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1.
J Exp Med ; 218(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33170215

RESUMO

The identification and characterization of rare immune cell populations in humans can be facilitated by their growth advantage in the context of specific genetic diseases. Here, we use autoimmune lymphoproliferative syndrome to identify a population of FAS-controlled TCRαß+ T cells. They include CD4+, CD8+, and double-negative T cells and can be defined by a CD38+CD45RA+T-BET- expression pattern. These unconventional T cells are present in healthy individuals, are generated before birth, are enriched in lymphoid tissue, and do not expand during acute viral infection. They are characterized by a unique molecular signature that is unambiguously different from other known T cell differentiation subsets and independent of CD4 or CD8 expression. Functionally, FAS-controlled T cells represent highly proliferative, noncytotoxic T cells with an IL-10 cytokine bias. Mechanistically, regulation of this physiological population is mediated by FAS and CTLA4 signaling, and its survival is enhanced by mTOR and STAT3 signals. Genetic alterations in these pathways result in expansion of FAS-controlled T cells, which can cause significant lymphoproliferative disease.

2.
Front Immunol ; 11: 535784, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193306

RESUMO

Human CD21low B cells are expanded in autoimmune (AI) diseases and display a unique phenotype with high expression of co-stimulatory molecules, compatible with a potential role as antigen-presenting cells (APCs). Thus, we addressed the co-stimulatory capacity of naïve-like, IgM-memory, switched memory and CD27negIgDneg memory CD21low B cells in allogenic co-cultures with CD4 T cells. CD21low B cells of patients with AI disorders expressed high levels of not only CD86, CD80, and HLA-DR (memory B cells) but also PD-L1 ex vivo and efficiently co-stimulated CD4 T cells of healthy donors (HD), as measured by upregulation of CD25, CD69, inducible co-stimulator (ICOS), and programmed cell death protein 1 (PD-1) and induction of cytokines. While the co-stimulatory capacity of the different CD21low B-cell populations was over all comparable to CD21pos counterparts of patients and HD, especially switched memory CD21low B cells lacked the increased capacity of CD21pos switched memory B-cells to induce high expression of ICOS, IL-2, IL-10, and IFN-γ. Acknowledging the limitation of the in vitro setting, CD21low B cells do not seem to preferentially support a specific Th effector response. In summary, our data implies that CD21low B cells of patients with AI diseases can become competent APCs and may, when enriched for autoreactive B-cell receptors (BCR), potentially contribute to AI reactions as cognate interaction partners of autoreactive T cells at sites of inflammation.

3.
Front Immunol ; 11: 589148, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193417

RESUMO

Background: Granulomatous lymphocytic interstitial lung disease (GLILD) is present in about 20% of patients with common variable immunodeficiency disorders (CVID). GLILD is characterized by nodules, reticulation, and ground-glass opacities on CT scans. To date, large cohort studies that include sensitive CT outcome measures are lacking, and severity of structural lung disease remains unknown. The aim of this study was to introduce and compare two scoring methods to phenotype CT scans of GLILD patients. Methods: Patients were enrolled in the "Study of Interstitial Lung Disease in Primary Antibody Deficiency" (STILPAD) international cohort. Inclusion criteria were diagnosis of both CVID and GLILD, as defined by the treating immunologist and radiologist. Retrospectively collected CT scans were scored systematically with the Baumann and Hartmann methods. Results: In total, 356 CT scans from 138 patients were included. Cross-sectionally, 95% of patients met a radiological definition of GLILD using both methods. Bronchiectasis was present in 82% of patients. Inter-observer reproducibility (intraclass correlation coefficients) of GLILD and airway disease were 0.84 and 0.69 for the Hartmann method and 0.74 and 0.42 for the Baumann method. Conclusions: In both the Hartmann and Baumann scoring method, the composite score GLILD was reproducible and therefore might be a valuable outcome measure in future studies. Overall, the reproducibility of the Hartmann method appears to be slightly better than that of the Baumann method. With a systematic analysis, we showed that GLILD patients suffer from extensive lung disease, including airway disease. Further validation of these scoring methods should be performed in a prospective cohort study involving routine collection of standardized CT scans. Clinical Trial Registration: https://www.drks.de, identifier DRKS00000799.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33223097

RESUMO

BACKGROUND: Interstitial lung disease (ILD) represents a severe clinical manifestation of systemic immune dysregulation in patients with common variable immunodeficiency (CVID). Its treatment often requires systemic immunosuppression beyond corticosteroids. OBJECTIVE: To assess the safety and efficacy of abatacept in patients with CVID and ILD. METHODS: Ten patients with confirmed diagnosis of CVID and ILD were included in a single-center, prospective, open-label, nonrandomized trial. Abatacept was administered subcutaneously at a dose of 125 mg/wk for 12 months. RESULTS: Abatacept was a safe treatment for ILD in CVID except for 1 case of bronchopulmonary aspergillosis. One additional patient terminated the trial prematurely because of recurrent bronchitis. Five of 8 patients treated per protocol benefited from the treatment according to American Thoracic Society/European Respiratory Society criteria. The primary end point of the study was met because single breath diffusing capacity of the lung for carbon monoxide was stable (62.5%) or improved (37.5%) in all patients treated per protocol. Although nodules (71%) and ground-glass opacities (57%) improved in most patients, other computed tomography pathologies were less responsive. Quality of life improved in 87.5% and fatigue in 57% of patients. Abatacept treatment was associated with significant improvement in CD4 T-cell dysregulation, signified by a decrease in serum soluble IL-2 receptor levels and of proliferating Ki67+ CD4 T cells, and a recovery of total lymphocytes, CD4+ T cells, and naive CD4 T cells. CONCLUSIONS: Abatacept may represent a treatment option for CVID-associated ILD. This pilot study demonstrated a good safety profile, steroid-sparing effect, positive immune modulation, and overall positive treatment response especially in quality of life. Larger controlled studies are needed to confirm these findings.

5.
J Hepatol ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33211012

RESUMO

BACKGROUND AND AIMS: Patients with decompensated liver cirrhosis suffer from recurrent infections and inadequate responses to prophylactic vaccinations. However, many patients present with hypergammaglobulinemia (HGG), indicating a sustained ability to generate antibody responses. As follicular T helper (Tfh) cells are central facilitators of humoral immunity by providing B cell help, we hypothesized that Tfh cell responses may be altered in advanced liver disease and aimed to identify underlying mechanisms. METHODS: Tfh, regulatory T (Treg) cells and B cells, circulating cytokines and immunoglobulins were analyzed in cohorts of patients with compensated (n = 37) and decompensated cirrhosis (n = 82) and in non-cirrhotic controls (n = 45). Intrahepatic T cells were analyzed in 8 decompensated patients. The influence of IL-2 on Tfh cell function was evaluated in vitro, including Tfh cell cloning and T cell-B cell co-cultures with clones and primary tonsil-derived Tfh cells. RESULTS: Tfh cell frequencies were reduced in patients with decompensated liver cirrhosis with phenotypic signatures indicative of increased IL-2 signaling. Soluble IL-2 receptor (sCD25) was elevated in these patients and CD4 T cells were more responsive to IL-2 signaling, as characterized by STAT5 phosphorylation. IL-2 exposure in vitro diminished the Tfh phenotype and resulted in impaired Tfh helper function in co-culture experiments with naïve B cells. Tfh cells were barely detectable in cirrhotic livers. IL-2 signatures on Tfh cells in decompensated patients correlated with immunoglobulin levels, which were found to be associated with improved survival. CONCLUSIONS: Tfh cell impairment represents a previously underestimated feature of cirrhosis-associated immune dysfunction that is driven by IL-2. Presence of HGG in decompensated patients predicts an intact Tfh cell compartment and is associated with a favorable outcome.

6.
J Clin Immunol ; 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33190167

RESUMO

Patients with common variable immunodeficiency (CVID) can develop immune dysregulation complications such as autoimmunity, lymphoproliferation, enteritis, and malignancy, which cause significant morbidity and mortality. We aimed to (i) assess the potential of serum proteomics in stratifying patients with immune dysregulation using two independent cohorts and (ii) identify cytokine and chemokine signaling pathways that underlie immune dysregulation in CVID. A panel of 180 markers was measured in two multicenter CVID cohorts using Olink Protein Extension Assay technology. A classification algorithm was trained to distinguish CVID with immune dysregulation (CVIDid, n = 14) from CVID with infections only (CVIDio, n = 16) in the training cohort, and validated on a second testing cohort (CVIDid n = 23, CVIDio n = 24). Differential expression in both cohorts was used to determine relevant signaling pathways. An elastic net classifier using MILR1, LILRB4, IL10, IL12RB1, and CD83 could discriminate between CVIDid and CVIDio patients with a sensitivity of 0.83, specificity of 0.75, and area under the curve of 0.73 in an independent testing cohort. Activated pathways (fold change > 1.5, FDR-adjusted p < 0.05) in CVIDid included Th1 and Th17-associated signaling, as well as IL10 and other immune regulatory markers (LAG3, TNFRSF9, CD83). Targeted serum proteomics provided an accurate and reproducible tool to discriminate between patients with CVIDid and CVIDio. Cytokine profiles provided insight into activation of Th1 and Th17 pathways and indicate a possible role for chronic inflammation and exhaustion in immune dysregulation. These findings serve as a first step towards the development of biomarkers for immune dysregulation in CVID.

7.
J Clin Immunol ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33111199

RESUMO

PURPOSE: Bacillus Calmette-Guerin (BCG) is a live attenuated vaccine with the potential of causing severe iatrogenic complications in patients with primary immunodeficiency diseases (PID) before and after hematopoietic stem cell transplantation (HSCT). We aim to investigate risk factors of post-HSCT BCG-related complications in PID patients. METHODS: A retrospective analysis of pediatric PID patients who had received the BCG vaccine and underwent HSCT at Hadassah-Hebrew University Medical Center, between 2007 and 2019. RESULTS: We found 15/36 (41.67%) patients who developed post-HSCT BCG-related complications. The most significant risk factor for developing BCG-related complications was T cell deficiency (47.6% of the non-complicated vs 83.3% of the BCGitis and 100% of the BCGosis groups had T cell lymphopenia, p = 0.013). None of the chronic granulomatous patients developed BCG-related manifestation post-transplant. Among T cell-deficient patients, lower NK (127 vs 698 cells/µl, p = 0.04) cell counts and NK-SCID were risk factors for ongoing post-HSCT BCGosis, as was pretransplant disseminated BCGosis (33.3% of patients with BCGosis vs none of the non-BCGosis patients, p = 0.04). Immune reconstitution inflammatory syndrome (IRIS) was observed in 3/5 patients with Omenn syndrome. Prophylactic antimycobacterial treatment was not proven effective. CONCLUSION: BCG vaccination can cause significant morbidity and mortality in the post-transplant T cell-deficient patient, especially in the presence of pre-transplant disease. Taking a detailed medical history prior to administering, the BCG vaccine is crucial for prevention of this complication.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33118209

RESUMO

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) can cure chronic granulomatous disease (CGD), but it remains debated whether all conventionally treated CGD patients benefit from HSCT. METHODS: We retrospectively analyzed 104 conventionally treated CGD patients, of whom 50 patients underwent HSCT. RESULTS: On conventional treatment, seven patients (13%) died after a median time of 16.2 years (interquartile range [IQR] 7.0-18.0). Survival without severe complications was 10 ± 3% (mean ± SD) at the age of 20 years; 85% of patients developed at least one infection, 76% one non-infectious inflammation. After HSCT, 44 patients (88%) were alive at a median follow-up of 2.3 years (IQR 0.8-4.9): Six patients (12%) died from infections. Survival after HSCT was significantly better for patients transplanted ≤8 years (96 ± 4%) or for patients without active complications at HSCT (100%). Eight patients suffered from graft failure (16%); six (12%) developed acute graft-vs-host disease requiring systemic treatment. Conventionally treated patients developed events that required medical attention at a median frequency of 1.7 (IQR 0.8-3.2) events per year vs 0 (IQR 0.0-0.5) in patients beyond the first year post-HSCT. While most conventionally treated CGD patients failed to thrive, catch-up growth after HSCT in surviving patients reached the individual percentiles at the age of diagnosis of CGD. CONCLUSION: Chronic granulomatous disease patients undergoing HSCT until 8 years of age show excellent survival, but young children need more intense conditioning to avoid graft rejection. Risks and benefits of HSCT for adolescents and adults must still be weighed carefully.

9.
J Immunol ; 205(8): 2016-2025, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32907998

RESUMO

An expansion of CD21low B cells has been described in a variety of diseases associated with persistent immune stimulation as in chronic infection, immunodeficiency, or autoimmunity. Different developmental stages of CD21low B cells have been highlighted in specific diseases; however, a systematic comparison of distribution, phenotype, and signaling capacity of these populations has not yet been performed to delineate the pivotal character of this unusual B cell population. Screening of more than 200 patients with autoimmune disease demonstrated that the prevalence of patients with expanded CD21low B cells varies between diseases. The expansion was frequent in patients with systemic lupus erythematosus, in which it correlated to relative B cell lymphopenia and duration of disease. Different proportions of distinct developmental stages of CD21low B cells co-occur in nearly all patients with autoimmune disease. Although in most patients, naive-like and CD27- switched memory B cells were the most prominent CD21low subpopulations, there was no detectable association of the pattern with the underlying disease. Despite their distinct developmental stage, all CD21low B cells share a common core phenotype including the increased expression of inhibitory receptors, associated with an elevated constitutive phosphorylation of proximal signaling molecules downstream of the BCR but impaired Ca2+ mobilization and NF-κB activation after BCR stimulation. Further, this was accompanied by impaired upregulation of CD69, although CD86 upregulation was preserved. Beyond maturation-associated differences, the common core characteristics of all CD21low B cell populations suggests either a common ancestry or a shared sustained imprint by the environment they originated in.

10.
Eur J Immunol ; 50(10): 1432-1446, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32845010

RESUMO

This evidence-based clinical guideline provides consensus-recommendations for the treatment and care of patients with primary antibody deficiencies (PADs). The guideline group comprised 20 clinical and scientific expert associations of the German, Swiss, and Austrian healthcare system and representatives of patients. Recommendations were based on results of a systematic literature search, data extraction, and evaluation of methodology and study quality in combination with the clinical expertise of the respective representatives. Consensus-based recommendations were determined via nominal group technique. PADs are the largest clinically relevant group of primary immunodeficiencies. Most patients with PADs present with increased susceptibility to infections, however immune dysregulation, autoimmunity, and cancer affect a significant number of patients and may precede infections. This guideline therefore covers interdisciplinary clinical and therapeutic aspects of infectious (e.g., antibiotic prophylaxis, management of bronchiectasis) and non-infectious manifestations (e.g., management of granulomatous disease, immune cytopenia). PADs are grouped into disease entities with definitive, probable, possible, or unlikely benefit of IgG-replacement therapy. Summary and consensus-recommendations are provided for treatment indication, dosing, routes of administration, and adverse events of IgG-replacement therapy. Special aspects of concomitant impaired T-cell function are highlighted as well as clinical data on selected monogenetic inborn errors of immunity formerly classified into PADs (APDS, CTLA-4-, and LRBA-deficiency).

11.
J Allergy Clin Immunol Pract ; 8(7): 2332-2340.e5, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32330665

RESUMO

BACKGROUND: Vaccination against influenza is recommended for patients with common variable immunodeficiency (CVID), although humoral immune responses in these patients are impaired and the evidence of effective T-cell responses in CVID is not well established. OBJECTIVE: To determine plasmablast and T-cellular vaccination responses against influenza in patients with CVID. METHODS: Patients with CVID and healthy controls were vaccinated with the quadrivalent vaccine Influsplit Tetra 2018/2019. Before and 1 week after vaccination plasmablasts and circulating inducible costimulator-expressing T follicular helper cells were measured to determine positive vaccine responses in these patients. In addition, antigen-specific T cells were determined by their upregulation of CD25 and OX40 after in vitro restimulation with the vaccine. RESULTS: Most healthy controls but only 1 patient with CVID mounted a positive humoral immune response, measured by an increase in plasmablasts 1 week after vaccination. In contrast, most patients with CVID showed an increase in inducible costimulator+ T follicular helper cells and/or an increase in antigen-specific CD25+OX40+ T cells 1 week after vaccination, demonstrating a positive T-cellular immune response. CONCLUSIONS: Despite the remaining challenge of accurately assessing the complexity of T-cell responses, the recommendation of vaccinating patients with CVID against influenza is reasonable.

13.
Blood ; 135(17): 1452-1457, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32157302

RESUMO

Common variable immunodeficiency (CVID) is a disease characterized by increased susceptibility to infections, hypogammaglobulinemia, and immune dysregulation. Although CVID is thought to be a disorder of the peripheral B-cell compartment, in 25% of patients, early B-cell development in the bone marrow is impaired. Because poor B-cell reconstitution after hematopoietic stem cell transplantation has been observed, we hypothesized that in some patients the bone marrow environment is not permissive to B-cell development. Studying the differentiation dynamics of bone marrow-derived CD34+ cells into immature B cells in vitro allowed us to distinguish patients with B-cell intrinsic defects and patients with a nonpermissive bone marrow environment. In the former, immature B cells did not develop and in the latter CD34+ cells differentiated into immature cells in vitro, but less efficiently in vivo. In a further group of patients, the uncommitted precursors were unable to support the constant development of B cells in vitro, indicating a possible low frequency or exhaustion of the precursor population. Hematopoietic stem cell transplantation would result in normal B-cell repopulation in case of intrinsic B-cell defect, but in defective B-cell repopulation in a nonpermissive environment. Our study points to the importance of the bone marrow niche in the pathogenesis of CVID.

15.
Ann Rheum Dis ; 79(1): 39-52, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31413005

RESUMO

To update the European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) published in 2011. Four systematic literature reviews were performed regarding the incidence/prevalence of vaccine-preventable infections among patients with AIIRD; efficacy, immunogenicity and safety of vaccines; effect of anti-rheumatic drugs on the response to vaccines; effect of vaccination of household of AIIRDs patients. Subsequently, recommendations were formulated based on the evidence and expert opinion. The updated recommendations comprise six overarching principles and nine recommendations. The former address the need for an annual vaccination status assessment, shared decision-making and timing of vaccination, favouring vaccination during quiescent disease, preferably prior to the initiation of immunosuppression. Non-live vaccines can be safely provided to AIIRD patients regardless of underlying therapy, whereas live-attenuated vaccines may be considered with caution. Influenza and pneumococcal vaccination should be strongly considered for the majority of patients with AIIRD. Tetanus toxoid and human papilloma virus vaccination should be provided to AIIRD patients as recommended for the general population. Hepatitis A, hepatitis B and herpes zoster vaccination should be administered to AIIRD patients at risk. Immunocompetent household members of patients with AIIRD should receive vaccines according to national guidelines, except for the oral poliomyelitis vaccine. Live-attenuated vaccines should be avoided during the first 6 months of life in newborns of mothers treated with biologics during the second half of pregnancy. These 2019 EULAR recommendations provide an up-to-date guidance on the management of vaccinations in patients with AIIRD.


Assuntos
Antirreumáticos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Infecções Bacterianas/prevenção & controle , Doenças Reumáticas/tratamento farmacológico , Vacinas/uso terapêutico , Viroses/prevenção & controle , Características da Família , Hepatite A/prevenção & controle , Vacinas contra Hepatite A/uso terapêutico , Hepatite B/prevenção & controle , Vacinas contra Hepatite B/uso terapêutico , Herpes Zoster/prevenção & controle , Vacina contra Herpes Zoster/uso terapêutico , Humanos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Tétano/prevenção & controle , Toxoide Tetânico/uso terapêutico , Vacinas Atenuadas/uso terapêutico
16.
Scand J Immunol ; 91(1): e12811, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31378960

RESUMO

Hypomorphic mutations in the gene encoding Bruton tyrosine kinase (BTK) may result in milder phenotypes and delayed diagnosis of B-cell related immunodeficiencies due to residual BTK function. Newborn screening for kappa-deleting-recombination-excision circles (KRECs) reliably identifies classical X-linked agammaglobulinaemia (XLA) patients with profound B-cell lymphopenia at birth but has not been evaluated in patients with residual BTK function. We aimed to evaluate clinical findings, BTK function and KREC copy numbers in three patients with BTK mutations presenting with impaired polysaccharide responsiveness without agammaglobulinaemia. One patient had an invasive pneumococcal infection at the age of 4 years. All three patients (two brothers) had visible tonsils, normal to slightly decreased immunoglobulin G levels, undetectable pneumococcal antibodies despite pneumococcal conjugate vaccinations, no antibody response after a diagnostic polysaccharide vaccination as well as profound B-cell lymphopenia with residual B-cell differentiation. BTK mutations were identified by Sanger sequencing. BTK staining and phosphorylation assays were performed on peripheral B cells. KREC copy numbers were determined from dried blood spots obtained within the first week of life as well as once at the age of 8, 6 and 3 years, respectively. BTK staining showed residual protein expression. Also, residual BTK activity could be demonstrated. KREC copy numbers from dried blood spots were above the threshold set for detection of patients with profound B-cell lymphopenia. Male patients with impaired polysaccharide responsiveness should be evaluated for B-cell lymphopenia followed by BTK analyses irrespective of immunoglobulin levels or tonsil size.


Assuntos
Tirosina Quinase da Agamaglobulinemia/genética , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/etiologia , Mutação , Fenótipo , Polissacarídeos/imunologia , Biomarcadores , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Seguimentos , Genótipo , Humanos , Imunofenotipagem , Recém-Nascido , Masculino , Triagem Neonatal , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/etiologia , Avaliação de Sintomas
17.
Clin Immunol ; 210: 108316, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31770611

RESUMO

Germline STAT3 gain-of-function (GOF) mutations have been linked to poly-autoimmunity and lymphoproliferation with variable expressivity and incomplete penetrance. Here we studied the impact of 17 different STAT3 GOF mutations on the canonical STAT3 signaling pathway and correlated the molecular results with clinical manifestations. The mutations clustered in three groups. Group 1 mutants showed altered STAT3 phosphorylation kinetics and strong basal transcriptional activity. They were associated with the highest penetrance of lymphoproliferation and autoimmunity. Group 2 mutants showed a strongly inducible transcriptional reporter activity and were clinically less penetrant. Group 3 mutants were mostly located in the DNA binding domain and showed the strongest DNA binding affinity despite a poor transcriptional reporter response. Thus, the GOF effect of STAT3 mutations is determined by a heterogeneous response pattern at the molecular level. The correlation of response pattern and clinical penetrance indicates a significant contribution of mutation-determined effects on disease manifestations.

18.
J Allergy Clin Immunol Pract ; 8(3): 1047-1062.e6, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31857261

RESUMO

BACKGROUND: Central nervous system (CNS) disease in adult common variable immunodeficiency (CVID) is rare, and therefore diagnostic and therapeutic protocols are lacking. OBJECTIVE: To provide clinical information aiming to establish awareness and first experience-based recommendations. METHODS: We reviewed clinical manifestations, genetic and immunological characteristics, diagnostic evaluation, and treatment of patients with CVID with abnormal magnetic resonance imaging (MRI) of the CNS disease in our cohort. RESULTS: Seventeen patients with CNS manifestation and a previous diagnosis of CVID were identified. Presenting symptoms of the CNS disease included loss of sensory or motoric function, headache, or epilepsy. Contrast-enhancing lesions of the brain or solely the spinal cord were the most common findings on MRI. The prevalence of splenomegaly, lymphadenopathy, interstitial lung disease, and autoimmune cytopenia was significantly increased compared with control CVID patients. In 8 patients, a molecular defect was identified, including mutations in CTLA4, NFKB1, and CECR1. Patients with CVID with CNS involvement generally displayed lymphopenia, skewed CD4+ T-cell subsets, and increased proportions of CD21low B cells in the peripheral blood. CNS involvement usually responded well to high-dose steroids, but regularly required maintenance therapy to prevent relapse. CONCLUSION: CNS disease is a severe but rare complication in CVID disorders, particularly affecting patients with other noninfectious disease symptoms. Diagnostic evaluation needs to rule out infectious causes by all means; a genetic evaluation is recommended given the high probability of an underlying monogenic disorder. Possible treatment consists of steroids with yet to be determined optimal maintenance therapy in case of relapse.

19.
RMD Open ; 5(2): e001041, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673420

RESUMO

Objectives: The aims of this study were to update the evidence on the incidence and prevalence rates of vaccine preventable infections (VPI) in patients with autoimmune inflammatory rheumatic diseases (AIIRD) and compare the data to the general population when available. Methods: A literature search was performed using Medline, Embase and Cochrane library (October 2009 to August 2018). The primary outcome was the incidence or prevalence of VPI in the adult AIIRD population. Meta-analysis was performed when appropriate. Results: Sixty-three publications out of 3876 identified records met the inclusion criteria: influenza (n=4), pneumococcal disease (n=7), hepatitis B (n=10), herpes zoster (HZ) (n=29), human papillomavirus (HPV) infection (n=13). An increased incidence of influenza and pneumococcal disease was reported in patients with AIIRD. HZ infection-pooled incidence rate ratio (IRR) was 2.9 (95% CI 2.4 to 3.3) in patients with AIIRD versus general population. Among AIIRD, inflammatory myositis conferred the highest incidence rate (IR) of HZ (pooled IRR 5.1, 95% CI 4.3 to 5.9), followed by systemic lupus erythematosus (SLE) (pooled IRR 4.0, 95% CI 2.3 to 5.7) and rheumatoid arthritis (pooled IRR 2.3, 95% CI 2.1 to 2.6). HPV infection-pooled prevalence ratio was 1.6, 95% CI 0.7 to 3.4 versus general population, based on studies mainly conducted in the SLE population in Latin America and Asia. Pooled prevalence of hepatitis B surface antigen and hepatitis B core antibody in patients with AIIRD was similar to the general population, 3%, 95% CI 1% to 5% and 15%, 95% CI 7% to 26%, respectively. Conclusion: Current evidence shows an increased risk of VPI in patients with AIIRD, emphasising that prevention of infections is essential in these patients.


Assuntos
Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Controle de Doenças Transmissíveis , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/etiologia , Doenças Reumáticas/complicações , Doenças Reumáticas/epidemiologia , Vacinas/imunologia , Doenças Autoimunes/tratamento farmacológico , Feminino , Humanos , Incidência , Razão de Chances , Prevalência , Doenças Reumáticas/tratamento farmacológico , Vacinação
20.
Gesundheitswesen ; 2019 Oct 15.
Artigo em Alemão | MEDLINE | ID: mdl-31614384

RESUMO

OBJECTIVE: The aim of the article was to describe the development of a training program to enhance the health literacy of patients with immunodeficiency. In addition, patient satisfaction and acceptance of the training will be evaluated. METHODS: Patients' needs were identified with a questionnaire (N=238). Additionally, interviews with clinical immunologists (N=5) and patients with common variable immunodeficiency (CVID) (N=9) were conducted. On this basis, the authors developed a manual for the intervention. It focuses on active communication with physicians as well as health-related communication at the workplace. The evaluation of patient satisfaction with the intervention was based on a questionnaire (N=49). RESULTS: The results show that the ratings of the patients were in the good to very good range (M=1.77; SD=0.38). From the analysis of the free text, hints for training improvement could be derived. CONCLUSION: Evaluation of the intervention showed that the new training was accepted and patients considered it comprehensible and relevant.

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