scholarly journals Immune Dysregulation Resulting From Impaired Interleukin-10 And The Interleukin-10 Receptor Signaling: A Systematic Review of 284 Monogenic Patients

2021 ◽  
Author(s):  
Niusha Sharifinejad ◽  
Majid Zaki-Dizaji ◽  
Roya Sepahvandi ◽  
Farimah Fayyaz ◽  
Maria Marluce dos Santos Vilela ◽  
...  
Keyword(s):  
Early Onset ◽  
Age Of Onset ◽  
Immunosuppressive Treatment ◽  
Genetic Diagnosis ◽  
Clinical Manifestations ◽  
Interleukin 10 ◽  
Hemopoietic Stem Cell ◽  
Target Tissue ◽  
Eligibility Criteria ◽  
Normal Ranges

Abstract Purpose: Interleukin-10 (IL-10) and IL-10 receptor (IL-10R) deficiency are monogenic inborn errors of immunity (IEI) causing early-onset inflammatory bowel diseases (IBD). Methods: We systematically reviewed articles that included related keywords using PubMed, Web of Science, and Scopus databases. The articles were screened for eligibility criteria before data extraction. Results: We assessed 284 patients (44.1% female) with IL-10 and/or IL-10R deficiencies who were predominantly from China (41.0%), Italy (14.1%), and South Korea (8.6%). The median age of onset was 1.0 (0.3-4.0) months with a median age of genetic diagnosis at 16.0 (7.4-81.0) months. Consanguinity was reported in all evaluable patients with IL-10 deficiency and in 38.8% of patients with IL-10R deficiency (23.4% of patients with IL-10RA, and 79.4% of patients with IL-10RB deficiency). The most prevalent mutations in IL-10RA were c.301C>T (p.R101W) and c.537G>A (p.T179T), those in IL-10RB were c.139A>G (p.K47E) and c.611G>A (p.W204X). Autoimmunity and enteropathy were present in all cases. The first presentation of both groups was protracted diarrhea (45.7%), bloody diarrhea (18.1%), and colitis (15.7%). Patients with IL-10R deficiency had a high frequency of dermatologic manifestations (50.5%) and failure to thrive (60%), while IL-10 deficient patients lacked those complications. In the majority of patients, the basic immunologic parameters were in normal ranges. Of the entire publications, 30% underwent hemopoietic stem cell transplantation, 61.5% surgery, and 87% immunosuppressive treatment. The ten-year survival rate was higher in patients with IL-10 deficiency than in patients with IL-10R deficiency.Conclusion: IL-10/IL-10R deficiency predominantly presents with treatment-resistant, early-onset IBD within the first months of life. No clear genotype-phenotype correlation was present among these patients. The high prevalence of distinct clinical manifestations reported in IL-10RA- and IL-10RB-deficient patients might be attributable to the interaction between the target tissue and cytokines other than IL- 10 capable of binding to IL-10RB. These results gain translational significance by contributing to earlier diagnosis, adequate therapy, and avoiding delay in the diagnosis and unfavorable outcome.

Early Onset Obsessive-Compulsive Disorder With and Without Tics

CNS Spectrums ◽  
2009 ◽  
Vol 14 (7) ◽  
pp. 362-370 ◽  
Author(s):  
Maria Alice de Mathis ◽  
Juliana B. Diniz ◽  
Roseli G. Shavitt ◽  
Albina R. Torres ◽  
Ygor A. Ferrão ◽  
...  
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Early Onset ◽  
Age Of Onset ◽  
Age At Onset ◽  
Clinical Manifestations ◽  
Tic Disorders ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Diagnostic And Statistical Manual ◽  
History Of

ABSTRACTIntroduction: Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations.Objective: The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated.Methods: Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the “early onset” group (EOG): before 11 years of age, 75 patients hadResults: The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the “aggression/violence” and “miscellaneous” dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the “contamination/cleaning” dimension.Conclusion: The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

scholarly journals Application of High-Throughput Sequencing in the Diagnosis of Inherited Immune-Thrombocytopenia from Children Chronic/Refractory ITP

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 86-86
Author(s):  
Ma Jingyao ◽  
Zhenping Chen ◽  
Huiqing LIU ◽  
Jialu Zhang ◽  
Hao GU ◽  
...  
Keyword(s):  
Platelet Count ◽  
High Throughput ◽  
Immune Thrombocytopenia ◽  
Conflicts Of Interest ◽  
Age Of Onset ◽  
Prognostic Significance ◽  
Genetic Diagnosis ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Refractory Itp

BACKGROUND: Inherited thrombocytopenias are a group of hereditary diseases with reduced platelet counts and associated bruising and bleeding as the main clinical manifestations. These entities may be hard to distinguish from ITP, particularly difficult immune thrombocytopenia complicates primary immunodeficiency and immunological treatments are effective in increasing the platelet count. Then when the course of thrombocytopenia is prolonged and other abnormalities, eg. infection, either are non-existent or subtle, distinguishing such diseases from ITP may be clinically almost impossible. However, in order to carry out proper disease management, accurate diagnosis is very necessary and urgently needed, especially in childhood. OBJECTIVES: To evaluate: 1) the detection rate of inherited immune thrombocytopenia by high-throughput, next-generation sequencing (NGS) from children with apparent chronic and refractory ITP, and 2) the value of NGS in screening and diagnosis of inherited "immune" thrombocytopenia. METHODS: We retrospectively collected 245 cases of chronic and refractory ITP in children with transient response to Intravenous Immunoglobulin (IVIG) and/ or glucocorticoid and/ or other immunosuppressive therapy, all of whom underwent genetic testing from April 2016 to April 2019. Their clinical data were systematically recorded and analyzed. We introduced a high-throughput, NGS platform into the routing diagnosis of those patients and analyzed the gene-sequencing results. We compared the differences between patients with positive gene mutations and those who carried suspected gene mutations. All subjects and their legal guardians gave written informed consent to the investigation. RESULTS: Sixteen patients were excluded as their final diagnosis was malignancy, aplastic anemia (AA), or myelodysplastic syndrome (MDS). Among the remaining 229 cases, 32 patients (14%) received a genetic diagnosis. Twenty-five patients (11%) had pathogenic mutations in 12 genes including CASP10(2), WAS(12), LRBA(1), CARD(1), ITGA2B(2), ITGB(1), CD36(1), NFKB2(1), NBEAL2(1), UNC13D(1), KMT2D(1), TNFRS13B(1) known to be included in lymphoproliferation or autoimmunity, whereas 7 patients (3%) carried a suspected pathogenic variant in 6 genes including: GATA(1), MYH-9(1), PTPN-11(1), RUNX(1), SLX4(2), TUBB1(1) that had not been reported in the context of autoimmune diseases. Among the 25 patients with known mutations, 16 patients (7%) could be definitely diagnosed as inherited immune thrombocytopenia and formed the Diagnosed Group (DG) according to their phenotype, inheritance and pathogenicity of the mutated gene, while 9 cases in this category and 7 patients who carried probable pathogenic variants constitute the Suspected Diagnosed Group (SDG). We compared their clinical and laboratory phenotype with the biggest difference identified in age of onset (median: 4.08 months in DG vs 54.00 months in SDG, P =0.002). Other variables analyzed included duration of time with misdiagnosis (median: 13.5 months vs 26.0 months, P=0.430), baseline platelet count (median: 6×109/L vs 5×109/L, P=.0.282), level of IL-4 (median: 0 vs 0, P=0.232), level of IL-6 (median: 13.32 vs 7.48 P=1.000), bleeding severity (without any bleeding: 1 vs 0; merely petechia/ecchymosis: 3 vs 6; bleeding in skin and one another location: 6 vs 4; bleeding in more than 2 location: 2 vs 2. P=0.542) and rate of identification of autoimmune antibodies between the two groups (P=0.662). CONCLUSIONS: Definite or suspected genetic etiologies consistent with inherited immune thrombocytopenia were identified in approximately one-seventh of cases of apparent chronic ITP. These cases would have been classified as "routine" cases of childhood ITP based on response to standard first-line ITP treatments and the absence of overt other findings. Eventually, their chronicity would have increased suspicion of an underlying etiology and the correct diagnosis made. The definite diagnosis group and the suspected group were identical clinically and in laboratory testing in every way except for age of onset suggesting that the suspected group was also likely inherited immune thrombocytopenia. Wide-ranging genetic screening (NGS) should be offered in children chronic/refractory ITP. The genetic findings have prognostic significance and may guide the choice of a targeted treatment in the future. Disclosures No relevant conflicts of interest to declare.

A glance on dystonias, how to recognize and handle them

2019 ◽  
pp. 22-29
Author(s):  
F. N. Mercan ◽  
E. Bayram ◽  
M. C. Akbostanci
Keyword(s):  
Differential Diagnosis ◽  
Movement Disorder ◽  
Age Of Onset ◽  
Clinical Manifestations ◽  
Body Part ◽  
Classification Model ◽  
Treatment Choices ◽  
Muscle Groups

Dystonia refers to an involuntary, repetitive, sustained, painful and twisting movements of the affected body part. This movement disorder was first described in 1911 by Hermain Oppenheim, and many studies have been conducted to understand the mechanism, the diagnosis and the treatment of dystonia ever since. However, there are still many unexplained aspects of this phenomenon. Dystonia is diagnosed by clinical manifestations, and various classifications are recommended for the diagnosis and the treatment. Anatomic classification, which is based on the muscle groups involved, is the most helpful classification model to plan the course of the treatment. Dystonias can also be classified based on the age of onset and the cause. These dystonic syndromes can be present without an identified etiology or they can be clinical manifestations of a neurodegenerative or neurometabolic disease. In this review we summarized the differential diagnosis, definition, classifications, possible mechanisms and treatment choices of dystonia.

Apresentação e Evolução Atípicas da Granulomatose de Wegener: Relato de Caso/Atypical Presentation and Evolution of Wegener's Granulomatosis: Case Report

1970 ◽  
Vol 5 (3) ◽  
pp. 53-67
Author(s):  
Aline Dos Santos ◽  
Ana Caroline Balducci Scafi ◽  
Luciene Azevedo Morais ◽  
Pablo Girardelli Mendonça Mesquita
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Case Report ◽  
Chronic Renal Failure ◽  
Early Diagnosis ◽  
Wegener’S Granulomatosis ◽  
Immunosuppressive Treatment ◽  
Clinical Manifestations ◽  
Wegener's Granulomatosis ◽  
Creatinine Concentration

RESUMOIntrodução: A Granulomatose de Wegener (GW) é uma vasculite rara e idiopática associada à presença do anticorpo Anticitoplasma de Neutrófilo (ANCA) que acomete, preferencialmente, os pequenos vasos. As manifestações clínicas são diversas, ocorrendo em mais de 90% dos casos, sintomas do trato respiratório. O comprometimento renal é tardio e preditor de mau prognóstico.  Sua morbidade a médio e longo prazo inclui insuficiência renal crônica. A probabilidade de sucesso de manutenção da função renal depende da concentração sérica de creatinina ao início do tratamento, o que indica a importância do diagnóstico e terapêutica adequada precoces. Casuística: Relata-se o caso de uma paciente do sexo feminino, 61 anos, portadora de GW com comprometimento renal avançado à apresentação não precedido por sintomas pulmonares esperados. O tratamento imunossupressor associado a plasmaferese permitiu a melhora da função renal da paciente poupando-a de tornar-se dialítica- dependente. Discussão: A paciente iniciou a doença através de insuficiência renal assintomática, com valores de função renal compatíveis com o estágio mais avançado de doença renal crônica, ultrassonografia dos rins sem alterações compatíveis e sem os sintomas respiratórios esperados. Segundo a literatura, a combinação de imunossupressores e plasmaferese associa-se à recuperação renal em três meses com sobrevivência sem necessidade de diálise por 12 meses, no caso relatado, obteve-se tal resultado em 22 dias sem a necessidade de diálise após um ano. Conclusão: Devido ao diagnóstico precoce, o tratamento adequado foi instalado rapidamente proporcionando à paciente um aumento da expectativa e da qualidade de vida, evitando dependência de terapia renal substitutiva.Palavras-Chave: Granulomatose de Wegener, Plasmaferese, Doença renal crônica.  ABSTRACTIntroduction: The Wegener's Granulomatosis (WG) is a rare and idiopathic vasculitis associated with the presence of Antineutrophil Cytoplasmic Antibody (ANCA), that affects, preferentially, the small vessels. The clinical manifestations are diverse, occurring in over 90% of cases, symptoms in the respiratory tract. Kidney damage is a late and bad prognostic predictor. Morbidity in the medium and long term includes chronic renal failure. The probability of renal function maintenance success depends on serum creatinine concentration at the beginning of treatment that indicates the importance of early diagnosis and deployment of an appropriate therapy. Case Report: We present a case of a 61-year-old female patient, carrier of GW with advanced renal impairment presentation, not preceded by expected pulmonary symptoms. The immunosuppressive treatment associated with plasmapheresis allowed the improvement of the patient’s renal function, saving her from becoming dialysis-dependent Discussion: The patient developed the disease through asymptomatic renal failure, renal function with values that are compatible with the most advanced stage of chronic kidney disease, ultrasound of the kidneys without compatible changes and without the expected respiratory symptoms. According to the literature, the combination of immunosuppressive drugs and plasmapheresis is associated with renal recovery in three months with survival without dialysis for 12 months. In this case, a result was obtained in 22 days without the need for dialysis after one year. Conclusion: Due to the early diagnosis, appropriate treatment was quickly installed giving the patient increased life expectancy and quality, preventing dependence on renal replacement therapy.Keywords: Wegener’s granulomatosis, Plasmapheresis, Chronic renal failure.

scholarly journals Pediatric leukemia susceptibility disorders: manifestations and management

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 242-250 ◽  
Author(s):  
Lisa J. McReynolds ◽  
Sharon A. Savage
Keyword(s):  
Early Onset ◽  
Ribosome Biogenesis ◽  
De Novo ◽  
Disease Risk ◽  
Bone Marrow Failure ◽  
Clinical Manifestations ◽  
Cancer Surveillance ◽  
Therapeutic Interventions ◽  
Pediatric Leukemia ◽  
Inherited Susceptibility

Abstract The clinical manifestations of inherited susceptibility to leukemia encompass a wide phenotypic range, including patients with certain congenital anomalies or early-onset myelodysplastic syndrome (MDS) and some with no obvious medical problems until they develop leukemia. Leukemia susceptibility syndromes occur as a result of autosomal dominant, autosomal recessive, or X-linked recessive inheritance, or de novo occurrence, of germline pathogenic variants in DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, and other critical cellular processes. Children and adults with cytopenias, MDS, dysmorphic features, notable infectious histories, immunodeficiency, certain dermatologic findings, lymphedema, unusual sensitivity to radiation or chemotherapy, or acute leukemia with a family history of early-onset cancer, pulmonary fibrosis, or alveolar proteinosis should be thoroughly evaluated for a leukemia susceptibility syndrome. Genetic testing and other diagnostic modalities have improved our ability to identify these patients and to counsel them and their family members for subsequent disease risk, cancer surveillance, and therapeutic interventions. Herein, the leukemia susceptibility syndromes are divided into 3 groups: (1) those associated with an underlying inherited bone marrow failure syndrome, (2) disorders in which MDS precedes leukemia development, and (3) those with a risk primarily of leukemia. Although children are the focus of this review, it is important for clinicians to recognize that inherited susceptibility to cancer can present at any age, even in older adults; genetic counseling is essential and prompt referral to experts in each syndrome is strongly recommended.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

scholarly journals AB1045 CLINICAL, ANALYTICAL AND RADIOLOGICAL CHARACTERISTICS OF A COHORT OF PATIENTS WITH SARCOIDOSIS.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1814.2-1814
Author(s):  
I. Madroñal García ◽  
C. Aguilera Cros ◽  
L. Mendez Diaz
Keyword(s):  
Systemic Disease ◽  
Immunosuppressive Treatment ◽  
Clinical Manifestations ◽  
Corticosteroid Treatment ◽  
Pulmonary Involvement ◽  
List Type ◽  
Chi Square ◽  
Course Of Disease ◽  
Chronic Course ◽  
Radiological Stage

Background:Sarcoidosis is a systemic disease whose etiology is unknown. It is characterized by the formation of granulomas in any tissue of the organism. Ganglionic, pulmonary and cutaneus involvement is the most prevalent.Objectives:Describe clinical characteristics of a cohort of patients with sarcoidosis diagnosed.Define the association between the ACE’s number at diagnosis, radiological lung stage, treatment and course of disease.Evaluate if the extrapulmonary involvement is related to the course of the disease.Methods:Descriptive retrospective study of patients with S diagnosis treated in our Hospital in 2019. Data were obtained by reviewing medical records. Chi-square tests and parametric tests have been used to establish the differences described in the objectives.Results:102 patients diagnosed with sarcoidosis have been included, (51% females) with an average age of 56±11 years. Suspected diagnosis at the onset of disease was S in 70.6% of patients, followed by suspected lymphoma (20.6%). The average time for the definitive diagnosis of S was 9.5 months. 70.6% of the patients had elevated ACE titles at the beginning. Regarding the clinical manifestations, 18.6% of the patients presented fever at the beginning and 66.7% extrathoracic clinical manifestations. 72.5% have lymph node adenopathies, and in 91% there is thoracic involvement (the most frequent pulmonary stage is stage II). A biopsy was performed in 84.3% of the patients, the lung biopsy being the most performed (52.3%). 88.2% of patients received corticosteroid treatment at the onset of the disease (currently under treatment with corticosteroids 37.3%). 50% of patients are treated with immunosuppressants, Methotrexate was the most used. 5 patients are treated with biological therapy (AntiTNF).Regarding the course of the disease, 51% of the patients have a chronic course, 45.1% are in remission and 3.9% have suffered a relapse of the disease. In this study, no significant relationship was found between the ACE values at the onset of the disease, the pulmonary stage and the course of the disease.According to our data, patients presenting with extrathoracic clinical manifestations need more frequently corticosteroid treatment (p = 0.017) and immunosuppressive treatment (p = 0.001) with respect to patients who do not have an extrathoracic clinic. In addition, patients with an extrathoracic clinic present more frequently a chronic course of the disease than those who do not (p = 0.019).Conclusion:The results described in this study are similar to those found in the literature. The differences found can be explained because patients presenting with extrathoracic clinical manifestations have a more complicated management and need more treatment than those with only pulmonary involvement, even patients with radiological stage I do not usually need treatment, only surveillance.Disclosure of Interests:None declared

Nongenetic Factors as Modifiers of the Age of Onset of Familial Alzheimer's Disease

2003 ◽  
Vol 15 (4) ◽  
pp. 337-349 ◽  
Author(s):  
Silvia Mejía ◽  
Margarita Giraldo ◽  
David Pineda ◽  
Alfredo Ardila ◽  
Francisco Lopera
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Logistic Regression ◽  
Early Onset ◽  
Age Of Onset ◽  
Univariate Analysis ◽  
Personal Factors ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease ◽  
High Level

Objective: The purpose of this research was to identify environmental and personal factors that could be related to the variability in the age of onset of familial Alzheimer's disease (FAD) (36–62 years). Methods: A sample was taken of 49 subjects with FAD and with the mutation E280A in the presenilin-1 gene on chromosome 14; the sample was divided into two subgroups: 27 individuals with age of onset of the disease between 36 and 46 years (early onset) and 22 individuals whose disease began between 47 and 62 years (late onset). Information on environmental and personal factors was collected by means of a questionnaire answered by the patients if their clinical condition allowed it, or by their relatives; such information was organized in a categorical way. Comparisons between the two groups for each categorical variable were done by means of the chi-square test. Noncollinear variables that showed statistical significance were included as independent variables in a logistic regression analysis to predict their association with early onset of the disease. Results: Only 5 of the 140 studied variables were different between the two groups in univariate analysis: education, surgical history, type of stressful event, depression, and affective losses. The logistic regression model was constituted by education, depression, and affective losses. High-level education had approximately 15 times more probability of association with an early onset of the disease; both the history of affective losses and depressive symptoms had 4 times more probability of a similar association. Conclusions: The association of high-level education and early onset of the disease could be related to an earlier detection of symptoms, in turn determined by greater intellectual and environmental demands. The occurrence of depression and affective losses has been considered a prodromic manifestation of the disease. Our findings are evidence of high clinical heterogeneity even in a genetically homogeneous group.

scholarly journals CD4+ CD25+ Foxp3+ Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

2010 ◽  
Vol 78 (11) ◽  
pp. 4763-4772 ◽  
Author(s):  
Raquel M. Gonçalves ◽  
Karina C. Salmazi ◽  
Bianca A. N. Santos ◽  
Melissa S. Bastos ◽  
Sandra C. Rocha ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Parasite Species ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Surface Expression ◽  
Interleukin 10 ◽  
Treg Cells ◽  
Experimental Models ◽  
Necrosis Factor Alpha

ABSTRACT Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4+ CD25+ Foxp3+ Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123+), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third of P. vivax-infected patients, but no P. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-α) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and long-lasting protective immunity to malaria.

Mucolipidosis Type IV: Clinical Spectrum and Natural History

PEDIATRICS ◽  
1987 ◽  
Vol 79 (6) ◽  
pp. 953-959
Author(s):  
Naomi Amir ◽  
Joel Zlotogora ◽  
Gideon Bach
Keyword(s):  
Age Of Onset ◽  
Clinical Manifestations ◽  
Psychomotor Retardation ◽  
Clinical Spectrum ◽  
Lysosomal Storage ◽  
Mucolipidosis Type Iv ◽  
Type Iv ◽  
First Year Of Life ◽  
Developmental Features ◽  
Mucolipidosis Type

The clinical spectrum and developmental features of mucolipidosis type IV, a recessive lysosomal storage disorder, are presented. The evaluation was based on information from the clinical charts and information obtained from the families of 20 patients between the ages of 2 to 17 years. The clinical manifestations of the disease, profound psychomotor retardation and visual impairment, appear during the first year of life. Definitive diagnosis is made by electron microscopy which reveals storage organelles typical of the mucolipidoses. This study details, for the first time, the heterogeneity of the ophthalmologic features, specifically as pertains to the age of onset, degree and clinical course of the corneal opacities, and the retinal involvement. Although the top developmental level was found to be 12 to 15 months in language and motor function, the course of the disease is protracted for some children, who show only a slight improvement, and others, little if any deterioration despite the early infantile onset of the disease. This presentation provides guidelines for the clinical diagnosis of mucolipidosis type IV.

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