Hereditary coagulation factor XI deficiency: a rare or neglected disease? Results from a retrospective, single-centre cohort in northern Italy.

To examine real-life clinical data regarding hereditary factor XI (FXI) deficiency from a secondary care centre. Retrospective review of clinical records for every FXI:C 0.7 IU/ml or less reported from 2012 to 2020. Seventy-nine patients were included. Six (7.6%) had a severe deficiency (FXI:C <0.2 IU/ml). Only 55 (69.6%) patients were referred to the Haemostasis Centre. Among them, six (15%) were subsequently not identified at increased haemorrhagic risk before a surgical/obstetrical procedure. Thirty-three (41.8%) experienced at least one bleeding event, minor (25 patients) and/or major (16 patients). Minor bleedings were predominantly spontaneous and more frequent in women, major events were mainly provoked. No correlation was found between FXI:C and risk of bleeding ( P  = 0.9153). Lower FXI:C, but not a positive bleeding history, was related with higher likelihood of being referred to the Haemostasis Centre ( P  = 0.0333). Hereditary FXI deficiency prevalence is likely underestimated, real-life clinical practices outside reference centres could be suboptimal.

[Post-transplant recurrence of glomerulonephritis: a complex clinical case]. / Recidiva di glomerulonefrite post-trapianto: un caso clinico complesso.

Lupus nephritis (LN) seldom recurs in a grafted kidney. By contrast, primary membranoproliferative glomerulonephritis (MPGN), which has been included, along with hemolytic uremic syndrome and age-related maculopathy, among the complement dysregulation diseases, has a high recurrence rate and is considered a contraindication to living-donor kidney transplant because of the poor prognosis. We report the case of a young girl with LN-related chronic renal failure who underwent a living donor transplant from her mother. After four months she had a recurrence that did not match the criteria for LN. Graft biopsies and revision of the clinical course pointed to type II MPGN on the basis of a lack of ARA criteria, persistent isolated low C3 levels, and response to plasma therapy. If confirmed by genetic analysis, the patient might benefit from treatment with the monoclonal antibody against the C5-C9 complex, eculizumab.

Identification and characterization of a new autoimmune protein in membranous nephropathy by immunoscreening of a renal cDNA library.

Membranous Nephropathy (MN) represents a large amount of Nephrotic Syndromes in the adult population and its definitive diagnosis is currently carried out through biopsy. An autoimmune condition has been demonstrated in idiopathic MN (iMN) in which some kidney structures are targeted by patient autoantibodies. Some candidate antigens have been described and other likely involved target proteins responsible for the disease are not known yet. In this work our aim is to identify these proteins by screening a lambda-phage library with patients' sera. We enrolled four groups of patients: two MN groups of 12 full iMN patients; one control group of 15 patients suffering from other renal diseases; one control group of 15 healthy individuals. A commercial cDNA phagemide library was screened using the above described sera, in order to detect positive signals due to antigen-antibody bond. We detected one phagemide clone expressing a protein which was shown to be targeted by the antibodies of the iMN sera only. Control sera were negative. The sequence analysis of cDNA matched the Synaptonemal Complex protein 65 (SC65) coding sequence. Further proteomic analyses were carried out to validate our results. We provide evidence of an involvement of SC65 protein as an autoimmune target in iMN. Considering the invasiveness and the resulting risk coming from renal biopsy, our ongoing aim is to set a procedure able to diagnose affected patients through a little- or non-invasive method such as blood sampling rather than biopsy.