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Clodoveo Ferri

Publications and source records attributed to Clodoveo Ferri.

At least 19 recordsLinked to original sources
PubMed2006

Cytomegalovirus-associated cutaneous vasculopathy and scleroderma sans inclusion body change.

Viruses have long been held to be of pathogenetic importance in the evolution of autoimmune connective tissue disease. We describe 7 adults who developed cutaneous connective tissue disease stigmata in temporal association with recent cytomegalovirus (CMV) infection but without the classic cytopathic changes of CMV infection. We examined 7 adults with clinical presentations encompassing cutaneous vasculitis in 4 and scleroderma in 3. In all 7 patients, there was either IgM seropositivity for CMV and/or CMV DNA isolation from peripheral blood. Although no CMV inclusions were seen, in situ hybridization studies revealed very focal CMV RNA transcript expression with localization mainly to the endothelium. The patients with vasculitis treated with ganciclovir had improvement or resolution of symptoms, whereas only 1 patient with scleroderma received antiviral therapy, without benefit. Another scleroderma patient responded to infliximab therapy. Abortive/partial CMV reactivation can be associated with a syndrome complex mimicking and/or triggering a primary immune-based cutaneous microvascular injury syndrome. Antiviral therapy appears to be of therapeutic value in those cases associated with active necrotizing vasculitic changes. The role of tumor necrosis factor alpha blockers in scleroderma cases temporally associated with CMV infection requires further evaluation.

Adult↗
PubMed2006

Etanercept maintains the clinical benefit achieved by infliximab in patients with rheumatoid arthritis who discontinued infliximab because of side effects.

OBJECTIVE: To evaluate the efficacy of switching to etanercept treatment in patients with rheumatoid arthritis who already responded to infliximab, but presented side effects. METHODS: Charts of 553 patients with rheumatoid arthritis were retrospectively reviewed to select patients who responded to the treatment with infliximab and switched to etanercept because of occurrence of adverse effects. Clinical data were gathered during 24 weeks of etanercept treatment and for the same period of infliximab treatment before infliximab was stopped. Disease Activity Score computed on 44 joints (DAS-44), erythrocyte sedimentation rate (ESR) 1st hour, Visual Analogue Scale (VAS) of pain, Health Assessment Questionnaire (HAQ), and C reactive protein (CRP) were assessed every 8 weeks. RESULTS: 37 patients were analysed. Adverse events to infliximab were mostly infusion reactions. No statistically significant difference between infliximab, before withdrawal, and etanercept, after 24 weeks, was detected in terms of DAS-44 (2.7 and 1.9, respectively), HAQ (0.75 and 0.75, respectively), ESR (21 and 14, respectively) and CRP (0.5 and 0.3, respectively). VAS pain decreased significantly after switching to etanercept treatment (40 and 24, respectively; p<0.05). CONCLUSIONS: Our study shows that etanercept maintains the clinical benefit achieved by infliximab, and suggests that a second tumour necrosis factor (TNF) alpha inhibitor can be the favourable treatment for rheumatoid arthritis when the first TNFalpha blocker has been withdrawn because of adverse events.

Adult↗
PubMed2006

Systemic sclerosis in childhood: clinical and immunologic features of 153 patients in an international database.

OBJECTIVE: To determine the clinical and immunologic features of systemic sclerosis (SSc) in a large group of children and describe the clinical evolution of the disease and compare it with the adult form. METHODS: Data on 153 patients with juvenile SSc collected from 55 pediatric rheumatology centers in Europe, Asia, and South and North America were analyzed. Demographic, clinical, and immunologic characteristics of children with juvenile SSc at the onset, at diagnosis, and during the disease course were evaluated. RESULTS: Raynaud's phenomenon was the most frequent symptom, followed by skin induration in approximately 75% of patients. Musculoskeletal symptoms were present in one-third of patients, and the most frequently involved internal organs were respiratory and gastrointestinal, while involvement of renal, cerebral, and cardiovascular systems was extremely rare. Antinuclear antibodies were present in the sera of 81% of patients. Anti-topoisomerase I (Scl-70) and anticentromere antibodies were found to be positive in 34% and 7.1% of patients, respectively. Involvement of the respiratory, gastrointestinal, and cardiovascular systems was more frequent and occurred earlier in patients who died than in those who survived. Compared with the adult form, juvenile SSc appears to be less severe, with the involvement of fewer internal organs, particularly at the time of diagnosis, and has a less characterized immunologic profile. CONCLUSION: This study provides information on the largest collection of patients with juvenile SSc ever reported. Juvenile SSc appears to be less severe than in adults because children have less internal organ involvement, a less specific autoantibody profile, and a better long-term outcome.

Adolescent↗
PubMed2006

Thyroid disorders in chronic hepatitis C virus infection.

The prevalence of thyroid disorders has been evaluated in patients with hepatitis C virus (HCV) infection by many studies. From a review of the published controlled studies, it is possible to observe that: (1) most investigated patients with chronic HCV hepatitis, while a minority evaluated hepatitis C virus antibody (HCVAb)- seropositive patients (the two conditions are not comparable with regards to thyroidal repercussions, in fact, HCVAb-seropositive patients do not necessarily display changes of the immune system present in chronically infected HCV patients); and (2) some authors selected as internal control hepatitis B virus (HBV)-infected patients, while others selected apparently healthy controls or HCVAb-negative subjects. Pooling all data about HCV-positive patients (with chronic hepatitis or HCVAb positivity) and using as control the sum of healthy controls, HBV-infected patients and sera negative for HCVAb, a significant increase of the prevalence has been observed both for thyroid autoimmune disorders (odds ratio [OR] = 1.6; 95% confidence interval = [C]) 1.4-1.9) as well as for hypothyroidism (OR = 2.9; 95% CI = 2.0-4.1). The results of the epidemiologic studies showing an association between HCV infection and thyroid cancer need to be confirmed. The abovementioned evidences seem sufficient to suggest careful thyroid monitoring during the follow-up of patients with HCV infection.

Autoimmune Diseases↗
PubMed2006

Cryoglobulinemic vasculitis.

PURPOSE OF REVIEW: Cryoglobulinemic vasculitis is an immune-complex-mediated systemic vasculitis involving small-medium-sized vessels. A causative role of hepatitis C virus in over 80% patients has been definitively established, with heterogeneous geographical distribution. This review focuses on recent etiopathogenetic, clinico-diagnostic, and therapeutical studies. RECENT FINDINGS: Hepatitis C virus cannot be integrated into the host genome; it may exert a chronic stimulus to the immune system. The interaction between hepatitis C virus envelope protein E2 with B-cell CD 81 receptor may increase the frequency of VDJ rearrangement in antigen-reactive B lymphocytes. One consequence is the activation of various protooncogenes, including anti-apoptotic Bcl-2. The extended B-cell survival is responsible for autoantibody and immune-complex production, including mixed cryoglobulins; some malignancies, mainly B-cell lymphomas, may complicate cryoglobulinemic vasculitis. Environmental or viral/host genetic cofactors should be relevant in the pathogenesis of hepatitis C virus-related diseases. Cryoglobulinemic vasculitis may overlap with other diseases (systemic vasculitides, Sjögren's syndrome, autoimmune hepatitis, lymphoma), which should be carefully considered for a correct diagnosis and treatment. Cumulative survival of cryoglobulinemic vasculitis is significantly lower compared with the general population. Therapeutic strategies for cryoglobulinemic vasculitis include etiologic (antiviral), pathogenetic (cyclophosfamide, rituximab), or symptomatic (steroids, plasmapheresis) treatments, which should be tailored to the individual patient according to the severity/activity of clinical symptoms. SUMMARY: Cryoglobulinemic vasculitis represents a crossroads among autoimmune and lymphoproliferative disorders; as hepatitis C virus infection is the major causative factor, cryoglobulinemic vasculitis is an important model for etiopathogenetic studies of virus-related diseases.

Cryoglobulinemia↗
PubMed2006

Autoimmune-like pulmonary disease in association with parvovirus B19: a clinical, morphologic, and molecular study of 12 cases.

Parvovirus B19, the agent responsible for fifth disease, has been emerging as a significant pathogenetic factor in various acute vasculitic syndromes such as Wegener's granulomatosis, Henoch-Schönlein purpura, and Kawasaki disease. It has also been implicated in more chronic vasculopathic syndromes, specifically in the context of scleroderma and dermatomyositis. The basis of this association is likely multifactorial; implicated mechanisms include the virus's affinity for endothelium, resulting in a state of neoantigenicity through varied mechanisms as well as the induction of tumor necrosis factor alpha, a factor involved in the propagation of ANCA-positive vasculitic syndromes. The authors present a series of 12 patients with interstitial lung disease including idiopathic pulmonary fibrosis, scleroderma-associated pulmonary fibrosis, lymphocytic interstitial pneumonitis, and septal capillaritis. In all cases there was evidence of chronic parvovirus B19 infection based on serologic assessment and the isolation of B19 DNA on lung samples in all patients. Furthermore, in two cases there was in situ localization of B19 RNA and tumor necrosis factor alpha to endothelium and stromal cells. On pathologic examination, there were varying degrees of both septal fibrosis and inflammation along with evidence of septal capillary injury. In those cases categorized as representing either scleroderma or idiopathic pulmonary fibrosis, the immunofluorescent studies showed evidence of anti-endothelial cell antibody formation. The ANCA-associated syndromes were, as expected, negative by fluorescent analysis. Significantly elevated factor VIII levels, a standard serologic index of endothelial cell injury, were seen in four of the six patients tested. The antiphospholipid profile revealed antiphospholipids in 7 of the 11 patients tested. This report highlights a possible causal role for parvovirus B19 in the pathogenesis of select pulmonary disorders.

Adult↗
PubMed2005

Incidence and characteristics of non-Hodgkin lymphomas in a multicenter case file of patients with hepatitis C virus-related symptomatic mixed cryoglobulinemias.

BACKGROUND: Some patients with cryoglobulinemic syndrome (CS) develop frank non-Hodgkin lymphoma (NHL), but the incidence and timing of this event are still poorly defined. METHODS: A retrospective multicenter study was performed of hepatitis C virus-positive patients with CS observed in 11 Italian centers belonging to the Italian Group for the Study of Cryoglobulinemia. RESULTS: The inclusion criteria were satisfied by 1,255 patients. During a cumulative follow-up of 8,928 patient-years, 59 cases of NHL were diagnosed, for an estimated rate of 660.8 new cases per 100,000 patient-years with 224.1 new cases of aggressive NHL subtypes per 100,000 patient-years. More than 90% of the patients developing NHLs had type II cryoglobulins. The NHLs were classified as nonaggressive in 31 cases (53%), aggressive in 20 (34%), and mucosa-associated lymphoid tissue lymphomas in 6 (10%); 2 cases were unclassifiable. The median time from the diagnosis of CS to the clinical onset of NHL was 6.26 years (range, 0.81-24 years). The clinical course and response to chemotherapy in the patients with CS who had NHL were similar to those usually described in patients with NHL without CS; the course of the CS only marginally benefited from chemotherapy. CONCLUSIONS: The overall risk of NHL in patients with CS is about 35 times higher than in the general population (12 times higher if nonaggressive lymphomas are excluded). The presence of CS did not significantly affect the treatment of newly diagnosed lymphomas.

Aged↗
PubMed2004

Thyroid disorders in chronic hepatitis C.

PURPOSE: To explore the association of hepatitis C virus (HCV) infection with thyroid disorders. METHODS: We investigated the prevalence of thyroid disorders in 630 consecutive patients with chronic hepatitis due to HCV infection; all patients were free of cirrhosis and hepatocarcinoma, and were not on interferon treatment. Also included were a control group of 389 subjects from an iodine-deficient area, another control group of 268 persons living in an area of iodine sufficiency, and 86 patients >40 years of age with chronic hepatitis B. Levels of thyroid-stimulating hormone (TSH), free thyroxine (T(4)), and triiodothyronine (T(3)), as well as anti-thyroglobulin and anti-thyroid peroxidase antibodies, were measured. RESULTS: Mean TSH levels were higher (P = 0.001), and free T(3) and free T(4) levels were lower (P <0.0001), in patients with chronic hepatitis C than in all other groups. Patients with chronic hepatitis C were more likely to have hypothyroidism (13% [n = 82]), anti-thyroglobulin antibodies (17% [n = 108]), and anti-thyroid peroxidase antibodies (21% [n = 132]) than were any of the other groups. CONCLUSION: Both hypothyroidism and thyroid autoimmunity are more common in patients with chronic hepatitis C-even in the absence of cirrhosis, hepatocellular carcinoma, or interferon treatment-than in normal controls or those with chronic hepatitis B infection.

Adult↗
PubMed2004

Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients.

BACKGROUND: Mixed cryoglobulinemia (MC) is a systemic vasculitis secondary to circulating immune complex deposition in the small vessels. In the overwhelming majority of patients, hepatitis C virus (HCV) infection represents the triggering factor of the disease. MC is characterized by multiple organ involvement, mainly skin, liver, renal, peripheral nerves, and less frequently by widespread vasculitis and cancer. OBJECTIVES: To investigate the demographic, clinical, serologic features, and survival in a large series of MC patients. METHODS: The study included 231 MC patients recruited between 1972 and 2001 at the Rheumatology Unit of the University of Pisa. All patients underwent wide clinicoserologic and virologic assessment. Cumulative survival rates were computed by the Kaplan-Meier method; moreover, the prognostic relevance of the main variables was investigated by Cox model analysis. RESULTS: In 92% of cases, the presence of HCV infection was demonstrated (anti-HCV antibody, 92%; HCV RNA, 90%), whereas hepatitis B virus (HBV) represented the possible causative agent in only 1.8% of patients (HBV DNA). Clinically, the MC syndrome followed a relatively benign clinical course in over 50% of cases, whereas a moderate-severe clinical course was observed in one third of patients whose prognosis was severely affected by renal and/or liver failure. In a limited, but significant, percentage (15%) of individuals, the disease was complicated by a malignancy, ie, B-cell lymphoma, and less frequently by hepatocellular carcinoma, or thyroid cancer. The survival study by the Kaplan-Meier method revealed a significantly lower cumulative 10th-year survival, calculated from time of diagnosis, in MC patients compared with expected death in the age- and sex-matched general population. Moreover, significantly lower survival rates were observed in males and in subjects with renal involvement. The multivariate analysis by the Cox proportional hazard regression model further supported the above findings: an increased mortality risk of 98% was observed for male gender (male/female hazard ratio, 1.978) and of 197% in patients with, compared with those without, renal involvement (hazard ratio, 2.967). At the end of the follow-up, 97 patients were deceased, and in 79 of 97 patients, the causes of death were ascertained: nephropathy (33%), malignancies (23%), liver involvement (13%), and diffuse vasculitis (13%) were the most frequent causes of death. CONCLUSIONS: Careful patient monitoring is recommended for a timely diagnosis of life-threatening MC complications, mainly nephropathy, widespread vasculitis, and B-cell lymphoma or other malignancies.

Aged↗
PubMed2004

Parvoviral infection of endothelial cells and stromal fibroblasts: a possible pathogenetic role in scleroderma.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease (CTD) which differs from other CTDs by progressive irreversible fibrosis in lung, kidney, skin, and heart. It has a worse prognosis compared to several other CTDs. The pathogenesis may reflect a humorally mediated microangiopathy in concert with the overproduction of collagen triggered by immune-mediated cytokine production. Having previously demonstrated parvovirus B19 (B19) DNA in bone marrow and skin biopsies of SSc patients in the absence of B19 viremia, we sought to further elucidate a role for B19 in the pathogenesis of SSc. DESIGN: Twelve patients who fulfilled American College of Rheumatology criteria for a diagnosis of SSc were encountered. Ten were serologically screened for B19 infection. Solution phase polymerase chain reaction (PCR) for B19 DNA was performed on skin tissue from six patients, and in all biopsies, reverse transcriptase in situ PCR (RT in situ PCR) for B19 and tumor necrosis factor (TNF)-alpha mRNA was performed. B19 viral protein (VP2) expression was sought by immunohistochemistry and correlated to PCR findings and to light microscopy of hematoxylin and eosin-stained sections. Frozen tissue was also available on five of the patients. Two control groups were assessed for B19 and TNF expression comprising one with irrelevant primers and the other representing 18 cases of inflammatory skin lesions where the etiology was known and unrelated to B19 infection. In addition, frozen and paraffin-embedded tissues procured from skin lesions unrelated to B19 infection were assessed for B19 genome. In all cases, pretreatment with RNase was also performed to verify that any positive signal was indeed RNA based. RESULTS: Diffuse SSc was seen in seven patients, and limited disease in five. All patients had an antinuclear antibody--specifically, an antinucleolar, anticentromere, and/or anti-Scl 70 antibody. Eleven of the 12 had lung involvement, whereas eight patients had myocardial disease. Of 12 patients tested serologically, nine had B19-specific antibodies, which included immunoglobulin M (IgM)-specific antibodies in two cases. Solution phase PCR showed B19 DNA in the skin in three cases and in the bone marrow in three cases, including two in whom skin-based B19 DNA was observed. In all cases, RT in situ PCR demonstrated B19 and TNF-alpha mRNA in endothelia, fibroblasts, mast cells, and perivascular inflammatory cells. Immunohistochemistry to assess VP2 was either negative or equivocal. Immunofluorescent studies revealed prominent deposition of C5b-9 within the cutaneous vasculature from biopsies of all patients tested. The control samples were negative for B19 and TNF RNA and DNA. CONCLUSIONS: Parasitism of endothelia and fibroblasts by B19 with resultant enhanced TNF-alpha expression may be of pathogenetic importance in SSc even in the absence of demonstrable viremia. The vascular deposition of C5b-9 suggests a role for humoral immunity possibly induced by a state of endothelial neoantigenicity evoked by virally mediated cell injury. Treatment strategies include anti-viral therapy, including in the context of intravenous gamma-globulin and anti-TNF therapy.

Adult↗
PubMed2003

The dermatopathologic manifestations of hepatitis C infection: a clinical, histological, and molecular assessment of 35 cases.

Cutaneous eruptions related to hepatitis C virus (HCV), a major cause of hepatitis in the setting of blood transfusion, intravenous drug abuse, organ transplantation, and hemodialysis, are typically reported as isolated cases. We encountered 35 cases of HCV infection associated with cutaneous eruptions. The present study evaluates paraffin-embedded, formalin-fixed tissue sections stained with hematoxylin and eosin from biopsy specimens of skin lesions from 35 patients seropositive for HCV. In 20 cases, reverse transcriptase polymerase chain reaction (RT-PCR) was performed using a probe for HCV RNA; the RNA was detected through the action of alkaline phosphatase on the chromogen nitroblue tetrazolium and bromochloroindolyl phosphate. The clinical spectrum comprised dermatomyositis-like photodistributed eruptions, palpable purpura, folliculitis, violaceous and perniotic acral lesions, ulcers, nodules, and urticaria. Lesions were also classified histopathologically by the dominant reaction pattern: vasculopathies of neutrophilic, lymphocytic, and granulomatous vasculitis and pauci-inflammatory subtypes (15 patients); palisading granulomatous inflammation (3 patients); sterile neutrophilic folliculitis (5 patients); dermatitis herpetiformis (1 patient); lobular panniculitis composed of neutrophilic lobular panniculitis in 2 patients and benign cutaneous polyarteritis nodosa in 1 patient; neutrophilic dermatoses, including neutrophilic urticaria, neutrophilic eccrine hidradenitis, and pyoderma gangrenosum (3 patients); interface dermatitis (3 patients); and low-grade lymphoproliferative disease of B-cell lineage representing marginal zone lymphoma in 1 patient and a clonal plasmacellular infiltrate in another patient. In most cases, whereas 1 of the aforementioned disorders defined the dominant reaction pattern, there was an accompanying secondary reaction pattern, defining a hybrid picture. Endothelial changes including endothelial cell enlargement and effaced heterochromatin with margination of the chromatin to the nuclear membrane were seen in several cases; in some cases similar cytopathic changes also involved the supporting pericytes, eccrine ductular cells, or keratinocytes. The RT-PCR analyses in 8 of 20 cases examined revealed HCV RNA expression in a focal, weak fashion in endothelia and perivascular inflammatory cells in those cases showing vasculopathic changes. Viral parasitism of endothelia may be important in cutaneous lesional propagation in the setting of HCV infection. Cross-reactivity between endogenous and viral antigens, leading to cellular and/or type II immune reactions; viral tropism to B lymphocytes, resulting in B cell expansion with resultant autoantibody production; and circulating immune complexes containing monoclonal cryoglobulins may also be of pathogenetic importance. Tropism of the virus to B lymphocytes provides a mechanism for the development of low-grade clonal B cell lymphoproliferative disease in this setting.

Adult↗
PubMed2003

The assessment of anti-endothelial cell antibodies in scleroderma-associated pulmonary fibrosis. A study of indirect immunofluorescent and western blot analysis in 49 patients with scleroderma.

We recently reported on the use of an indirect immunofluorescent method designated the rodent lung assay; this test assesses for the presence of circulating antibodies directed at components of the microvasculature. Serum samples from 49 patients with scleroderma were incubated with rodent lung tissue sections and visualized with fluoresceinated human anti-IgG. The assay also was performed on samples from a control group. Western blot analysis was performed with endothelial cell protein extracts using serum samples from patients with scleroderma and from healthy control subjects. The control subjects had a negative indirect immunofluorescent assay result. In the patients with scleroderma, there was a significant positive correlation between intensity of indirect immunofluorescent staining and pulmonary fibrosis (r = 0.316; P = .0347) and hypertension (r = 0.310; P = .0408). Western blot analysis revealed antibody binding to proteins in extracts of human endothelial cells in all patients in whom there was evidence of pulmonary disease. The indirect immunofluorescent rodent lung assay and Western blot data support a potential role of anti-endothelial cell antibodies in the propagation of scleroderma-associated pulmonary disease.

Adult↗
PubMed2003

Spontaneous chromosome damage (micronuclei) in systemic sclerosis and Raynaud's phenomenon.

OBJECTIVE: To evaluate the prevalence of spontaneous chromosome damage in cultured peripheral lymphocytes of patients with systemic sclerosis (SSc), idiopathic Raynaud's phenomenon (RP), and suspected secondary RP, by means of molecular cytogenetic analysis. METHODS: We studied 43 patients with SSc, 13 with idiopathic RP, and 16 with suspected secondary RP and 25 healthy controls. As a marker of chromosome alteration we used the micronucleus (MN) assay. All subjects were also classified for antinuclear antibodies, anticentromere antibodies (ACA), or Scl70. To identify the mechanism of MN formation, we also performed MN fluorescence in situ hybridization (FISH) analysis using a pancentromeric DNA probe. RESULTS: Patients with SSc and subjects with RP showed significantly higher MN frequencies than controls (25.9 +/- 1.7 and 19.1 +/- 2.15, respectively, vs 9.4 +/- 2.2; p < 0.001). Subjects with suspected secondary RP displayed MN frequency (23.5 +/- 2.7) comparable to that of SSc patients, while spontaneous MN level in idiopathic RP subjects (13.6 +/- 3.0) did not differ significantly from controls (9.4 +/- 2.2). ACA positive subjects showed the highest MN frequencies (32.8 +/- 1.7) compared to subjects with a different antibody pattern (18.3 +/- 1.6). CONCLUSION: Our results show the presence of higher levels of micronuclei in circulating lymphocytes of patients with SSc and subjects with suspected secondary RP. They also suggest a possible role of ACA in determining cytogenetic anomalies. FISH analysis indicated that both aneuploidogenic and clastogenic events contributed to the formation of MN observed in SSc patients and subjects with suspected secondary RP.

Adult↗
PubMed2002

Prevalence of bcl-2 rearrangement in patients with hepatitis C virus-related mixed cryoglobulinemia with or without B-cell lymphomas.

BACKGROUND: Hepatitis C virus (HCV) infection is strictly associated with mixed cryoglobulinemia, a benign B-cell lymphoproliferative disorder that may evolve to lymphoma. An increased prevalence of bcl-2 rearrangement (the t(14;18) translocation) has been shown in patients infected with HCV. OBJECTIVE: To evaluate the prevalence of bcl-2 rearrangement in patients with HCV-related mixed cryoglobulinemia and patients with chronic hepatitis but no cryoglobulinemia. DESIGN: Prospective study. SETTING: Two university hospitals. PATIENTS: 37 consecutively recruited patients with HCV-related mixed cryoglobulinemia and 101 patients with chronic HCV infection but without mixed cryoglobulinemia. MEASUREMENTS: Clinical and serologic characteristics; liver biopsy; bcl-2 rearrangement, Bcl-2 expression, and the ratio of Bcl-2 to Bax in total peripheral blood mononuclear cells and cell subgroups; and sequence analysis of the junction of bcl-2 and IgH joining segments in positive samples. RESULTS: Rearrangement of bcl-2 was observed in 28 of 37 (75.7%) patients with mixed cryoglobulinemia (65% of those with type III disease and 85% of those with type II disease, including 3 of 4 patients with lymphoma) and in 38 of 101 (37.6%) patients with chronic HCV infection but not mixed cryoglobulinemia (P < 0.001). Overexpression of Bcl-2 protein and a high ratio of Bcl-2 to Bax were observed in samples from patients with bcl-2 rearrangement. In 2 patients followed over time, peripheral blood cells bearing the t(14;18) translocation disappeared after antiviral therapy. CONCLUSIONS: Rearrangement of bcl-2 was found with increased frequency in patients with chronic HCV infection and mixed cryoglobulinemia. The frequency was greatest in patients with type II mixed cryoglobulinemia. The high ratio of Bcl-2 to Bax in patients with bcl-2 rearrangement and disappearance of the rearrangement with antiviral therapy suggest that the translocation is associated with the antiapoptotic function of Bcl-2 and that HCV infection is linked to inhibition of B-cell apoptosis.

Chromosomes, Human, Pair 14↗