RESUMO
BACKGROUND: Amyloidosis leads to deposition of abnormal protein with beta-pleated sheet structure in specific compartments of the affected organs. The histological localization of these amyloid deposits determines the overall survival of the patient. METHODS: In this study we have assessed the histological localization and severity of amyloid deposition in 35 patients with biopsy-proven renal amyloidosis and have compared those to clinical parameters, histo-pathological injury criteria and respective patient outcome. Comparisons were statistically analyzed using thus comparison between the different study groups, which was done using Student t-test and analysis of variance. RESULTS: We find that the glomerulus is by far the most commonly and most severely affected renal compartment and patients with severe glomerular amyloidosis advance faster towards end stage renal disease (ESRD) and death, compared to those patients without glomerular amyloid deposits. Patients with severe glomerular amyloidosis showed higher serum creatinine and urine protein levels, while patients with severe vascular amyloidosis showed higher levels of interstitial inflammatory infiltrate. CONCLUSION: In kidneys affected by amyloidosis, the amyloid proteins are predominantly deposited along vessels, especially the small vessels including glomerular capillary loops. The severity of glomerular amyloid deposition enhances the risk of developing ESRD and increases the risk for premature death.
Assuntos
Amiloide/metabolismo , Amiloidose/patologia , Falência Renal Crônica/patologia , Glomérulos Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/metabolismo , Amiloidose/mortalidade , Biópsia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Rim/metabolismo , Rim/patologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/mortalidade , Glomérulos Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/patologia , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
PURPOSE: HHLA2 (B7H7/B7-H5/B7y) is a newly identified B7 family member that regulates human T-cell functions. However, its protein expression in human organs and significance in human diseases are unknown. The objective of this study was to analyze HHLA2 protein expression in normal human tissues and cancers, as well as its prognostic significance, to explore mechanisms regulating HHLA2 expression, and to identify candidate HHLA2 receptors. EXPERIMENTAL DESIGN: An immunohistochemistry protocol and a flow cytometry assay with newly generated monoclonal antibodies were developed to examine HHLA2 protein. HHLA2 gene copy-number variation was analyzed from cancer genomic data. The combination of bioinformatics analysis and immunologic approaches was established to explore HHLA2 receptors. RESULTS: HHLA2 protein was detected in trophoblastic cells of the placenta and the epithelium of gut, kidney, gallbladder, and breast, but not in most other organs. In contrast, HHLA2 protein was widely expressed in human cancers from the breast, lung, thyroid, melanoma, pancreas, ovary, liver, bladder, colon, prostate, kidney, and esophagus. In a cohort of 50 patients with stage I-III triple-negative breast cancer, 56% of patients had aberrant expression of HHLA2 on their tumors, and high HHLA2 expression was significantly associated with regional lymph node metastasis and stage. The Cancer Genome Atlas revealed that HHLA2 copy-number gains were present in 29% of basal breast cancers, providing a potential mechanism for increased HHLA2 protein expression in breast cancer. Finally, Transmembrane and Immunoglobulin Domain Containing 2 (TMIGD2) was identified as one of the receptors for HHLA2. CONCLUSIONS: Wide expression of HHLA2 in human malignancies, together with its association with poor prognostic factors and its T-cell coinhibitory capability, suggests that the HHLA2 pathway represents a novel immunosuppressive mechanism within the tumor microenvironment and an attractive target for human cancer therapy.
Assuntos
Imunoglobulinas/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Células 3T3 , Sequência de Aminoácidos , Animais , Antígenos CD28/química , Antígenos CD28/metabolismo , Linhagem Celular Tumoral , Variações do Número de Cópias de DNA , Feminino , Expressão Gênica , Glicosilação , Humanos , Imunoglobulinas/genética , Metástase Linfática , Camundongos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Processamento de Proteína Pós-Traducional , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Multiple myeloma (MM) is a plasma cell disorder, which often causes parenchymal kidney disease. Light chain (LC) cast nephropathy represents the most common renal lesion. In some instances, LC crystals precipitate within renal tubular lumens and deposit within proximal tubular cell cytoplasms. Importantly, urine microscopy in such patients can provide insight into the underlying LC-related lesion. Here we present two patients with MM complicated by acute kidney injury (AKI) where LC crystalline casts were observed on urinary sediment analysis. Kidney biopsy revealed acute tubular injury with LC crystal casts within both tubular lumens and renal tubular epithelial cell cytoplasms. These findings suggest that the urinary sediment may be a non-invasive way to diagnose LC crystalline-induced AKI in patients with MM.
Assuntos
Injúria Renal Aguda/diagnóstico , Cadeias Leves de Imunoglobulina/urina , Mieloma Múltiplo/urina , Urinálise/métodos , Injúria Renal Aguda/urina , Biópsia/métodos , Cristalografia , Citoplasma/patologia , Células Epiteliais/patologia , Humanos , Imunoglobulina A/urina , Imunoglobulina G/urina , Cadeias kappa de Imunoglobulina/urina , Cadeias lambda de Imunoglobulina/urina , Túbulos Renais/patologia , Masculino , Microscopia , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológicoRESUMO
Bile acid nephropathy, also known as cholemic nephrosis or nephropathy, is an entity that can be seen in patients with severe cholestatic liver disease. It typically is associated with acute kidney injury (AKI) with various forms of hepatic disease. Most often, patients with severe obstructive jaundice develop this lesion, which is thought to occur due to direct bile acid injury to tubular cells, as well as obstructing bile acid casts. Patients with end-stage liver disease also can develop AKI, in which case a more heterogeneous lesion occurs that includes hepatorenal syndrome and acute tubular injury/necrosis. In this circumstance, acute tubular injury develops from a combination of hemodynamic changes with some contribution from direct bile acid-related tubular toxicity and obstructive bile casts. We present a case of AKI due to bile acid nephropathy in a bodybuilder who developed severe cholestatic liver disease in the setting of anabolic androgenic steroid use.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Anabolizantes/efeitos adversos , Androgênios/efeitos adversos , Ácidos e Sais Biliares , Metandrostenolona/efeitos adversos , Nandrolona/efeitos adversos , Esportes , Esteroides/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Testosterona/efeitos adversos , Adulto , Humanos , MasculinoRESUMO
Patients with hypopigmented mycosis fungoides (HMF) present at a younger age than those with classic MF. Our goal was to describe the clinical presentation, histopathologic features and long-term outcome in patients who developed HMF before the age of 21. It was observed that among 69 pediatric patients diagnosed with MF between 1992 and 2010, 50 had HMF. Thirty-five patients had clinical follow-up. There were 37 males and 32 females with a mean age of 13.6 years. Most patients were African American or Hispanic and presented with multiple hypopigmented patches. All biopsies showed epidermotropism of T-lymphocytes, whereas fibroplasia and lichenoid infiltrate were variable. All specimens tested were CD8+. Treatment modalities included topical steroids, narrow band ultraviolet B and psoralen and ultraviolet A. HMF patients were followed for <1-12 years. Most children responded to treatment, but recurrence rates were high. One patient progressed to plaque/tumor stage. Others did not progress; however, many were lost to follow-up. We present a large cohort of children with HMF and report on the features of disease and progression. A major difference in histology of HMF was lack of fibroplasia and lichenoid infiltrate, probably because of presentation in the early patch stage. Most patients have a waxing-and-waning course and relapse after discontinuation of therapy, requiring repetitive treatment.