Invasive meningococcal disease in three siblings with hereditary deficiency of the 8th component of complement: Evidence for the importance of an early diagnosis

Deficiency of the eighth component of complement (C8) is a very rare primary immunodeficiency, associated with invasive, recurrent infections mainly caused by Neisseria species. We report functional and immunochemical C8 deficiency diagnosed in three Albanian siblings who presented with severe meningococcal infections at the age of 15 years, 4 years and 17 months, respectively. The youngest suffered serious complications (necrosis of fingers and toes requiring amputation). METHODS: Functional activity of the classical, alternative and mannose-binding lectin complement pathways was measured in serum from the 3 siblings and their parents (37-year-old woman and 42-year-old man). Forty healthy subjects (20 males and 20 females aged 4-38 years) served as normal controls. Serum complement factors were measured by haemolytic assays and immunoblotting. Sequence DNA analysis of the C8B gene was performed. RESULTS: Analyses of the three complement pathways revealed no haemolytic activity and also absence of C8beta in serum samples from all three siblings. The genetic analysis showed that the three siblings were homozygous for the p.Arg428* mutation in the C8B gene on chromosome 1p32 (MIM 120960). The parents were heterozygous for the mutation and presented normal complement activities. A 2-year follow-up revealed no further infective episodes in the siblings after antibiotic prophylaxis and meningococcal vaccination. CONCLUSIONS: Complement deficiencies are rare and their occurrence is often underestimated. In presence of invasive meningococcal infection, we highlight the importance of complement screening in patients and their relatives in order to discover any genetic defects which would render necessary prophylaxis to prevent recurrent infections and severe complications

Controlo químico de infestantes

Uma planta é considerada infestante quando nasce espontaneamente num local e momento indesejados, podendo interferir negativamente com a cultura instalada. As infestantes competem com as culturas para o espaço, a luz, água e nutrientes, podendo atrasar e prejudicar as operações de colheita, depreciar o produto final e assegurarem a reinfestação nas culturas seguintes. Dado o modo de propagação diferenciado das diversas espécies de infestantes, com as anuais a propagarem-se por semente e as perenes ou vivazes a assegurarem a sua propagação através de órgãos vegetativos (rizomas, bolbos, tubérculos, etc.), assim, também o seu controlo quer químico, quer mecânico terá que ser diferenciado, ou seja, para controlar infestantes anuais será suficiente destruir a sua parte aérea, enquanto para controlar infestantes perenes teremos que destruir os seus órgãos reprodutivos. O controlo de infestantes poderá ser químico, através da utilização de herbicidas, ou mecânico pela utilização de alfaias agrícolas, tais como a charrua de aivecas, a charrua de discos, a grade de discos, o escarificador e a fresa. Quando a técnica utilizada na instalação das culturas é a sementeira directa, o controlo das infestantes terá que ser obrigatoriamente químico, enquanto se o recurso à mobilização do solo for a técnica mais utilizada (sistema de mobilização tradicional ou sistema de mobilização reduzida), o controlo das infestantes tanto poderá ser químico como mecânico. Neste trabalho iremos abordar apenas, o controlo químico de infestantes

The Use Of Reverse Transcription-pcr For The Diagnosis Of X-linked Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is an inherited disorder of the innate immune system characterized by a defective oxidative burst of phagocytes and subsequent impairment of their microbicidal activity. Mutations in one of the NADPH-oxidase components affect gene expression or function of this system, leading to the phenotype of CGD. Defects in gp91-phox lead to X-linked CGD, responsible for approximately 70% of CGD cases. Investigation of the highly heterogeneous genotype of CGD patients includes mutation analysis, Northern blot or Western blot assays according to the particular case. The aim of the present study was to use reverse transcription (RT)-PCR for the analysis of molecular defects responsible for X-linked CGD in eight Brazilian patients and to assess its potential for broader application to molecular screening in CGD. Total RNA was prepared from Epstein B virus-transformed B-lymphocytes and reverse transcribed using random hexamers. The resulting cDNA was PCR-amplified by specific and overlapping pairs of primers designed to amplify three regions of the gp91-phox gene: exons 1-5, 3-9, and 7-13. This strategy detected defective gp91-phox expression in seven patients. The RT-PCR results matched clinical history, biochemical data (nitroblue tetrazolium or superoxide release assay) and available mutation analysis in four cases. In three additional cases, RT-PCR results matched clinical history and biochemical data. In another case, RT-PCR was normal despite a clinical history compatible with CGD and defective respiratory burst. We conclude that this new application of RT-PCR analysis--a simple, economical and rapid method--was appropriate for screening molecular defects in 7 of 8 X-linked CGD patients.37625-3

Guidelines for the use of human immunoglobulin therapy in patients with primary immunodeficiencies in Latin America

Antibodies are an essential component of the adaptative immune response and hold long-term memory of the immunological experiences throughout life. Antibody defects represent approximately half of the well-known primary immunodeficiencies requiring immunoglobulin replacement therapy. In this article, the authors review the current indications and therapeutic protocols in the Latin American environment. Immunoglobulin replacement therapy has been a safe procedure that induces dramatic positive changes in the clinical outcome of patients who carry antibody defects.Fil: Condino Neto, A.. Universidade de Sao Paulo; BrasilFil: Costa Carvalho, B. T.. Universidade Federal de Sao Paulo; BrasilFil: Grumach, A. S.. No especifíca;Fil: King, A.. No especifíca;Fil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Área de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Oleastro, M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Leiva, L.. Louisiana Tech University; Estados UnidosFil: Porras, O.. Hospital Nacional de Ninos ˜ Dr Carlos Sáenz Herrera"; Costa RicaFil: Espinosa Rosales, F. J.. Instituto Nacional de Pediatría; MéxicoFil: Franco, J. L.. Universidad de Antioquia; ColombiaFil: Sorensen, R. U.. Universidad de La Frontera; Chil

Hereditary angioedema: quality of life in Brazilian patients

OBJECTIVE: Hereditary angioedema is a serious medical condition caused by a rare autosomal dominant genetic disorder and it is associated with deficient production or dysfunction of the C1 esterase inhibitor. In most cases, affected patients experience unexpected and recurrent crises of subcutaneous, gastrointestinal and laryngeal edema. The unpredictability, intensity and other factors associated with the disease impact the quality of life of hereditary angioedema patients. We evaluated the quality of life in Brazilian hereditary angioedema patients. METHODS: Patients older than 15 years with any severity of hereditary angioedema and laboratory confirmation of C1 inhibitor deficiency were included. Two questionnaires were used: a clinical questionnaire and the SF-36 (a generic questionnaire). This protocol was approved by the Ethics Committee of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTS: The SF-36 showed that 90.4% (mean) of all the patients had a score below 70 and 9.6% had scores equal to or higher than 70. The scores of the eight dimensions ranged from 51.03 to 75.95; vitality and social aspects were more affected than other arenas. The internal consistency of the evaluation was demonstrated by a Cronbach's alpha value above 0.7 in seven of the eight domains. CONCLUSIONS: In this study, Brazilian patients demonstrated an impaired quality of life, as measured by the SF-36. The most affected domains were those related to vitality and social characteristics. The generic SF-36 questionnaire was relevant to the evaluation of quality of life; however, there is a need for more specific instruments for better evaluation

The use of reverse transcription-PCR for the diagnosis of X-linked chronic granulomatous disease

Chronic granulomatous disease (CGD) is an inherited disorder of the innate immune system characterized by a defective oxidative burst of phagocytes and subsequent impairment of their microbicidal activity. Mutations in one of the NADPH-oxidase components affect gene expression or function of this system, leading to the phenotype of CGD. Defects in gp91-phox lead to X-linked CGD, responsible for approximately 70% of CGD cases. Investigation of the highly heterogeneous genotype of CGD patients includes mutation analysis, Northern blot or Western blot assays according to the particular case. The aim of the present study was to use reverse transcription (RT)-PCR for the analysis of molecular defects responsible for X-linked CGD in eight Brazilian patients and to assess its potential for broader application to molecular screening in CGD. Total RNA was prepared from Epstein B virus-transformed B-lymphocytes and reverse transcribed using random hexamers. The resulting cDNA was PCR-amplified by specific and overlapping pairs of primers designed to amplify three regions of the gp91-phox gene: exons 1-5, 3-9, and 7-13. This strategy detected defective gp91-phox expression in seven patients. The RT-PCR results matched clinical history, biochemical data (nitroblue tetrazolium or superoxide release assay) and available mutation analysis in four cases. In three additional cases, RT-PCR results matched clinical history and biochemical data. In another case, RT-PCR was normal despite a clinical history compatible with CGD and defective respiratory burst. We conclude that this new application of RT-PCR analysis - a simple, economical and rapid method - was appropriate for screening molecular defects in 7 of 8 X-linked CGD patients.62563

Variability of disease activity in patients with hereditary angioedema type 1/2: longitudinal data from the Icatibant Outcome Survey.

Funder: Takeda Pharmaceuticals International AG, Zurich, SwitzerlandBACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (HAE-1/2) is a chronic and debilitating disease. The unpredictable clinical course represents a significant patient burden. OBJECTIVE: To analyse longitudinal registry data from the Icatibant Outcome Survey (IOS) in order to characterize temporal changes in disease activity in patients with HAE-1/2. METHODS: Icatibant Outcome Survey (NCT01034969) is an international observational registry monitoring the clinical outcomes of patients eligible for icatibant treatment. The current analyses are based on data collected between July 2009 and July 2019. Retrospective data for attacks recorded in the 12 months prior to IOS enrolment and for each 12-month period up to 7 years were analysed. RESULTS: Included patients reported angioedema attacks without long-term prophylaxis (LTP; n = 315) and with LTP (n = 292) use at the time of attack onset. Androgens were the most frequently used LTP option (80.8%). At the population level, regardless of LTP use, most patients (52-80%) reporting <5 attacks in Year 1 continued experiencing this rate; similarly, many patients (25-76%) who reported high attack frequency continued reporting ≥10 attacks/year. However, year on year, 31-51% of patients experienced notable changes (increase/decrease of ≥5 attacks) in annual attack frequency. Of patients who reported an absolute change of ≥10 attacks from Year 1 to 2, 17-50% continued to experience a change of this magnitude in subsequent years. CONCLUSION: At the population level, attack frequency was generally consistent over 7 years. At the small group level, 28.8-34.5% of patients reported a change in attack frequency of ≥5 attacks from Year 1 to Year 2; up to half of these patients continued to experience this magnitude of variation in disease activity in later years, reflecting high intra-patient variability

The do's, don't and maybe's

Publisher Copyright: © 2025 The AuthorsChronic spontaneous urticaria (CSU), with or without angioedema, is heterogeneous and comprised of different endotypes and phenotypes. Because acute urticaria will mostly resolve spontaneously, routine testing and laboratory evaluation is not required unless supported by the clinical history or physical examination. With the advent of omalizumab, there has been a surge of interest in identifying biomarkers that could predict response to this treatment. In the process of investigating biomarkers as prognosticators, several CSU phenotypes and endotypes have emerged, which have made it evident that novel therapies targeting non-IgE mechanistic pathways are needed to control symptoms in patients unresponsive to the currently recommended therapies by the most recent international guidelines. The current data support peripheral eosinophils, autoantibodies against IgE or FcεRI α subunit measured by basophil histamine release assays, total IgE levels and IgG autoantibodies against thyroid peroxidase (TPO) as specific markers to differentiate type 1 autoimmune (autoallergic) CSU from type 2b autoimmune CSU before starting treatment especially with omalizumab. These markers have been included as exploratory endpoints in many clinical trials investigating novel therapies or for repurposing existing biologics to determine responders and non-responders, but these data are not completely clear at this time. Therefore, further randomized controlled studies and real-world studies are needed to demonstrate more conclusively the utility of ordering these tests in CSU patients when they initially present or when it is determined they are not responsive to high dose second generation H1-antihistamines (SGAH) before they can be included in evidence-based CSU guidelines. This review examines the value of obtaining diagnostic tests in the initial evaluation of CSU patients to predict treatment response.publishersversionpublishe

Consensus on treatment goals in hereditary angioedema : a global Delphi initiative

Background: Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder characterized by recurrent episodes of subcutaneous or submucosal angioedema. The ultimate goals of treatment for HAE remain ill-defined. Objectives: The aim of this Delphi process was to define the goals of HAE treatment and to examine which factors should be considered when assessing disease control and normalization of the patient's life. Methods: The Delphi panel comprised 23 participants who were selected based on involvement with scientific research on HAE or coauthorship of the most recent update and revision of the World Allergy Organization/European Academy of Allergy and Clinical Immunology guideline on HAE. The process comprised 3 rounds of voting. The final round aimed to aggregate the opinions of the expert panel and to achieve consensus. Results: Two direct consensus questions were posed in round 2, based on the responses received in round 1, and the panel agreed that the goals of treatment are to achieve total control of the disease and to normalize the patient's life. For the third round of voting, 21 statements were considered, with the participants reaching consensus on 18. It is clear from the wide-ranging consensus statements that the burdens of disease and treatment should be considered when assessing disease control and normalization of patients’ lives. Conclusions: The ultimate goal for HAE treatment is to achieve no angioedema attacks. The availability of improved treatments and disease management over the last decade now makes complete control of HAE a realistic possibility for most patients