RESUMO
Background: Increasing evidence indicating that coronavirus disease 2019 (COVID-19) increased the incidence and related risks of pericarditis and whether COVID-19 vaccine is related to pericarditis has triggered research and discussion. However, mechanisms behind the link between COVID-19 and pericarditis are still unknown. The objective of this study was to further elucidate the molecular mechanisms of COVID-19 with pericarditis at the gene level using bioinformatics analysis. Methods: Genes associated with COVID-19 and pericarditis were collected from databases using limited screening criteria and intersected to identify the common genes of COVID-19 and pericarditis. Subsequently, gene ontology, pathway enrichment, protein-protein interaction, and immune infiltration analyses were conducted. Finally, TF-gene, gene-miRNA, gene-disease, protein-chemical, and protein-drug interaction networks were constructed based on hub gene identification. Results: A total of 313 common genes were selected, and enrichment analyses were performed to determine their biological functions and signaling pathways. Eight hub genes (IL-1ß, CD8A, IL-10, CD4, IL-6, TLR4, CCL2, and PTPRC) were identified using the protein-protein interaction network, and immune infiltration analysis was then carried out to examine the functional relationship between the eight hub genes and immune cells as well as changes in immune cells in disease. Transcription factors, miRNAs, diseases, chemicals, and drugs with high correlation with hub genes were predicted using bioinformatics analysis. Conclusions: This study revealed a common gene interaction network between COVID-19 and pericarditis. The screened functional pathways, hub genes, potential compounds, and drugs provided new insights for further research on COVID-19 associated with pericarditis.
Assuntos
COVID-19 , Pericardite , Humanos , Vacinas contra COVID-19 , COVID-19/genética , Biologia Computacional , Biologia de Sistemas , Pericardite/genéticaRESUMO
We report a case of gonococcal pericarditis, which was unexpected due to its extremely unusual occurrence. A 42-year-old man presented with fever, chest pain, dyspnea, and tachycardia. He was initially stable but rapidly deteriorated, developing pericardial effusion with tamponade requiring a pericardial window. Incompletely decolorized gram stain of the pericardial fluid initially suggested the presence of gram-positive diplococci, which wrongly directed treatment toward possible pneumococcal infection. Because cultures were negative, identification of the causative organism was attempted by molecular and genotyping analysis. These techniques identified Neisseria gonorrhoeae-multi-antigen sequence type 14994 (por 5136/tbpB 33) as the etiology, which has been associated with disseminated gonococcal disease. Real-time polymerase chain reaction showed no evidence of mutations within the N. gonorrhoeae penA gene responsible for causing ceftriaxone resistance. This was crucial in guiding antibiotic treatment, in light of the high prevalence of multi-drug-resistant N. gonorrhoeae. This case highlights the utility of diagnostic molecular techniques in identifying N. gonorrhoeae as the etiology of an exceedingly rare case of pericarditis.
Assuntos
Gonorreia , Derrame Pericárdico , Pericardite , Masculino , Humanos , Adulto , Gonorreia/complicações , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Neisseria gonorrhoeae/genética , Pericardite/diagnóstico , Pericardite/tratamento farmacológico , Pericardite/genética , Derrame Pericárdico/diagnóstico , Antígenos de Bactérias , Testes de Sensibilidade MicrobianaRESUMO
Background Idiopathic recurrent pericarditis (IRP) is an orphan disease that carries significant morbidity, partly driven by corticosteroid dependence. Innate immune modulators, colchicine and anti-interleukin-1 agents, pioneered in monogenic autoinflammatory diseases, have demonstrated remarkable efficacy in trials, suggesting that autoinflammation may contribute to IRP. This study characterizes the phenotype of patients with IRP and monogenic autoinflammatory diseases, and establishes whether autoinflammatory disease genes are associated with IRP. Methods and Results We retrospectively analyzed the medical records of patients with IRP (n=136) and monogenic autoinflammatory diseases (n=1910) attending a national center (London, UK) between 2000 and 2021. We examined 4 genes (MEFV, MVK, NLRP3, TNFRSF1A) by next-generation sequencing in 128 patients with IRP and compared the frequency of rare deleterious variants to controls obtained from the Genome Aggregation Database. In this cohort of patients with IRP, corticosteroid dependence was common (39/136, 28.7%) and was associated with chronic pain (adjusted odds ratio 2.8 [95% CI, 1.3-6.5], P=0.012). IRP frequently manifested with systemic inflammation (raised C-reactive protein [121/136, 89.0%] and extrapericardial effusions [68/136, 50.0%]). Pericarditis was observed in all examined monogenic autoinflammatory diseases (0.4%-3.7% of cases). Rare deleterious MEFV variants were more frequent in IRP than in ancestry-matched controls (allele frequency 9/200 versus 2932/129 200, P=0.040). Conclusions Pericarditis is a feature of interleukin-1 driven monogenic autoinflammatory diseases and IRP is associated with variants in MEFV, a gene involved in interleukin-1ß processing. We also found that corticosteroid dependence in IRP is associated with chronic noninflammatory pain. Together these data implicate autoinflammation in IRP and support reducing reliance on corticosteroids in its management.
Assuntos
Doenças Hereditárias Autoinflamatórias , Pericardite , Corticosteroides , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Doenças Hereditárias Autoinflamatórias/genética , Humanos , Pericardite/diagnóstico , Pericardite/tratamento farmacológico , Pericardite/genética , Pirina/genética , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
This study explores demographic, clinical, and therapeutic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a cohort of 80 patients recruited from 19 Italian referral Centers. Patients' data were collected retrospectively and then analyzed according to age groups (disease onset before or after 16 years) and genotype (high penetrance (HP) and low penetrance (LP) TNFRSF1A gene variants). Pediatric- and adult-onset were reported, respectively, in 44 and 36 patients; HP and LP variants were found, respectively, in 32 and 44 cases. A positive family history for recurrent fever was reported more frequently in the pediatric group than in the adult group (p < 0.05). With reference to clinical features during attacks, pericarditis and myalgia were reported more frequently in the context of adult-onset disease than in the pediatric age (with p < 0.01 and p < 0.05, respectively), while abdominal pain was present in 84% of children and in 25% of adults (p < 0.01). Abdominal pain was significantly associated also to the presence of HP mutations (p < 0.01), while oral aphthosis was more frequently found in the LP variant group (p < 0.05). Systemic amyloidosis occurred in 25% of subjects carrying HP variants. As concerns laboratory features, HP mutations were significantly associated to higher ESR values (p < 0.01) and to the persistence of steadily elevated inflammatory markers during asymptomatic periods (p < 0.05). The presence of mutations involving a cysteine residue, abdominal pain, and lymphadenopathy during flares significantly correlated with the risk of developing amyloidosis and renal impairment. Conversely, the administration of colchicine negatively correlated to the development of pathologic proteinuria (p < 0.05). Both NSAIDs and colchicine were used as monotherapy more frequently in the LP group compared to the HP group (p < 0.01). Biologic agents were prescribed to 49 (61%) patients; R92Q subjects were more frequently on NSAIDs monotherapy than other patients (p < 0.01); nevertheless, they required biologic therapy in 53.1% of cases. At disease onset, the latest classification criteria for TRAPS were fulfilled by 64/80 (80%) patients (clinical plus genetic items) and 46/80 (57.5%) patients (clinical items only). No statistically significant differences were found in the sensitivity of the classification criteria according to age at onset and according to genotype (p < 0.05). This study describes one of the widest cohorts of TRAPS patients in the literature, suggesting that the clinical expression of this syndrome is more influenced by the penetrance of the mutation rather than by the age at onset itself. Given the high phenotypic heterogeneity of the disease, a definite diagnosis should rely on both accurate working clinical assessment and complementary genotype.
Assuntos
Febre Familiar do Mediterrâneo/sangue , Febre Familiar do Mediterrâneo/patologia , Fator de Necrose Tumoral alfa/sangue , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , Mutação/genética , Mialgia/sangue , Pericardite/genética , Prognóstico , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Estudos Retrospectivos , Adulto JovemRESUMO
We find that cardiac group 2 innate lymphoid cells (ILC2s) are essential for the development of IL-33-induced eosinophilic pericarditis. We show a pathogenic role for ILC2s in cardiac inflammation, in which ILC2s activated by IL-33 drive the development of eosinophilic pericarditis in collaboration with cardiac fibroblasts. ILCs, not T and B cells, are required for the development of pericarditis. ILC2s transferred to the heart of Rag2-/-Il2rg-/- mice restore their susceptibility to eosinophil infiltration. Moreover, ILC2s direct cardiac fibroblasts to produce eotaxin-1. We also find that eosinophils reside in the mediastinal cavity and that eosinophils transferred to the mediastinal cavity of eosinophil-deficient ΔdblGATA1 mice following IL-33 treatment migrate to the heart. Thus, the serous cavities may serve as a reservoir of cardiac-infiltrating eosinophils. In humans, patients with pericarditis show higher amounts of ILCs in pericardial fluid than do healthy controls and patients with other cardiac diseases. We demonstrate that ILCs play a critical role in pericarditis.
Assuntos
Imunidade Inata , Linfócitos/imunologia , Pericardite/imunologia , Animais , Movimento Celular/efeitos dos fármacos , Quimiocina CCL11/genética , Quimiocina CCL11/metabolismo , Suscetibilidade a Doenças , Eosinófilos/efeitos dos fármacos , Eosinófilos/patologia , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/fisiopatologia , Testes de Função Cardíaca/efeitos dos fármacos , Humanos , Imunidade Inata/efeitos dos fármacos , Proteína 1 Semelhante a Receptor de Interleucina-1/deficiência , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/farmacologia , Interleucina-5/metabolismo , Linfócitos/efeitos dos fármacos , Masculino , Mediastino/patologia , Camundongos Endogâmicos BALB C , Pericardite/genética , Pericardite/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
X-linked agammaglobulinemia (XLA) is a rare form of inherited immunodeficiency due to an impairment in B-lymphocyte differentiation and maturation. In the majority of cases XLA is diagnosed in childhood, particularly among males affected by recurrent infections and with a family history of immunodeficiency. Infections of respiratory tract, gastrointestinal apparatus, eyes, nose and ears are frequent in XLA patients; on the contrary, infections of myocardium, cardiac valves and pericardium are rarely described in XLA. A 34-year-old man with unknown XLA was hospitalized because of syncope, due to pericardial tamponade, caused by acute primary purulent pericarditis. Immediate pericardiocentesis was effective in improving hemodynamics, and empiric antibiotic therapy was successful in controlling the infection. Purulent pericarditis is a rare disease with high mortality rate: it is usually caused by hematogenous bacterial propagation, direct infection of pericardial space by chest wounds or thoracic surgery, or extension of infection from adjacent tissues. However, this patient had no recent local or systemic infections. Because of unusual clinical picture during hospitalization he underwent further clinical and laboratory evaluations, that showed low immunoglobulin levels. After exclusion of acquired immunodeficiency, genetic tests were performed: they detected deletion of exons 8-9-10 of Bruton Tyrosine Kinase gene on X chromosome, leading to the diagnosis of XLA. Acute purulent primary pericarditis may also occur in adult XLA patients as first clinical manifestation. According to this case report, a primary immunodeficiency syndrome should be considered in patients with atypical cardiac infections and no predisposing conditions, regardless of age.
Assuntos
Tirosina Quinase da Agamaglobulinemia/genética , Agamaglobulinemia/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Mutação/genética , Pericardite/diagnóstico , Doença Aguda , Adulto , Agamaglobulinemia/genética , Agamaglobulinemia/terapia , Antibacterianos/uso terapêutico , Tamponamento Cardíaco , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Masculino , Pericardiocentese , Pericardite/genética , Pericardite/terapia , SíncopeRESUMO
The aim of this study was to evaluate the biomarkers of cardiac damage such as heart-type fatty acid-binding protein (H-FABP), pentraxin-3 (PTX-3), and thrombomodulin (TM) for the detection and prognosis of bovine traumatic pericarditis (TP). Spontaneous TP was diagnosed on the basis of history, clinical signs, complete blood count, glutaraldehyde test, ultrasonography, and pericardiocentesis findings. H-FABP, PTX-3 and TM levels in serum were compared between 25 Holstein cows diagnosed with spontaneous TP and 10 healthy control cows using bovine-specific ELISA kits. Serum H-FABP in cattle with TP was significantly (P < 0.05) higher than in the control group and positively correlated with cardiac troponin-I (cTnI), creatine kinase myocardial band (CK-MB), PTX-3 and TM (r = 0.683, 0.342, 0.448 and 0.424, respectively; P < 0.05). The serum levels of PTX-3 (P < 0.05) and TM (P < 0.05) in cattle with TP were significantly higher than in the control group. Cardiac damage biomarkers H-FABP, PTX-3 and TM may be useful in the diagnosis of bovine TP.
Assuntos
Proteína C-Reativa/metabolismo , Doenças dos Bovinos/genética , Proteína 3 Ligante de Ácido Graxo/sangue , Pericardite/veterinária , Componente Amiloide P Sérico/metabolismo , Trombomodulina/sangue , Animais , Biomarcadores/metabolismo , Bovinos , Doenças dos Bovinos/metabolismo , Feminino , Pericardite/genética , Pericardite/metabolismoRESUMO
BACKGROUND: Recurrent pericarditis is a state of repetitive inflammation of the pericardium with intervals of remission. The etiology of recurrent pericarditis is still largely unknown, yet most causes are presumed to be immune mediated. Genetic factors, including human leukocyte antigen (HLA) haplotypes, can be involved in dysregulation of the immune system and as a predisposition to several autoimmune conditions, including recurrent pericarditis. Several diseases are frequently associated with such manifestations. They include systemic lupus erythematosus, familial Mediterranean fever, and tumor necrosis factor receptor-associated periodic syndrome. However, idiopathic recurrent pericarditis remains the most frequently observed clinical condition and the conundrum of this disease still needs to be solved.
Assuntos
Doenças Autoimunes/genética , Predisposição Genética para Doença , Pericardite/fisiopatologia , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/imunologia , Antígenos HLA/genética , Haplótipos , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Pericardite/genética , Pericardite/imunologia , RecidivaRESUMO
Recently, a study has shown that a polymorphism in the region of MIR1279 modulates the expression of the TRAF3IP2 gene. Since polymorphisms in the TRAF3IP2 gene have been described in association with systemic lupus erithematosus (SLE) susceptibility and with the development of pericarditis, our aim is to verify if the MIR1279 gene variability could also be involved. The rs1463335 SNP, located upstream MIR1279 gene, was analyzed by allelic discrimination assay in 315 Italian SLE patients and 201 healthy controls. Moreover, the MIR1279 gene was full sequenced in 50 patients. A case/control association study and a genotype/phenotype correlation analysis were performed. We also constructed a pericarditis genetic risk profile for patients with SLE. The full sequencing of the MIR1279 gene in patients with SLE did not reveal any novel or known variation. The variant allele of the rs1463335 SNP was significantly associated with susceptibility to pericarditis ( P = 0.017 and OR = 1.67). A risk profile model for pericarditis considering the risk alleles of MIR1279 and three other genes (STAT4, PTPN2 and TRAF3IP2) showed that patients with 4 or 5 risk alleles have a higher risk of developing pericarditis ( OR = 4.09 with P = 0.001 and OR = 6.04 with P = 0.04 respectively). In conclusion, we describe for the first time the contribution of a MIR1279 SNP in pericarditis development in patients with SLE and a genetic risk profile model that could be useful to identify patients more susceptible to developing pericarditis in SLE. This approach could help to improve the prediction and the management of this complication.
Assuntos
Lúpus Eritematoso Sistêmico/complicações , MicroRNAs/genética , Pericardite/etiologia , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Itália , Lúpus Eritematoso Sistêmico/genética , Masculino , Pessoa de Meia-Idade , Pericardite/genética , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 2/genética , Fator de Transcrição STAT4/genética , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/genéticaRESUMO
OBJECTIVE: Complete deficiency of Complement C4 component is a strong genetic risk factor for SLE. C4 is encoded by two different genes, C4A and C4B, which show considerable gene copy number (GCN) variation. This study investigates the association of total C4, C4A and C4B GCN with JSLE. METHODS: Ninety JSLE patients, 170 adult-onset SLE (aSLE) patients and 200 healthy individuals were evaluated for C4A and C4B GCN by quantitative real-time PCR. RESULTS: JSLE patients had lower GCN for C4A (mean = 1.7; 95% CI: 1.5, 1.9) and C4B (mean = 1.5; 95% CI: 1.3, 1.6) compared with healthy individuals (mean C4A = 2.3; 95% CI: 2.2, 2.5, P < 0.001; C4B = 2.0; 95% CI: 1.8, 2.1; P < 0.001) or with aSLE patients (mean C4A = 1.9; 95% CI: 1.8, 2.1, P = 0.006; mean C4B = 1.8; 95% CI: 1.7, 1.9, P < 0.001). Low total C4 GCN (<4 copies) was more frequent in JSLE than in healthy individuals (59% vs 28%; P < 0.001). The same was observed for low C4A (⩽1 copy) (52% vs 18%; P < 0.001) and for low C4B (60% vs 31%; P < 0.001). JSLE had a stronger association with low total C4 (OR = 3.68, 95% CI: 2.19, 6.20), C4A (OR = 4.98, 95% CI: 2.88, 8.62) and C4B (OR = 3.26; 95% CI: 1.95, 5.47) than aSLE (C4 OR = 2.03; 95% CI: 1.32, 3.13; C4A OR = 2.36; 95% CI: 1.46, 3.81; C4B OR = 1.13; 95% CI: 0.73, 1.74). In addition, pericarditis in JSLE patients was associated with low C4 (OR = 4.13; 95% CI: 1.02, 16.68; P = 0.047) and low C4A (OR = 5.54; 95% CI: 1.37, 22.32; P = 0.016). CONCLUSION: Low total C4, C4A and C4B GCN were associated with a stronger risk for developing JSLE than aSLE. Additionally, low total C4 and C4A GCN are risk factors for pericarditis in JSLE.
Assuntos
Complemento C4/genética , Dosagem de Genes , Lúpus Eritematoso Sistêmico/genética , Adolescente , Adulto , Fatores Etários , Idade de Início , Idoso , Estudos de Casos e Controles , Complemento C4/deficiência , Complemento C4a/genética , Complemento C4b/genética , Feminino , Predisposição Genética para Doença , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Pericardite/etiologia , Pericardite/genética , Pericardite/imunologia , Fatores de Risco , Adulto JovemRESUMO
Congenital plasminogen deficiency is a rare autosomal recessive disorder, characterized by chronic mucosal membranous lesions. Although the most common clinical manifestation is eye involvement as ligneous conjunctivitis, extra-ocular lesions affecting other mucosal surfaces indicates a systemic disease. In this report we describe two cases with atypical extra-ocular involvement that includes pericarditis and recurrent hematocolpos, and one with paradoxical correlation between ocular lesions and plasminogen levels. In ligneous conjunctivitis, although different treatment strategies have been tried with mild success, the only effective therapy is topical or systemic plasminogen concentrates that are not commercially available. Unfortunately there is not either effective management for cases with multisystemic disease. Hence, treatment for plasminogen deficiency is still a challenge and the variability of the clinical spectrum in this pathology makes necessary a multidisciplinary approach.
Assuntos
Transtornos Herdados da Coagulação Sanguínea , Plasminogênio/administração & dosagem , Plasminogênio/deficiência , Transtornos Herdados da Coagulação Sanguínea/sangue , Transtornos Herdados da Coagulação Sanguínea/tratamento farmacológico , Transtornos Herdados da Coagulação Sanguínea/genética , Transtornos Herdados da Coagulação Sanguínea/patologia , Pré-Escolar , Conjuntivite/sangue , Conjuntivite/tratamento farmacológico , Conjuntivite/genética , Conjuntivite/patologia , Feminino , Hematocolpia/sangue , Hematocolpia/tratamento farmacológico , Hematocolpia/genética , Hematocolpia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pericardite/sangue , Pericardite/tratamento farmacológico , Pericardite/genética , Pericardite/patologiaRESUMO
Pericardial fluid (PF) is often considered to be reflection of the serum by which information regarding the physiological status of the heart can be obtained. Some local and systemic disorders may perturb the balance between synthesis and discharge of PF and may cause its aberrant accumulation in the pericardial cavity as pericardial effusion (PE). PE may then lead to an increased intrapericardial pressure from which the heart function is undesirably affected. For some cases, the causes for the perturbance of fluid balance are well understood, but in some other cases, they are not apparent. It may, thus, be helpful to understand the molecular mechanisms behind this troublesome condition to elucidate a clinical approach for therapeutic uses. In this study, protein profiles of PEs from idiopathic pericarditis patients were analyzed. Control samples from patients undergoing elective cardiac surgery (ECS) were included for comparison. In addition to high abundant serum-originated proteins that may not hold significance for understanding the molecular mechanisms behind this disease, omentin-1 was identified and its level was higher for more than two-fold in PE of IP patients. Increased levels of omentin-1 in PE may open a way for understanding the molecular mechanisms behind idiopathic pericarditis (IP).
Assuntos
Proteínas Sanguíneas/isolamento & purificação , Coração/fisiopatologia , Derrame Pericárdico/genética , Pericardite/genética , Adulto , Idoso , Proteínas Sanguíneas/biossíntese , Proteínas Sanguíneas/genética , Eletroforese em Gel Bidimensional , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/patologia , Pericardite/patologiaRESUMO
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease. Although genetic factors confer susceptibility to the disease, only 15 % of the genetic contribution has been identified. TRAF3IP2 gene, associated with susceptibility to psoriatic arthritis and psoriasis, encodes for Act1, a negative regulator of adaptive immunity and a positive signaling adaptor in IL-17-mediated immune responses. The aim of this study was to assess the role of TRAF3IP2 gene variability in SLE susceptibility and disease phenotype in an Italian population. Two hundred thirty-nine consecutive SLE patients were enrolled. Study protocol included complete physical examination; the clinical and laboratory data were collected. Two hundred seventy-eight age- and ethnicity-matched healthy subjects served as controls. TRAF3IP2 polymorphisms (rs33980500, rs13190932, and rs13193677) were analyzed in both cases and controls. Genotype analysis was performed by allelic discrimination assays. A case-control association study and a genotype-phenotype correlation were performed. The rs33980500 and rs13193677 resulted significantly associated with SLE susceptibility (P = 0.021, odds ratio (OR) = 1.71, and P = 0.046, OR = 1.73, respectively). All three TRAF3IP2 single nucleotide polymorphisms resulted associated with the development of pericarditis; in particular, rs33980500 showed the strongest association (P = 0.002, OR 2.59). This association was further highlighted by binary logistic regression analysis. In conclusion, our data show for the first time the contribution of TRAF3IP2 genetic variability in SLE susceptibility, providing further suggestions that common variation in genes that function in the adaptive and innate arms of the immune system are important in establishing SLE risk. Our study also shows that this gene may affect disease phenotype and, particularly, the occurrence of pericarditis.
Assuntos
Predisposição Genética para Doença/genética , Lúpus Eritematoso Sistêmico/genética , Pericardite/genética , Polimorfismo de Nucleotídeo Único , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/genética , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença/etnologia , Genótipo , Haplótipos , Humanos , Itália , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Pericardite/etnologia , Pericardite/patologia , Fenótipo , Fatores de Risco , População Branca/genética , Adulto JovemRESUMO
Although idiopathic recurrent acute pericarditis (IRAP) is generally presumed to derive from an autoimmune process, increasing interest is currently being devoted to autoinflammatory diseases, a group of disorders of the innate immune system caused by mutations of genes involved in the regulation or activation of the inflammatory response, without any apparent involvement of autoimmunity. The tumour necrosis factor receptor-1-associated periodic syndrome is the most common autosomal dominant autoinflammatory disorder and is caused by mutations in the TNFRSF1A gene encoding the 55-kD receptor for tumour necrosis factor-α. IRAP patients carrying TNFRSF1A gene mutations have been recently described. We report herein the first IRAP patients carrying the rare R104Q and D12Eâ TNFRSF1A gene mutations, thus expanding the spectrum of tumour necrosis factor receptor-1-associated periodic syndrome mutations in IRAP patients.
Assuntos
Mutação/genética , Pericardite/diagnóstico , Pericardite/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Doença Aguda , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
Myhre syndrome is a rare disorder characterized by pre- and postnatal short stature, brachydactyly, facial dysmorphism (short palpebral fissures, maxillary hypoplasia, prognathism and short philtrum), thick skin, muscular-appearing body build, decreased joint mobility, mixed hearing loss, and cleft lip and palate. Other clinical features include skeletal dysplasia, developmental delay with intellectual disability and/or behavioral disturbance, cardiac defects, cryptorchidism, and bone anomalies. The disease is caused by recently identified SMAD4 mutations. Here we describe a 7-year-old boy with a molecularly proven Myhre syndrome who presented life-threatening recurrent pericarditis and systemic inflammatory symptoms that required treatment with steroid and recombinant interleukin-1 receptor antagonist.
Assuntos
Criptorquidismo/complicações , Transtornos do Crescimento/complicações , Deformidades Congênitas da Mão/complicações , Hipertrofia/complicações , Deficiência Intelectual/complicações , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Artropatias/complicações , Pericardite/complicações , Prednisona/uso terapêutico , Proteína Smad4/genética , Criança , Criptorquidismo/tratamento farmacológico , Criptorquidismo/genética , Fácies , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/genética , Deformidades Congênitas da Mão/tratamento farmacológico , Deformidades Congênitas da Mão/genética , Humanos , Hipertrofia/tratamento farmacológico , Hipertrofia/genética , Deficiência Intelectual/tratamento farmacológico , Deficiência Intelectual/genética , Artropatias/tratamento farmacológico , Artropatias/genética , Masculino , Pericardite/tratamento farmacológico , Pericardite/genética , Recidiva , Resultado do TratamentoRESUMO
Idiopathic recurrent acute pericarditis (IRAP) represents the most troublesome complication of acute pericarditis and occurs in up to 20-50% of patients. It is generally idiopathic or postcardiac injury. IRAP is a disease of suspected immune-mediated pathogenesis. On the other hand, it has been suggested that some of these patients might have an atypical or subclinical form of an autoinflammatory disease, e.g. genetic disorders characterized by primary dysfunction of the innate immune system and caused by mutations of genes involved in the inflammatory response. We found that IRAP patients were negative for mutations associated with familial Mediterranean fever, but 6% (8/131 patients) carry a mutation in the TNFRSF1A gene, encoding the receptor for tumor necrosis factor-alfa. C-reactive protein (CRP) may be useful to follow the disease activity and guide the appropriate length of therapy, with continuation of the attack doses of the drugs until CRP normalization, at which time tapering may be considered. IRAP often needs a multidrug therapy: NSAIDs or aspirin at high dosages every 6-8h, corticosteroids only rarely, at low dosages and with a very gradual tapering (months) and colchicine at low dosages if tolerated. Anakinra could be a solution for patients who do not tolerate other therapies.
Assuntos
Doenças Autoimunes/imunologia , Inflamação/imunologia , Pericardite/tratamento farmacológico , Pericardite/imunologia , Doenças Autoimunes/genética , Humanos , Inflamação/genética , Pericardite/genética , Pericardite/patologia , RecidivaRESUMO
BACKGROUND: The potential clinical expression of tumor necrosis factor receptor-associated periodic syndrome (TRAPS), in the form of idiopathic recurrent acute pericarditis (IRAP) has not been explored in the medical literature. The aim of this study was to evaluate the incidence of TRAPS mutations in patients with recurrent pericarditis and identify possible clues to TRAPS diagnosis. METHODS: Therefore, 131 consecutive Caucasian IRAP patients were investigated for mutations of the TRAPS gene and prospectively evaluated. RESULTS: Out of 131 patients, 8 (6.1%) carried a mutation in the TNFRSF1A gene. Compared with those without genetic mutations, patients with TRAPS mutations had more frequently a positive family history for pericarditis and periodic fever syndromes (p < 0.001), a higher mean number of recurrences after the first year (p < 0.001), on colchicine treatment (p < 0.001), and a higher need of immunosuppressive therapies (p < 0.001). CONCLUSION: TRAPS is a cause of recurrent pericarditis in 6% of unselected cases with recurrent pericarditis. A positive family history for pericarditis or periodic fever syndromes, a poor response to colchicine, recurrences after the first year from the index attack or on colchicine treatment, as well as the need of immunosuppressive agents are clues of the possible presence of TNFRSF1A gene mutations in patients with recurrent pericarditis.
Assuntos
Doenças Hereditárias Autoinflamatórias/diagnóstico , Mutação , Pericardite/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Doença Aguda , Corticosteroides/uso terapêutico , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Colchicina/uso terapêutico , Análise Mutacional de DNA , Feminino , Febre , Frequência do Gene , Predisposição Genética para Doença , Doenças Hereditárias Autoinflamatórias/complicações , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/imunologia , Humanos , Imunossupressores/uso terapêutico , Itália , Masculino , Pessoa de Meia-Idade , Razão de Chances , Linhagem , Pericardite/tratamento farmacológico , Pericardite/imunologia , Fenótipo , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de RiscoRESUMO
Biglycan is a proteoglycan ubiquitously present in extracellular matrix of a variety of organs, including heart, and it was reported to be overexpressed in myocardial infarction. Myocardial infarction may be complicated by perimyocarditis through unknown mechanisms. Our aim was to investigate the capacity of TLR2/TLR4 ligand biglycan to enhance the presentation of specific Ags released upon cardiomyocyte necrosis. In vitro, OVA-pulsed bone marrow-derived dendritic cells from wild-type (WT; C57BL/6) and TLR2-, TLR4-, MyD88-, or TRIF-deficient mice were cotreated with LPS, biglycan, or vehicle and incubated with OVA-recognizing MHC I- or MHC II-restricted T cells. Biglycan enhanced OVA-specific cross-priming by >80% to MHC I-restricted T cells in both TLR2- and TLR4-pathway-dependent manners. Accordingly, biglycan-induced cross-priming by both MyD88- and TRIF-deficient dendritic cells (DCs) was strongly diminished. OVA-specific activation of MHC II-restricted T cells was predominantly TLR4 dependent. Our first in vivo correlate was a model of experimental autoimmune perimyocarditis triggered by injection of cardiac Ag-pulsed DCs (BALB/c). Biglycan-treated DCs triggered perimyocarditis to a comparable extent and intensity as LPS-treated DCs (mean scores 1.3 ± 0.3 and 1.5 ± 0.4, respectively). Substitution with TLR4-deficient DCs abolished this effect. In a second in vivo approach, WT and biglycan-deficient mice were followed 2 wk after induction of myocardial infarction. WT mice demonstrated significantly greater myocardial T lymphocyte infiltration in comparison with biglycan-deficient animals. We concluded that the TLR2/4 ligand biglycan, a component of the myocardial matrix, may enhance Ag-specific T cell priming, potentially via MyD88 and TRIF, and stimulate autoimmune perimyocarditis.