Renal transplantation using kidneys from hepatitis C-infected donors: A review of 30-years’ experience / Trasplante renal con órganos de donantes infectados por hepatitis C: 30 años de experiencia

Kidney transplantation is the optimal therapy for end-stage kidney disease but limited by the available number of organs. Using HCV+ donors, both in HCV+ and HCV− recipients, is a rational response to the organ shortage. We review the historic experience using HCV+ donors in HCV+ recipients and assess long-term results. We also discuss contemporary practices, including the transplantation of HCV-viremic kidneys into HCV− recipients with different approaches to posttransplant HCV therapy. (AU)

El trasplante renal es el tratamiento óptimo de la insuficiencia renal terminal pero está limitado por el número de órganos disponibles. El uso de los riñones de los donantes VHC+, tanto en receptores VHC+ como VHC−, es una respuesta racional a la escasez de órganos. En este artículo revisamos la experiencia histórica usando riñones de donantes VHC+ en receptores VHC+ y evaluamos los resultados a largo plazo. Además, discutiremos las prácticas contemporáneas incluyendo el trasplante de órganos VHC+ virémicos en receptores VHC− con diferentes opciones de tratamiento VHC postrasplante. (AU)

Renal transplantation using kidneys from hepatitis C-infected donors: A review of 30-years' experience.

Kidney transplantation is the optimal therapy for end-stage kidney disease but limited by the available number of organs. Using HCV+ donors, both in HCV+ and HCV- recipients, is a rational response to the organ shortage. We review the historic experience using HCV+ donors in HCV+ recipients and assess long-term results. We also discuss contemporary practices, including the transplantation of HCV-viremic kidneys into HCV- recipients with different approaches to posttransplant HCV therapy.

Increased incidence of Graves' disease during the SARS-CoV2 pandemic.

INTRODUCTION: COVID-19 has a wide spectrum of clinical severity and there is evidence that SARS-Cov2 affects several organs and systems. Among the organs affected since the beginning of the pandemic, the relationship between SARS-CoV-2 infection and thyroid involvement has been demonstrated. Novel and highly effective messenger RNA and DNA-based vaccines have been rapidly developed to decrease SARS-CoV-2 morbidity and mortality. Early after mass vaccinations, cases of thyroid dysfunction mainly including episodes of subacute thyroiditis, began to be reported like adverse effects. The objective of this study is to determine the impact of the pandemic, both due to SARS-CoV2 infections and vaccinations, on the incidence of Graves' disease (GD). METHODS: Cross-sectional, observational study comparing incidence of GD in adult population (over 18 years) before (2017-2019) and after (2020-2021) Covid-19 pandemic. Only patients with new cases of GD, no relapsed diseases, were included. SARS-CoV-2 diagnosis was based on nucleic acid amplification tests on nasopharyngeal swabs or measurement of class M and class G antibodies to SARS-CoV-2 by highly specific assays. Data on incidence and vaccination related to SARS-CoV-2 infection were obtained from the public records from Castilla y León autonomous regional government. RESULTS: A total of 180 subjects were diagnosed and treated for GD during the study period. We observed a notable increase in expected GD cases in 2021 compared to 2017-19. The number of GD cases was higher in the second (Q2) quarter. Among 2021 GD cases, 42/66 patients (63.6%) had been vaccinated in the 90 days before symptom onset, but none of them in the first quarter of the year. A total of 97.7% were women with a mean age of 48.9 (SD 15.6) years. On average they were diagnosed 19.9 (SD 17.6) days after receiving the vaccine. A total of 7/42 (16.67%) had another previously diagnosed autoimmune disease and 11/42 (26.19%) were smokers. DISCUSSION: Our results show a notable increase in the incidence of GD during the year 2021, specially in women with a history of smoking. Hyper activation of the immune system induced by SARS-CoV2 and by the recently released SARS-COV-2 vaccines has been highlighted in recent months. To assess whether this observed increase in the incidence of GD is sustained in the coming years or has simply been a precipitous trigger for individuals who were already predisposed to develop the disease, future studies will be needed.

Protocolo del servicio para la realización, trazabilidad y seguimiento de los resultados obtenidos de test de diagnóstico y autodiagnóstico de antígenos de SA R S- CoV-2 / Protocol for the performance, traceability and monitoring of the results obtained from the SARS-CoV-2 antigen diagnostic and self-diagnostic test

Introducción: A través de un acuerdo de colabora-ción entre el Departamento de Sanidad del Gobier-no de Aragón y el Consejo de Colegios Oficiales de Farmacéuticos de Aragón, las oficinas de farmacia de Aragón tienen la posibilidad de adherirse volun-tariamente para su colaboración en la vigilancia epidemiológica, mediante la realización de test de antígenos, comunicación de los resultados y emi-sión de certificados.Método: Previamente a la adhesión, las farmacias han de cumplir una serie de requisitos, incluyen-do una declaración de responsabilidad. Ante la solicitud de un paciente asintomático que desea realizarse un test, el farmacéutico debe seguir un algoritmo de decisión.Resultados: A fecha 3 de octubre de 2021,303 far-macias en Aragón han participado. Se han emitido 6.021 Certificados COVID Digitales de la UE, tras la realización de un test de diagnóstico de antíge-nos en la oficina de farmacia, con 92 resultados positivos. Conclusiones: Las oficinas de farmacia han resul-tado esenciales en la realización de test de antí-genos, comunicación de resultados y emisión de Certificados COVID Digitales de la UE. (AU)

Introduction: Through a collaboration agreement between the Department of Health of the Govern-ment of Aragon and the Council of Official Associa-tions of Pharmacists of Aragon, those pharmacies that voluntarily wanted to register were incorporat-ed into the epidemiological surveillance system. In this way, they can carry out diagnostic and self-diagnosis tests on patients, issue certificates and communicate positive results directly to the Department of Health.Method: In order to accede to this agreement, some requirements must be met by the pharma-cies, including a statement of responsibility. At the request of an asymptomatic patient who wishes to undergo a test, the pharmacist must follow a decision algorithm.Results: As of October 3, 2021, 303 pharmacies in Aragón participated in this collaboration. 6.021 EU Digital COVID Certificates were issued, after having carried out an antigen diagnostic test at the phar-macy. 92 positive results were reported.Conclusions: Pharmacies have been essential in carrying out antigen tests, communicating results and issuing EU Digital COVID Certificates. (AU)

Artificial Stone Silicosis: Rapid Progression Following Exposure Cessation.

BACKGROUND: Silicosis is rapidly emerging in high-income countries in relation to the replacement of natural stone with artificial stone, especially in the manufacturing and installation of kitchen and bathroom countertops. Progression of this form of silicosis following the cessation of exposure is unknown. RESEARCH QUESTION: The objective of this study was to determine the radiologic progression and lung function in individuals with artificial stone silicosis. STUDY DESIGN AND METHODS: Between 2009 and 2018, a total of 106 patients were diagnosed with artificial stone silicosis in the Bay of Cádiz area (southern Spain), 14.15% by using biopsy results and the remainder according to chest radiography and high-resolution CT imaging. Follow-up consisted of respiratory function tests and radiographic studies. All patients stopped working in the stone industry following diagnosis. RESULTS: All patients were men; their mean ± SD age at diagnosis was 36.2 ± 7.0 years, and the mean duration of exposure was 12.0 ± 4.3 years. At diagnosis, 99 patients were considered to have simple silicosis (93.4%) and seven to have progressive massive fibrosis (PMF) (6.6%). After a mean follow-up of 4.01 ± 2.1 years, disease in 56% of patients had progressed two or more International Labour Office subcategories, and the number of patients with PMF had increased to 40 (37.7%). Regarding lung function, there was a decrease in FVC and FEV1, with an average decrease of 86.8 and 83.4 mL per year, respectively; in 25% of patients, the annual decrease was > 157 mL in FVC and > 133 mL in FEV1. Multivariable analysis showed that lower FVC at diagnosis and longer duration of exposure to silica were associated with progression to PMF. INTERPRETATION: Artificial stone silicosis rapidly progresses to PMF even following exposure cessation, and a significant percentage of patients experience a very rapid decrease in lung function.

Critical role of interleukin (IL)-17 in inflammatory and immune disorders: An updated review of the evidence focusing in controversies.

Interleukin 17 (IL-17) is a proinflammatory cytokine that has been the focus of intensive research because of its crucial role in the pathogenesis of different diseases across many medical specialties. In this context, the present review in which a panel of 13 experts in immunology, dermatology, rheumatology, neurology, hematology, infectious diseases, hepatology, cardiology, ophthalmology and oncology have been involved, puts in common the mechanisms through which IL-17 is considered a molecular target for the development of novel biological therapies in these different fields. A comprehensive review of the literature and analysis of the most outstanding evidence have provided the basis for discussing the most relevant data related to IL-17A blocking agents for the treatment of different disorders, such as psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, cardiovascular disorders, non alcoholic fatty liver disease, multiple sclerosis, inflammatory bowel disease, uveitis, hematological and solid cancer. Current controversies are presented giving an opening line for future research.

Hepatitis C y trasplante renal: el tiempo de la erradicación del virus ha llegado / Hepatitis C and kidney transplant: The eradication time of the virus has arrived

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The IgA Isotype of Anti-ß2 Glycoprotein I Antibodies Recognizes Epitopes in Domains 3, 4, and 5 That Are Located in a Lateral Zone of the Molecule (L-Shaped).

Background: Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with presence of anti-phospholipid antibodies (aPL). The APS classification criteria only consider the aPL of IgG/IgM isotype, however testing of aPL of IgA isotype is recommended when APS is suspected and consensus aPL are negative. IgA anti-ßeta-2 glycoprotein-I (B2GP1) has been clearly related with occurrence of thrombotic events. Antibodies anti-B2GP1 of IgG/M isotypes recognize an epitope in Domain 1 (R39-G43), the epitopes that recognize IgA anti-B2GP1 antibodies are not well-identified. Aim: To determine the zones of B2GP1 recognized by antibodies of IgA isotype from patients with APS symptomatology and positive for IgA anti-B2GP1. Methods: IgA antibodies to Domain-1(D1) and Domain-4/5(D4/5) of B2GP1 (ELISA) and epitope mapping on oligopeptide arrays of B2GP1 were evaluated in sera from a group of 93 patients with at least one thrombotic and with isolated positivity for IgA anti-B2GP1 antibodies (negative for other aPL). Results: A total of 47 patients (50.5%) were positive for anti-D4/5 and 23(25%) were positive for anti-D1. When peptide arrays were analyzed, three zones of B2GP1 reactivity were identified for more than 50% of patients. The center of these zones corresponds to amino acids 140(D3), 204(D4), and 264(D5). The peptides recognized on D3 and D4 contain amino acid sequences sharing high homology with proteins of microorganism that were previously related with a possible APS infectious etiology. In the three-dimensional structure of B2GP1, the three peptides, as the R39-G43 epitope, are located on the right side of the molecule (L-shape). The left side (J-shape) does not bind the antibodies. Conclusions: Patients with thrombotic APS clinical-criteria, and isolated IgA anti-B2GP1 positivity appear to preferentially bind, not to the D1 or D4/5 domains of B2GP1, but rather to three sites in D3, D4, and D5. The sites on D3 and D4 were previously described as the target identified by human monoclonal antibodies derived from patients that were capable of inducing APS in animal models. The localization of these epitopes opens a new route to explore to increase understanding of the patholophysiology of the APS and to propose new alternatives and therapeutic targets.

Hepatitis C and kidney transplant: The eradication time of the virus has arrived. / Hepatitis C y trasplante renal: el tiempo de la erradicación del virus ha llegado.

Hepatitis C virus (HCV) infection is a factor that reduces the survival of the patient and the graft in renal transplant (RT). The availability of directly acting antivirals agents (DAAs), very effective and with an excellent safety profile, it allows eradicate HCV from patients with kidney disease, and this is a revolutionary radical change in the natural evolution of this infection, until now without effective and safe treatment for the contraindication use of interferon in kidney transplant patients. The efficiency of some DAAs for all genotypes, even in patients with renal insufficiency constitutes a huge contribution to eradicate HCV in the RT population independently the genotype, severity of kidney failure, progression of liver disease and previous anti HCV therapy. All this is raising, although with controversies, the possibility of use kidneys from infected HCV+ donors for transplant in uninfected receptors and can be treated successfully in the early post-TR, thus increasing the total "pool" of kidneys for RT.

Unexpected relevant role of gene mosaicism in patients with primary immunodeficiency diseases.

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

Antiphospholipid Syndrome and Renal Allograft Thrombosis.

Renal allograft thrombosis is the most frequent and devastating complication in the early postrenal transplantation period. Several risk factors to develop graft thrombosis depending on donors and recipients are well known. Antiphospholipid syndrome (APS) is well recognized as an important cause of kidney injury, with specific clinical and histological features that may lead to renal injury caused by thrombosis at any location within the renal vasculature. There are 3 forms of APS, primary (the most common form), associated to other systemic autoimmune diseases (SAD-APS), and catastrophic. Nevertheless, patients with SAD-APS and renal failure only represent 2% to 5% in hemodialysis or transplantation. The presence of pretransplant antiphospholipid antibodies increases risk of graft thrombosis. A new form of APS based on IgA anti-ß-2-glycoprotein-I (B2GPI) antibodies, representing up to 30% of patients in end-stage renal disease and renal transplantation, is the main independent risk factor for graft thrombosis and early graft loss after renal transplantation. In addition, B2GP1 bound to IgA aB2GP1 immunocomplexes have been described as a marker to predict thrombosis after renal transplantation in patients with antiphospholipid antibodies. Anticoagulation remains the main treatment to prevent renal allograft thrombosis, although new preventive strategies are coming. Future studies may help to identify better therapeutic targets.

Risk factors for intracranial lesions and mortality in older patients with mild traumatic brain injuries.

PRIMARY OBJECTIVE: To identify risk factors for intracerebral lesion (ICL) in older adults with mild traumatic brain injury (MTBI) and evaluate the influence of comorbidities on outcomes. RESEARCH DESIGN: Prospective cohort study. METHODS AND PROCEDURES: Information was gathered on clinical history/examination, cranial computed tomography, admission Glasgow Coma Scale (GCS) score, analytical and coagulation findings, and mortality at 1 week post-discharge. Bivariate and multivariate logistic regression analyses were performed, calculating odds ratios for ICL with 95% confidence interval. P < 0.05 was considered significant. MAIN OUTCOMES AND RESULTS: Data were analyzed on 504 patients with mean±SD age of 79.37 ± 8.06 years. Multivariate analysis showed that traffic accident, GCS score of 14/15, transient consciousness loss, nausea, and receipt of antiplatelets were predictors of ICL, while SRRI and/or benzodiazepine intake was a protective factor. A score was assigned to patients by rounding OR values, and a score ≥1 indicated moderate/high risk of ICL. CONCLUSIONS: MTBI management should be distinct in over-60 year-olds, who may not present typical symptoms, with frequent comorbidities. Knowledge of risk factors for post-MTBI ICL, associated with higher mortality, is important to support clinical decision-making. Further research is warranted to verify our novel finding that benzodiazepines and/or SSRI inhibitors may act as neuroprotectors.

Exceso de peso corporal y calidad de vida relacionada con la salud de adolescentes latino-americanos / Overweight and health-related quality of life in Latin American adolescents

El objetivo del estudio fue identificar diferencias en los componentes de la calidad de vida relacionada con la salud (CVRS) según el estado ponderal en una muestra de adolescentes de tres ciudades localizadas en Argentina, Brasil y Chile. Se aplicó el cuestionario Kidscreen-52 a 1.357 adolescentes con edades comprendidas entre 12 y 17 años (48,6% chicos) en muestras seleccionadas en los tres países. El estado ponderal (eutrófico, sobrepeso y obesidad) fue definido mediante el índice de masa corporal, utilizándose los puntos de corte sugeridos por la International Obesity Task Force. Para establecer comparaciones entre los estratos formados, se utilizó el análisis de covarianza mediante el control de las puntuaciones asociadas a la ciudad/país de origen, sexo y edad. Considerando la totalidad de los adolescentes reunidos en el estudio, el 35,2% de las chicas y el 28,6% de los chicos presentaron exceso de peso corporal, de los cuales, 6,4% y el 4,7% respectivamente, mostraron ser obesos. Se observó aumento en las prevalencias de sobrepeso y obesidad con la edad, sobretodo en el grupo de los chicos. En comparación con los adolescentes eutróficos, los adolescentes obesos obtuvieron puntuaciones significativamente más comprometidas en los diez componentes de CVRS. Los adolescentes con sobrepeso mostraron valores significativamente menores que los adolescentes eutróficos en los componentes de Bienestar Físico, Bienestar Psicológico, Estado de Ánimo y Emociones, Autopercepción, Amigos y Apoyo Social, Entorno Escolar y Rechazo Social/Bullying. Además, en la comparación entre adolescentes con sobrepeso y obesos, las diferencias demostraron estadísticamente significativas para los componentes de Bienestar Físico, Autopercepción y Rechazo Social/Bullying. Por consiguiente, las evidencias encontradas apuntan hacia la importancia de monitorizar e intervenir en los componentes de CVRS relacionados con la propuesta de programas dirigidos la reversión del sobrepeso/obesidad y al control del peso corporal

The purpose of the study was to identify differences in the components of health-related quality of life (HRQL) across weight status in samples of adolescents from three cities in Argentina, Brazil, and Chile. The Kidscreen-52 questionnaire was administered to 1357 adolescents between 12 and 17 years of age (48.6% of them male) in selected samples in the three countries. To define the weight status (eutrophic, overweight, obesity) we used the gender-and-age-specific body mass index cut-offs recommended by theInternational Obesity Task Force - IOFT. Analysis of covariance was used to make comparisons between strata formed by controlling the scores associated with the city/country of origin, sex and age. Considering all adolescents in the study, 35.2% of girls and 28.6% of boys were overweight, of which 6.4% and 4.7%, respectively, showed to be obese. Magnitude of the prevalence increases with age, being these values more pronounced among the boys. Compared to eutrophic adolescents, the obese adolescents presented scores significantly more injured in the ten components of HRQL. The overweight adolescents showed significantly lower values than eutrophic adolescents in the components equivalent to Physical Well-being, Psychological Well-being, Moods and Emotions, Self-Perceptions, Social Support and Peers, School Environment, and Social Acceptance/Bullying. In addition, the comparison between overweight and obese adolescents showed statistically significant differences for the components of Physical Well-being, Self-Perceptions, and Social Acceptance/Bullying. Therefore the evidences found indicate to the importance of monitoring and intervening in HRQOL components related to the proposed programs for the reversal of overweight/obesity and weight control

Gluten-degrading bacteria are present in the human small intestine of healthy volunteers and celiac patients.

Gluten is the only known environmental factor that triggers celiac disease. Several studies have described an imbalance between the intestinal microbiota of different individuals based on diagnoses. Moreover, recent studies have suggested that human bacteria may play an important role in gluten hydrolysis. However, there has been no research focusing on the small intestine. This study aimed to characterize the adult small intestine microbiota possibly implicated in gluten hydrolysis. Duodenal biopsies from different diagnosed individuals were cultured in a gluten-containing medium, and the grown microbiota was analyzed by culture dependent/independent methods. Results showed that gluten-degrading bacteria can be found in the human small intestine. Indeed, 114 bacterial strains belonging to 32 species were isolated; 85 strains were able to grow in a medium containing gluten as the sole nitrogen source, 31 strains showed extracellular proteolytic activity against gluten protein and 27 strains showed peptidolytic activity towards the 33 mer peptide, an immunogenic peptide for celiac disease patients. We found that there are no differences based on the diagnosis, but each individual has its own population of gluten-hydrolyzing bacteria. These bacteria or their gluten-degrading enzymes could help to improve the quality of life of celiac disease patients'.

The Presence of Pretransplant Antiphospholipid Antibodies IgA Anti-ß-2-Glycoprotein I as a Predictor of Graft Thrombosis After Renal Transplantation.

BACKGROUND: Vessel thrombosis is a severe complication after renal transplantation. Antibodies anti-ß-2 glycoprotein-I of IgA isotype (IgA-aB2GP1) have been linked to thrombotic events and mortality in hemodialysis patients. METHODS: All kidney transplanted patients from 2000 to 2011 (n = 1375) in our hospital were followed up for 2 years, evaluating 3 time periods. RESULTS: At transplantation, 401 patients were positive for IgA-aB2GPI (29.2%, group 1), and the remaining patients were negative (group 2). Graft loss at 6 months posttransplantation was higher in group 1 (18% vs 7.2%; P < 0.001). The most frequent cause of early graft loss was vessel thrombosis, especially in group 1 (12.2% vs 2.6% of patients; P < 0.001). In fact, vessel thrombosis was the most important cause of graft loss in the 3 time periods, irrespective of demographic changes and introduction of transplantation with asystolic donors.Notably, IgA-aB2GP1 was an independent risk factor for graft thrombosis (odds ratio, 5.047; P < 0.001). Furthermore, the presence of IgA-aB2GP1 was associated with early graft loss and delayed graft function. Mortality at 24 months was also higher in group 1. CONCLUSIONS: In conclusion, pretransplant IgA-aB2GP1 was the main risk factor for graft thrombosis and early graft loss. Further research should be made on whether anticoagulation in antibody-positive patients could ameliorate this catastrophic complication.

Bone marrow fibrosis in myelodysplastic syndromes: a prospective evaluation including mutational analysis.

The biological and molecular events that underlie bone marrow fibrosis in patients with myelodysplastic syndromes are poorly understood, and its prognostic role in the era of the Revised International Prognostic Scoring System (IPSS-R) is not yet fully determined. We have evaluated the clinical and biological events that underlie bone marrow fibrotic changes, as well as its prognostic role, in a well-characterized prospective patient cohort (n=77) of primary MDS patients. The degree of marrow fibrosis was linked to parameters of erythropoietic failure, marrow cellularity, p53 protein accumulation, WT1 gene expression, and serum levels of CXCL9 and CXCL10, but not to other covariates including the IPSS-R score. The presence of bone marrow fibrosis grade 2 or higher was associated with the presence of mutations in cohesin complex genes (31.5% vs. 5.4%, p=0.006). By contrast, mutations in CALR, JAK2, PDGFRA, PDGFRB,and TP53 were very rare. Survival analysis showed that marrow fibrosis grade 2 or higher was a relevant significant predictor for of overall survival, and independent of age, performance status, and IPSS-R score in multivariate analysis.

Early renal graft function deterioration in recipients with preformed anti-MICA antibodies: partial contribution of complement-dependent cytotoxicity.

BACKGROUND: We previously reported that preformed anti-MHC class I-related chain A (MICA) antibodies increase the risk for renal graft rejection and enhance the deleterious effect of PRA(+) status early after transplantation. METHODS: We studied 727 kidney recipients. Days to reach optimal serum creatinine level, estimated glomerular filtration rate (eGFR) at Month 3 and chronic kidney disease (CKD) stages were recorded. Anti-MICA specificities and C1q binding were tested by solid-phase assay. Complement-dependent cytotoxicity (CDC) and flow cytometry (FC) cross-matches with HeLa and PMA/CD28-T-blasts were performed. RESULTS: PRA(+)MICA(+) recipients exhibited longer time to reach optimal serum creatinine level after transplantation (P = 0.005) and had the lowest eGFR at Month 3 (P = 0.006). PRA(+)MICA(+) status independently increased the risk for CKDT stage 5 at Month 3 [hazard ratio (HR) 4.92, P = 0.030]. Pre-transplant anti-MICA antibodies were polyspecific and showed stronger reactions when coexisting with anti-HLA antibodies (mean standard fluorescent intensity 112 157 ± 44 426 in HLA(+)MICA(+) sera versus 49 680 ± 33 116 in HLA(-)MICA(+) sera, P = 0.0006). Anti-AYVE supereplet reactivity was significantly higher in HLA(+)MICA(+) versus HLA(-)MICA(+) patients (P < 0.001) and significantly superior than anti-CMGWS supereplet within HLA(+)MICA(+) patients (P = 0.001). Three of 13 anti-MICA(+) pre-transplant sera were positive for the C1q binding assay; one of them (serum 3) exclusively recognized AYVE supereplet with a strong reactivity against MICA*027 antigen (same as MICA*008). Anti-MICA antibodies in anti-HLA-absorbed serum 3 bound native MICA molecules in MICA*008(+) HeLa and PMA/CD28-T-blasts and mediated cell death by activating complement. CONCLUSION: Preformed anti-MICA antibodies may occasionally be cytotoxic by fixing and activating complement. This way they might contribute to worse early kidney graft function.

Frontal fibrosing alopecia and lichen planopilaris in HLA-identical mother and daughter.

Frontal fibrosing alopecia (FFA) is a lymphocyte-mediated scarring alopecia thought to be a variant of lichen planopilaris (LPP). We present a 67-year-old woman with frontal fibrosing alopecia whose daughter was diagnosed to have lichen planopilaris. Both patients had identical human leukocyte antigen (HLA) D types, supporting a phenotypical relationship between the two clinical entities. Interestingly, our patient also had of autoimmune chronic atrophic gastritis, a previously unreported association.

High proportion of pretransplantation activated regulatory T cells (CD4+CD25highCD62L+CD45RO+) predicts acute rejection in kidney transplantation: results of a multicenter study.

BACKGROUND: Prognostic biomarkers of acute rejection (AR) in solid organ transplantation have been addressed in multiple small retrospective studies, and there is a critical need for multicenter studies. Because of their tolerogenic properties, regulatory T cells (Tregs) play an important role in transplant outcome. METHODS: In the present multicenter study, we have retrospectively examined different Treg subpopulations in an independent cohort of kidney transplant patients within first year after kidney transplantation. All participating centers used identical flow cytometry standard operating procedures. RESULTS: Seventy-five renal transplant patients were included, and six of them experienced an AR episode. The activated Treg (aTreg) subpopulation (CD4CD25CD62LCD45RO) was increased in the AR group before transplantation, and an aTreg percentage higher than 1.46% before kidney transplantation conferred an increased risk of AR. The univariate logistic regression model achieved an area under the curve of 81.6%. By including recipient age and thymoglobulin induction as variables in a multivariate logistic regression model, the prediction of AR improved to 92.4%. CONCLUSION: The evaluation of CD4CD25CD62LCD45RO aTreg cells may be useful as pretransplantation predictive biomarker of AR in kidney transplant patients. Definitive confirmation of our results awaits tests in validation groups.