platelets (8.5%). In addition, the gradual increase in activation of stimulated platelets with incubation at room temperature showed that activation continued after stimulation. CONCLUSION: The results showed that these microfluidic devices can be used for platelet activation to enhance the effect of PRP treatment and might reduce adverse immune reactions that may happened due to the use of exogenous activator substances. SIGNIFICANCE: Fast-response, low-cost, easy-to-use and controllable biomedical device have been developed for PRP applications.
Assuntos
Ativação Plaquetária , Plasma Rico em Plaquetas , Plaquetas/metabolismo , Dispositivos Lab-On-A-Chip , Plasma Rico em Plaquetas/metabolismo , Estresse MecânicoRESUMO
PURPOSE: MALT1 deficiency is a combined immune deficiency characterized by recurrent infections, eczema, chronic diarrhea, and failure to thrive. Clinical and immunological characterizations of the disease have not been previously reported in large cohorts. We sought to determine the clinical, immunological, genetic features, and the natural history of MALT-1 deficiency. METHODS: The clinical findings and treatment outcomes were evaluated in nine new MALT1-deficient patients. Peripheral lymphocyte subset analyses, cytokine secretion, and proliferation assays were performed. We also analyzed ten previously reported patients to comprehensively evaluate genotype/phenotype correlation. RESULTS: The mean age of patients and disease onset were 33 ± 17 and 1.6 ± 0.7 months, respectively. The main clinical findings of the disease were recurrent infections (100%), skin involvement (100%), failure to thrive (100%), oral lesions (67%), chronic diarrhea (56%), and autoimmunity (44%). Eosinophilia and high IgE were observed in six (67%) and two (22%) patients, respectively. The majority of patients had normal T and NK cells, while eight (89%) exhibited reduced B cells. Immunoglobulin replacement and antibiotics prophylaxis were mostly ineffective in reducing the frequency of infections and other complications. One patient received hematopoietic stem cell transplantation (HSCT) and five patients died as a complication of life-threatening infections. Analyzing this cohort with reported patients revealed overall survival in 58% (11/19), which was higher in patients who underwent HSCT (P = 0.03). CONCLUSION: This cohort provides the largest analysis for clinical and immunological features of MALT1 deficiency. HSCT should be offered as a curative therapeutic option for all patients at the early stage of life.
Assuntos
Insuficiência de Crescimento , Transplante de Células-Tronco Hematopoéticas , Diarreia , Estudos de Associação Genética , Humanos , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/genética , Fenótipo , ReinfecçãoRESUMO
Biallelic mutations in the genes encoding CD27 or its ligand CD70 underlie inborn errors of immunity (IEIs) characterized predominantly by Epstein-Barr virus (EBV)-associated immune dysregulation, such as chronic viremia, severe infectious mononucleosis, hemophagocytic lymphohistiocytosis (HLH), lymphoproliferation, and malignancy. A comprehensive understanding of the natural history, immune characteristics, and transplant outcomes has remained elusive. Here, in a multi-institutional global collaboration, we collected the clinical information of 49 patients from 29 families (CD27, n = 33; CD70, n = 16), including 24 previously unreported individuals and identified a total of 16 distinct mutations in CD27, and 8 in CD70, respectively. The majority of patients (90%) were EBV+ at diagnosis, but only â¼30% presented with infectious mononucleosis. Lymphoproliferation and lymphoma were the main clinical manifestations (70% and 43%, respectively), and 9 of the CD27-deficient patients developed HLH. Twenty-one patients (43%) developed autoinflammatory features including uveitis, arthritis, and periodic fever. Detailed immunological characterization revealed aberrant generation of memory B and T cells, including a paucity of EBV-specific T cells, and impaired effector function of CD8+ T cells, thereby providing mechanistic insight into cellular defects underpinning the clinical features of disrupted CD27/CD70 signaling. Nineteen patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) prior to adulthood predominantly because of lymphoma, with 95% survival without disease recurrence. Our data highlight the marked predisposition to lymphoma of both CD27- and CD70-deficient patients. The excellent outcome after HSCT supports the timely implementation of this treatment modality particularly in patients presenting with malignant transformation to lymphoma.
Assuntos
Ligante CD27/deficiência , Doenças Genéticas Inatas , Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/deficiência , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/imunologia , Doenças Genéticas Inatas/mortalidade , Doenças Genéticas Inatas/terapia , Humanos , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/mortalidade , Síndromes de Imunodeficiência/terapia , Lactente , Masculino , Estudos Retrospectivos , Taxa de SobrevidaAssuntos
Complexo CD3/genética , Transplante de Células-Tronco Hematopoéticas , Mutação/genética , Imunodeficiência Combinada Severa/genética , Alelos , Complexo CD3/metabolismo , Quimerismo , Consanguinidade , Antígenos HLA/imunologia , Humanos , Lactente , Masculino , Complexos Multiproteicos/metabolismo , Linhagem , Receptores de Antígenos de Linfócitos T/metabolismo , Imunodeficiência Combinada Severa/terapia , Resultado do TratamentoRESUMO
PURPOSE: Autosomal recessive (AR) CARD9 deficiency is an inherited immune disorder which results in impaired innate immunity against various fungi. Superficial and invasive fungal infections, mainly caused by Candida or Trichophyton species, are the hallmark of CARD9 deficiency. Together with the increasing number of CARD9-deficient patients reported, different pathogenic fungal species have been described such as Phialophora, Exophiala, Corynespora, Aureobasidium, and Ochroconis. Saprochaete capitata is an opportunistic infectious agent in immunocompromised patients and is a common cause of invasive fungal disease in patients with hematological malignancies. In this study, we investigated the causative genetic defect in a patient with S. capitata fungal infection which disseminated to lymph nodes and common bile duct. METHODS: The identification of the isolated yeast strain was made by direct microscopic examination and confirmed by internal transcribed spacer (ITS) sequencing. We applied whole exome sequencing to search for the disease-causing mutation. Sanger sequencing was used to validate the mutation in the patient and his parents. RESULTS: S. capitata was isolated from the biopsy specimen as the causative microorganism responsible for the invasive fungal disease in the patient. Whole exome sequencing revealed a homozygous c.883C > T, (p.Q295*) mutation in CARD9, confirmed by Sanger sequencing. CONCLUSIONS: This is the first report of invasive Saprochaete infection associated with autosomal recessive (AR) CARD9 deficiency in the literature and thereby further extends the spectrum of fungal diseases seen in these patients.
Assuntos
Proteínas Adaptadoras de Sinalização CARD/genética , Candidíase Mucocutânea Crônica/diagnóstico , Colestase/diagnóstico , Infecções Fúngicas Invasivas/diagnóstico , Saccharomycetales/fisiologia , Deleção de Sequência/genética , Adolescente , Candidíase Mucocutânea Crônica/genética , Colestase/genética , Transtornos Cromossômicos , Genes Recessivos , Humanos , Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/genética , Iraque , Masculino , Sequenciamento do ExomaRESUMO
Background: Primary immunodeficiencies (PIDs) are a heterogeneous group of congenital disorders characterized by susceptibility to recurrent infections, allergy, malignancies and autoimmunity. The identification of disease-causing genetic defects is critically important for treatment options. In last decade, next-generation sequencing (NGS)-based methods has enabled the rapid genetic screening and the discovery of new genetic defects in PIDs. In this study, we investigated causative mutations in patients with PID by NGS. Methods: We applied whole-exome sequencing in 8 PID patients. Detected mutations by NGS were validated by Sanger sequencing. Results: We made a genetic diagnosis in 5 of 8 (63%) patients, including 3 novel disease-causing variants. The identified mutations were found in RAG1, RAG2, JAK3, RFXANK, and CYBA genes. Conclusions: Our results show that whole-exome sequencing can facilitate the genetic diagnosis of the patients with PID.
Assuntos
Sequenciamento do Exoma , Predisposição Genética para Doença , Testes Genéticos/métodos , Doenças da Imunodeficiência Primária/genética , Criança , Análise Mutacional de DNA/métodos , Proteínas de Ligação a DNA/genética , Feminino , Proteínas de Homeodomínio/genética , Humanos , Lactente , Janus Quinase 3/genética , Masculino , Mutação , NADPH Oxidases/genética , Proteínas Nucleares/genética , Doenças da Imunodeficiência Primária/diagnóstico , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: The consumption of lentil is common in the Mediterranean area and is one of the causes of IgE-mediated food allergy in many countries. Len c 1 is a well-defined allergen of lentil and approximately 80% of the patients with lentil allergy recognize the purified Len c 1 protein. We sought to identify IgE and IgG4 sequential epitopes of Len c 1 in patients with red and/or green lentil allergy. We also aimed to determine IgE and IgG4 binding differences between those patients who had outgrown or remained reactive to lentil. METHODS: Children with IgE-mediated lentil allergy were included in the study. We applied a microarray immunoassay to determine the characterization of positive IgE and IgG4 binding to Len c 1 epitopes in the patients' sera. RESULTS: The peptides specifically recognized by IgE and IgG4 antibodies were mainly detected between peptides 107 and 135 of Len c 1. The signal intensities of positive epitopes were significantly greater in reactive patients than tolerant ones (P = .008 for IgE and P = .002 for IgG4). Moreover, IgE and IgG4 antibodies bound largely the same sequential epitopes in patients who remained reactive or outgrew their allergy. CONCLUSION: IgG4-binding epitopes in lentil allergy were identified and IgE and IgG4 binding to epitopes in both red and green lentils was compared. Our data regarding signal intensity differences between reactive and outgrown patients and overlap binding of IgE and IgG4 antibodies may be important for the development of more accurate diagnostic tests and understanding of natural tolerance development.
Assuntos
Alérgenos/metabolismo , Epitopos de Linfócito B/metabolismo , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Proteínas de Armazenamento de Sementes/genética , Adolescente , Alérgenos/genética , Alérgenos/imunologia , Criança , Pré-Escolar , Mapeamento de Epitopos , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Feminino , Humanos , Tolerância Imunológica , Lens (Planta)/imunologia , Masculino , Análise em Microsséries , Ligação Proteica , Proteínas de Armazenamento de Sementes/imunologiaRESUMO
V(D)J recombination, during which recognition and repair of broken DNA chains are accomplished by non-homologous end joining pathway, is a critical process in B and T cell development.Null mutations of each enzyme or protein of this pathway result in T- B- NK+ severe combined immunodeficiency whereas hypomorphic mutations result in atypical(leaky)severe combined immunodeficiency forms. We present two siblings with PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) mutation who presented with granulomatous skin lesions and recurrent lung infections. Primary immune deficiencies may initially present with skin findings. Disruption in central and peripheral B-cell tolerance and impaired intrathymic T-cell maturation,a central player in T-cell tolerance, have been identified as the mechanism of autoimmunity and granuloma seen in patients. The variation in clinical phenotypes of patients with PRKDC mutation suggests that additional factors such as modifying genes, epigenetic and environmental factors may affect the severity and clinical phenotype of the disease. Functional studies during the follow-up and evaluation before and after hematopoeitic stem cell transplantation will hopefully increase our knowledge about the autoimmune and inflammatory process of the disease spectrum.
Assuntos
Proteína Quinase Ativada por DNA/genética , Granuloma/genética , Histiocitose de Células não Langerhans/genética , Proteínas Nucleares/genética , Imunodeficiência Combinada Severa/genética , Dermatopatias/genética , Pré-Escolar , Feminino , Granuloma/imunologia , Granuloma/patologia , Transplante de Células-Tronco Hematopoéticas , Histiocitose de Células não Langerhans/imunologia , Histiocitose de Células não Langerhans/patologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lactente , Recém-Nascido , Pneumonia Bacteriana/genética , Pneumonia Bacteriana/imunologia , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/patologia , Imunodeficiência Combinada Severa/terapia , Irmãos , Dermatopatias/imunologia , Dermatopatias/patologiaRESUMO
PURPOSE: One of the key immune cells involved in the pathogenesis of lung cancer is natural killer (NK) cells and these cells are novel targets for therapeutic applications in lung cancer. The purpose of this review is to summarize the current literature on lung cancer pathogenesis with a focus on the interaction between NK cells and smoking, how these factors are related to the pathogenesis of lung cancer and how NK cell-based immunotherapy effect lung cancer survival. METHODS: The relevant literature from PubMed and Medline databases is reviewed in this article. RESULTS: The cytolytic potential of NK cells are reduced in lung cancer and increasing evidence suggests that improving NK cell functioning may induce tumor regression. Recent clinical trials on NK cell-based novel therapies such as cytokines including interleukin (IL)-15, IL-12 and IL-2, NK-92 cell lines and allogenic NK cell immunotherapy showed promising results with less adverse effects on the lung cancer survival. CONCLUSIONS: The NK cell targeting strategy has not yet been approved for lung cancer treatment. More clinical studies focusing on the role of NK cells in lung cancer pathogenesis are warranted to develop novel NK cell-based therapeutic approaches for the treatment of lung cancer.
Assuntos
Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/imunologia , Animais , Humanos , Células Matadoras Naturais/patologia , Neoplasias Pulmonares/patologiaRESUMO
Interstitial lung disease (ILD) is a rare and heterogeneous group of disorder affecting the lung parenchyma and has a detrimental effect on gas exchange. Chronic granulomatous disease (CGD), when it affects primarily lungs, may cause ILD. We report a 16-year-old patient with CGD caused by homozygous deletion of NCF1 who atypically presented with ILD. The patient had many pigeons and was a pigeon breeder. Exacerbated clinical symptoms were linked to hypersensitivity pneumonitis (HP), and the patient was suggested to keep away from pigeons. In addition to allergen avoidance and prophylactic antibacterial therapy, treatment with corticosteroids and hydroxychloroquine was started for mainly obstructive and persistant symptoms of ILD. CGD is known to cause a hyperinflammatory state and the patients present with excessive granuloma formation and HP. Control of inflammation either by avoidance of allergen exposure and by anti-inflammatory drugs is necessary for the relief of symptoms.
Assuntos
Alveolite Alérgica Extrínseca/diagnóstico , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Adolescente , Alveolite Alérgica Extrínseca/complicações , Biomarcadores , Humanos , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Radiografia Torácica , Testes de Função Respiratória , Tomografia Computadorizada por Raios XRESUMO
Streptococcus pneumoniae is a common pathogen responsible for pulmonary infections and the leading cause of mortality and morbidity in patients with particularly B cell immunodeficiencies. Antibody production is the principal protective immune response against S. pneumoniae and measurement of the production of antipolysaccharide antibodies is important in the evaluation of B cell deficiencies. We quantified serotype-specific immunoglobulin G antibodies against seven common pneumococcal serotypes before and three weeks after unconjugated vaccine in 416 patients with recurrent respiratory tract infections; fifty-five (13%) of whom showed impaired antibody response. We could evaluate 41 of these 55 patients for their particular clinical features. Specific antibody deficiency, was diagnosed in 10 of these patients, common variable immunodeficiency in 18, ataxia telangiectasia in 10 and other antibody deficiencies in 7 (transient hypogammaglobulinemia in 4, IgG subclass deficiency in 1, partial and selective IgA deficiency in 1) patients. Evaluation of the antibody response to polysaccharide antigens should be considered early on in patients with recurrent respiratory infections and required particularly for the diagnosis of specific antibody deficiency and the decision of the appropriate treatment approaches.
Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Pneumocócicas/imunologia , Infecções Respiratórias/imunologia , Streptococcus pneumoniae/imunologia , Adolescente , Adulto , Formação de Anticorpos , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina G/sangue , Síndromes de Imunodeficiência/diagnóstico , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/prevenção & controle , Recidiva , Adulto JovemRESUMO
Statins possess a wide variety of pleiotropic properties that are independent of their lipid-lowering abilities such as attenuating inflammation, oxidative stress, coagulation, platelet aggregation and stimulating bone formation. The aim of the study is to evaluate the effect of statins on clinical periodontal parameters and gingival crevicular fluid (GCF) levels of IL-1ß, IL-10, and myeloperoxidase (MPO) in inflammatory periodontal diseases. Seventy-nine subjects with hyperlipidemia and 48 systemically healthy controls (C) were included. Hyperlipidemic patients were either given a diet (HD) or prescribed statin (HS). Patients were classified into three subgroups as those who were periodontally healthy (h), who had gingivitis (g), or who had chronic periodontitis (p). Blood samples were collected for the measurement of lipid profiles. Plaque index (PI), gingival index (GI), probing pocket depth (PD), clinical attachment level (CAL), and percentage of bleeding on probing (BOP) were recorded. Gingival crevicular fluid levels of IL-1ß, IL-10, and MPO were measured in order to determine the anti-inflammatory and antioxidant effects of statins. Probing depth values of the HSp group were significantly lower than those of the Cp group. Percentage of BOP of the HSg group was significantly lower than those of the HDg and Cg groups. While the IL-1ß level of the HSp group was significantly lower than that of the HDp group, IL-10 levels of the HSg group were significantly higher than those of the HDg group. MPO levels were significantly lower in the HSg group when compared to those in the HDg and Cg groups. Statin use decreased the IL-1ß and MPO levels and enhanced IL-10 in GCF. It can be suggested that statins may attenuate periodontal inflammation and progression of periodontal inflammation.
Assuntos
Líquido do Sulco Gengival/química , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Interleucina-10/análise , Interleucina-1beta/análise , Peroxidase/análise , Estudos de Casos e Controles , Periodontite Crônica/sangue , Estudos de Coortes , Gengivite/sangue , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/dietoterapia , Hiperlipidemias/tratamento farmacológico , Inflamação/prevenção & controle , Interleucina-1beta/efeitos dos fármacos , Periodonto/efeitos dos fármacos , Periodonto/patologia , Peroxidase/efeitos dos fármacosRESUMO
Combined immunodeficiencies (CIDs) are heterogeneous group of disorders characterized by abrogated/impaired T cell development and/or functions that resulted from diverse genetic defects. In addition to the susceptibility to infections with various microorganisms, the patients may have lymphoproliferation, autoimmunity, inflammation, allergy and malignancy. Recently, three groups have independently reported patients having mutations in STK4 gene that cause a novel autosomal recessive (AR) CID. We describe here two siblings with a novel STK4 mutation identified during the evaluation of a group of patients with features highly overlapping with those of DOCK-8 deficiency, a form of AR hyperimmunoglobulin E syndrome. The patients' clinical features include autoimmune cytopenias, viral skin (molluscum contagiosum and perioral herpetic infection) and bacterial infections, mild onychomycosis, mild atopic and seborrheic dermatitis, lymphopenia (particularly CD4 lymphopenia), and intermittent mild neutropenia. Determination of the underlying defect and reporting the patients are required for the description of the phenotypic spectrum of each immunodeficiency.