Identification of a novel HLA-B*15 variant allele, HLA-B*15:276, in an umbilical cord blood donor.

A newly identified allele, named HLA B*15:276, differs from B*15:01:01:01 by the single nucleotide substitution 511T-C at codon 147 (Trp → Arg) in exon 3.

A novel allele, HLA-DPB1*296:01, identified by sequence-based typing in a Thai bone marrow donor.

A novel HLA-DPB1 allele, named DPB1*296:01, was identified in the Thai mother of a hematologic patient.

Identification and characterization of a novel HLA-A allele, HLA-A*68:105, by genomic sequencing.

A novel HLA-A allele, HLA-A*68:105, was detected by sequence-based typing (SBT) in an Italian bone marrow donor. It differs from HLA-A*68:01:02 at five nucleotides, three intronic, nt 699 T->G (intron 2), nt 705 T->C (intron 2) and nt 2770 G->A (intron 7), and two located in exon 3, at positions 726 A-G (codon 94 Ile->Val) and 733 T-G (codon 97 Arg->Met), respectively.

Identification of a novel HLA-DRB1*13 variant allele: DRB1*13:154.

A newly identified allele, named HLA-DRB1*13:154, differs from DRB1*13:13 by the single nucleotide substitution 227T-A at codon 47 in exon 2.

A novel HLA-DRB1 allele, DRB1*01:54, identified by sequence-based typing.

The new HLA DRB1*01:54 differs from DRB1*01:02:01 by one nucleotide at exon 2.

Solvent detergent vs. fresh frozen plasma in cirrhotic patients undergoing liver transplant surgery: a prospective randomized control study.

BACKGROUND: Although orthotopic liver transplantation (OLT) is nowadays considered standard practice at experienced centres, it can still be affected by a significant risk of massive bleeding and its related complications. Solvent/detergent plasma (S/D Plasma) has been proposed as an alternative to fresh frozen plasma (FFP) to curtail such complications. This study aimed at evaluating the efficacy of S/D Plasma in OLT patients by comparing it to FFP. MATERIALS AND METHODS: Sixty-three OLT patients were randomized into two groups depending on whether they were transfused with FFP or S/D plasma. A thromboelastography-based protocol aimed at achieving and maintaining predetermined coagulation goals was used to guide plasma transfusions. At the beginning and the end of surgery, standard laboratory coagulation tests were performed together with the assessment of the VII, VIII, V, XII factors and S protein blood levels. RESULTS: The two study groups equally achieved the thromboelastography goals but with a reduced amount of transfusions in the S/D plasma group (P < 0.0001). At the end of surgery, factors V and XII and S protein blood levels were lower in the S/D plasma patients who also showed lower INR, aPTT and antithrombin III levels. CONCLUSION: In cirrhotic patients undergoing OLT, the use of S\D plasma associated with thromboelastography allows the same clinical results but with a significant reduction in the amount of plasma transfusions.

A novel HLA-B*51:01:29 allele identified by sequence-based typing.

A novel HLA-B*51:01:29 allele differs from B*51:01:01 at one nucleotidic position in the exon 3.

Identification of a novel HLA-DRB1 allele through sequence-based typing of an Italian patient candidate for kidney transplant.

In this report, we describe the identification of the novel HLA-DRB1*13:120 that differs from the closest matching allele HLA-DRB1*13:65 at two nucleotidic position in the exon 2.

The combination of immunosuppressive drugs with 8-methoxypsoralen and ultraviolet a light modulates the myeloid-derived dendritic cell function.

The functional properties of myeloid dendritic cells (DCs) differ, depending on microenvironmental factors as well as on their stage of maturation. The main approaches for the selective enhancement of the tolerogenic properties of DCs include the induction of a pharmacological arrest of the DCs maturation and the genetical engineering of DCs expressing immunosuppressive molecules. Several immunosuppressive/anti-inflammatory agents have been discovered that potentially inhibit DC maturation and immunogenicity. Photopheresis (ECP) is an immunomodulatory therapy in which leucocytes are exposed to 8-methoxypsoralen (8-MOP) and ultraviolet (UV) A radiation (PUVA). The combination of ECP with immunosuppressive agents has demonstrated efficacy in the management of transplanted patients by reducing either the incidence of organ rejection or the pharmacological toxicity. In particular, we have observed in hepatitis C virus (HCV)-positive patients that the same combination has reduced the immunosuppressive burden and improved sustainability and efficacy of pre-emptive antiviral therapy after liver transplantation. Therefore, in our work we investigated the in vitro effects of PUVA, combined with immunosuppressive drugs (IDs), on both in vitro human DC generation and maturation, in order to contribute to understanding the immunological mechanisms underlying this pharmacological combination. Monocyte PUVA-treatment was performed by using an in vitro experimental protocol that we previously described. PUVA-treated or -untreated highly purified CD14+ cells were incubated with the association of the immunosuppressive drugs, used in the management of liver transplantation, at two different concentrations, in the presence of IL-4 and GM-CSF. The treatment with IDs at the highest concentration (corresponding to that used in clinical practice), alone or in association with PUVA, induced an immunosuppressive effect, by impairing both DC generation and maturation. Neither immunosuppressive drugs at the lowest concentration nor their combination with PUVA affected myeloid DC generation, but modified DC functions, strengthening the induction of a tolerogenic pattern. As this ID concentration was arbitrarily chosen, further experiments could highlight whether lower concentrations than those used in clinical practice would elicit the same effect on DCs and potentially improve their functional properties. This work describes an original experimental approach exploring the in vitro mechanism of action of the combined procedure of PUVA with immunosuppressive drugs, used in liver transplantation, on DCs generation and function. Our results contribute to the knowledge of the mechanisms of action of this combined procedure on DCs, suggesting useful therapeutic implications for the in vivo therapy.

Identification of a novel HLA-DRB1*11 variant allele, DRB1*1189.

Here, we describe the identification of a novel human leukocyte antigen (HLA)-DRB1 allele, DRB1*1189, that was found in an Italian Caucasian individual. This sequence differs from HLA-DRB1*1134 by three nucleotide exchange at positions 286 (C-->T), 296 (A-->G), and 308 (C-->A) in exon 2.

Feasibility and safety of granulocytapheresis in Crohn's disease: a prospective cohort study.

BACKGROUND AND OBJECTIVE: This study evaluated the feasibility and safety of granulocytapheresis (GCAP) in inducing and maintaining remission in refractory Crohn's disease. The relationship between the clinical outcomes and the location (ileal or ileocolonic) of disease was also assessed. PATIENTS: We evaluated 16 patients with ileal location (group A), 14 with ileocolonic location (group B). The patients underwent five sessions (1 session/wk) of GCAP (Adacolumn(TM)). CDAI was measured at the end of the GCAP, at 6, 9 and 12 months. RESULTS AND CONCLUSIONS: No major complications were observed. At the end of GCAP, 19 (63.3%) patients showed a clinical remission: 10 (62.5%) in group A versus 9 (64.2%) in group B. At 6 months, 16 (53.3%) of the cases had maintained remission: 9 (56.2%) in group A versus 7 (50.0%) in group B. At 9 months, 13 (43.3%) patients had maintained remission: 7 (43.7%) in group A versus 6 (42.8%) in group B. At 12 months, 12 (40%) patients were still in clinical remission: 7 (43.7%) in group A versus 5 (35.7%) in group B. Risk of relapse was not related to disease location. The procedure was well tolerated and feasible in an important percentage of Crohn's disease patients.

Partial remission of refractory RA after Adacolumn cytapheresis: a case report.

We report on a female case of rheumatoid arthritis (RA) with hepatitis C virus comorbidity. The patient was treated once weekly over ten consecutive weeks with Adacolumn device. Clinical assessment and HCV-RNA concentration were monitored at weeks-1, 4, 9, 14 and during follow-up over 6 months. At the end of the treatment: the number of tender and swollen joints, patient's global assessment of disease activity (VAS), physician's VAS, C-reactive protein (CRP) decreased, respectively; ACR response was >20. This improvement was maintained for over 2 months. At week 38, the patient was re-treated achieving again an ACR response >20.

Potential applications of extracorporeal photopheresis in liver transplantation.

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy performed through a temporary peripheral venous access with documented efficacy in heart and renal transplantation. We originally reported that ECP represented a valuable alternative to treat graft rejection in selected liver transplant (OLT) recipients. We have investigated potential applications of ECP for prophylaxis of allograft rejection. The first field explored was the use of ECP for delayed introduction of calcineurin inhibitors (CNI) among high-risk OLT recipients seeking to avoid CNI toxicity. In 42 consecutive patients that we assigned to prophylaxis with ECP, we were able to delay CNI introduction after postoperative day 8 in one-third of them. The second field was the use of ECP for prophylaxis of acute cellular rejection among ABO-incompatible OLT recipients. In our experience, none of 11 patients treated with ECP developed a cell-mediated rejection. The third field was ECP application in hepatitis C virus-positive patients seeking to reduce the immunosuppressive burden and improve sustainability and efficacy of preemptive antiviral treatment with interferon and ribavirin. Among 78 consecutive patients, we were able to start preemptive antiviral treatment in 69.2% of them at a median time from OLT of 14 days (range = 7 to 130 days). Thirty-six (66.7%) patients completed the treatment course with an end of treatment virological response of 50.0% and a sustained virological response of 38.9%. These preliminary results await validation in larger prospective studies with longer follow-up periods.

Characterization of a novel HLA-C allele, HLA-C*04:288, in an Italian patient.

The novel HLA-C*04:288 differs from HLA-C*04:01:01:06 by a single nucleotide substitution in exon 2.

Identification of two new HLA class I alleles in Italian bone marrow donors: A*31:125 and B*44:269.

Two novel alleles, HLA-A*31:125 and HLA-B*44:269, are described in Italian bone marrow donors.

Treatment of patients with acute ulcerative colitis: conventional corticosteroid therapy (MP) versus granulocytapheresis (GMA): a pilot study.

AIM: The aim of our pilot study is to report the efficacy of granulocytapheresis in patients with acute ulcerative colitis with respect to the use of conventional corticosteroids such as methylprednisolone. METHODS: The activity of disease was evaluated by clinical activity index and endoscopic index. Forty patients with acute ulcerative colitis were randomly divided in two groups of 20 subjects each: one group was treated with five sessions of granulocytapheresis, the other one with methylprednisolone for 5 weeks. Complete response was defined as clinical activity index lower than 6 and endoscopic index lower than 4 after 6 weeks of follow-up. Partial response was defined as clinical activity index lower than 6 but endoscopic index more than 4 after 6 weeks of follow-up. All the conditions not included are classified as nonresponders. RESULTS: All the patients completed the trial. Complete clinical response was observed in 70% of patients treated with granulocytapheresis versus 60% of patients treated with methylprednisolone. A partial response was observed in 20% of patients treated with granulocytapheresis versus 15% of patients treated with methylprednisolone. During the sessions of granulocytapheresis only a transient mild headache was recorded in 10% of patients, while side effects were more common (50%) in the patients treated with methylprednisolone. CONCLUSION: Granulocytapheresis represents a new and promising approach to active ulcerative colitis. In fact, even if more expensive than conventional corticosteroids, it seems slightly more effective and, above all, with side effects much less frequent and serious. Thus, granulocytapheresis cycles could be prolonged or repeated, if necessary, in more severe diseases without significant risks for the patients.

Characterization of a novel HLA-DRB1 allele, HLA-DRB1*13:215, in an Italian bone marrow donor.

One nucleotide substitution at residue 142 of the HLA-DRB1*13:01:01 results in a new allele, HLA-DRB1*13:215.

Combined twice-daily plasma exchange and continuous veno-venous hemodiafiltration for bridging severe acute liver failure.

Aiming to remove the toxins produced during the course of severe hepatic failure, we combined hemodiafiltration and plasma exchange (patient plasma replaced by fresh frozen plasma in a twice-daily regimen) for treatment of five patients: two affected by primary nonfunction of a liver graft and three by fulminant hepatic failure. The simultaneous use of the two extracorporeal techniques allowed a rapid reduction in the administration of vasoactive drugs and a rapid, significant decrease in the indices of liver necrosis. Native liver functional recovery occurred in one case, and the wait for a second graft was made possible in the other four. Although it has been reported that the detoxifying efficacy of plasma exchange is optimal when the replaced volume of plasma is high, such a technique requires both long treatment times and high blood flows in the extracorporeal circuit, making it often hemodynamically intolerable. Our approach leads to replacement of smaller volumes, allowing lower blood flows that are better tolerated despite the often unstable hemodynamics of these patients. Liver transplantation and retransplantation remains the definite therapy for severe liver failure or primary nonfunction. However, the organ waiting time is unpredictable and often does not coincide with the patients' clinical needs. Thus alternative strategies must be developed until a suitable donor is found or there is spontaneous recovery. From this point of view, in our albeit limited experience, twice-daily plasma exchange combined with hemodiafiltration has proved to be an effective therapeutic approach.

Plasma exchange for polyradiculoneuropathy following kidney transplantation: a case report.

We describe a case of polyradiculoneuropathy (PRN) following living donor kidney transplantation, without clinical evidence of preexisting infection. In this study plasma exchange treatment resulted 6 days later in improvement in extremity weakness and paresthesias in the upper and lower extremities. Total neurological recovery was obtained 3 months after the onset of symptoms.