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Smooth muscle antibodies (SMA) with anti-microfilament actin (MF-SMA) specificity are regarded as highly specific markers of type 1 autoimmune hepatitis (AIH-1) but their recognition relying on immunofluorescence of vessel, glomeruli, and tubules (SMA-VGT pattern) in rodent kidney tissue, is restricted by operator-dependent interpretation. A gold standard method for their identification is not available. We assessed and compared the diagnostic accuracy for AIH-1 of an embryonal aorta vascular smooth muscle (VSM) cell line-based assay with those of the rodent tissue-based assay for the detection of MF-SMA pattern in AIH-1 patients and controls. Sera from 138 AIH-1 patients and 295 controls (105 primary biliary cholangitis, 40 primary sclerosing cholangitis, 50 chronic viral hepatitis, 20 alcohol-related liver disease, 40 steatotic liver disease, and 40 healthy controls) were assayed for MF-SMA and SMA-VGT using VSM-based and rodent tissue-based assays, respectively. MF-SMA and SMA-VGT were found in 96 (70%) and 87 (63%) AIH-1 patients, and 2 controls (Pâ <â 0.0001). Compared with SMA-VGT, MF-SMA showed similar specificity (99%), higher sensitivity (70% vs 63%, Pâ =â ns) and likelihood ratio for a positive test (70 vs 65). Nine (7%) AIH-1 patients were MF-SMA positive despite being SMA-VGT negative. Overall agreement between SMA-VGT and MF-SMA was 87% (kappa coefficient 0.870, [0.789-0.952]). MF-SMA were associated with higher serum γ-globulin [26 (12-55) vs 20 g/l (13-34), Pâ <â 0.005] and immunoglobulin G (IgG) levels [3155 (1296-7344) vs 2050 mg/dl (1377-3357), Pâ <â 0.002]. The easily recognizable IFL MF-SMA pattern on VSM cells strongly correlated with SMA-VGT and has an equally high specificity for AIH-1. Confirmation of these results in other laboratories would support the clinical application of the VSM cell-based assay for reliable detection of AIH-specific SMA.
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Actinas , Autoanticuerpos , Hepatitis Autoinmune , Músculo Liso Vascular , Humanos , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/sangre , Actinas/inmunología , Actinas/metabolismo , Masculino , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Músculo Liso Vascular/inmunología , Persona de Mediana Edad , Adulto , Femenino , Animales , Anciano , Sensibilidad y Especificidad , Línea Celular , Miocitos del Músculo Liso/inmunología , Miocitos del Músculo Liso/metabolismo , Técnica del Anticuerpo Fluorescente/métodos , Ratas , Citoesqueleto de Actina/inmunología , Adolescente , Biomarcadores/sangre , Adulto JovenRESUMEN
BACKGROUND AND AIMS: During recent years, there have been major insight into the pathogenesis, diagnosis and treatment of autoimmune hepatitis (AIH). We aim to evaluate modifications of the clinical-epidemiological phenotype of AIH patients from 1980 to our days. METHODS: Single-centre, tertiary care retrospective study on 507 consecutive Italian patients with AIH. Patients were divided into four subgroups according to the decade of diagnosis: 1981-1990, 1991-2000, 2001-2010 and 2011-2020. We assessed clinical, laboratory and histological features at diagnosis, response to treatment and clinical outcomes. Acute presentation is defined as transaminase levels >10-fold the upper limit and/or bilirubin >5 mg/dL. Complete response is defined as the normalization of transaminases and IgG after 12 months. Clinical progression is defined as the development of cirrhosis in non-cirrhotic patients and hepatic decompensation/hepatocellular carcinoma development in compensated cirrhosis. RESULTS: Median age at diagnosis increased across decades (24, 31, 39, 52 years, p < .001). Acute onset became more common (39.6%, 44.4%, 47.7%, 59.5%, p = .019), while cirrhosis at diagnosis became less frequent (36.5%, 16.3%, 10.8%, 8.7%, p < .001). Complete response rates rose (11.1%, 49.4%, 72.7% 76.2%, p < .001) and clinical progression during follow-up decreased (54.3%, 29.9%, 16.9%, 11.2%, p < .001). Anti-nuclear antibodies positivity increased (40.7%, 52.0%, 73.7%, 79.3%, p < .001), while IgG levels/upper limit progressively decreased (1.546, 1.515, 1.252, 1.120, p < .001). Liver-related death and liver transplantation reduced from 17.1% to 2.1% (p < .001). CONCLUSIONS: In the new millennium, the typical AIH patient in Italy is older at diagnosis, more often presents with acute hepatitis, cirrhosis is less frequent and response to treatment is more favourable.
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Carcinoma Hepatocelular , Hepatitis Autoinmune , Neoplasias Hepáticas , Humanos , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/epidemiología , Hepatitis Autoinmune/tratamiento farmacológico , Estudios Retrospectivos , Cirrosis Hepática/epidemiología , Carcinoma Hepatocelular/epidemiología , Fibrosis , Transaminasas/uso terapéutico , Fenotipo , Inmunoglobulina G , Progresión de la Enfermedad , Derivación y ConsultaRESUMEN
BACKGROUND AND AIMS: The International Autoimmune Hepatitis Group retrospective registry (IAIHG-RR) is a web-based platform with subjects enrolled with a clinical diagnosis of autoimmune hepatitis (AIH). As prognostic factor studies with enough power are scarce, this study aimed to ascertain data quality and identify prognostic factors in the IAIHG-RR cohort. METHODS: This retrospective, observational, multicenter study included all patients with a clinical diagnosis of AIH from the IAIHG-RR. The quality assessment consisted of external validation of completeness and consistency for 29 predefined variables. Cox regression was used to identify risk factors for liver-related death and liver transplantation (LT). RESULTS: This analysis included 2559 patients across 7 countries. In 1700 patients, follow-up was available, with a completeness of individual data of 90% (range: 30-100). During a median follow-up period of 10 (range: 0-49) years, there were 229 deaths, of which 116 were liver-related, and 143 patients underwent LT. Non-White ethnicity (HR 4.1 95% CI: 2.3-7.1), cirrhosis (HR 3.5 95% CI: 2.3-5.5), variant syndrome with primary sclerosing cholangitis (PSC) (HR 3.1 95% CI: 1.6-6.2), and lack of complete biochemical response within 6 months (HR 5.7 95% CI: 3.4-9.6) were independent prognostic factors. CONCLUSIONS: The IAIHG-RR represents the world's largest AIH cohort with moderate-to-good data quality and a relevant number of liver-related events. The registry is a suitable platform for patient selection in future studies. Lack of complete biochemical response to treatment, non-White ethnicity, cirrhosis, and PSC-AIH were associated with liver-related death and LT.
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Colangitis Esclerosante , Hepatitis Autoinmune , Trasplante de Hígado , Humanos , Hepatitis Autoinmune/diagnóstico , Estudios Retrospectivos , Cirrosis Hepática/complicaciones , Respuesta Patológica Completa , Colangitis Esclerosante/complicacionesRESUMEN
Autoimmune hepatitis is an inflammatory disease of the liver of unknown cause that may progress to liver cirrhosis and end stage liver failure if diagnosis is overlooked and treatment delayed. The clinical presentation is often that of acute hepatitis, sometimes very severe; less frequently, it can be insidious or completely asymptomatic. The disease can affect people of any age and is more common in women; its incidence and prevalence seem to be on the rise worldwide. An abnormal immune response targeting liver autoantigens and inducing persistent and self-perpetuating liver inflammation is the pathogenic mechanism of the disease. A specific set of autoantibodies, increased IgG concentrations, and histological demonstration of interface hepatitis and periportal necrosis are the diagnostic hallmarks of autoimmune hepatitis. Prompt response to treatment with corticosteroids and other immunomodulatory drugs is almost universal and supports the diagnosis. The aims of treatment are to induce and maintain long term remission of liver inflammation. Treatment can often even reverse liver fibrosis, thus preventing progression to advanced cirrhosis and its complications. Most patients need lifelong maintenance therapy, and repeated follow-up in experienced hands improves the quality of care and quality of life for affected patients.
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Hepatitis Autoinmune , Humanos , Femenino , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/tratamiento farmacológico , Calidad de Vida , Cirrosis Hepática , Autoanticuerpos , InflamaciónRESUMEN
Hepatocellular carcinoma (HCC) is rarely associated with autoimmune paraneoplastic syndromes. We report a case of anti-transcriptional intermediary factor-1 gamma (TIF1-γ)-positive dermatomyositis (DM) as clinical presentation of HCC recurrence in a 72-year-old male patient admitted to our hospital due to fatigue, myalgia, and typical skin rash. His medical history was notable for hepatitis C-related cirrhosis, successful treatment with direct-acting antiviral agents, and previously efficacious treatment of HCC. Laboratory testing showed significant rhabdomyolysis with anti-TIF1-γ antibodies at high titer, and DM was diagnosed. After a careful diagnostic workup, HCC recurrence was diagnosed. After first-line corticosteroid treatment, azathioprine and intravenous immunoglobulin treatments were administered; unfortunately, he mounted only partial response. Owing to the compromised performance status, no HCC treatment was feasible, and, according to international guidelines, he received only best supportive care. Here, we discuss the diagnostic, prognostic, and pathogenic roles of anti-TIF1-γ antibodies associated with paraneoplastic DM and the scant literature data on its occurrence in HCC patients. Considering the TIF1 gene family's established role in oncogenesis, we also review the role of TIF1-γ as a tumor-related neoantigen, leading to the development of clinically overt anti-TIF1-γ antibodies-positive DM.
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BACKGROUND: Extensor mechanism rupture is a severe complication with an incidence of 0.1-2.5% after total knee arthroplasty (TKA). Achilles tendon allograft (ATA) and extensor mechanism allograft (EMA) in TKA surgery have yielded mixed clinical results. Our systematic review aims to identify the proportion of failure in extensor mechanism reconstruction after TKA using allograft and evaluate clinical and functional outcomes and the most common complications. Furthermore, we performed a meta-analysis among studies dealing with isolated patellar tendon ruptures to assess the failure rate, surgical complications, and clinical findings (extensor lag and knee range of motion) of extensor mechanism reconstruction using either ATA or EMA grafts. METHODS: A systematic review of the literature was performed following the PRISMA guidelines, including the studies dealing with the use of EMA and ATA for extensor mechanism rupture following TKA. Coleman Methodology Score and the MINORS score were used to assess the quality of the studies. A meta-analysis was performed to evaluate the failure rate, complications, and clinical findings (extensor lag and knee range of motion) of the ATA and EMA treatments in isolated patellar tendon ruptures. RESULTS: A total of 238 patients (245 knees), with a mean age ranging from 54 to 74 years, who underwent extensor mechanism reconstruction with an allograft were identified in the 18 included studies. We analysed 166 patellar tendon ruptures, 29 quadriceps tendon ruptures, and 29 patellar fractures in the analysis. A chronic injury was described in the majority of included cases. ATA and whole EMA were used in 89 patients (92 knees) and 149 patients (153 knees), respectively. The overall failure percentage was 23%, while EMA and ATA were 23 and 24%. The most common complication was extensor lag (≥ 20°). The overall incidence of postoperative infection was 7%. Eleven of 14 included papers reported more than 100° of the mean postoperative knee flexion. The percentage of patients requiring walking aids is 55 and 34.5% in ATA and EMA, respectively. The failure outcome after extensor mechanism reconstruction in isolated patellar tendon ruptures was 27%, with no statistical difference between EMA and ATA in terms of failure rate and clinical outcomes. CONCLUSIONS: Extensor mechanism reconstruction with allograft represents a valid treatment option in patients with acute or chronic rupture following total knee arthroplasty. Persistent extensor lag represents the most common complication. EMA is associated with a lower frequency of patients requiring walking aids at last follow-up, although it has similar clinical and functional outcomes to ATA. In patellar tendon ruptures, ATA has a comparable success rate with EMA. LEVEL OF EVIDENCE: Level IV, therapeutic study. TRIAL REGISTRATION: PROSPERO 2019 CRD42019141574.
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Tendón Calcáneo , Artroplastia de Reemplazo de Rodilla , Traumatismos de la Rodilla , Ligamento Rotuliano , Traumatismos de los Tendones , Humanos , Persona de Mediana Edad , Anciano , Artroplastia de Reemplazo de Rodilla/efectos adversos , Ligamento Rotuliano/cirugía , Tendón Calcáneo/trasplante , Articulación de la Rodilla/cirugía , Traumatismos de los Tendones/cirugía , Traumatismos de los Tendones/etiología , Traumatismos de la Rodilla/cirugía , Rotura/cirugía , Rotura/etiología , Rango del Movimiento Articular , Aloinjertos/cirugía , Resultado del TratamientoRESUMEN
Debridement, antibiotic, and implant retention (DAIR) can be used as a first surgical procedure for acute infections in patients who have well-fixed components. However, its use in hematogenous or late acute infections is still debated. This systematic review of literature aims to clarify the effectiveness of DAIR procedure in the treatment of hematogenous periprosthetic knee infections. DAIR is an effective way to treat acute hematogenous PJIs of the knee and reaches its best efficacy when performed within one week from the onset of symptoms, modular components are exchanged, and a pathogen-oriented antibiotic therapy can be set. It is safe, economic, and effective technique, but has to be performed in a very narrow temporal window.
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BACKGROUND: Postoperative rehabilitation after extensor mechanism reconstruction (EMR) with allograft following total knee arthroplasty (TKA) is not standardized. This meta-analysis aimed to evaluate the effectiveness of early and late knee mobilization after EMR. The range of motion (ROM) and extensor lag in both groups were also assessed as the secondary endpoint. METHODS: Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, a systematic review of the literature was performed, including studies dealing with the use of allograft for EMR following TKA. Failure was defined as the persistence of extensor lag > 20°. Coleman Methodology Score and Methodological Index for Non-Randomized Studies (MINORS) score were used to assess the quality of studies included. The failure rate was set as the primary outcome in early (4 weeks) and late (8 weeks) mobilization groups after EMR with allograft. Secondary outcomes were postoperative extensor lag and ROM. RESULTS: Twelve articles (129 knees) were finally selected for this meta-analysis. Late and early knee mobilization was described in five and seven studies, respectively. No difference was noted between both groups' failure rates (11/84 vs. 4/38, respectively; p = 0.69). The mean extensor lag at last follow-up was 9.1° ± 8.6 in the early mobilization group, and 6.5° ± 6.1 in the late mobilization group is not significantly different (p > 0.05). The mean postoperative knee flexion was 107.6° ± 6.5 and 104.8° ± 7 in the early and late mobilization group, respectively. CONCLUSION: While immobilization after EMR in TKA is mandatory to allow tissue healing, early knee mobilization after four weeks can be recommended with no additional risk of failure and increased extensor lag compared to a late mobilization protocol. LEVEL OF EVIDENCE: IV, therapeutic study. Registration PROSPERO (International Prospective Register of Systematic Reviews): CRD42019141574.
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Aloinjertos , Artroplastia de Reemplazo de Rodilla , Ambulación Precoz , Articulación de la Rodilla/cirugía , Artroplastia de Reemplazo de Rodilla/efectos adversos , Humanos , Rango del Movimiento Articular , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Autoimmune hepatitis (AIH) has been well characterised and codified through the development of diagnostic criteria. These criteria have been adapted and simplified and are widely used in clinical practice. However, there is a need to update and precisely define the criteria for both treatment response and treatment. METHODS: A systematic review was performed and a modified Delphi consensus process was used to identify and redefine the response criteria in autoimmune hepatitis. RESULTS: The consensus process initiated by the International Autoimmune Hepatitis Group proposes that the term 'complete biochemical response' defined as 'normalization of serum transaminases and IgG below the upper limit of normal' be adopted to include a time point at 6 months after initiation of treatment. An insufficient response by 6 months was a failure to meet the above definition. Non-response was defined as '<50% decrease of serum transaminases within 4 weeks after initiation of treatment'. Remission is defined as liver histology with a Hepatitis Activity Index <4/18. Intolerance to treatment was agreed to stand for 'any adverse event possibly related to treatment leading to potential drug discontinuation'. CONCLUSIONS: These definitions provide a simple and reproducible framework to define treatment response and non-response, irrespective of the therapeutic intervention. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable inter-study comparisons. Future prospective database studies are needed to validate these endpoints. LAY SUMMARY: Consensus among international experts on response criteria and endpoints in autoimmune hepatitis is lacking. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable the comparison of results between clinical trials. Therefore, the International Autoimmune Hepatitis Group (IAIHG) herein presents a statement on 5 agreed response criteria and endpoints: complete biochemical response, insufficient response, non-response, remission, and intolerance to treatment, which can be used to guide future reporting.
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Hepatitis Autoinmune , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/tratamiento farmacológico , Humanos , Estudios Prospectivos , TransaminasasRESUMEN
Peri-prosthetic joint infections (PJIs) dramatically affect human health, as they are associated with high morbidity and mortality rates. Two-stage revision arthroplasty is currently the gold standard treatment for PJI and consists of infected implant removal, an accurate debridement, and placement of antimicrobial impregnated poly-methyl-metha-acrylate (PMMA) spacer. The use of antibiotic-loaded PMMA (ALPMMA) spacers have showed a success rate that ranges from 85% to 100%. ALPMMA spacers, currently available on the market, demonstrate a series of disadvantages, closely linked to a low propensity to customize, seen as the ability to adapt to the patients' anatomical characteristics, with consequential increase of surgical complexity, surgery duration, and post-operative complications. Conventionally, ALPMMA spacers are available only in three or four standard sizes, with the impossibility of guaranteeing the perfect matching of ALPMMA spacers with residual bone (no further bone loss) and gap filling. In this paper, a 3D model of an ALPMMA spacer is introduced to evaluate the cause- effect link between the geometric characteristics and the correlated clinical improvements. The result is a multivariable-oriented design able to effectively manage the size, alignment, stability, and the patients' anatomical matching. The preliminary numerical results, obtained by using an "ad hoc" 3D virtual planning simulator, clearly point out that to restore the joint line, the mechanical and rotational alignment and the surgeon's control on the thicknesses (distal and posterior thicknesses) of the ALPMMA spacer is mandatory. The numerical simulations campaign involved nineteen patients grouped in three different scenarios (Case N° 1, Case N° 2 and Case N° 3) whose 3D bone models were obtained through an appropriate data management strategy. Each scenario is characterized by a different incidence rate. In particular, the observed rates of occurrence are, respectively, equal to 17% (Case N° 1), 74% (Case N° 2), and 10% (Case N° 3).
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More than 90% of cases of hepatocellular carcinoma (HCC) occurs in patients with cirrhosis, of which hepatitis B virus and hepatitis C virus are the leading causes, while the tumor less frequently arises in autoimmune liver diseases. Advances in understanding tumor immunity have led to a major shift in the treatment of HCC, with the emergence of immunotherapy where therapeutic agents are used to target immune cells rather than cancer cells. Regulatory T cells (Tregs) are the most abundant suppressive cells in the tumor microenvironment and their presence has been correlated with tumor progression, invasiveness, as well as metastasis. Tregs are characterized by the expression of the transcription factor Foxp3 and various mechanisms ranging from cell-to-cell contact to secretion of inhibitory molecules have been implicated in their function. Notably, Tregs amply express checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4 and programmed cell-death 1 receptor and therefore represent a direct target of immune checkpoint inhibitor (ICI) immunotherapy. Taking into consideration the critical role of Tregs in maintenance of immune homeostasis as well as avoidance of autoimmunity, it is plausible that targeting of Tregs by ICI immunotherapy results in the development of immune-related adverse events (irAEs). Since the use of ICI becomes common in oncology, with an increasing number of new ICI currently under clinical trials for cancer treatment, the occurrence of irAEs is expected to dramatically rise. Herein, we review the current literature focusing on the role of Tregs in HCC evolution taking into account their opposite etiological function in viral and autoimmune chronic liver disease, and we discuss their involvement in irAEs due to the new immunotherapies.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Factores de Transcripción Forkhead , Humanos , Inmunoterapia , Linfocitos T Reguladores , Factores de Transcripción , Microambiente TumoralRESUMEN
Liver biopsy is crucial for the diagnosis of autoimmune hepatitis (AIH), and new reproducible histological criteria would be highly desirable, especially in acute-on-chronic cases. The aims of the present study were (i) to evaluate the AIH histopathological criteria as a function of the time and modality of AIH onset, and (ii) to validate the count of apoptotic bodies in the portal tracts as a histopathological criterion for AIH diagnosis. Sixty-five patients were retrospectively enrolled: 20 underwent biopsy for the first diagnosis and 45 had a previous histological AIH diagnosis. Biopsies were revised, and all histological variables were collected, including the lymphocytic apoptotic bodies in the portal tracts. Clinical and serological data were revised as well. First-diagnosis patients showed a higher grade of inflammation (p = 0.001), but also worse portal fibrosis (p = 0.001). The apoptotic body count was higher in first-diagnosis patients than in follow-up patients (p = 0.002), and it was strongly correlated to inflammation. Using the apoptotic body count among the simplified AIH score variables, the first-biopsy patients in the "definite" category rose from 42 to 68%. Our results confirm the histopathological criteria proposed by the literature and introduce the count of portal apoptotic bodies for the diagnosis of active AIH, especially in first biopsies without other classic features, as well as in AIH diagnostic score, albeit future studies are required to find a definite cutoff.
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Hepatitis Autoinmune/diagnóstico , Cirrosis Hepática/diagnóstico , Hígado/patología , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Biopsia , Femenino , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/patología , Humanos , Italia , Hígado/inmunología , Cirrosis Hepática/inmunología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Derivación y Consulta , Reproducibilidad de los Resultados , Estudios Retrospectivos , Centros de Atención Terciaria , Factores de TiempoRESUMEN
Autoimmune Hepatitis (AIH) is a chronic inflammatory liver disease of unknown aetiology characterized by the presence of autoantibodies, hypergammaglobulinaemia with specific IgG increase and interface hepatitis on liver histology. The clinical course of AIH is classically characterized by fluctuating periods of decreased or increased disease activity and therefore its clinical spectrum is variable ranging from no symptoms to severe acute hepatitis and even fulminant hepatic failure. Acute presentation may not differ from acute hepatitis of other causes and diagnosis can be difficult. We describe our experience on diagnostic performance of the two AIH scoring systems in acute onset of AIH and found that revised version of the original criteria (1999) achieves the diagnosis in about 30% of patients who presented with normal IgG serum levels and lower frequency of autoantibody positivity in whom the simplified score did not allow the diagnosis.
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Hepatitis Autoinmune , Enfermedad Aguda , Autoanticuerpos , Hepatitis Autoinmune/diagnóstico , HumanosAsunto(s)
COVID-19/complicaciones , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/inmunología , Antivirales/uso terapéutico , COVID-19/inmunología , Portador Sano , Femenino , Humanos , Masculino , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/virologíaRESUMEN
BACKGROUND & AIMS: The simplified criteria for the diagnosis of autoimmune hepatitis (AIH) include immunofluorescence testing (IFT) of antinuclear and smooth muscle autoantibodies (ANA and SMA) on rodent tissue sections. We aimed to establish scoring criteria for the implementation of ANA IFT on human epithelioma-2 (HEp-2) cells and ELISA-based testing. METHODS: ANA and SMA reactivity of 61 AIH sera and 72 non-alcoholic fatty liver disease controls were separately assessed on tissue sections and HEp-2 cells to compare the diagnostic value at increasing titers. A total of 113 patients with AIH at diagnosis and 202 controls from 3 European centers were assessed by IFT as well as 3 different commercially available ANA ELISA and 1 anti-F-actin ELISA. RESULTS: ANA assessment by IFT on liver sections had 83.6% sensitivity and 69.4% specificity for AIH at a titer of 1:40. On HEp-2 cells, sensitivity and specificity were 75.4% and 73.6%, respectively, at an adjusted titer of 1:160. Area under the curve (AUC) values of ANA ELISA ranged from 0.70-0.87, with ELISA coated with HEp-2 extracts in addition to selected antigens performing significantly better. SMA assessment by IFT had the highest specificity for the SMA-VG/T pattern and anti-microfilament reactivity on HEp-2 cells. ELISA-based anti-F-actin evaluation was a strong predictor of AIH (AUC 0.88) and performed better than SMA assessment by IFT (AUC 0.77-0.87). CONCLUSION: At adjusted cut-offs, both ANA IFT using HEp-2 cells and ELISA-based autoantibody evaluation for ANA and SMA are potential alternatives to tissue-based IFT for the diagnosis of AIH. LAY SUMMARY: Autoantibodies are a hallmark of autoimmune hepatitis and are traditionally tested for by immunofluorescence assays on rodent tissue sections. Herein, we demonstrate that human epithelioma cells can be used as a reliable substrate for immunofluorescence testing. ELISA-based testing is also a potentially reliable alternative for autoantibody assessment in autoimmune hepatitis. We propose the implementation of these testing methods into the simplified criteria for the diagnosis of autoimmune hepatitis.
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Anticuerpos Antinucleares , Autoanticuerpos , Técnica del Anticuerpo Fluorescente/métodos , Hepatitis Autoinmune , Animales , Anticuerpos Antinucleares/análisis , Anticuerpos Antinucleares/aislamiento & purificación , Autoanticuerpos/análisis , Autoanticuerpos/aislamiento & purificación , Carcinoma , Línea Celular Tumoral , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/inmunología , Humanos , Ratas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Simplificación del TrabajoRESUMEN
Coronavirus disease 2019 (COVID-19) is often associated with interstitial pneumonia. However, there is insufficient knowledge on the presence of autoimmune serological markers in patients with COVID-19. We analyzed the presence and role of autoantibodies in patients with COVID-19-associated pneumonia. We prospectively studied 33 consecutive patients with COVID-19, 31 (94%) of whom had interstitial pneumonia, and 25 age-matched and sex-matched patients with fever and/or pneumonia with etiologies other than COVID-19 as the pathological control group. All patients were tested for the presence of antinuclear antibodies (ANAs), anti-antiphospholipid antibodies, and anti-cytoplasmic neutrophil antibodies (ANCAs). Clinical, biochemical, and radiological parameters were also collected. Fifteen of 33 patients (45%) tested positive for at least one autoantibody, including 11 who tested positive for ANAs (33%), 8 who tested positive for anti-cardiolipin antibodies (immunoglobulin (Ig)G and/or IgM; 24%), and 3 who tested positive for anti-ß2-glycoprotein antibodies (IgG and/or IgM; 9%). ANCA reactivity was not detected in any patient. Patients that tested positive for auto-antibodies had a significantly more severe prognosis than other patients did: 6 of 15 patients (40%) with auto-antibodies died due to COVID-19 complications during hospitalization, whereas only 1 of 18 patients (5.5%) who did not have auto-antibodies died (P = 0.03). Patients with poor prognosis (death due to COVID-19 complications) had a significantly higher respiratory rate at admission (23 breaths per minute vs. 17 breaths per minute; P = 0.03) and a higher frequency of auto-antibodies (86% vs. 27%; P = 0.008). In conclusion, auto-antibodies are frequently detected in patients with COVID-19 possibly reflecting a pathogenetic role of immune dysregulation. However, given the small number of patients, the association of auto-antibodies with an unfavorable prognosis requires further multicenter studies.
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Autoanticuerpos/fisiología , COVID-19/inmunología , Enfermedades del Sistema Inmune/etiología , SARS-CoV-2 , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , COVID-19/patología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: High frequency (130 Hz) subthalamic Deep-Brain-Stimulation (STN-DBS) optimally improves cardinal motor symptoms in Parkinson disease (PD). Low stimulation frequencies (60-80 Hz) improve axial symptoms in some patients and, according to preliminary evidences, may also have a beneficial effect on the cognitive component of motor planning. OBJECTIVE: To analyze the configuration of the P300 component of cortical event-related auditory potentials (ERPs), a reliable index of attentive cognitive functions, at different stimulation frequencies in STN-DBS in PD patients. METHODS: 12 PD patients underwent ERPs recordings using a standard oddball auditory paradigm with STN-DBS at 60 Hz, 80 Hz, 130 Hz, and OFF-stimulation, applied in a randomized double-blind sequence. ERPs analysis considered the peak amplitude and latency of the P300 components at midline electrode positions (Fz, Cz, Pz). RESULTS: P300 latency over Cz and Pz electrodes significantly increased with STN-DBS at 130 Hz compared to OFF-stimulation. P300 latency was also significantly increased, though to a lesser degree, over Pz electrode with stimulation at 80 Hz. No significant P300 latency modifications were detected at 60 Hz stimulation compared to OFF-stimulation condition. P300 amplitude did not change significantly for any of the stimulation conditions tested. CONCLUSIONS: Low frequency STN-DBS is associated with minor modifications of P300 latency compared to conventional stimulation at 130 Hz, possibly suggesting that 60 and 80 Hz may have less interference with attentive and cognitive processes in PD patients.
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Estimulación Encefálica Profunda , Potenciales Relacionados con Evento P300/fisiología , Potenciales Evocados Auditivos/fisiología , Enfermedad de Parkinson/terapia , Núcleo Subtalámico , Anciano , Atención/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Percepción de la Altura Tonal/fisiologíaRESUMEN
It is a comment on a recent review published on the Journal.