RESUMO
Calprotectin (CLP) is a calcium-binding protein produced by neutrophils and monocytes in the course of inflammation. Today, the role of faecal CLP in chronic IBD is well known, but in recent years attention has shifted towards circulating CLP. In fact, this molecule can be measured in different biological fluids: blood, saliva and urine, using different analytic methods that are described in this review. Furthermore, different data confirm the relevant role of serum CLP in autoimmune diseases. In this review we will highlight the correlation between high levels of circulating CLP and specific autoantibodies of major autoimmune pathologies paving the way to the employment of CLP measurement as useful biomarker for monitoring outcome in different pathologies.
Assuntos
Doenças Inflamatórias Intestinais , Complexo Antígeno L1 Leucocitário , Humanos , Complexo Antígeno L1 Leucocitário/análise , Inflamação , Biomarcadores/metabolismo , Fezes/química , Neutrófilos/metabolismoRESUMO
Skin is the forestage for a series of many-sided functions of tumor necrosis factor-alpha (TNF-α), a proinflammatory cytokine with staggering versatility and sizable implications for tissue homeostasis, immune responses, angiogenesis, apoptosis, local and systemic inflammation. An aberrant TNF-α-mediated crosstalk has been linked to the pathogenesis of acute and chronic skin inflammatory diseases, and indeed, TNF-α dysregulation can contribute to the development and progression of psoriasis, vitiligo, local damage following exposition to ultraviolet light radiations, cutaneous lupus erythematosus, and acne vulgaris. Therapies that target TNF-α are conspicuously used in the treatment of different skin disorders, aiming to modulate the in vivo immune functions triggered by many cutaneous cells, including keratinocytes, mast cells, or Langerhans cells, and reduce inflammation taking place within the skin. Herein, we focus on the key relationships between TNF-α and distinct skin non-neoplastic inflammatory or physiologic conditions, showing that a natural induction of TNF-α may have a protective significance but that TNF-α overproduction may be harmful or even lethal. Many questions remain unraveled in the therapeutic practice, and caution should be exercised due to eventual backlashes exerted by TNF-α in maintaining skin health or in provoking skin disease.
Assuntos
Pele , Fator de Necrose Tumoral alfa , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Animais , Dermatopatias/metabolismo , Dermatopatias/etiologia , Dermatopatias/patologia , Inflamação/metabolismo , Inflamação/patologiaRESUMO
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder affecting the peripheral nervous system. Despite the established diagnostic criteria, monitoring disease activity and treatment remains challenging. To address this limitation, we investigated serum neurofilament light chain (sNfL) and serum free light chains (sFLCs) as potential biomarkers. A total of 32 CIDP patients undergoing immunoglobulin therapy and 32 healthy controls enrolled in the present study, and agreed to have their blood plasma sNfL and sFLCs analyzed, while CIDP severity was assessed through the modified Rankin Scale (mRS) and the Overall Neuropathy Limitations Scale (ONLS). In line with the immunoglobulin treatment aimed at limiting neuronal damage administered to the majority of patients, sNfL levels did not exhibit significant differences between the two groups. However, CIDP patients showed significantly elevated sFLC and sFLC ratios, while the marker levels did not correlate with the clinical scores. The study confirms the potential of sFLCs as a sensitive biomarker of inflammatory processes in CIDP. Additionally, the present study results regarding neurofilaments strengthen the role of sNfL in monitoring CIDP treatments, confirming the effectiveness of immunoglobulin therapy. Overall, our results demonstrate how combining these markers can lead to better patient characterization for improved treatment.
Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Filamentos Intermediários , Cadeias Leves de Imunoglobulina , BiomarcadoresRESUMO
Inflammation and inflammasomes have been proposed as important regulators of the host-microorganism interaction, playing a key role in morbidity and mortality due to the coronavirus disease 2019 (COVID-19) in subjects with chronic conditions and compromised immune system. The inflammasome consists of a multiprotein complex that finely regulates the activation of caspase-1 and the production and secretion of potent pro-inflammatory cytokines such as IL-1ß and IL-18. The pyrin containing NOD (nucleotide-binding oligomerization domain) like receptor (NLRP) is a family of intracellular receptors, sensing patterns associated to pathogens or danger signals and NLRP3 inflammasome is the most deeply analyzed for its involvement in the innate and adaptive immune system as well as its contribution to several autoinflammatory and autoimmune diseases. It is highly expressed in leukocytes and up-regulated in sentinel cells upon inflammatory stimuli. NLRP3 expression has also been reported in B and T lymphocytes, in epithelial cells of oral and genital mucosa, in specific parenchymal cells as cardiomyocytes, and keratinocytes, and chondrocytes. It is well known that a dysregulated activation of the inflammasome is involved in the pathogenesis of different disorders that share the common red line of inflammation in their pathogenetic fingerprint. Here, we review the potential roles of the NLRP3 inflammasome in cardiovascular events, liver damage, pulmonary diseases, and in that wide range of systemic inflammatory syndromes named as a cytokine storm.
Assuntos
Síndrome da Liberação de Citocina , Cardiopatias , Inflamassomos , Hepatopatias , Pneumopatias , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Proteínas de Transporte/metabolismo , Síndrome da Liberação de Citocina/imunologia , Inflamassomos/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Pneumopatias/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Cardiopatias/imunologia , Hepatopatias/imunologiaRESUMO
Prolonged B cells stimulation due to the Hepatitis C virus (HCV) can result in autoimmunity, stigmatized by rising levels of cryoglobulins (CGs), the rheumatoid factor (RF), and free light chains (FLC) of immunoglobulins (Ig) associated with a range of symptoms, from their absence to severe cryoglobulinemic vasculitis and lymphoma. Here, we aimed to identify an immunological signature for the earliest stages of vasculitis when cryoprecipitate is still not detectable. We firstly analyzed the IgG subclasses, FLC, and RF in 120 HCV-RNA-positive patients divided into four groups according to the type of cryoprecipitate and symptoms: 30 asymptomatic without cryoprecipitate (No Cryo), 30 with vasculitis symptoms but without CGs that we supposed were circulating but still not detectable (Circulating), 30 type II and 30 type III mixed cryoglobulinemia (Cryo II and Cryo III, respectively). Our results revealed that patients with supposed circulating CGs displayed a pattern of serological parameters that closely resembled Cryo II and Cryo III, with a stronger similarity to Cryo II. Accordingly, we analyzed the groups of Circulating and Cryo II for their immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements, finding a similar mixed distribution of monoclonal, oligoclonal, and polyclonal responses compared to a control group of ten HCV-RNA-negative patients recovered from infection, who displayed a 100% polyclonal response. Our results strengthened the hypothesis that circulating CGs are the origin of symptoms in HCV-RNA-positive patients without cryoprecipitate and demonstrated that an analysis of clonal IGH and TCR rearrangements is the best option for the early diagnosis of extrahepatic complications.
Assuntos
Crioglobulinemia , Crioglobulinas , Hepatite C Crônica , Vasculite , Vasculite/diagnóstico , Vasculite/imunologia , Vasculite/virologia , Humanos , Masculino , Feminino , Crioglobulinemia/diagnóstico , Crioglobulinemia/virologia , Crioglobulinas/análise , Fator Reumatoide/sangue , Imunoglobulinas/sangue , Hepatite C Crônica/sangue , Hepatite C Crônica/complicaçõesRESUMO
Immunoglobulins free light chains (FLCs) are assayable in several biological fluids. Currently, there are no reports on FLCs in seminal plasma. The aims of our study were to investigate the presence and detectability of FLCs in seminal plasma and to evaluate the usefulness of this assay in the diagnostic approach to infertile patients. Weâ¯enrolledâ¯61 patients aged 18-50 years. Semen analysis was performed. They were divided into four groups: controls-normozoospermic, 10 patients, mean ± SEM age 35 ± 1.5 years; varicoceles (VAR), 18 patients aged 24.3 ± 0.96 years; inflammatory (INF) seminal fluids, 24 patients, aged 38.8 ± 2.2 years; and varicoceles and inflammatory (VAR/INF) seminal fluids, 9 patients, aged 29.5 ± 0.71 years. A trend towards higher λ FLCs levels was evidenced in the INF and VAR/INF groups. κ FLCs were higher in normozoospermic patients with lower levels in VAR, both isolated and associated with inflammatory parameters. This differential pattern of the two types of FLCs reached statistical significance when comparing κ/λ ratio, with significant lower levels in VAR vs controls. This is the first report of FLCs assay in seminal plasma. We can hypothesize that λ FLCs are increased in inflammatory processes, whether κ FLCs seem to be influenced by other molecular mechanisms related to varicocele.
Assuntos
Cadeias Leves de Imunoglobulina , Cadeias lambda de Imunoglobulina , Adolescente , Adulto , Secreções Corporais , Humanos , Cadeias kappa de Imunoglobulina , Masculino , Pessoa de Meia-Idade , Dados Preliminares , Adulto JovemRESUMO
Circulating free light chains (FLCs), considered biomarkers of B cell activity, are frequently elevated in patients affected by systemic inflammatory autoimmune diseases. As the systemic sclerosis (SSc) clinical course can be variable, this study is aimed at evaluating FLCs levels in affected individuals as biomarkers of disease activity. We assessed FLC levels in serum and urine of 72 SSc patients and 30 healthy controls (HC). Results were analyzed in comparison with overall clinical and laboratory findings, disease activity index (DAI) and disease severity scale (DSS). SSc patients displayed increased levels of κ and λ FLC in serum significantly higher than HC (p = 0.0001) alongside the mean values of free κ/λ ratio and κ + λ sum (p = 0.0001). SSc patients showed increased free κ in urine with a κ/λ higher than HC (p = 0.0001). SSc patients with increased κ + λ in serum showed that erythro-sedimentation rate (p = 0.034), C-reactive protein (p = 0.003), DAI (p = 0.024) and DSS (p = 0.015) were higher if compared to SSc patients with normal levels of FLC. A positive linear correlation was found between serum levels of free κ and DAI (r = 0.29, p = 0.014). In addition, SSc patients with increased free κ in urine had higher DAI (p = 0.048) than SSc patients with normal κ levels. Our results strengthen the role of serum FLC as useful biomarker in clinical practice to early diagnosis and monitor disease activity, showing for the first time that also urine FLC levels correlated with disease activity in SSc patients.
Assuntos
Biomarcadores/sangue , Biomarcadores/urina , Cadeias Leves de Imunoglobulina/sangue , Cadeias Leves de Imunoglobulina/urina , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/urina , Idoso , Linfócitos B/imunologia , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Feminino , Humanos , Cadeias kappa de Imunoglobulina/sangue , Cadeias kappa de Imunoglobulina/urina , Cadeias lambda de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/urina , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The biomarkers of an immunological dysregulation due to a chronic HBV infection are indeed understudied. If untreated, this condition may evolve into liver impairment co-occurring with extrahepatic involvements. Here, we aim to identify a new panel of biomarkers [including immunoglobulin G (IgG) subclasses, RF, and Free Light Chains (FLCs)] that may be useful and reliable for clinical evaluation of HBV-related cryoglobulinemia. METHODS: We retrospectively analysed clinical data from 44 HBV-positive patients. The patients were stratified (according to the presence/absence of mixed cryoglobulinemia) into two groups: 22 with cryoglobulins (CGs) and 22 without CGs. Samples from 20 healthy blood donors (HDs) were used as negative controls. Serum samples were tested for IgG subclasses, RF (-IgM, -IgG, and -IgA type), and FLCs. RESULTS: We detected a strikingly different distribution of serum IgG subclasses between HDs and HBV-positive patients, together with different RF isotypes; in addition, FLCs were significantly increased in HBV-positive patients compared with HDs, while no significant difference was shown between HBV-positive patients with/without mixed cryoglobulinemia. CONCLUSION: The immune-inflammatory response triggered by HBV may be monitored by a peculiar profile of biomarkers. Our results open a new perspective in the precision medicine era; in these challenging times, they could also be employed to monitor the clinical course of those COVID-19 patients who are at high risk of HBV reactivation due to liver impairment and/or immunosuppressive therapies.
Assuntos
Biomarcadores/sangue , COVID-19/imunologia , Crioglobulinemia/imunologia , Crioglobulinemia/virologia , Vírus da Hepatite B/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2RESUMO
In the natural history of SARS-CoV-2 infection, liver injury is frequent but quite mild and it is defined as any liver damage occurring during disease progression and treatment of infection in patients with or without pre-existing liver diseases. The underlying mechanisms for hepatic injury in patients with COVID-19 are still unclear but the liver damage in SARS-CoV-2 infection seems to be directly caused by virus-induced cytopathic effects. In this review, we will summarize all data of updated literature, regarding the relationship between SARS-CoV-2 infection, acute response and liver involvement. An overview will be given on liver injury, liver transplant and the possible consequences of COVID-19 in patients with pre-existing liver diseases.
Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Hepatopatias/imunologia , Fígado/imunologia , SARS-CoV-2/imunologia , Antivirais/imunologia , Antivirais/uso terapêutico , COVID-19/epidemiologia , COVID-19/virologia , Síndrome da Liberação de Citocina/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Hepatócitos/imunologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/patologia , Fígado/fisiopatologia , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Pandemias/prevenção & controle , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologiaRESUMO
Cryoglobulinaemia consists of circulating monoclonal and/or polyclonal immunoglobulins with rheumatoid factor (RF) activity that precipitate at temperatures <37°C. Cryoglobulinaemic syndrome, characterised by clinical signs of systemic vasculitis, is associated with chronic infection of hepatitis C virus (HCV) and might evolve in B-cell malignancies. In about one third of all HCV infection cases, serum autoantibodies are commonly found. This is probably due directly to the transformation of infected B cells but, also, indirectly, to the viral chronic stimulation of a pool of autoreactive B cells. The pattern of IgG subclasses seems to contribute to the worsening progression of HCV infection into lymphoproliferative and/or autoimmune diseases. Many evidences showed that B cells circulating in patients with HCV-associated mixed cryoglobulinaemia (MC) are profoundly abnormal; moreover, in most of cases, normal B cells are replaced by expanded clonal B cells characterized by the low expression of CD21. After viral eradication, these cells persist in circulation and their occurrence does not correlate with serum cryoglobulins nor with vasculitis response or relapse. It is probably due to the persistence of monoclonal B cells producing RF, that in course of MC can be reactivated by circulating immune complexes, highly produced during infections or tumours. Here, we aimed to review current literature focusing the pathogenesis of MC referring to specificity and immunochemical characteristics of the immunoglobulins involved in cryoprecipitation.
Assuntos
Crioglobulinemia , Hepatite C , Imunidade Adaptativa , Crioglobulinas , Hepacivirus , HumanosRESUMO
The loss of tolerance to self-antigens is the unequivocal "red line" of autoimmunity: both development of autoreactive T and B cells and production of polyclonal autoantibodies represent seminal keys to the pathogenesis of protean autoimmune diseases. Most of these autoantibodies are immunoglobulins G (IgG), functionally distinguished in four subclasses named IgG1, IgG2, IgG3, and IgG4, due to structural differences in the hinge and heavy chain constant regions. Different studies analyzed serum levels of IgG subclasses in the course of different disorders, showing that they might have a pathogenic role by regulating interactions among immunoglobulins, Fc-gamma receptors, and complement. To date, the mechanisms promoting different IgG subclasses distribution during the natural history of most autoimmune diseases remain somewhat unclear. Evidence from the medical literature shows that the serum IgG profile is peculiar for many autoimmune diseases, suggesting that different subclasses could be specific for the underlying driving autoantigens. A better knowledge of IgG subsets may probably help to elucidate their pathological task, but also to define their relevance for diagnostic purposes, patients' personalized management, and prognosis assessment.
Assuntos
Imunoglobulina G/imunologia , Animais , Doenças Autoimunes/imunologia , Humanos , Imunoglobulina G/químicaRESUMO
Hepatitis C virus (HCV) represents the major risk factor for mixed cryoglobulinemia (MC), a small-vessel vasculitis that may evolve into an overt B-cell non-Hodgkin's lymphoma. Here, we aimed to identify a biomarker signature for the early diagnosis of minimal residual disease (MRD). We assessed free light chains (FLCs), IgM k,and IgM λ heavy/light chain (HLC) pairs, and vascular endothelial growth factor (VEGF) in sera from 34 patients with MC vasculitis (32 HCV- and 2 HBV-related), treated with low-dose rituximab (RTX). FLCs and IgM HLCs were measured by turbidimetric assay; VEGF by an enzyme-linked immunosorbent assay. After RTX, the positive (complete + partial) clinical and laboratory responses were of 85.29% and 50%, respectively; in contrast, the mean levels of FLCs, IgM HLCs, and VEGF were substantially unaffected in most patients and still above the normal range. In those achieving a reduction of FLCs and IgM k and λ chains values within the range of normality, we found that post-treatment free λ chains and IgM k values correlated with clinical and laboratory response. Our results suggest that high levels of FLCs, IgM HLCs, and VEGF could represent the signature of "dormant" B cell clones' activity that could be very useful to identify MRD indicative of possible relapse or worsening outcome.
Assuntos
Crioglobulinemia , Imunoglobulina M/sangue , Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Rituximab/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Crioglobulinemia/sangue , Crioglobulinemia/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Myasthenia gravis with antibodies (Abs) against the muscle-specific tyrosine kinase (MuSK) is a rare autoimmune disorder (AD) of the neuromuscular junction (NMJ) and represents a prototype of AD with proven IgG4-mediated pathogenicity. Thanks to the mechanism of Fab-arm exchange (FAE) occurring in vivo, resulting MuSK IgG4 k/λ Abs increase their interference on NMJ and pathogenicity. The characterization of hybrid MuSK IgG4 as a biomarker for MG management is poorly investigated. Here, we evaluated total IgG4, hybrid IgG4 k/λ, and the hybrid/total ratio in 14 MuSK-MG sera in comparison with 24 from MG with Abs against acetylcholine receptor (AChR) that represents the not IgG4-mediated MG form. In both subtypes of MG, we found that the hybrid/total ratio reflects distribution reported in normal individuals; instead, when we correlated the hybrid/total ratio with specific immune-reactivity we found a positive correlation only with anti-MuSK titer, with a progressive increase of hybrid/total mean values with increasing disease severity, indirectly confirming that most part of hybrid IgG4 molecules are engaged in the anti-MuSK pathogenetic immune-reactivity. Further analysis is necessary to strengthen the significance of this less unknown biomarker, but we retain it is full of a diagnostic-prognostic powerful potential for the management of MuSK-MG.
Assuntos
Imunoglobulina G/imunologia , Miastenia Gravis/imunologia , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Biomarcadores/sangue , Humanos , Imunoglobulina G/sangue , Miastenia Gravis/sangue , Junção Neuromuscular/metabolismo , Junção Neuromuscular/patologiaRESUMO
Along years, the advent of biological therapy widely modified treatment of rheumatic diseases and other disorders. However, many agents may elicit in anti-drug antibodies (ADAbs) upon consecutive infusions, with a loss of response. For the right strategy of a personalized medicine, the therapeutic monitoring of TNF-α inhibitors and ADAbs represents an important effort in diagnostic-therapeutic pathway, to improve overall patient management and favoring an appropriate clinical approach. A raising number of diagnostic tests have been designed to elucidate the efficacy and/or safety of a specific drug or class of drugs for a targeted patient's group. Our paper reviewed the current understanding of the immunogenicity of biological drugs employed in the treatment of inflammatory diseases underlying the laboratory role.
Assuntos
Anti-Inflamatórios/uso terapêutico , Terapia Biológica , Serviços de Laboratório Clínico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anti-Inflamatórios/imunologia , Biomarcadores/sangue , Doença Crônica , Monitoramento de Medicamentos , Humanos , Inflamação/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease for which auto-antibodies fully validated as diagnostic and prognostic biomarkers are widely desired. Recently, an immunoreactivity against the inward rectifying potassium channel 4.1 (KIR4.1) has been reported in a large proportion of a group of MS patients, with amino acids 83-120 being the major epitope. Moreover, a strong correlation between anti-KIR4.183-120 and anti-full-length-protein auto-antibodies titer was reported. However, this finding received limited confirmation. OBJECTIVE: Validation of the diagnostic potential of anti-KIR4.183-120 antibodies in 78 MS patients, 64 healthy blood donors, and 42 individuals with other neurological diseases. METHODS: Analysis of anti-KIR4.183-120 antibodies by enzyme-linked immunosorbent assay (ELISA) using a mouse antiserum we produced as a new ELISA reliability control. Additionally, evaluation of reactivity against 293-T cells transiently transfected with full-length KIR4.1 by flow cytometry. RESULTS: We found antibodies to KIR4.183-120 only in 13 out of 78 (16.6%) MS patients; among these, only 2 were positive for anti-full-length KIR4.1 antibodies. CONCLUSION: Employing a new reliability control and a new cytofluorometric assay, we cannot support anti-KIR4.183-120 auto-antibodies as a reliable biomarker in MS.
Assuntos
Autoanticorpos/sangue , Biomarcadores/sangue , Esclerose Múltipla/diagnóstico , Canais de Potássio Corretores do Fluxo de Internalização/imunologia , Adulto , Autoantígenos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/imunologiaAssuntos
Adalimumab/imunologia , Anticorpos/imunologia , Certolizumab Pegol/imunologia , Adalimumab/sangue , Adalimumab/uso terapêutico , Idoso , Anticorpos/sangue , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Certolizumab Pegol/sangue , Certolizumab Pegol/uso terapêutico , Feminino , Humanos , Masculino , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Falha de TratamentoRESUMO
Pertrochanteric fractures are common injuries in adults and source of morbidity and mortality among the elderly. Different surgical techniques were recommended for their treatment but undoubtedly they add an additional inflammatory trauma along the fracture itself. Many attempts to quantify the degree of approach-related trauma are carried out through measurements of systemic inflammatory parameters. In this study we prospectively analyzed laboratory data of 20 patients over eighty with pertrochanteric fracture of the femur treated with proximal femoral nail antirotation (PFNA). This is an excellent device for osteosynthesis because it can be easily and quickly inserted by a mini-incision providing stable fixation and early full mobilization. Serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and plasma creatin kinase (CK) were evaluated 1 hour preoperatively and 24 hours postoperatively. Our results show that PFNA did not induce significant increments in serum levels of inflammatory cytokines TNF-α and IL-6; CRP was elevated preoperatively in correlation with waiting time for surgery; CRP and CK showed a significant increment in the first postoperatory day; CK increment was correlated with surgical time length. We conclude that, for the markers we analyzed, PFNA shows a low biomechanical-inflammatory profile that represents an advantage over other techniques.
Assuntos
Biomarcadores/metabolismo , Fraturas do Fêmur/imunologia , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas , Inflamação/imunologia , Inflamação/metabolismo , Necrose/imunologia , Necrose/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Feminino , Fraturas do Fêmur/sangue , Humanos , Inflamação/sangue , Interleucina-6/sangue , Masculino , Necrose/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Myasthenia gravis (MG) is a prototypical antibody-mediated disease characterized by muscle weakness and fatigability. Serum antibodies to the acetylcholine receptor and muscle-specific tyrosine kinase receptor (MuSK) are found in about 85% and 8% of patients respectively. We have previously shown that more than 70% of MG patients with MuSK antibodies share the HLA DQ5 allele. The aim of the present study was to analyze the T cell receptor (TCR) repertoire specific for recombinant human MuSK protein. We used the CDR3 TRBV-TRBJ spectratyping (immunoscope) to analyze the T cell response to MuSK from 13 DQ5+ MuSK-MG patients and from 7 controls (six DQ5+ MuSK negative subjects and one DQ5- DQ3+ MuSK positive patient). DQ5+ MuSK-MG patients but not controls used a restricted set of TCR VJ rearrangements in response to MuSK stimulation. One semiprivate (TRBV29-TRBJ2.5) rearrangement was found in 5/13 patients, while 4 other semiprivate (one in TRBV28-TRBJ2.1 and in TRBV3-TRBJ1.2, and two in TRBV28-TRBJ1.2) rearrangements were differently shared by 4/13 patients each and were absent in controls. When we sequenced the TRBV29-TRBJ2.5 rearrangement, we obtained 26 different sequences of the expected 130 bp length from 117 samples of the 5 positive patients: two common motifs GXGQET/TEHQET were shared in 4 patients as semiprivate motifs. Thus, the MuSK-specific T-cell response appears to be restricted in DQ5+ MuSK-MG patients, with a semiprivate repertoire including a common motif of TRBV29. This oligoclonal restriction of T cells will allow the identification of immunodominant epitopes in the antigen, providing therefore new tools for diagnosis and targeted therapy.
Assuntos
Genes Codificadores dos Receptores de Linfócitos T/genética , Miastenia Gravis/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Células Cultivadas , Criança , Feminino , Antígenos HLA-DQ/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Análise de Sequência de DNA , Adulto JovemRESUMO
Interstitial lung disease (ILD) is a life-threatening complication of systemic sclerosis (SSc). Type 2 (Th2) cytokines play a pivotal role in airway disease. Study aim was to evaluate serum level of Th2 interleukin (IL) and chemokine in SSc-ILD. Serum levels of IL-4, IL-5, IL-11, IL-13, IL-21, IL-31 and CXCL-13 were measured by Bio-Plex Multiplex Immunoassays in 60 SSc patients and 20 healthy controls (HC). Pulmonary function tests with diffusion lung capacity for carbon monoxide (DLco) and high resolution computed tomography (HRCT) were performed in SSc patients. ILD is defined as fibrotic changes (ground glass, reticular and honeycombing), assessed by Computer-Aided Lung Informatics for Pathology Evaluation and Ratings (CALIPER) software, affecting at least 10% of the lungs. Serum levels of Th2 cytokines were higher in SSc patients than HC. A linear correlation was observed between ground glass and IL-13 (r = 0.342, p < 0.01), IL-21 (r = 0.345, p < 0.01), IL-31 (r = 0.473, p < 0.001), IL-4 (r = 0.863, p < 0.001), IL-5 (r = 0.249, p < 0.05) and peripheral blood eosinophils (r = 0.463, p < 0.001). We found a negative correlation between DLco and IL-4 (r = - 0.511, p < 0.001) and peripheral blood eosinophils (r = - 0.446, p < 0.001). In the logistic regression analysis, IL-4 is associated with DLco ≤ 60% of the predicted [OR 1.039 (CI 95%: 1.015-1.064), p < 0.001], whilst mRSS [OR 1.138 (CI 95%: 1.023-1.266), p < 0.05] and IL-4 [OR 1.017 (CI 95%: 1-1.034), p < 0.05] were associated with ILD. Th2 inflammation could play a key role in early phase of SSc-ILD.
Assuntos
Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Citocinas , Interleucina-13 , Interleucina-4 , Interleucina-5 , Doenças Pulmonares Intersticiais/etiologia , Pulmão/patologiaRESUMO
Systemic sclerosis (SSc) patients have an increased frequency of CD21low B cells and of serum interleukin-4 (IL-4) and IL-21, each possible markers of joint involvement in inflammatory arthritis. The aim of this study was to investigate the possible influence of CD21low B cells, IL-4, and IL-21 on joint involvement in a cohort of 52 SSc patients. The DAS28-ESR was correlated with CD21low B cells (r = 0.452, p < 0.001), IL-4 (r = 0.478, p < 0.001), and IL-21 (r = 0.415, p < 0.001). SSc patients with a DAS28-ESR > 3.2 had more CD21low B cells (12.65% (IQR: 7.11-13.79) vs. 5.08% (IQR: 3.76-7.45), p < 0.01), higher IL-4 levels (132.98 pg/mL (IQR: 99.12-164.12) vs. 100.80 pg/mL (IQR: 62.78-121.13), p < 0.05), and higher IL-21 levels (200.77 pg/mL (IQR: 130.13-302.41) vs. 98.83 pg/mL (IQR: 35.70-231.55), p < 0.01) than patients with a DAS28-ESR ≤ 3.2. The logistic regression analysis models showed that the DAI (OR: 2.158 (95% CI: 1.120; 4.156), p < 0.05) and CD21low B cells (OR: 1.301 (95% CI: 1.099; 1.540), p < 0.01), the DAI (OR: 2.060 (95% CI: 1.082; 3.919), p < 0.05) and IL-4 level (OR: 1.026 (95% CI: 1.006; 1.045), p < 0.01), and the DAI (OR: 1.743 (95% CI: 1.022; 2.975), p < 0.05) and IL-21 level (OR: 1.006 (95% CI: 1.000; 1.011), p < 0.05) were independently associated with a DAS28-ESR > 3.2. An elevated CD21low B cell percentage, IL-4 level, and IL-21 level was associated with higher articular disease activity in patients, suggesting a possible role in the pathogenesis of SSc joint involvement.