A new human leukocyte antigen class I allele: HLA-A*02:374.

HLA-A*02:374 differs from HLA-A*02:01:01 by one amino acid change at codon 112 where G is replaced by V.

HLA DR-DQ combination associated with the increased risk of developing human HCV positive non-Hodgkin's lymphoma is related to the type II mixed cryoglobulinemia.

This investigation was focused on the contribution of individual human leukocyte antigen (HLA)-DR and -DQ alleles to the human hepatitis C virus (HCV)(+) non-Hodgkin's lymphoma (NHL), with and without mixed cryoglobulinemia (MC), to study whether individual HLA class II alleles are expressed preferentially or equally in human HCV-specific NHL. For this purpose, peripheral blood mononuclear cells were obtained from two groups of patients with HCV(+) NHL and with or without MC (70 and 71 cases, respectively), and from 4575 blood donors. Eighty-three subjects with HCV infection only, and 118 patients with MC, only without lymphoma, were added as additional control groups. Individual HLA-DR and -DQ alleles were determined using high-resolution sequence-based typing and then data were collected by considering the HLA-DRB1 and DQB1 supertypes on the basis of common structural and functional features, proposed by in silico Bioinformatic studies. From the data, it is evidenced that the DR5-DQ3 HLA combination was strongly associated with the HCV (+) MC (+) NHL group of patients compared with bone marrow donor population (P

Selective depletion of the OKT 4+ 4B4+ subset in lymph nodes from HIV+ patients.

We have used 4B4 and 2H4 monoclonal antibodies in conjunction with OKT 4 to quantify T cell subsets in lymph node suspensions from human immunodeficiency virus (HIV) positive subjects with lymphadenopathy syndrome. The data indicate that the reduced OKT 4:OKT 8 ratio was due to a depletion of the OKT 4+ 4B4+ subset. In contrast, there were no differences compared to reactive controls, considering the OKT8+ subpopulation. These alterations may be related to the immunological deficiency associated with HIV infection.

Hepatitis C virus-related hepatocellular carcinoma and B-cell lymphoma patients show a different profile of major histocompatibility complex class II alleles.

Comparison of human leukocyte antigen (HLA) frequencies in patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and in patients with HCV-associated non-Hodgkin's lymphoma (NHL) has not been addressed previously. To this aim, we investigated the distribution of HLA class II alleles in two selected groups of HCV-infected patients. Group 1 included 50 patients with HCV-associated NHL; group 2 included 29 patients with HCV-associated HCC. A control group included 144 hospitalized patients without NHL or HCC and who were negative for HCV, hepatitis B virus, and human immunodeficiency virus antibodies. Polymerase chain reaction sequence DRB1 and DQB1 specific-primer methods were used. DRB1*1101/DQB1*0301 haplotype, which mainly favors the spontaneous clearance of HCV infection, was lower in HCC subjects than in controls, whereas HLA-DRB1*1104/DQB1*0301, was higher in NHL patients. These findings suggest different pathogenic pathways in HCC and in NHL development. In patients with HCV-associated HCC, a major protective role of DQB1*0301 allele, rather than DRB1*11, was found, probably because of a better HLA class II-associated virus clearance. By contrast, the same allele as HLA-DRB1*04 showed an increase in HCV-associated NHL. These data suggest that NHL and HCC development may be associated to a different response with respect to chronic HLA class II-restricted antigen presentation (perhaps a switch toward CD4+Th2 response in NHL?) or, alternatively, that these alleles could be in linkage disequilibrium to unrelated gene(s), or are in synergy with other immunomodulatory genes that may confer increased risk for NHL.

Risk factors for HIV infection in drug addicts from the northeast of Italy.

Prevalence and determinants of HIV infection were assessed in 313 parenteral drug addicts admitted to five Centers for Drug-Addict Assistance and two prisons located in the northeast of Italy (Friuli Venezia-Giulia), an area some distance from the major Italian cities first reached by the AIDS epidemic. The overall prevalence of HIV positivity was also rather high in this area, ie 30% with 24-36% confidence interval. The most important risk factors (besides syringe sharing applicable to all drug addicts), turned out to be of a geographical nature, ie living in Pordenone province (where a US military base is located) or coming from other endemic areas and having travelled long distances in the past three years. Prostitution also seemed to increase the risk of infection, but duration of drug addiction had little effect. In addition to persistent generalized lymphadenopathy (closely linked to HIV infection), reversal of helper:suppressor T-cell ratio was found in 67% of HIV positive individuals, but also in 31% of HIV negative ones. Clinical signs and symptoms strongly linked with HIV positivity were fatigue, weight loss, splenomegaly, fever and nocturnal sweats.

Infections in an Alpine environment: antibodies to hantaviruses, leptospira, rickettsiae, and Borrelia burgdorferi in defined Italian populations.

From 1987 to 1991, a seroepidemiologic survey for antibodies to hantaviruses, leptospira, rickettsiae, and Borrelia was conducted in selected Italian population groups. In the mountainous areas of northeastern Italy, the prevalence of antibody to hantaviruses, as detected by indirect immunofluorescent antibody (IFA) assay, was 7.1%, 4.8%, 4.3%, and 4% in 265 forestry workers, 82 rangers, 395 farmers, and 75 hunters, respectively. Among 299 Alpine soldiers, the prevalence was lower (0.7%). Of those with Hantaan antibody, the reactivity pattern using Hantaan, Puumala, and Fojnica viruses suggested a prevalence of antibody to Hantaan virus, with titers reaching levels of 128. The presence of leptospiral antibodies (by microagglutination test), which included the prevalence of antibodies to Leptospira icterohaemorrhagiae, L. bratislava, and L. saxkoening serotypes, was observed in 10-12% of the farmers and forestry workers in these Alpine mountain regions. Only a few sporadic clinical cases of leptospirosis have been reported from these regions. Antibodies to Borrelia burgdorferi (by IFA) were observed in 19% of the rangers and forestry workers, with lower values in farmers (10%) and hunters (8%). These data suggest the presence of a large number of asymptomatic infections with B. burgdorferi and the leptospires in the densely wooded areas of the Alpine Italian regions. Furthermore, the recent identification of a case of Hantaan acute nephropathy in a man living in the mountainous northeastern area of Italy confirms the presence of hantavirus in the Italian Alpine zones, especially those near the Slovenian border.

HCV and lymphoproliferative diseases.

METHODS: Genomic and replicative forms of HCV-RNA in B lymphocytes were detected by RT-PCR, and HCV genotyping was performed using universal and type-specific primers for the core region. Immunoglobulin gene rearrangement was detected by RT-PCR. RESULTS: The presence of genomic and replicative forms of HCV-RNA in the 5'NC region was investigated on total RNA extracted from subpopulations of PBMC. The frequency of HCV-RNA was higher in the B lymphocytes than in other PBMC. In two patients a larger sized band was present in the B lymphocytes and PMN; this band could represent either another form of HCV-RNA or a cross-reaction between cellular RNA and HCV primers. HCV-RNA detected using primers for the core region was negative in the patients examined. Immunoglobulin monoclonal gene rearrangement was present on the cDNA in all of the HCV and type II cryoglobulinemia positive samples except two; in contrast, it was absent in the HCV positive and cryoglobulinemia negative samples. The analysis of immunoglobulin monoclonal gene rearrangement on DNA showed the presence of new positive samples among the HCV positive, type II cryoglobulinemia negative patients, who had been negative when PCR was performed on cDNA. Denaturing sequencing gel showed clearer results than agarose gel. CONCLUSIONS: The early detection of immunoglobulin monoclonal gene rearrangement and expression is very important because it could provide evidence of the possible lymphoproliferative evolution of HCV infection. In addition, these investigations together with PCR product sequencing could show us the steps in the clonal selection of B lymphocytes towards malignant transformation, in which HCV plays a direct and/or indirect role.

HCV genotypes and cryoglobulinemia.

OBJECTIVE: To evaluate the HCV genotype distribution in subjects affected by cryoglobulinemia in order to verify its possible role in the pathogenesis of the disease and to provide the clinician with a useful datum for therapy. METHODS: Nested PCR with universal and type-specific primers was used for the genotyping. RESULTS: Genotype I (1a) was never present in cryoglobulinemia, while it was present in 7 (4.3%) patients with chronic hepatopathy and in 4 (10.8%) asymptomatic patients. Type II (1b) was present in 28 (58.3%) and in 8 (47.1%) cryoglobulinemic patients with and without hepatopathy, respectively, in 106 (64.6%) patients with chronic hepatitis; in one patient with acute hepatitis; and in 14 (37.9%) asymptomatic patients. Type III (2a) was present in 2 (4.2%) and 2 (11.8%) cryoglobulinemic patients with and without hepatopathy, respectively; in 1 (0.6%) patient with chronic hepatopathy; and in 2 (5.4%) asymptomatic subjects. Type IV (2b) was present in 1 (2.1%) and in 2 (11.8%) cryoglobulinemic patients with and without hepatopathy, respectively; in 5 (3%) patients with chronic hepatopathy; and in 1 (2.7%) asymptomatic subject. Coinfections were present in 42 cases: 6 (12.5%) cryoglobulinemia with hepatopathy, 4 (23.5%) cryoglobulinemia without hepatopathy, 25 (15.3%) chronic hepatopathy, and in 7 (18.9%) asymptomatic subjects. For 41 (15.4%) strains typing was not possible. Eight of the "untypable" strains and 3 strains from patients with coinfection proved to belong to a new genotype. CONCLUSIONS: Genotype II (1b) was the most frequent in patients with and without cryoglobulinemia; genotype I (1a) was absent in all 65 patients with cryoglobulinemia, in whom, however, as in the subjects without cryoglobulinemia, all the other genotypes could be found. An interferon-resistant genotype characterized by an elevated homology with Simmonds' type 2c (rare genotype) was present.

Interferon versus steroids in patients with hepatitis C virus-associated cryoglobulinaemic glomerulonephritis.

BACKGROUND/AIMS: The association between mixed cryoglobulinaemia, cryoglobulinaemic glomerulonephritis, and chronic hepatitis C virus infection has recently been described. The renal disease had usually been treated with immunosuppressive therapy, but, given the presence of viral infection, this therapy is no longer recommended. In this study, we compare steroid vs interferon therapy in a group of patients affected by hepatitis C virus-positive cryoglobulinaemic glomerulonephritis in the stationary phase. PATIENTS/METHODS: The diagnosis of cryoglobulinaemic glomerulonephritis was made bearing in mind standard criteria. Patients were randomly assigned to 2 groups receiving oral prednisone 0.2 mg/kg/die for 6 months (6 patients, group A) or lymphoblastoid interferon 3 MU, three times a week for 6 months [7 patients, group B). Hepatitis C virus-RNA was determined by reverse transcription-polymerase chain reaction and hepatitis C virus genotype according to Okamoto. Hepatitis C virus-RNA quantitation was performed by competitive polymerase chain reaction. RESULTS; The 2 groups were comparable in terms of age and severity of kidney failure. All genotypes of hepatitis C virus were found with a prevalence of Type 1b. In group A, 4 patients showed a partial response; in group B, 1 patient achieved complete remission, 4 a partial response, 2 patients in both groups showed no response. At the end of the treatment, all patients in both groups relapsed. Only 1 patient in group B became hepatitis C virus-RNA negative, and recovered from cryoglobulinaemic glomerulonephritis. CONCLUSIONS: Interferon seems to be an effective drug in the treatment of cryoglobulinaemic glomerulonephritis, but dosage and length of treatment still need to be addressed by large multicentre studies.

[Prevalence and determinants of HIV infection in 581 drug addicts in the Northeastern Italy, from 1984 to 1988]. / Prevalenza e determinanti dell'infezione da HIV in 581 tossico-dipendenti nel Nord Est Italia, dal 1984 al 1988.

Prevalence and determinants for human immunodeficiency (HIV) virus infection was assessed in 581 heterosexual intravenous drug users, recruited from public drug assistance centers in the northeast of Italy between 1984 and 1988. The overall seroprevalence rate for HIV antibody was 39% (95% confidence interval-CI-35-43%). HIV prevalence had risen from 32% in 1984-85 to 47% in 1986-88. Age was not associated with HIV infection risk, whereas gender was, women being at lower risk of infection than men (odds ratio-OR- = 0.7, 95% CI: 0,5-1.0). Seropositivity rates showed a strong east-west geographical gradient: intravenous drug users living in the western part of the study area had a nearly sevenfold higher risk of infection (95% CI = 4.4-13.9) than those living in the eastern part. Sharing of drug injection equipment was by far the most important risk factor. IVDUs who reported to always share injection equipment had a fourfold higher risk of HIV infection, as compared with those who never did (95% CI = 1.6-12.7). The duration of drug addiction (odds ratio = 2.6), the use of heroin in high-incidence cities (odds ratio = 2.3) and of cocaine in addition to heroin (odds ratio = 1.5) and the practice of prostitution (odds ratio = 2.3) were also important determinants of HIV infection. Over the study period, the odds ratios associated with area of residence decreased, whereas those associated with the use of heroin in high-incidence cities and with prostitution increased.

Linoleic acid, vitamin D and other nutrient intakes in the risk of non-Hodgkin lymphoma: an Italian case-control study.

BACKGROUND: Dietary habits have been suggested as a factor related to the increase of non-Hodgkin lymphoma (NHL) incidence in western populations, but the role of individual nutrients is still unclear. PATIENTS AND METHODS: A hospital-based case-control study was conducted in Italy, 1999-2002. CASES: 190 incident, histologically-confirmed NHL cases aged 18-84 years. CONTROLS: 484 subjects admitted to hospital for acute, non-neoplastic diseases unrelated to diet. Dietary habits were assessed by a validated food-frequency questionnaire; nutrient intakes were computed using the Italian food composition database. Odds ratios (ORs) and corresponding 95% confidence intervals (CI) for tertiles of intake of nutrient were computed using the energy-adjusted residual models. RESULTS: Inverse association emerged for polyunsaturated fatty acids (OR=0.6; 95% CI: 0.4-0.9), linoleic acid (OR=0.6; 95% CI: 0.4-0.9), and vitamin D (OR=0.6; 95% CI: 0.4-0.9). The protective effect for linoleic acid (OR=0.3; 95% CI: 0.2-0.7) and vitamin D (OR=0.4; 95% CI: 0.2-0.9) was stronger in women; no differences emerged according to age. Linoleic acid was inversely related to follicular and diffuse large B-cell lymphoma; the protective effect of vitamin D emerged most clearly for follicular subtypes. CONCLUSIONS: Our study suggests that a diet rich in polyunsaturated fatty acids and vitamin D is associated with a reduced risk of NHL.

[Methods of evaluation of the activity of disinfectants through the use of 2 laboratory technics, one manual and one semi-automated]. / Proposta di valutazione dell'attività dei disinfettanti attraverso l'impiego di due techniche di laboratorio, una manuale ed una semiautomatizzata.

We describe Kelsey-Sykes's method for in vitro analysis of the activity of disinfectants and propose some modifications in order to obtain an easier test for routine analysis.