Targeting the Endothelin A Receptor in IgA Nephropathy

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and carries a substantial risk of kidney failure. New agency-approved therapies, either specifically for IgAN or for chronic kidney disease (CKD) in general, hold out hope for mitigating renal deterioration in patients with IgAN. The latest addition to this therapeutic armamentarium targets the endothelin-A receptor (ETAR). Activation of ETAR on multiple renal cell types elicits a host of pathophysiological effects, including vasoconstriction, cell proliferation, inflammation, apoptosis, and fibrosis. Blockade of ETAR is renoprotective in experimental models of IgAN and reduces proteinuria in patients with IgAN. This review discusses the evidence supporting the use of ETAR blockade in IgAN as well as addressing the potential role for this class of agents among the current and emerging therapies for treating this disorder.</p

Targeting the Endothelin A Receptor in IgA Nephropathy

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and carries a substantial risk of kidney failure. New agency-approved therapies, either specifically for IgAN or for chronic kidney disease (CKD) in general, hold out hope for mitigating renal deterioration in patients with IgAN. The latest addition to this therapeutic armamentarium targets the endothelin-A receptor (ETAR). Activation of ETAR on multiple renal cell types elicits a host of pathophysiological effects, including vasoconstriction, cell proliferation, inflammation, apoptosis, and fibrosis. Blockade of ETAR is renoprotective in experimental models of IgAN and reduces proteinuria in patients with IgAN. This review discusses the evidence supporting the use of ETAR blockade in IgAN as well as addressing the potential role for this class of agents among the current and emerging therapies for treating this disorder.</p

Status in Diffuse Large B Cell Lymphoma not otherwise specified: A single center study from Argentina

BackgroundDiffuse large B-cell Lymphoma (DLBCL) is a heterogeneous disease. Based on Hans? algorithm, DLBCL not otherwise specified (NOS) is classified by cell-of-origin into germinal center B-cell (GCB) and non-GCB subtypes. Non-GCB ones have frequently NF-kB pathway activation and worse prognosis compared to GCB cases. MYD88 is an adaptor protein of toll-like and IL-1 receptor signalling, leading downstream NF-kB pathway activation. MYD88 L265P mutation confers the protein constitutional activation. This mutation is present in around 20% of non-GCB subtype, and rarely found in GCB subtype of DLBCL. The prognostic value of MYD88 L265P mutation in DLBCL has been matter of controversy.AimsThe aim of the study was to determine the prevalence of MYD88 L265P mutation in DLBCL NOS cases of Argentina, and compare it with previous reports in the literature.MethodsA retrospective cohort of 73 DLBCL NOS cases diagnosed in the Italian Hospital of Buenos Aires (Argentina) between 2010 and 2016 was studied. Complete clinical records, Hans? algorithm, and available material for molecular testing were inclusion criteria. Patients with prior diagnosis of low-grade lymphoma or diagnosis of immunodeficiency-associated, post-transplant, EBV+, primary mediastinal, primary testicular, primary CNS, primary effusion, leg-type or intravascular DLBCL were excluded. DNA was extracted from tissue blocks using QIAamp mini kit (Qiagen). MYD88 L265P was assessed using an in-house allele-specific probe-based Real-Time PCR assay. Positive (primary testicular DLBCL) and negative controls (tonsil) were added to each run. Every case was checked subsequently using qBiomarker MYD88 L265P Somatic Mutation Assay (Qiagen). Prevalences were expressed as percentage, confident intervals were calculated using Clopper-Pearson exact method. Kaplan Meier curves and Log-rank test were used to evaluate overall survival (OS).Results36 patients (49,31%) were female, and median age at diagnosis was 66 years (range 26-89). 33 patients (45,20%) had extranodal involvement (gastrointestinal tract: 14 cases; liver: 5 cases; bone: 4 cases; other locations: 10 cases). 44 cases (60,27%) were GCB and 29 (39,73%) were non-GCB DLBCLs. MYD88 L265P mutation was present in 2 cases (2,74% ; CI 95%: 0,33-9,55%) among all DLBCLs, including 1 GCB case (2,27% ; CI 95%: 0,06-12,02%) and 1 non-GCB case (3,45% ; CI 95%: 0,09-17.76%). There was no significant association between MYD88 L265P status, Hans´algorithm subtype, sex, age or Ki67 index and OS.ConclusionIn the analyzed population, the prevalence of GCB and non-GCB subtypes among DLBCL NOS cases was similar to international reports, although we did not find significant difference between both groups regarding OS (p=0,712). MYD88 L265P mutation was found only in 2 patients (1 GCB and 1 non-GCB), accounting for 2,74% (CI 95%: 0,33-9,55%) and 2,27% (CI 95%: 0,06-12,02%) of all DLBCL NOS and non-GCB cases, respectively. Both prevalences are significantly lower than those published in 2017 by Lee et al. in a meta-analysis, where they found that MYD88 L265P is present in 16% (CI 95%: 15-18,09%) and 20,63% (CI 95%: 18,41-23%) of patients among all DLBCLs and non-GCB subtype, respectively. However, MYD88 L265P prevalence in primary SNC, testicular and leg-type DLBCLs diagnosed in our institution are similar to the literature (data not shown).Fil: Jauk, Federico. Hospital Italiano; ArgentinaFil: Kohan, Dana. Hospital Italiano; ArgentinaFil: Ortega, Leandro Ismael. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diaz de Arce, Heidy. Hospital Italiano; ArgentinaFil: Cristaldo, Nancy. Hospital Italiano; ArgentinaFil: RANUNCOLO, Stella Maris. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Warley, Fernando. Hospital Italiano; ArgentinaFil: Otero, Victoria. Hospital Italiano; ArgentinaFil: Garcia Rivello, Hernan Jorge. Hospital Italiano; Argentina24th Congress of the European Hematology AssociationAmsterdamHolandaEscuela Europea de Hematologí

Ileitis as presentation of lymphoma in Wiskott-Aldrich syndrome

El síndrome de Wiskott-Aldrich (SWA) es un raro síndrome de inmunodeficiencia primaria ligado al cromosoma X que se asocia con aumento de incidencia de infecciones, trastornos autoinmunes y neoplasias. Se presenta el caso de un varón de 41 años con diagnóstico de síndrome de Wiskott-Aldrich y cuadro de ileítis como forma de presentación de un síndrome linfoproliferativo. La ileítis, en el contexto del paciente, representa un problema clínico dado el gran número de diagnósticos diferenciales (enfermedad inflamatoria intestinal, infecciones, neoplasias y enfermedades linfoproliferativas) por lo que suele requerir diagnóstico anatomopatológico y consideraciones particulares respecto al posterior tratamiento específico.Wiskott-Aldrich syndrome is a rare X chromosome-linked primary immunodeficiency syndrome associated with an increased incidence of infections, autoimmune disorders and neoplasms. We present the case of a 41-year-old man with a diagnosis of Wiskott-Aldrich syndrome with ileitis as a form of presentation of a lymphoproliferative syndrome. The ileitis, in the context of the patient, represents a clinical challenge given the large number of differential diagnoses (inflammatory bowel disease, infections, neoplasms and lymphoproliferative diseases), so it usually requires anatomopathological diagnosis and particular considerations regarding the subsequent specific treatment.Fil: Odstrcil Bobillo, María Silvina. Hospital Italiano; ArgentinaFil: Kohan, Dana. Hospital Italiano; ArgentinaFil: Heller, Paula Graciela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Otero, Victoria. Hospital Italiano; ArgentinaFil: Russo, Maria Paula. Hospital Italiano; ArgentinaFil: Basquiera, Ana Lisa. Hospital Italiano; Argentin