Challenges to the development of antigen-specific breast cancer vaccines

Continued progress in the development of antigen-specific breast cancer vaccines depends on the identification of appropriate target antigens, the establishment of effective immunization strategies, and the ability to circumvent immune escape mechanisms. Methods such as T cell epitope cloning and serological expression cloning (SEREX) have led to the identification of a number target antigens expressed in breast cancer. Improved immunization strategies, such as using dendritic cells to present tumor-associated antigens to T lymphocytes, have been shown to induce antigen-specific T cell responses in vivo and, in some cases, objective clinical responses. An outcome of successful tumor immunity is the evolution of antigen-loss tumor variants. The development of a polyvalent breast cancer vaccine, directed against a panel of tumor-associated antigens, may counteract this form of immune escape

Actualización en síndrome hemolítico urémico atípico: diagnóstico y tratamiento. Documento de consenso

Trobareu una actualització (2015) d'aquest document a: http://hdl.handle.net/2445/99427Haemolytic uraemic syndrome (HUS) is a clinical entity defined as the triad of nonimmune haemolytic anaemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by systemic thrombotic microangiopathy (TMA). Atypical HUS (aHUS) is a sub-type of HUS in which the TMA phenomena are the consequence of decreased regulation of the alternative complement pathway on cell surfaces due to a genetic cause. aHUS is an extremely rare disease that, despite the administration of standard treatment with plasma therapy, often progresses to terminal chronic renal failure with a high associated rate of mortality. In recent years, research has established the key role that the complement system plays in the induction of endothelial damage in patients with aHUS, through the characterisation of multiple mutations and polymorphisms in the genes that code for certain complement factors. Eculizumab is a monoclonal antibody that inhibits the terminal fraction of the complement protein, blocking the formation of a cell membrane attack complex. In prospective studies in patients with aHUS, administering eculizumab produces a rapid and sustained interruption in the TMA process, with significant improvements in long-term renal function and an important decrease in the need for dialysis or plasma therapy. In this document, we review and bring up to date the important aspects of this disease, with special emphasis on how recent advancements in diagnostic and therapeutic processes can modify the treatment of patients with aHUS

Resumen ejecutivo del documento de consenso sobre el manejo de la patología renal en pacientes con infección por VIH

El objetivo de este documento es actualizar las recomendaciones sobre la evaluación y el manejo de la afectación renal en pacientes con infección por el VIH del año 2010. La función renal debe monitorizarse en todos los pacientes e incluir la medida de la concentración sérica de creatinina, la estimación del filtrado glomerular (ecuación CKD-EPI), la medida del cociente proteína/creatinina en orina y un sedimento urinario. El estudio básico de la función tubular ha de incluir la concentración sérica de fosfato y la tira reactiva de orina (glucosuria). En ausencia de alteraciones, el cribado será anual. En pacientes tratados con tenofovir o con factores de riesgo para el desarrollo de enfermedad renal crónica (ERC), se recomienda una evaluación más frecuente. Se debe evitar el uso de antirretrovirales potencialmente nefrotóxicos en pacientes con ERC o factores de riesgo para evitar su progresión. También se revisan las indicaciones de la biopsia renal, cuándo enviar el paciente al nefrólogo y las indicaciones, evaluación y manejo del paciente en diálisis o del trasplante renal

Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy

\ua9 2024 International Society of Nephrology. Introduction: C3 glomerulopathy (C3G) is a complex, chronic, ultra rare, progressive primary glomerulonephritis, resulting from alternative complement pathway overactivation, leading to kidney failure in most patients, and frequent recurrence in transplants. Iptacopan (LNP023) is an oral, proximal complement inhibitor specifically targeting factor B, that selectively inhibits the alternative complement pathway. Methods: This was a phase 2 extension study of 26 adult patients with native kidney (cohort A), or recurrent C3G (post kidney transplantation; cohort B) receiving open label iptacopan. Results: At 12 months, patients in cohort A had a significant reduction in 24-hour urine protein-to-creatinine ratio (UPCR; 57%; P < 0.0001; confidence interval [CI]: 0.31–0.59), an improvement in estimated glomerular filtration rate (eGFR; 6.83 ml/min per 1.73 m2; P = 0.0174; CI: 1.25–12.40), and an increase in serum C3 levels (geometric mean ratio to baseline: 3.53; P < 0.0001; CI: 3.01–4.15). In cohort B, most patients had normal urinary protein excretion at baseline (mean [range] 24-hour UPCR: 121 [9–445]), which was slightly lower by 12 months (21% reduction; CI: 0.48–1.31; P = 0.3151). In cohort B at 12 months, mean eGFR was at baseline values (mean change from baseline: −0.96 ml/min per 1.73 m2; P = 0.7335; CI: −6.60 to 4.69). Cohort B patients had significantly higher serum C3 values at 12 months compared with baseline (ratio:1.96; CI: 1.70–2.27; P < 0.0001). In cohorts A + B combined, the median difference in C3 deposit score on renal biopsy from baseline was −7.00 (CI: −12.00 to 4.00;) at 9 to 12 months treatment with iptacopan. Conclusion: These data provide a clinical rationale for further evaluation of long-term treatment of C3G with iptacopan

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC): Compound heterozygous mutation in the claudin 16 (CLDN16) gene

<p>Abstract</p> <p>Background</p> <p>Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive disorder of renal calcium and magnesium wasting frequently complicated by progressive chronic renal failure in childhood or adolescence.</p> <p>Methods</p> <p>A 7 year old boy was investigated following the findings of marked renal insufficiency and nephrocalcinosis in his 18-month old sister. He too was found to have extensive nephrocalcinosis with increased fractional excretion of magnesium: 12.4% (<4%) and hypercalciuria: 5.7 mmol (< 2.5/24 hours). He had renal impairment, partial distal renal tubular acidosis and defective urinary concentrating ability. Therapy with thiazide diuretics and magnesium supplements failed to halt the progression of the disorder. Both children subsequently underwent renal transplantation. Both children's parents are unaffected and there is one unaffected sibling.</p> <p>Results</p> <p>Mutation analysis revealed 2 heterozygous mutations in the claudin 16 gene <it>(CLDN16</it>) in both affected siblings; one missense mutation in exon 4: C646T which results in an amino acid change Arg216Cys in the second extracellular loop of <it>CLDN16 </it>and loss of function of the protein and a donor splice site mutation which changes intron 4 consensus splice site from 'GT' to 'TT' resulting in decreased splice efficiency and the formation of a truncated protein with loss of 64 amino acids in the second extracellular loop.</p> <p>Conclusion</p> <p>The mutations in <it>CLDN16 </it>in this kindred affect the second extra-cellular loop of claudin 16. The clinical course and molecular findings suggest complete loss of function of the protein in the 2 affected cases and highlight the case for molecular diagnosis in individuals with FHHNC.</p

A scoring system to predict renal outcome in IgA nephropathy: a nationwide 10-year prospective cohort study

Background. Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis, and a substantial number of patients succumb to end-stage renal disease (ESRD). However, prediction of the renal outcome in individual patients remains difficult. We have already published a scoring system using the data in a prospective cohort of IgAN patients followed up from 1995 to 2002