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Biomedical subjects

G Longombardo

Publications and source records attributed to G Longombardo.

At least 37 records · Page 2Linked to original sources

Hepatitis C virus infection in patients with non-Hodgkin's lymphoma.

Hepatitis C virus (HCV), which is both a hepatotropic and a lymphotropic virus, has been proposed as a possible causative agent of mixed cryoglobulinaemia. This 'benign' lymphoproliferative disorder can switch over to a malignant B-cell non-Hodgkin's lymphoma (NHL). Therefore HCV infection has been investigated in a series of 50 unselected Italian patients with B-cell NHL. Antibodies against HCV were found in 30% of NHL and HCV viraemia in 32% of cases. HCV-related markers were detected in 34% (17/50) of our NHL patients; this prevalence is particularly significant when compared with HCV seropositivity in Hodgkin's lymphoma (3%) and healthy controls (1.3%).

Adult↗

Autoantibodies from mixed cryoglobulinaemia patients bind glomerular antigens.

Mixed cryoglobulinaemia (MC) is a disorder characterized by the presence of large amounts of cryoprecipitating IgM-IgG complexes. An immune complex glomerulonephritis develops in one third of all patients, but its occurrence does not seem related to the amount of cryoglobulins in the sera, nor to their complement-fixing ability. In this study we investigated the presence of IgG antibodies reactive with kidney antigens in 33 MC patients (11 with glomerulonephritis, 22 without renal involvement). A total glomerular extract was run on a 10% acrylamide gel, blotted to nitrocellulose and probed with the patients' sera. Sera from half of the patients without renal involvement reacted with several glomerular antigens whose molecular weight ranged between 200 and 29 kD. In the group with renal involvement, sera from 7/11 patients reacted with an antigen of 50 kD, which is also expressed in thymus, but not in the heart or liver. In a follow-up study of four patients with renal involvement, the amount of serum antibody specific for the 50-kD antigen fluctuated, either spontaneously or in response to therapy. These results show that antibodies specific for glomerular antigens are detectable in MC sera. The immune response against a 50-kD antigen expressed in the kidney and thymus seems to be restricted to a subset of MC patients with renal involvement. Circulating autoantibodies specific for glomerular antigens might contribute to the induction of glomerulonephritis in MC forming immune complexes in situ.

Antibody Specificity↗

Hepatitis C virus chronic infection as a common cause of mixed cryoglobulinaemia and autoimmune liver disease.

OBJECTIVES: Mixed cryoglobulinaemia (MC) and autoimmune chronic hepatitis (AI-CH) are frequently associated with hepatitis C virus (HCV) chronic infection. Because HCV represents a possible common aetiological factor, the aim of the present study is to investigate the clinico-serological alterations of both MC and AI-CH and to verify a possible overlap between these disorders. SETTING: Patients from three tertiary referral centres. SUBJECTS: Two Italian series of 88 MC patients and 30 AI-CH type 1 were studied. RESULTS: MC and AI-CH share several clinico-serological features. The patients' mean age (MC vs. AI-CH: 60 +/- 9 vs. 57 +/- 13 years), disease duration (10.5 +/- 5 vs. 9.6 +/- 6 years), and female/male ratio (3.4 vs. 3.3) were very similar in the two series. Typical hallmarks of MC, i.e. purpura, arthralgias, and weakness, circulating mixed cryoglobulins with rheumatoid factor activity, and hypocomplementemia were also recorded in a significant number of AI-CH patients. Similarly, chronic active hepatitis was found in 68% of MC patients and its histological and serological alterations were comparable with those of AI-CH; moreover, amongst various autoantibodies, antinuclear antibodies and/or anti-smooth-muscle antibodies were detected in half of the cases of MC. Anti-HCV antibodies, detected by second-generation Chiron ELISA and RIBA, were present in a high percentage of both MC and AI-CH (94 vs. 80%), and frequently associated with HCV viraemia (86 vs. 77%). Finally, anti-GOR, the HCV-related autoantibodies, were found in half cases of MC and AI-CH. CONCLUSIONS: On the whole, these data suggest that HCV in combination with other infectious and environmental and genetic factors can trigger a complex immunological disorder with different clinical patterns.

Aged↗

Infection of peripheral blood mononuclear cells by hepatitis C virus in mixed cryoglobulinemia.

A striking association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has been shown; thus, HCV seems to play an important etiopathogenetic role in this lymphoproliferative disorder. Because HCV is both a hepatotropic and lymphotropic virus, this study aimed to investigate the prevalence of HCV infection of peripheral blood mononuclear cells (PBMCs) in a series of 16 patients with type II (IgMk) MC. Antibodies against HCV were detected by commercially available kits (Second Generation Chiron enzyme-linked immunosorbent assay [ELISA] and recombinant-based immunoblot assay [RIBA]), and the presence of HCV RNA was evaluated in both sera and isolated PBMCs using the polymerase chain reaction technique. A previous exposure to HCV was shown by ELISA and confirmed by RIBA in all cases (100%). Moreover, HCV RNA was present in the sera of 8 of 16 patients (50%), whereas its frequency markedly increased (13 of 16 [81%]) when genomic sequences were detected in peripheral lymphocytes. HCV RNA was never detected in the PBMCs of 20 control subjects. These findings showed that HCV infection, alone or in combination with other factors, may be responsible for the clonal B-cell expansion underlying the systemic manifestations of MC, and may explain the appearance of a malignant non-Hodgkin's lymphoma in some subjects.

Aged↗

Interferon-alpha in mixed cryoglobulinemia patients: a randomized, crossover-controlled trial.

The effects of interferon-alpha (IFN-alpha) on clinical and serologic manifestations of mixed cryoglobulinemia (MC) were investigated by randomized, crossover-controlled trial in 26 patients. The trial alternated 6 months with and 6 months without IFN-alpha therapy (2 x 10(6) IU daily for a month, then every other day for 5 months). In 22 patients, pretreatment steroid dosage remained unchanged during the study. Six patients dropped out (three because of side effects), whereas another 20 patients experienced a significant improvement of purpura (P < .02) and serum transaminases (P < .005) during IFN-alpha treatment. The presence of clinical improvement was supported by the outcome measurements of several immunologic parameters. In particular, serum cryoglobulins were significantly reduced (P < .04) during IFN-alpha therapy. A rebound phenomenon of clinical and serologic parameters was observed after IFN-alpha discontinuation. In addition, no variations were recorded during 6 months without therapy. Hepatitis C virus (HCV) RNA was detected in 91% (20/22) of our MC patients; in 2/13 cases HCV RNA was no longer detectable in serum samples after IFN-alpha therapy. Thus, IFN-alpha could be considered as treatment for MC in patients with HCV seropositivity.

Alanine Transaminase↗

Hepatitis C virus-related autoimmunity in patients with porphyria cutanea tarda.

Hepatitis C virus (HCV) infection is frequently found in autoimmune hepatitis and mixed cryoglobulinaemia. In these conditions HCV could be responsible for immuno-mediated organ alterations. The aim of this study was to evaluate the presence of immunological alterations in PCT patients, in which HCV infection has been frequently found. Twenty-three PCT patients were evaluated for clinical and serological alterations, including: chronic hepatitis, other systemic symptoms, serum cryoglobulins and rheumatoid factor (RF), haemolytic complement, serum immunoglobulins, anti-nuclear (ANA), anti-smooth muscle (ASMA), anti-liver-kidney-microsomal (anti-LKM1), anti-soluble-liver-antigen (SLA), anti-mitochondrial (AMA), anti-GOR antibodies, anti-HCV and HCV RNA. Abnormal serum ALT were present in the majority of cases (20/23, 87%), while liver biopsy revealed a chronic persistent hepatitis or chronic active hepatitis in 15/20 (75%) PCT patients. In a high percentage of subjects (91%) the presence of anti-HCV was detected by ELISA and RIBA II (Chiron, Emeryville CA, USA). In 17/22 (77%) cases the ongoing HCV replication in the serum was demonstrated by the detection of HCV genomes (polymerase chain reaction). The prevalence of both anti-HCV and HCV RNA in PCT was significantly higher if compared to 22 systemic immunological diseases (P < 0.001) and 47 healthy subjects (P < 0.001). A possible HCV-induced autoimmunity in PCT was suggested by the presence of the following immunological parameter alterations: anti-GOR in 13/23 (57%), ANA in 4/23 (17%), ASMA in 18/23 (78%), anti-LKM1 in 1/23 (4%), RF in 23/23 (100%), mixed cryoglobulins in 4/23 (17%), complement consumption in 10/23 (43%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Interferon alfa-2b in mixed cryoglobulinaemia: a controlled crossover trial.

To confirm the positive results of a preliminary trial, 26 patients with mixed cryoglobulinaemia were enrolled in a controlled, randomised, crossover trial with interferon alfa-2b. A significant improvement was seen in the purpura score and alanine aminotransferase activities during six months' treatment, and was associated with a significant decrease in cryocrit and a returning to normal of the lymphocyte CD4/CD8 ratio (in eight of nine patients). No significant variations were seen during the six month period without interferon. Only six patients withdrew from treatment, three because of side effects and three because of poor compliance.

Cryoglobulinemia↗

Cryoglobulinemic membranoproliferative glomerulonephritis associated with hepatitis C virus.

A striking association between hepatitis C virus (HCV) and mixed cryoglobulinemia (MC) has been reported by various authors, regardless of the presence of chronic hepatitis. The aim of this study is to evaluate the prevalence of HCV-related markers in cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) which is one of the most severe complications of MC. Antibodies against HCV have been detected by second-generation Chiron ELISA and RIBA in 26/26 (100%) cryoglobulinemic MPGN. In addition, serum HCV RNA, expression of the ongoing viral replication, was present in 7/7 patients by the polymerase chain reaction technique. The high percentage of anti-HCV seropositivity suggests that this virus may play an important role in the pathogenesis of this immunemediated glomerulonephritis.

Cryoglobulinemia↗

Low-antigen-content diet in the treatment of patients with IgA nephropathy.

Since dietary macromolecular antigens can be involved in the pathogenesis of IgA nephropathy (IgAN), the effect of a low-antigen-content diet was evaluated in 21 patients (10 women, 11 men, mean age 27.7 +/- 10 years) with immunohistochemical findings of active IgAN. The diet was followed for a 14-24-week period (mean 18.8 +/- 6); in all cases the effects of the treatment were evaluated by clinical and serological parameters, and in 11 patients also by repeat renal biopsy. After dietetic therapy a significant reduction of urinary proteins was recorded (P < 0.001); in particular, heavy proteinuria (> 1 g/day), present in 12 cases during the 6 months preceding the treatment, was markedly reduced or disappeared in 11. At post-treatment control biopsy mesangial and parietal deposits of immunoglobulins, complement C5 fraction and fibrinogen were significantly reduced. The improvement of the objective parameters such as heavy proteinuria, a strong predictor of a poor prognosis, and of immunohistochemical alterations indicate that a low-antigen diet can positively affect patients with IgAN. These results could be ascribed to a reduction of nephritogenic food antigen input and to a putative functional restoration of the mononuclear phagocytic system.

Adolescent↗

Peripheral neuropathy in mixed cryoglobulinemia: clinical and electrophysiologic investigations.

Peripheral neuropathy has been described in different rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus and systemic vasculitis, but usually in limited numbers of patients. Nerve injury is more frequently reported in mixed cryoglobulinemia. In earlier studies generally performed in small series of patients, prevalence of peripheral neuropathy varied widely. We evaluated prevalence of peripheral neuropathy in 33 unselected patients with mixed cryoglobulinemia (25 women, 8 men, aged from 45-71 years). Neurologic involvement was detected using a complete clinical and electrophysiologic assessment, including sensory motor conduction velocities, F wave and H reflex. Neurologic examination revealed a neuropathy in 48% of subjects, while electrophysiologic variables were altered in 82%; a percentage similar to that of subjective symptoms (91%). Among electrophysiologic investigations, F wave was altered in 22/33 subjects (67%); therefore, this variable seems to be the most reliable for the detection of neurologic involvement. Cryocrit levels were significantly higher in patients with peripheral neuropathy: abnormal examination (p less than 0.01), sensory motor conduction (p less than 0.04), and F wave alterations (p less than 0.008). In addition, hemorheological abnormalities seem to contribute to the pathogenesis of nerve injury. Our results indicate that peripheral neuropathy, to a variable degree, is present in the majority of patients with mixed cryoglobulinemia, and a complete clinical and electrophysiologic investigation can be useful for an early and correct diagnosis.

Aged↗