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Lung cancer is the leading cause of cancer-related deaths, in part due to its late diagnosis. Increased epidermal growth factor receptor (EGFR) expression in cancer cells is associated with a poor prognosis, and EGFR tyrosine kinase inhibitors are widely used in cancer treatment. This study aimed to clarify the relationship between EGFR expression on T cells and cancer prognosis in patients with non-small cell lung cancer (NSCLC). Forty patients with NSCLC and 40 healthy volunteers were included in this study. Peripheral CD4+T helper (Th1, Th2, Th9, Th17, Th1Th17, follicular and peripheral Th) and cytotoxic T lymphocyte (CD8+follicular and peripheral T) subsets were identified with flow cytometry according to their chemokine receptors. EGFR expression on T lymphocytes in relation to overall survival (OS) was investigated in patients with NSCLC. The patients [mean age (min-max) = 64.03 (45-83); 20 stage I-III and 20 stage IV] had increased EGFR expression on CD3+T, CD4+Th, Th1, Th2, and Th17 cells compared to the controls (p < 0.05). High EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells was associated with poor OS. Also, PD-1 expression on lymphocytes, CD3+T, and Th cells was increased in patients with NSCLC compared to controls. The high expression of EGFR and PD-1 on Th cells and the reduced percentage of lymphocytes and Th cells, especially in stage IV patients with NSCLC, revealed that increased EGFR activity may trigger apoptosis of Th cells and promote the development of metastases, while high EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells may be an independent poor prognostic marker in NSCLC.
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AIM: Primary immunodeficiencies (PIDs) are a heterogeneous disorder group characterized by an impaired immune system, leading to an increased susceptibility to infections and a wide range of clinical manifestations, including gastrointestinal (GI) complications. This study aimed to assess the GI manifestations of PID patients and highlight the significance of atypical gastrointestinal symptoms in the early diagnosis of these patients. METHODS: A retrospective analysis was conducted on pediatric patients diagnosed with PIDs at Selcuk University Medical Faculty from 2011 to 2021. The study focused on demographic data, clinical presentation, genetic mutations, and GI manifestations, including endoscopic evaluation. Patients were categorized according to the International Union of Immunological Societies (IUIS) PID classifications. Statistical analyses were performed to identify significant associations between PID types and GI manifestations. RESULTS: The cohort comprised 101 patients, with 46% presenting with GI symptoms, including malnutrition and chronic diarrhea, as the most common findings. Primary antibody deficiency (PAD) emerged as the most prevalent PID with GI involvement, followed by combined immunodeficiencies (CID) with associated or syndromic features. Endoscopic evaluations revealed inflammatory bowel disease (IBD)-like colitis in a significant subgroup of patients. The analysis showed that some GI symptoms were more common in specific PID categories, highlighting the importance of early gastroenterological assessment in PID patients. CONCLUSION: Recognition of common GI symptoms in pediatric patients with PIDs may facilitate early diagnosis and prompt multidisciplinary management, potentially improving patient outcomes. The study highlights the necessity of considering PIDs in diagnosing persistent or severe GI symptoms in children.
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Enfermedades Gastrointestinales , Humanos , Masculino , Femenino , Estudios Retrospectivos , Preescolar , Niño , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/diagnóstico , Lactante , Adolescente , Enfermedades de Inmunodeficiencia Primaria/complicaciones , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , Diarrea/etiología , Síndromes de Inmunodeficiencia/complicacionesRESUMEN
Monogenic immune dysregulation diseases (MIDD) are caused by defective immunotolerance. This study was designed to increase knowledge on the prevalence and spectrum of MIDDs, genetic patterns, and outcomes in Middle East and North Africa (MENA). MIDD patients from 11 MENA countries (Iran, Turkey, Kuwait, Oman, Algeria, Egypt, United Arab Emirates, Tunisia, Jordan, Qatar, and Azerbaijan) were retrospectively evaluated. 343 MIDD patients (58% males and 42% female) at a median (IQR) age of 101 (42-192) months were enrolled. The most common defective genes were LRBA (23.9%), LYST (8.2%), and RAB27A (7.9%). The most prevalent initial and overall manifestations were infections (32.2% and 75.1%), autoimmunity (18.6% and 41%), and organomegaly (13.3% and 53.8%), respectively. Treatments included immunoglobulin replacement therapy (53%), hematopoietic stem cell transplantation (HSCT) (14.3%), immunosuppressives (36.7%), and surgery (3.5%). Twenty-nine (59.2%) patients survived HSCT. Along with infectious complications, autoimmunity and organomegaly may be the initial or predominant manifestations of MIDD.
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Enfermedades de Inmunodeficiencia Primaria , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Niño , Preescolar , Egipto , Femenino , Humanos , Masculino , Enfermedades de Inmunodeficiencia Primaria/genética , Sistema de Registros , Estudios Retrospectivos , Túnez , Turquía , Proteínas de Transporte Vesicular/genética , Proteínas rab27 de Unión a GTP/genéticaRESUMEN
The novel coronavirus disease 2019 (COVID-19) remains a global health emergency, and understanding the interactions between the virus and host immune responses is crucial to preventing its lethal effects. The expansion of myeloid-derived suppressor cells (MDSCs) in COVID-19, thereby suppressing immune responses, has been described as responsible for the severity of the disease, but the correlation between MDSC subsets and COVID-19 severity remains elusive. Therefore, we classified patients according to clinical and laboratory findings-aiming to investigate the relationship between MDSC subsets and laboratory findings such as high C-reactive protein, ferritin and lactate dehydrogenase levels, which indicate the severity of the disease. Forty-one patients with COVID-19 (26 mild and 15 severe; mean age of 49.7 ± 15 years) and 26 healthy controls were included in this study. MDSCs were grouped into two major subsets-polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs-by flow cytometric immunophenotyping, and PMN-MDSCs were defined as mature and immature, according to CD16 expressions, for the first time in COVID-19. Total MDSCs, PMN-MDSCs, mature PMN-MDSCs and monocytic MDSCs were significantly higher in patients with COVID-19 compared with the healthy controls (P < .05). Only PMN-MDSCs and their immature PMN-MDSC subsets were higher in the severe subgroup than in the mild subgroup. In addition, a significant correlation was found between C-reactive protein, ferritin and lactate dehydrogenase levels and MDSCs in patients with COVID-19. These findings suggest that MDSCs play a role in the pathogenesis of COVID-19, while PMN-MDSCs, especially immature PMN-MDSCs, are associated with the severity of the disease.
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Proteínas de Fase Aguda/metabolismo , Proteína C-Reactiva/metabolismo , COVID-19/metabolismo , Ferritinas/sangre , L-Lactato Deshidrogenasa/sangre , Células Supresoras de Origen Mieloide/inmunología , SARS-CoV-2/fisiología , Adulto , Anciano , COVID-19/inmunología , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS-CoV-2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID-19 outcomes. METHODS: We studied 34 IEI patients (19M/15F, 12 [min: 0.6-max: 43] years) from six centers. We diagnosed COVID-19 infection by finding a positive SARS-CoV-2 PCR test (n = 25) and/or a lung tomography scoring (CORADS) ≥4 (n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. RESULTS: Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID-related death (OR: 2.630, 95% CI; 1.198-5.776, p < .001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin-T, ferritin, and total-lung-score (p = .020, p = .003, p = .014, p = .013, p = .020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG (p = .012, p = .022, p = .011; respectively). CONCLUSION: Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID-19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS-Cov-2 therapy trials.
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COVID-19 , Síndromes de Inmunodeficiencia , Enfermedades de Inmunodeficiencia Primaria , Adolescente , Humanos , Estudios Prospectivos , SARS-CoV-2RESUMEN
BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the role of T- and B-regulatory cells (Tregs and Bregs) in the pathogenesis of idiopathic granulomatous mastitis (IGM). METHODS: This study includes 47 patients with pathologically proven IGM (Group P) and 26 healthy subjects (Group C). The patients in Group P were divided into two groups according to whether their lesions were active (Group PA, n: 21) or in remission (Group PR, n: 26). By using flow-cytometry, the frequencies of CD3+CD4+CD45RA-Foxp3high activated Tregs (aTregs), CD3+CD4+CD45RA-Foxp3low non-suppressive Tregs, CD3+CD4+CD45RA+Foxp3low resting Tregs (rTregs), CD3+CD4+CD25+Foxp3- T-effector cells (Teff), total Tregs and Bregs were analyzed in all subjects. RESULTS: The frequency of the Teff cells was statistically higher in Group P when compared with Group C (p =.004). The Foxp3 expression of Treg cells and the frequency of non-suppressive Tregs in Group P were statistically lower than Group C (p =.032 and p =.02, respectively). In addition, Group PR's Foxp3 expressions were statistically lower than Group C (p =.027); Group PR's aTregs ratio was statistically lower than Group PA (p =.021); and the non-suppressive Tregs ratio of Group PR was lower than both Group PA and Group C (p =.006 and p <.0001). No significant differences were seen Bregs and B cell subsets. CONCLUSION: Significant changes in Foxp3 expression and Treg subsets were seen in patients with active IGM lesion and in remission. This study shows an intrinsic defect of Tregs in patients with IGM.
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Mastitis Granulomatosa , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead , Humanos , Antígenos Comunes de Leucocito , Linfocitos T ReguladoresRESUMEN
Skin manifestations can serve as critical clues for early diagnosis of inborn errors of immunity. We report a patient with a double novel mutation in the BTK gene, who presented with skin abscesses caused by Pseudomonas aeruginosa. This case illustrates the importance of immune evaluation in patients with therapy-resistant skin lesions.
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Agammaglobulinemia , Enfermedades Genéticas Ligadas al Cromosoma X , Enfermedades de la Piel , Absceso/genética , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Masculino , Mutación , PseudomonasRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) has a wide clinical spectrum from asymptomatic to mild, moderate, and severe cases. There are still many unknowns about the role of immunoregulatory mechanisms in COVID-19. We aimed to study regulatory T cells (Tregs) and B cell subsets and evaluate their correlations with severity of COVID-19. METHODS: In total, 50 patients with COVID-19 confirmed by PCR (mean age = 49.9 ± 12.8 years) and 40 healthy control (mean age = 47.9 ± 14.7 years) were included in this study. The patients were classified as 14 mild (median age = 35.5 [24-73] years), 22 moderate (median age = 51.5 [28-67] years) and 14 severe (median age = 55.5 [42-67] years). Within 24 h of admission, flow cytometry was used to assess the lymphocyte subsets, Tregs and Bregs without receiving any relevant medication. RESULTS: In all patients with COVID-19, the proportion of CD3+CD8+ T cells was reduced (p = 0.004) and the CD8+ Tregs were increased compared with control (p = 0.001). While the levels of regulatory B cells, plasmablasts, and mature naive B cells were found to be significantly high, primarily memory B-cell levels were low in all patients compared with controls (p < 0.05). Total CD3+ T cells were negatively correlated with the length of stay in the hospital (r = -0.286, p = 0.044). DISCUSSION: The changes in T and B cell subsets may show the dysregulation in the immunity of patients with COVID-19. In this context, the association between CD8+ Tregs and COVID-19 severity may help clinicians to predict severe and fatal COVID-19 in hospitalized patients.
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Subgrupos de Linfocitos B , COVID-19 , Humanos , Adulto , Persona de Mediana Edad , Linfocitos T Reguladores , Recuento de Linfocitos , Linfocitos T CD8-positivosRESUMEN
Increased levels of acute-phase reactants and lymphopenia are predictors of disease severity in coronavirus disease 2019 (COVID-19). This study aimed to investigate the role of apoptosis in the etiology of lymphopenia in patients with COVID-19. This multicentered, prospective, and case-control study was conducted with polymerase chain reaction (+) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients, and an age-gender-matched control group. Samples were taken at the time of diagnosis and analyzed via flow cytometry within 24 h. The participants' demographic data and initial laboratory tests were also recorded. In total, 33 patients with COVID-19 (mean age = 45.4 ± 17.2) and 25 controls (mean age = 43.4 ± 17.4) participated in the study. All patients were identified as having mild (16), moderate (5), or severe (12) disease severity. Both early and late apoptotic cells in B and T lymphocytes were increased in all patients with COVID-19 (p < .05). Early apoptotic (EA) B and T lymphocytes were also higher in severe cases compared to mild cases (p = .026). There was no significant difference between lymphopenia and apoptosis in patients with COVID-19. However, patients with lymphopenia (n = 14) and severe COVID-19 (p = .013) had increased EA T lymphocytes. This study's results show that B and T lymphocytes' apoptosis increases in patients with COVID-19. In addition, enhanced T lymphocyte apoptosis is associated with disease severity in lymphopenic patients with COVID-19.
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Apoptosis , COVID-19/inmunología , Linfopenia/inmunología , Índice de Severidad de la Enfermedad , Linfocitos T/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2 , Adulto JovenRESUMEN
The authors present a case of delayed radiation myelopathy in a 12-year-old girl with Hodgkin lymphoma and Artemis mutation. This is the first of such a case presented in the literature.
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Proteínas de Unión al ADN/genética , Endonucleasas/genética , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/radioterapia , Enfermedades de la Médula Espinal/etiología , Niño , Femenino , Humanos , Mutación , Traumatismos por Radiación/etiología , Traumatismos por Radiación/patología , Enfermedades de la Médula Espinal/patología , Columna Vertebral/patología , Columna Vertebral/efectos de la radiaciónRESUMEN
Background and aim: This study analyzed peripheral blood lymphocyte subsets to determine their role in the etiopathogenesis of IGM. Materials and methods: This study includes 51 pathologically proven IGM patients (active disease: 26 and in remission: 25) and 28 healthy volunteers. The analyses of lymphocyte subsets were performed by flow cytometric immunophenotyping. Results: The percentage of T helper lymphocyte of all IGM patients were lower than control groups (p = 0.001). Absolute cytotoxic T lymphocyte count (p = 0.03), both percentage (p = 0.035) and absolute count (p = 0.002) of the natural killer cells, and both percentage (p = 0.038) and absolute count (p = 0.008) of natural killer T cells, were higher than the control group. The T helper lymphocyte percentage of the patients with active disease was lower than the control group (p = 0.0003). The absolute cytotoxic T lymphocyte (p = 0.029) and natural killer T cells (p = 0.012) of the patients with active disease were higher than the control group. Conclusion: Idiopathic granulomatous mastitis is defined as a localized form of granulomatous disorders. However, the observed changes in T cells, NK, and NKT cells suggest that there is systemic immune dysregulation in patients with IGM.
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Mastitis Granulomatosa , Inmunofenotipificación/métodos , Subgrupos Linfocitarios , Adulto , Femenino , Citometría de Flujo , Mastitis Granulomatosa/diagnóstico , Voluntarios Sanos , Humanos , Inmunoglobulina M , Recuento de Linfocitos , Subgrupos Linfocitarios/inmunología , Persona de Mediana EdadRESUMEN
BACKGROUND: Dedicator of cytokinesis 8 (DOCK8) deficiency is the main cause of the autosomal recessive hyper-IgE syndrome (HIES). We previously reported the selective loss of group 3 innate lymphoid cell (ILC) number and function in a Dock8-deficient mouse model. In this study, we sought to test whether DOCK8 is required for the function and maintenance of ILC subsets in humans. METHODS: Peripheral blood ILC1-3 subsets of 16 DOCK8-deficient patients recruited at the pretransplant stage, and seven patients with autosomal dominant (AD) HIES due to STAT3 mutations, were compared with those of healthy controls or post-transplant DOCK8-deficient patients (n = 12) by flow cytometry and real-time qPCR. Sorted total ILCs from DOCK8- or STAT3-mutant patients and healthy controls were assayed for survival, apoptosis, proliferation, and activation by IL-7, IL-23, and IL-12 by cell culture, flow cytometry, and phospho-flow assays. RESULTS: DOCK8-deficient but not STAT3-mutant patients exhibited a profound depletion of ILC3s, and to a lesser extent ILC2s, in their peripheral blood. DOCK8-deficient ILC1-3 subsets had defective proliferation, expressed lower levels of IL-7R, responded less to IL-7, IL-12, or IL-23 cytokines, and were more prone to apoptosis compared with those of healthy controls. CONCLUSION: DOCK8 regulates human ILC3 expansion and survival, and more globally ILC cytokine signaling and proliferation. DOCK8 deficiency leads to loss of ILC3 from peripheral blood. ILC3 deficiency may contribute to the susceptibility of DOCK8-deficient patients to infections.
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Inmunidad Innata , Síndrome de Job , Citocinas , Factores de Intercambio de Guanina Nucleótido , Humanos , Síndrome de Job/genética , Linfocitos , MutaciónRESUMEN
PURPOSE: Allergic rhinitis (AR), is an IgE-mediated inflammation of the nose. Regulatory T cells (Tregs) and inflammatory cytokines have been shown to play a critical role in allergic airway inflammation. The aim of the study was to compare the levels of blood T lymphocyte subsets and IL-10, IL-17 and neopterin concentrations in serum and nasal lavage of patients with AR compared to healthy subjects. METHODS: The study included 38 subjects with moderate-severe AR and 36 sex- and age-matched controls. Peripheral blood CD3+, CD3+CD4+ and CD4+CD25+Foxp3 percentages were evaluated using flow cytometry. Levels of IL-10, IL-17 and neopterin were measured both in serum and nasal lavage fluid with ELISA and HPLC, respectively. RESULTS: No difference was found in the percentages of T lymphocyte subsets between the two groups (p > 0.05). Serum IL-10 levels were similar (p > 0.05), whereas nasal IL-10 was lower in AR subjects compared to control group (2.22 ± 0.91 and 3.12 ± 1.45 pg/ml, respectively) (p < 0.05). Mean serum and nasal IL-17 were higher in AR (107.7 ± 79.61 and 527.36 ± 738.7 pg/ml) than the control group (76.29 ± 28.94 and 328.9 ± 430.8 pg/ml) (p < 0.05 and p > 0.05). There were no significant differences in serum and nasal neopterin levels (p > 0.05). CONCLUSIONS: Although there were no differences in the distribution of lymphocyte subsets between the AR and control groups, the finding of higher levels of serum and nasal IL-17 and lower levels of nasal IL-10 support the cytokine imbalance in the pathogenesis of AR.
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Neopterin , Rinitis Alérgica , Linfocitos T Reguladores , Adulto , Femenino , Humanos , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Masculino , Líquido del Lavado Nasal , Mucosa Nasal , Neopterin/metabolismo , Rinitis Alérgica/inmunología , Linfocitos T Reguladores/inmunología , Adulto JovenRESUMEN
Background/aim: The serum immunoglobulin levels are used routinely in clinical practice because they provide key information on the humoral immune status. This study aimed to determine the age-related reference values of serum immunoglobulin levels in healthy children. Materials and methods: A total of 330 healthy children, aged between 0 and 18 years, were included in this study. The serum immunoglobulin levels were measured using a nephelometric method in a total of 11 groups, each group consisting of 30 individuals, and IgG subclasses in 6 groups of children aged more than 2 years. Results: The serum IgG levels were high during the newborn period, decreased until the sixth month, and again increased to a maximum level at the age of 18 years. The level of IgA was found to be extremely low in the newborn period and then increased with age. While the lowest value was in the newborn period for serum IgM level, the highest value was in the 16- to 18-year-old period. The IgG subclasses varied depending on the age groups. Conclusion: The updated reference intervals of immunoglobulin levels in children may be used for the accurate diagnosis of immune deficiencies.
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Inmunodeficiencia Variable Común/sangre , Inmunidad Humoral/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Adolescente , Niño , Preescolar , Inmunodeficiencia Variable Común/inmunología , Voluntarios Sanos , Humanos , Lactante , Recién Nacido , Masculino , Nefelometría y Turbidimetría , Valores de Referencia , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: The diagnosis of 22q11.2 deletion syndrome depends on a time-consuming and expensive method, fluorescence in situ hybridisation (FISH). OBJECTIVES: We aimed to determine new parameters which can aid for in the diagnosis of 22q11.2 deletion syndrome. METHODS: Twenty two patients with 22q11.2 or 10p13 deletion were evaluated retrospectively. RESULTS: Facial-dysmorphism and mental-motor retardation were detected in 100% of patients. Mean platelet (PLT) counts were lower (224,980 versus 354,000, p = 0.001), mean PLT volume (MPV) (9.95 versus 7.07, p = 0.002), and MPV/PLTx105 ratios (5.36 versus 2.08, p < 0.001) were higher in patients with 22q11.2 deletion compared with the control group. Area under the receiver-operator characteristic (ROC) curve was 0.864, sensitivity was 84.6%, specificity was 90.9%, positive predictive value (PPV) was 91.7%, and negative predictive value (NPV) was 83.3% when MPV was 8.6. Area under ROC curve was 0.864, sensitivity was 76.9%, specificity was 90.1%, PPV was 90.1%, and NPV was 76.3% when PLT was 265,500. Area under ROC curve was 0.906, sensitivity was 84.6%, specificity was 100%, PPV was 100%, and NPV was 84.6% when MPV/PLTx105 was 3.3. Expression of PLT surface markers which were not in the GPIb-V-IX receptor complex (CD61, CD41a) increased as the surface area increased, but markers which were in a complex (CD42a, CD42b) did not change. CONCLUSIONS: High MPV/PLT value can be a good predictor for the diagnosis of 22q11.2 deletion syndrome. We suggest that in patients with facial dysmorphism and retardation in neurodevelopmental milestones and if MPV≥8.6fl, MPV/PLTx105 ratio≥3.3 and PLT count ≤265,500/mm3, the patients should be tested by FISH analysis to confirm the 22q11.2 deletion. If there are no macrothrombocytes, the 10p13 deletion should be tested in suspected cases.
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Plaquetas , Síndrome de DiGeorge/diagnóstico , Volúmen Plaquetario Medio , Recuento de Plaquetas , Adolescente , Adulto , Área Bajo la Curva , Niño , Desarrollo Infantil , Preescolar , Síndrome de DiGeorge/sangre , Síndrome de DiGeorge/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lactante , Discapacidad Intelectual/sangre , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Masculino , Actividad Motora , Fenotipo , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Immunological and molecular evaluation of a patient presenting with recurrent infections caused by Streptococcus pneumoniae and low complement component 3 (C3) levels. METHODS: Immunological evaluation included complement components and immunoglobulin level quantification as well as number and function of T cells, B cells and neutrophils. Serotype-specific immunoglobulin G antibodies against S. pneumoniae capsular polysaccharides were quantified by ELISA in serum samples before and after vaccination with unconjugated polysaccharide vaccine. For the molecular analysis, genomic DNA from the patient and parents were isolated and all exons as well as exon-intron boundaries of the C3 gene were sequenced by Sanger sequencing. RESULTS: A 16-year-old male, born to consanguineous parents, presented with recurrent episodes of pneumonia caused by S. pneumoniae and bronchiectasis. The patient showed severely reduced C3 and immunoglobulin A levels, while the parents showed moderately reduced levels of C3. Mutational analysis revealed a novel, homozygous missense mutation in the C3 gene (c. C4554G, p. Cys1518Trp), substituting a highly conserved amino acid in the C345C domain of C3 and interrupting one of its disulfide bonds. Both parents were found to be carriers of the affected allele. Vaccination against S. pneumoniae resulted in considerable clinical improvement. CONCLUSIONS: We report a novel homozygous mutation in the C3 gene in a patient with concomitant selective IgA deficiency who presented with a marked clinical improvement after vaccination against S. pneumoniae. This observation underlines the notion that vaccination against this microorganism is an important strategy for treatment of PID patients, particularly those presenting with increased susceptibility to infections caused by this agent.
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Complemento C3/genética , Deficiencia de IgA/genética , Deficiencia de IgA/inmunología , Mutación Missense , Adolescente , Bronquiectasia/complicaciones , Bronquiectasia/genética , Bronquiectasia/inmunología , Niño , Preescolar , Comorbilidad , Complemento C3/antagonistas & inhibidores , Complemento C3/biosíntesis , Femenino , Humanos , Deficiencia de IgA/complicaciones , Masculino , Mutación Missense/genética , Mutación Missense/inmunología , Linaje , Vacunas Neumococicas/uso terapéutico , Neumonía Neumocócica/genética , Neumonía Neumocócica/inmunología , Neumonía Neumocócica/prevención & control , Mutación Puntual/genética , Mutación Puntual/inmunología , Homología de Secuencia de AminoácidoRESUMEN
Background: Seeds are widely consumed as a traditional snack and have rich contents beneficial to health. With an increase in consumption rates, allergic reactions occur more frequently. We focus on multiple seed consumption related to recurrent anaphylaxis in this case. Case Presentation: We evaluated an 11-year-old boy with recurrent anaphylaxis. According to his medical records, he had been hospitalized several times, diagnosed with anaphylaxis, and treated. The family noticed direct (eating) or indirect contact with pumpkin seeds. In addition, the family mentioned another anaphylactic episode after watermelon seed and poppy seed bread consumption. We conducted skin prick-to-prick tests, examined total immunoglobulin E levels, and prescribed the treatment with an adrenalin autoinjector and preventive dietary recommendations. Conclusion: Anaphylaxis, particularly recurrent ones, should be evaluated with detailed anamnesis and supported with laboratory tests. Although seeds are beneficial and highly nutritious, it is necessary to consider them a source of allergens.
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Anafilaxia , Citrullus , Cucurbita , Hipersensibilidad a los Alimentos , Masculino , Humanos , Niño , Anafilaxia/diagnóstico , Hipersensibilidad a los Alimentos/diagnóstico , Semillas/efectos adversosRESUMEN
The presence of two different genetic conditions in the same individual is possible, especially in populations with consanguinity. In this case report, we present the coexistence of Artemis deficiency (OMIM 602450) and Three M (3M) syndrome (OMIM 273750). A 10-months-old male patient with neuromotor developmental delay was evaluated for immunodeficiency due to recurrent respiratory infections diarrhea and oral moniliasis from the age of 1.5 months. He had facial dysmorphism with rotated ears, flat nose and hypertelorism. Neurological examination revealed generalized hypotonia and mental motor delay. Immunological screening of the patient demonstrated mild lymphopenia, hypogammaglobulinemia, reduced number of CD3+ T cells (980 cells/mm3) and CD19+ B cells (35 cells/mm3). He was diagnosed with leaky T-B-NK+ SCID. Exome sequence analysis showed the presence of a homozygous pathogenic DCLRE1C variant [c.194C > T; p.T65I (NM_001033855)] and a homozygous pathogenic variant in OBSL1, a gene associated with 3M syndrome [c.3922C > T; p.R1308X (NM_001173431)]. Our proband died of sepsis and multiple organ failure. This case illustrates that different clinical findings in patients might not be explained with a single genetic defect, and consanguinity increases the change for coexistence of autosomal recessive diseases. Clinicians should consider exome sequencing to identify disease-causing mutations in patients with heterogeneity of clinical findings.