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1.
Biol Res Nurs ; : 1099800419889192, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31763930

RESUMO

RESULTS: hs-CRP correlated significantly with SLEDAI-2K (p = .036), SDI (p = .00), anti-dsDNA titers (p = .034), diabetes (p = .005), and obesity (p = .027). hs-CRP and Hcy correlated with triglyceride (TG) levels (p = .032 and p < .001, respectively), TG/high-density lipoprotein cholesterol index (p = .020 and p = .001, respectively), and atherogenic index of plasma (p = .006 and p = .016, respectively). hs-CRP levels >3 mg/L correlated with SDI score (p = .012) and several CVD risk factors. DISCUSSION: Findings suggest SLE patients with elevated hs-CRP and/or Hcy have a higher prevalence of CVD risk factors.

2.
Nat Commun ; 10(1): 4955, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672989

RESUMO

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.

3.
Acta Reumatol Port ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31575843

RESUMO

OBJECTIVE: The purpose of this study was to evaluate serum Endothelin-1(ET-1) levels in women Rheumatoid Arthritis (RA) patients compared with healthy controls, examine possible associations between ET-1 with different characteristic of the disease and investigate possible associations between ET-1 with surrogate markers of cardiovascular disease (CVD). METHODS: This cross-sectional study was performed in Vega-Baja Hospital, Orihuela (Spain) from November 2016 to May 2018. Sixty-three women with RA and sixty-five age and sex healthy controls were included in this study. Serum ET-1 was analyzed using ELISA. RESULTS: Serum levels of ET-1 in RA women patients were higher than those in healthy controls (p ˂0.001). Serum levels of ET-1 were positively associated with N-terminal pro-brain natriuretic peptide (NT-proBNP) (r = 0.27, p < 0.05) and with C-reactive protein (CRP) (r = 0.36, p < 0.05). ET-1 levels in women with RA were higher in smokers. Prednisone use was associated with lower ET-1 levels. No association with carotid intima media thickness was found. CONCLUSIONS: we observed the presence of higher levels of serum ET-1 in RA women patients compared with healthy controls. These increased levels of ET-1 are associated with inflammation and smoking and reduced by prednisone intake.

4.
J Acad Nutr Diet ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31492654

RESUMO

BACKGROUND: Patients with systemic lupus erythematosus (SLE), a chronic inflammatory autoimmune disease, have an increased risk of developing cardiovascular diseases. Environmental factors like diet and nutrition are known to play a key role in modulating inflammation and the prognosis of cardiovascular diseases. OBJECTIVE: To investigate the relationship between Dietary Inflammatory Index score and cardiovascular disease risk markers in a population of women with SLE. DESIGN: A cross-sectional study was conducted in women with SLE recruited from 2016 through 2017. PARTICIPANTS/SETTINGS: Clinically stable women with SLE were enrolled from three public hospitals in the Andalusian region of Spain. Participants with chronic renal failure, active infections, recent trauma, pregnancy, and/or other autoimmune diseases were excluded. MAIN OUTCOME MEASURES: A 24-hour diet recall was used to estimate Dietary Inflammatory Index score and physical activity was assessed through the International Physical Activity Questionnaires. Cardiovascular disease risk markers included blood lipid profile (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels), high-sensitivity C-reactive protein levels, and homocysteine levels, along with diagnosis of obesity, diabetes mellitus, hypertension, dyslipidemia, and ankle-brachial index measurement. STATISTICAL ANALYSIS: Comparisons of cardiovascular disease risk markers across Dietary Inflammatory Index score tertiles were analyzed through a one-way analysis of variance and linear regressions adjusting for age, physical activity level, and medical treatment. RESULTS: A total of 105 women (aged 45.4±12.8 years) were included. Linear regression analysis revealed that Dietary Inflammatory Index score was significantly associated with total cholesterol levels (ß=.26, 95% CI 1.66 to 14.28; P=0.014) after adjusting for age, physical activity, and the use of medical treatment. No significant associations were observed between Dietary Inflammatory Index score and the other cardiovascular markers considered. CONCLUSIONS: Higher inflammatory potential of the diet was positively associated with higher total cholesterol levels in women with SLE. These findings suggest that the inflammatory potential of a person's diet may play a role in lipid profiles in this population. Future intervention studies are needed to build on these results and explore the effect of anti-inflammatory diets on health outcomes in individuals with SLE.

5.
BMC Geriatr ; 19(1): 200, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31357946

RESUMO

BACKGROUND: Giant cell arteritis is a vasculitis of large and middle-sized arteries that affects patients aged over 50 years. It can show a typical clinical picture consisting of cranial manifestations but sometimes nonspecific symptoms and large-vessel involvement prevail. Prompt diagnosis and treatment is essential to avoid irreversible damage. DISCUSSION: There has been an increasing knowledge on the occurrence of the disease without the typical cranial symptoms and its close relationship and overlap with polymyalgia rheumatica, and this may contribute to reduce the number of underdiagnosed patients. Although temporal artery biopsy is still the gold-standard and temporal artery ultrasonography is being widely used, newer imaging techniques (FDG-PET/TAC, MRI, CT) can be of valuable help to identify giant cell arteritis, in particular in those cases with a predominance of extracranial large-vessel manifestations. CONCLUSIONS: Giant cell arteritis is a more heterogeneous condition than previously thought. Awareness of all the potential clinical manifestations and judicious use of diagnostic tests may be an aid to avoid delayed detection and consequently ominous complications.

7.
Arthritis Rheumatol ; 71(12): 2081-2089, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31237427

RESUMO

OBJECTIVE: To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first-line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to Behçet's disease (BD). METHODS: We conducted an open-label multicenter study of IFX versus ADA for BD-related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first-line biologic agent based on physician and patient agreement. Patients received 3-5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4-8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups. RESULTS: The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best-corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042). CONCLUSION: Although both IFX and ADA are efficacious in refractory BD-related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow-up.

8.
Clin Exp Rheumatol ; 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-31025926

RESUMO

OBJECTIVES: We aimed to compare serum Klotho and fibroblast growth factor-23 (FGF-23) levels between rheumatoid arthritis (RA) patients and healthy controls. Possible association between FGF-23 and soluble Klotho with different characteristic of the disease as well as their potential role as surrogate markers of cardiovascular disease (CVD) were studied. METHODS: Sixty-three patients with RA recruited at Vega-Baja Hospital, Orihuela (Spain) from November 2016 to May 2018 and sixty-five age- and sex-matched healthy controls were included in this study. Serum Klotho and FGF-23 were analysed using ELISA. RESULTS: Patients had higher serum levels of Klotho than healthy controls (p˂0.0001). They were positively associated with the presence of anticitrullinated peptide antibody and rheumatic factor (p<0.05). Klotho serum levels were higher in RA patients treated with biologic agents than in those undergoing conventional therapy (p=0.008). However, no association with carotid intima media thickness was found. Although no significant differences in serum FGF-23 levels between patients and controls were found (p=0.43), FGF-23 levels were positively associated with low-density lipoprotein (LDL-c) level (p<0.05) and smoking (p=0.008) in patients with RA. CONCLUSIONS: The increased serum Klotho levels in RA patients, especially in those undergoing biologic therapy, may indicate a potential implication in the pathogenesis of the disease. Although levels of FGF-23 were related to LDL-c levels, the FGF-23-Klotho axis does not seem to be related to subclinical arteriosclerosis in RA.

10.
Nutrients ; 11(3)2019 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-30884776

RESUMO

The prognostic nutritional index (PNI), controlling nutritional status (CONUT) score and nutritional risk index (NRI) have been described as useful screening tools for patient prognosis in several diseases. The aim of this study was to examine the relationship between PNI, CONUT and NRI with clinical disease activity and damage in 173 patients with systemic lupus erythematous (SLE). Disease activity was assessed with the SLE disease activity index (SLEDAI-2K), and disease-related organ damage was assessed using the SLICC/ACR damage index (SDI) damage index. PNI and NRI were significantly lower in active SLE patients than in inactive SLE patients (p < 0.001 and p = 0.012, respectively). PNI was inversely correlated with the SLEDAI score (p < 0.001) and NRI positively correlated with SLEDAI and SDI scores (p = 0.027 and p < 0.001). Linear regression analysis adjusting for age, sex and medications showed that PNI was inversely correlated with SLEDAI (ß (95% CI) = -0.176 (-0.254, -0.098), p < 0.001) and NRI positively correlated with SLEDAI (ß (95% CI) = 0.056 (0.019, 0.093), p = 0.003) and SDI (ß (95% CI) = 0.047 (0.031, 0.063), p < 0.001). PNI (odds ratio (OR) 0.884, 95% confidence interval (CI) 0.809⁻0.967, p = 0.007) and NRI ((OR) 1.067, 95% CI 1.028⁻1.108, p = 0.001) were independent predictors of active SLE. These findings suggest that PNI and NRI may be useful markers to identify active SLE in clinical practice.


Assuntos
Progressão da Doença , Lúpus Eritematoso Sistêmico/sangue , Avaliação Nutricional , Estado Nutricional , Índice de Gravidade de Doença , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
11.
Sci Rep ; 9(1): 2777, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808881

RESUMO

Behçet's disease (BD) is an immune-mediated systemic disorder with a well-established genetic base. In a previous study, using a next generation sequencing approach, we found many rare variants and some functional polymorphisms in genes related to autoinflammatory syndromes (AID): CECR1, MEFV, MVK, NLRP3, NOD2, PSTPIP1 and TNFRSF1A in our BD cohort. Our strategy did not allow us to establish either number of patients with variants, proportion of individuals accumulating them or relationship with other genetic factors. With the goal to answer these questions, the individual samples were sequenced. Additionally, three functional polymorphisms: NLRP3 p.Gln703Lys, NOD2 p.Arg702Trp and p.Val955Ile were genotyped using TaqMan assays. A total of 98 patients (27.6%) carried at least one rare variant and 13 of them (3.7%) accumulated two or three. Functional regression model analysis suggests epistatic interaction between B51 and MEFV (P = 0.003). A suggestive protective association of the minor allele of NOD2 p.Arg702Trp (P = 0.01) was found in both, B51 positive and negative individuals. Therefore, a high percentage of patients with BD have rare variants in AID genes. Our results suggest that the association of MEFV with BD could be modulated by the HLA molecules; whereas the protective effect of NOD2 p.Arg702Trp would be independent of HLA.

13.
J Rheumatol ; 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770503

RESUMO

OBJECTIVE: Monotherapy is an option as first-line therapy for pulmonary arterial hypertension (PAH). However, combination therapy is a beneficial alternative. Our objective was to evaluate the efficacy of monotherapy versus combination therapy in patients with systemic sclerosis (SSc)-associated PAH. METHODS: All patients with SSc-associated PAH from the Spanish Scleroderma Registry (RESCLE) were reviewed. Patients were split into 3 groups: monotherapy versus sequential combination versus upfront combination therapy. The primary endpoint was death from any cause at 1, 3, and 5 years from PAH diagnosis. RESULTS: Seventy-six patients (4.2%) out of 1817 had SSc-related PAH. Thirty-four patients (45%) were receiving monotherapy [endothelin receptor antagonist (n = 22; 29%) or phosphodiesterase-5 inhibitors (n = 12; 16%)], 25 (33%) sequential combination, and 17 (22%) upfront combination therapy. A lower forced vital capacity/DLCO in the sequential combination group was reported (2.9 ± 1.1 vs 1.8 ± 0.4 vs 2.3 ± 0.8; p = 0.085) and also a higher mean pulmonary arterial pressure in combination groups (37.2 ± 8.7 mmHg vs 40.8 ± 8.8 vs 46 ± 15.9; p = 0.026) at baseline. Treatment regimen (p = 0.017) and functional class (p = 0.007) were found to be independent predictors of mortality. Sequential combination therapy was found to be an independent protective factor (HR 0.11, 95% CI 0.03-0.51; p = 0.004), while upfront combination therapy showed a trend (HR 0.68, 95% CI 0.23-1.97; p = 0.476). Survival from PAH diagnosis among monotherapy, sequential, and upfront combination groups was 78% versus 95.8% versus 94.1% at 1 year, 40.7% versus 81.5% versus 51.8% at 3 years, and 31.6% versus 56.5% versus 34.5% at 5 years (p = 0.007), respectively. Side effects were not significantly different among groups. CONCLUSION: Combination sequential therapy improved survival in our cohort.

14.
Clin Rheumatol ; 38(4): 1117-1124, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30535994

RESUMO

INTRODUCTION: Our objective was to evaluate the pulmonary hypertension (PH) data for Spanish patients with systemic sclerosis (SSc), define the PH types and determine the associated factors. METHOD: Descriptive study of PH-related data from the multicentre RESCLE registry. Estimated systolic pulmonary artery pressure (esPAP), measured via echocardiogram was considered elevated if ≥ 35 mmHg. Left heart disease (LHD) and interstitial lung disease (ILD) were identified. When performed, data from right heart catheterisation (RHC) were collected. RESULTS: esPAP was elevated in 350 of 808 patients (43.3%). One hundred and forty-four patients (17.8%) were considered to have PH (88 via RHC and the rest due to elevated esPAP along with evidence of significant LHD or ILD): PAH 3.7%, secondary to ILD 8.3%, secondary to LHD 2.8% and unclassified 3%. Prevalence of elevated esPAP was greater in diffuse SSc (dSSc) than in limited scleroderma (lSSc) (50.5 vs. 42.2%, p 0.046). In the group with elevated esPAP, a lower prevalence of anti-centromere antibodies (41.9% vs. 52.3%, p 0.006) and a greater prevalence of anti-topoisomerase-1 antibodies (ATA) (25.1% vs. 18.6%, p 0.04) were observed compared to the group with normal esPAP. Patients with elevated esPAP had a lower rate of digital ulcers (50.6% vs. 60.2%, p 0.007) and esophageal involvement (83.6% vs. 88.7%, p 0.07) and higher rate of renal crisis (4.6% vs. 1.8%, p 0.066). CONCLUSIONS: Prevalence of PAH was lower than expected (3.7%). Probability of having elevated esPAP was higher among patients with dSSc and among those with ATA.


Assuntos
Hipertensão Pulmonar/epidemiologia , Escleroderma Sistêmico/epidemiologia , Adulto , Idoso , Anticorpos Antinucleares , Centrômero/imunologia , Comorbidade , Feminino , Humanos , Hipertensão Pulmonar/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , Escleroderma Sistêmico/imunologia , Espanha/epidemiologia
15.
PLoS One ; 13(12): e0209343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30586461

RESUMO

BACKGROUND: The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT→A) of this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. METHODS: A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. RESULTS: No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75-1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91-1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. CONCLUSION: Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.


Assuntos
Fator Ativador de Células B/genética , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Escleroderma Sistêmico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Casos e Controles , Estudos de Coortes , Europa (Continente) , Feminino , Redes Reguladoras de Genes/genética , Técnicas de Genotipagem , Arterite de Células Gigantes/patologia , Humanos , Mutação INDEL , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/patologia
17.
Endocrinol. diabetes nutr. (Ed. impr.) ; 65(9): 533-539, nov. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-176445

RESUMO

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. Despite the influence of diet on inflammation, dietary habits in patients with systemic lupus erythematosus (SLE) are not well established. The study objective was to assess dietary intake and nutritional status in SLE patients. Patients and methods: A cross-sectional study was conducted in 92 patients with SLE. Nutritional status was determined by body mass index (BMI) and energy/nutrient distribution of diet was analyzed and compared to a control group. Dietary reference intakes (DRIs) issued by the Spanish Societies of Nutrition, Feeding and Dietetics (FESNAD) and the Spanish Society of Community Nutrition (SENC) were used as reference. Results: Body mass index was normal in 53.26% of patients, while 43.48% had excess weight. Energy, protein, and fat intake was significantly lower in the SLE group (p=0.003, p=0.000, and p=0.001 respectively). Protein and fat contribution to total energy was higher, while that of carbohydrate and fiber was lower than recommended. Most patients did not reach the recommended intake for iron (88%), calcium (65.2%), iodine (92.4%), potassium (73.9%), magnesium (65%), folate (72.8%), and vitamins E (87%) and D (82.6%), but exceeded the recommendations for sodium and phosphorus. Conclusions: Spanish SLE patients have an unbalanced diet characterized by low carbohydrate/fiber and high protein/fat intakes. Significant deficiencies were seen in micronutrient intake. Dietary counseling to improve nutrition would therefore be advisable in management of SLE


Introducción: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune, crónica e inflamatoria. La dieta tiene un importante impacto en este tipo de enfermedades. Así, el objetivo de este estudio fue conocer la ingesta dietética y el estado nutricional en pacientes con LES. Pacientes y métodos: Se realizó un estudio transversal que incluyó 92 pacientes diagnosticados de LES. Se determinó el estado nutricional y la ingesta dietética de los pacientes contrastando con un grupo control usando como referencia las recomendaciones de la Federación Española de Sociedades de Nutrición, Alimentación y Dietética (FESNAD) y la Sociedad Española de Nutrición Comunitaria (SENC). Resultados: El índice de masa corporal (IMC) fue normal en el 53,26% de los pacientes, mientras que el 43,48% se ubicó en categorías de exceso. La ingesta calórica, proteica y de grasas fue significativamente menor en el grupo con LES (p=0,003, p=0,000 y p=0,001, respectivamente). La contribución de la ingesta proteica y de grasa a la energía total fue mayor que la recomendada, mientras que la de carbohidratos y fibra, menor. La mayoría de los pacientes no alcanzaron las recomendaciones de ingesta de hierro (88%), calcio (65,2%), iodo (92,4%), potasio (73,9%), magnesio (65%), folato (72,8%), vitaminas E (87%) y D (82,6%) y excedieron las de sodio y fósforo. Conclusiones: La dieta de los pacientes con LES analizados no es equilibrada en el consumo de macronutrientes y fibra, observándose deficiencias en la ingesta de micronutrientes esenciales. Por lo tanto, sería aconsejable el asesoramiento dietético como parte de su tratamiento


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Consumo de Alimentos , Estado Nutricional/fisiologia , Lúpus Eritematoso Sistêmico/dietoterapia , Índice de Massa Corporal , Ingestão de Alimentos , Doenças Autoimunes , Estudos Transversais/métodos
19.
Artigo em Inglês | MEDLINE | ID: mdl-30273710

RESUMO

BACKGROUND: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. OBJECTIVE: We sought to investigate the incidence of gene mosaicism in patients with PIDs. METHODS: The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. RESULTS: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate-to-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. CONCLUSION: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs.

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