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ID PMID Title PublicationDate abstract
9643312 Systemic lupus erythematosus VII: frequency and impact of secondary Sjøgren's syndrome. 1998 BACKGROUND: The prognosis of patients with systemic lupus erythematosus (SLE) largely depends on the severity of cumulative organ damage during the course of the disease. While Sjøgren's syndrome (SS) predominantly affects exocrine glands, a considerable number of patients develop visceral organ damage. Thus, the occurrence of a secondary SS (2(o)SS) in SLE patients, may result in more extensive organ damage and thereby adversely affect prognosis. PATIENTS/METHODS: 138 patients meeting the 1982 American College of Rheumatology (ACR) classification criteria for SLE were prospectively studied over a mean period of ninety months. 2(o)SS was diagnosed according to the 1993 European Study Group criteria and complication rates and prognosis were compared between patients with and without SS. RESULTS: 27 patients (19%) developed SS after a mean period of 48 months. There was a gradual increase in SS prevalence over time after SLE-onset. 2(o)SS patients were older (mean age 41 vs 35 years, P = 0.03), had less renal disease (19% vs 38%, P = 0.04), more thrombocytopenia (26% vs 9%, P = 0.05) and similar serological profiles (including anti-SSa) as patients without SS. Overall mortality was lower in patients with SS (4% vs 13.5%, P = 0.01), while lifetable analysis showed improved survival estimates for 2 SS patients with borderline statistical significance (P = 0.06). CONCLUSIONS: 2(o)SS develops in about one-fifth of SLE patients in a time-dependent fashion: these patients are older, have less renal involvement and their prognosis is at least as good as for those remaining free of SS.
11439148 Cytokine polymorphisms in systemic lupus erythematosus and Sjögren's syndrome. 2001 Jul Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are defined genetically as complex diseases where multiple genes are involved in their pathogenesis. Among the genes of interest are those coding for the cytokines, molecules involved in immunoregulation that have been shown to play important roles in these diseases. Whether abnormalities in cytokine production are owing to genetic polymorphisms within the genes themselves is a matter of intensive study. The finding of functional polymorphisms within cytokine genes and their potential association with disease will open new avenues in their treatment.
11359451 Activation of epithelial and myoepithelial cells in the salivary glands of patients with S 2001 Apr ICAM.1 (CD54) is a surface protein expressed on epithelial and other nonhematopoietic cells upon activation and is known to play an important role in the stimulation of T cells by the provision of cellular adhesion and costimulatory support. Sjogren's syndrome (SS) is an autoimmune exocrinopathy, which is characterized by chronic lymphocytic infiltration of exocrine glands and aberrant activation of epithelial tissues. To address the contribution of ICAM.1 in the pathogenesis of SS, the expression of this protein was studied by immunohistochemistry and flow cytometry in minor salivary gland (SG) biopsies as well as in cultured SG epithelial cell (SGEC) lines obtained from 18 SS patients and 16 controls. In biopsies from SS patients (but not controls), strong ICAM.1 was expressed by infiltrating mononuclear cells (52%) and by a significant proportion of periacinar myoepithelial cells (18%). In addition, a patchy pattern of moderate ICAM.1 expression was detected in 31% of ductal epithelia of SS patients. These ICAM.1-expressing epithelial and myoepithelial cells were observed throughout glandular tissues and were not confined in areas proximal to lymphoid infiltrates. In support to an intrinsic activation profile of SGEC in SS, long-term cultured non-neoplastic SGEC lines derived from SS patients displayed significantly upregulated spontaneous expression of ICAM.1, compared to controls (P < 0.05). The high expression of ICAM.1 protein by the salivary epithelium of SS patients is likely suggestive of its important role in the pathogenesis of the disorder. Further, our results support a model of intrinsic activation of salivary epithelial and myoepithelial cells in SS, whereby these cells actively participate in the induction and maintenance of lymphocytic infiltrates of patients.
9933443 Ro/SS-A-reactive B lymphocytes in salivary glands and peripheral blood of patients with Sj 1999 Jan The aim of this study was to investigate the production of anti-Ro/SS-A antibodies in labial salivary glands (LSG) and peripheral blood (PB) of Sjögren's syndrome (SS) patients. The ELISPOT method was performed to quantify the frequency of LSG lymphocytes and PB lymphocytes spontaneously secreting anti-Ro/SS-A antibodies. The total number of IgG-, IgA- and IgM-producing cells was also quantified. The bovine Ro 60-kD protein was used as target antigen. Six of six primary SS patients had LSG B cells producing anti-bovine Ro 60 kD of the IgG isotype, and two of two primary SS patients had in addition PB lymphocytes producing anti-bovine Ro 60 kD of the IgG isotype. The six patients who had IgG antibodies against the Ro/SS-A antigen in LSG all had focus scores of >/= 7 in biopsies of LSG. The results indicate that SS patients with a high degree of local inflammation in LSG have B cells producing anti-Ro/SS-A antibodies in both LSG and PB. Thus, the anti-Ro/SS-A antibodies may have pathogenic importance in the progression of the exocrinopathy of SS.
9764611 Apoptosis in labial salivary glands from Sjögren's syndrome (SS) patients: comparison wit 1998 Oct Apoptosis is a type of cell death that occurs during morphogenesis and development of the immune system. One of the mechanisms is mediated through the Fas and Fas ligand (FasL) pathway. To determine the possible involvement of Fas and its ligand in salivary gland destruction, we analysed the appearance of nuclei with DNA fragmentation by using nick end labelling (TUNEL) and the expression of Fas and FasL by immunohistochemistry in labial salivary glands. Furthermore, we compared the features of apoptosis in labial salivary glands between HTLV-I- and HTLV-I+ SS. When the frozen sections of 10 primary SS patients in the absence of anti-HTLV-I antibody were examined, several apoptotic cells were found in the acinar and ductal epithelial cells as well as infiltrated mononuclear cells. Both Fas and FasL were detected in the infiltrated mononuclear cells. Acinar epithelial cells, which are surrounded by FasL+ mononuclear cells, were also double-positive with Fas and FasL, although the expression of FasL was localized at their apical border, suggesting that apoptosis of mononuclear cells was achieved by activation-induced mechanisms through Fas/FasL pathways, and that of acinar epithelial cells was mediated by FasL derived from either acinar epithelial cells themselves or infiltrated mononuclear cells. Interestingly, Fas expression in ductal epithelial cells was localized around the lumen side of the ducts, indicating that FasL secreted from acinar epithelial cells may induce Fas-mediated apoptosis of ductal epithelial cells. We also studied the labial salivary glands from nine SS patients with anti-HTLV-I antibodies. There was no significant difference in the occurrence of apoptotic cells or in the expression of Fas and FasL between HTLV-I+ and HTLV-I- SS patients. It was of note that neither the expression of Fas and FasL nor the presence of apoptotic cells were determined in labial salivary glands from subjects without SS. These findings indicate that Fas-mediated apoptosis in salivary glands could be involved in the pathological manifestations of SS, irrespective of HTLV-I seropositivity.
9480721 Ro/SS-A and La/SS-B antibody level variation in patients with Sjögren's syndrome and syst 1998 Feb To examine both possible correlations between anti-Ro/SS-A and anti-La/SS-B levels and their correlation with clinical disease activity in patients with Sjögren's syndrome (SS) or systemic lupus erythematosus (SLE), an ELISA was developed using purified recombinant Ro 60 kDa, Ro 52 kDa and La antigens. The ELISA was used for testing sequential serum samples from 16 patients with either SS or SLE. The patients were followed for periods between 15 and 128 months, and 3-15 serum samples per patient were analysed and compared with clinically apparent disease activity at the time of sampling in 14 patients. A temporal correlation of antibody levels to Ro and La antigens was found, and antibodies to different epitopes of the Ro 60 kDa protein showed parallel variation in seven of eight patients tested. Co-variation of autoantibody levels and disease activity was found in 11 of 14 patients. In seven of these 11 patients the anti-Ro and anti-La levels were stable and changes in disease activity were minimal during the observation period. In the other four of these 11, changes in disease activity were noted, with an associated change in autoantibody levels. The results suggest that the serological response to Ro and La antigens, as well as to different epitopes of the Ro 60 kDa protein, is antigen driven and regulated by common mechanisms, and indicate a correlation of Ro and La antibodies with pathogenic events.
9279251 CD4-positive T-lymphocytes infiltrate the bronchial mucosa of patients with Sjögren's syn 1997 Aug To investigate the degree and the type of inflammation in the bronchial mucosa in patients with Sjögren's syndrome, we examined lobar bronchial biopsies obtained from 10 patients with Sjögren's syndrome (six with primary and four with secondary) and eight control subjects. Histochemistry with hematoxylin-eosin was performed both to identify the number of mononuclear cells and eosinophils and to measure the thickness of the basement membrane. Immunohistochemistry was performed to identify neutrophils (neutrophil-elastase), macrophages (CD68), and T-lymphocyte subpopulations (CD4 and CD8) in the submucosa. Subjects with Sjögren's syndrome presented a greater number of CD4-positive T-lymphocytes than did the normal control subjects (p = 0.0129). Instead, eosinophils, neutrophils, macrophages, CD8 positive T-lymphocytes, and basement membrane thickness were similar in the two groups. There were no differences in cell counts between patients with primary and those with secondary Sjögren's syndrome and between symptomatic and asymptomatic patients. No correlation was found between cell counts, symptoms, lung volumes, and disease duration. This study has shown that patients with Sjögren's syndrome have an increased number of CD4 positive T-lymphocytes in the bronchial mucosa outside of the bronchial glands, supporting the concept that, in the airways. Sjögren's syndrome involves also extraglandular tissues.
9165994 Assessment of anti-endothelial cell antibodies in systemic sclerosis and Sjögren's syndro 1997 Apr OBJECTIVES: Anti-endothelial cell antibodies (AECA) have been detected in 19 to 30% of patients with systemic sclerosis (SSc). The objective of this study was first to assess the role of a secondary Sjögren's syndrome (SS) in the occurrence of AECA in SSc. Secondly, we researched AECA in patients with primary SS, and investigated whether AECA were associated with vascular manifestations (Raynaud's phenomenon and vasculitis). METHODS: IgG-AECA were tested by an ELISA method in serum samples from 50 patients with SSc (16 of them had also a secondary SS), 50 patients with primary SS, and 50 healthy controls. RESULTS: AECA levels were significantly higher in patients with SSc or primary SS than in healthy controls (p < 0.01 and p < 0.01, respectively). In patients with SSc, AECA values were significantly higher in patients with secondary SS (p < 10(-5)). In patients with primary SS, AECA levels were significantly higher in patients with Raynaud's phenomenon (p < 0.01), but not in patients with vasculitis. CONCLUSION: In patients with SSc, AECA are associated with a secondary SS. In patients with primary SS, AECA are associated with Raynaud's phenomenon, but not with vasculitis.
9556352 Primary biliary cirrhosis an epithelitis: evidence of abnormal salivary gland immunohistoc 1997 Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown etiology. Nearly 93% of patients with PBC exhibit evidence of focal sialoadenitis. In an earlier study, we reported evidence of aberrant expression of PDC-E2, or a mimeotope, in the salivary glands of patients with PBC that had Sjogren's syndrome. At the time of the previous study, data was not yet available regarding patients with PBC without sicca complaints. Therefore, to investigate the extent of salivary gland involvement in PBC, we collected lip biopsy sections from 9 PBC patients diagnosed as PBC by liver biopsy, without clinical or histologic features of Sjogren's syndrome and 9 PBC patients with established Sjogren's syndrome. Using immunohistochemical staining with both a murine monoclonal antibody. C355.1, and a human combinatorial antibody, SP4, we examined the ducts of these salivary glands for the presence of the characteristic aberrant staining pattern found in patients with PBC. We report that 6/9 PBC patients fulfilling established Sjogren's syndrome criteria and 6/9 PBC patients lacking features of Sjogren's syndrome showed intense staining of the ductal epithelial cells of the salivary gland. These data suggest that the PBC-specific antigen recognized by C355.1 and SP4 in bile duct epithelial cells is expressed aberrantly in the salivary gland in 66% of patients with PBC, independent of Sjogren's syndrome. This finding suggests a common disease process in these two tissues. Further, expression of this molecule may be an early marker of salivary gland involvement in patients with PBC.
10355149 [Peripheral blood dendritic cell dysfunction in patients with Sjögren's syndrome]. 1999 Apr The function of dendritic cell (DC), that has the strongest antigen-presenting ability, was investigated for the purpose of clarifying immune abnormalities in Sjögren's syndrome (SS) from the point of view of antigen-presenting cells. DCs were separated from peripheral blood of SS patients, and mixed lymphocyte reaction (MLR) with DCs was observed to examine the function of DC. Autologous MLR (AMLR), which was induced by mixed culture of DCs with autologous T cells, significantly decreased in SS patients (p < 0.01). Allogeneic MLR (alloMLR), which was induced by mixed culture of DCs with allogeneic T cells, also decreased in SS patients, suggesting the presence of DC dysfunction. Cell surface expression rates of HLA-DR, CD 80, and CD 83, which are a first signal of cell surface antigen presentation, a second signal, and a specific antigen of DC, respectively, were then examined. Among HLA-DR-positive cells, CD 80-positive cells and CD 83-positive cells increased in SS patients, compared with normal subjects (p < 0.0003 and p < 0.00009, respectively). From these results, it was inferred that SS patients have not only DC dysfunction, but abnormalities in cell surface antigens as well.
10872895 Structure of IL-10 and its role in autoimmune exocrinopathy. 2000 Cytokines are implicated in the pathogenesis of a variety of autoimmune disorders. Whether the presence of cytokines is primary or secondary and the extent to which these factors may contribute to the development and progression of clinicopathologic alterations in these disorders remain largely unknown but are highly important questions. Our research focuses on evaluating these issues by using a transgenic approach to direct the constitutive expression of cytokines to epithelial cells in the intact exocrine glands of mice. Our recent studies have focused on the potential of the regulatory cytokine IL-10 produced by type 2 T-helper cells to inhibit inflammation and the development of autoimmue diseases. Using targeted introduction of this molecule into the exocrine gland epithelial cells, we found that IL-10 induced apoptosis of glandular tissues destruction and lymphocyte infiltration consisting primarily of Fas-ligand+ CD4+ T cells, as well as in vitro upregulation of FasL expression on T cells. These results suggest that IL-10 is necessary and sufficient for exocrine gland dysfunction in the transgenic mice. This article discusses recent advances in IL-10 and its role in the pathological conditions of autoimmune exocrinopathy.
9517768 Prevalence of symptoms of dry mouth and their relationship to saliva production in communi 1998 Mar OBJECTIVE: To estimate the prevalence of dry mouth symptoms and their correlation with saliva production in a population based sample of elderly people in the United States. METHODS: Two dry mouth questions were administered to and a modified Saxon test was performed in participants in a population based prevalence survey conducted among 2520 noninstitutionalized community dwelling residents of Salisbury, Maryland, aged 65-84 years. RESULTS: Seventeen percent reported having either dryness of mouth or waking at night feeling dryness in the mouth and needing to drink fluids often or all the time; 10.7% noted the former and 11.5% the latter. The prevalence of dry mouth symptoms increased with increasing age, was greater in women than men, and was greater in whites than blacks. The mean (SD) amount of saliva production was 2.38 (1.00) g/min; mean saliva production decreased with increasing age and was lower in women than men; no difference was noted by race. Persons with dry mouth symptom either often or all the time had significantly lower salivary production, even after adjustment for age and sex. CONCLUSION: Symptoms of dry mouth are common in the community dwelling elderly population, especially in white women, and correlate with decreased salivary production.
10463003 Remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome). 1999 Jul A 63-year-old man presented with acute symmetrical polysynovitis associated with pitting edema of both the hands and feet. He was seronegative for rheumatoid factor and no radiologically evident erosion was noted in the joints of his hands and feet. Evaluation excluded congestive heart failure, nephrotic syndrome, and hypothyroidism as the cause of edema. Treatment with nonsteroidal anti-inflammatory drugs and low-dose steroids induced complete remission. The clinical manifestations of this patients were consistent with those of a distinctive, although rare, form of arthritis called remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. This syndrome has a good prognosis in elderly patients.
9162782 [Prognostic factors in the evolution of psoriatic arthritis]. 1997 Feb 1 BACKGROUND: The aim of this study is to determine the evolution and prognostic factors in the patients with psoriatic arthritis. PATIENTS AND METHODS: We have reviewed retrospectively the follow-up of 96 patients with psoriatic arthritis seen in our service. We have collected the following data at onset of the disease: age and sex, age at onset of cutaneous and articular manifestations, clinical form, distal interphalangeal affection, axial involvement, erythrocyte sedimentation rate, rheumatoid factor, antinuclear antibody and HLA antigen. Likewise, we have collected the present functional class. We have correlated the data at onset of the disease with the present functional class. RESULTS: Mean +/- SD age of 96 patients (48 male, 48 female) was 51 +/- 14 years. The majority of patients (78%) were in ACR functional class I or II. The most frequent clinical form was the oligoarticular (46%), except in the female group, in which the most frequent was the symmetric polyarticular one (46%). We found statistically significant correlation between the present functional class and the clinical form at onset and the disease duration. We didn't found a statistically correlation between the present functional class and the axial involvement. CONCLUSIONS: Patients with psoriatic arthritis and symmetric polyarthritis are more frequently female, and have a worse prognosis. The axial involvement does not imply a worse prognosis.
11723826 [Elastase inhibitors]. 2001 The serine proteinase elastase is located in the azurophil granules of mature circulating polymorphonuclear neutrophils. This neutrophil elastase or NE is a potent non specific serine protease which plays a role as bactericidal agent and in the degradation of immune complexes by intraphagosomal processes. It promotes inflammation when the granule contents are secreted in the extracellular environment. In certain pathological circumstances, an imbalance between NE and its major plasmatic inhibitor alpha 1-PI (formerly, alpha 1-antitrypsin) leads to abnormal tissue destruction and disease development. Genetic or acquired alpha 1-PI deficiency is thought to be involved in the pathogenesis of pulmonary emphysema. A variety of degenerative and degradative disorders are also associated to uncontrolled proteolysis by NE (rheumatoid arthritis, glomerulonephritis, adult respiratory distress symptom, psoriasis, cancer). Numerous inhibitors of NE have been reported. Various molecules are currently undergoing clinical trials for emphysema and other pulmonary diseases.
11402516 [Large granular lymphocyte proliferations. Clinical and pathogenic aspects]. 2001 May INTRODUCTION: The clinical course, biological features, and recent data on the pathogenesis of large granular lymphocyte (LGL) leukemia are reviewed. CURRENT KNOWLEDGE AND KEY POINTS: Clonal diseases of LGL disorders can arise from a CD3+, CD57+ T-cell lineage, which are the most frequent, or from a CD3-, CD56+ NK-cell lineage. The diagnosis of LGL leukemia is suspected on the basis of a persistent excess of LGL, usually with neutropenia and splenomegaly. It is assessed by immunophenotypic and molecular studies of T-cell receptor clonality (southern blot, PCR). Association with autoimmune diseases (rheumatoid arthritis, erythroblastopenia, etc.) is a main feature of chronic LGL proliferation. Questions about a viral agent (HTLV1?), facilitation of clonal expansion by cytokines (IL-12, IL-15), and the defective Fas apoptotic pathway are discussed. Treatment of symptomatic LGL proliferations is based on immunosuppressive agents (principally methotrexate and cyclophosphamide). FUTURE PROSPECT AND PROJECTS: The epidemiology, prognosis factors, therapeutics and the pathogenesis of LGL leukemia are unknown. We proposed the creation of a French register of LGL expansions to explore these different aspects.
10051698 The anti-IgE/anti-FcepsilonRIalpha autoantibody network in allergic and autoimmune disease 1999 Jan Basophil granulocytes and tissue mast cells and their mediators play a role in the pathogenesis of several immune and inflammatory disorders. Human basophils and mast cells (FcepsilonRI+ cells) can be activated through immunological interaction with the IgE-FcepsilonRI network. FcepsilonRI+ cells can be triggered by cross-linking between the Fab portions of IgE and multivalent antigens (direct anaphylaxis). 'Reverse type' anaphylaxis can occur through three distinct mechanisms: antibodies against the Fcepsilon portion of IgE (anti-IgE), antibodies against epitopes of the alpha chain of FcepsilonRI (anti-FcepsilonRIalpha) and anti-IgG acting on IgG-IgE complexes bound to FcepsilonRI. Anti-IgE autoantibodies are occasionally present even in normal donors and more frequently in a variety of allergic (chronic urticaria, atopic dermatitis and bronchial asthma) and autoimmune disorders (rheumatoid arthritis, lupus erythematosus and systemic sclerosis). IgG anti-IgE from a small percentage of patients induces the release of mediators from human FcepsilonRI+ cells. Some of the anti-IgE autoantibodies present in allergic patients are non-anaphylactogenic, thus representing a possible protective mechanism preventing the association of IgE with FcepsilonRI. Anti-FcepsilonRIalpha autoantibodies also occur in a significant percentage of patients of chronic urticaria and probably non-allergic asthma and some autoimmune diseases. Although anti-IgE and anti-FcepsilonRIalpha autoantibodies, present in a percentage of patients with immune disorders, are relevant to the pathogenesis of these conditions, much remains to be learnt about their immunochemistry, their prevalence and precise role in various inflammatory diseases.
11762204 The V kappa III subgroup light chain proteins in AL amyloidosis & autoimmune diseases. 2001 Jul BACKGROUND & OBJECTIVES: Light chain associated amyloidosis (AL) is characterized by extracellular deposition of immunoglobulin light chain and its fragments. In vitro and in vivo studies have shown that some light chains are nonamyloidogenic and nonnephrotoxic, whereas others are potentially amyloidogenic. Some light chains are prone to be deposited as rheumatoid materials, and also as nodular amorphous aggregates (light chain deposition diseases). These findings suggest that specific sequence element(s) may control the various kinds of light chain associated diseases. In this study we tried to identify such sequence element(s). METHODS: Two Bence Jones proteins (BJPs), NIG93 and NIG2 of subgroup V kappa III, were characterized and compared with other members of the same subgroup whose sequences are available in the data base. RESULTS: Both NIG93 and NIG2 proteins had sequences characteristics of V kappa IIIa as distinguished from V kappa IIIb, subsubgroup proteins. They also contained several novel substitutions, such as Met-37, Leu-40, Val-58, and IIe-85 in NIG93, and Val-2, His-29, Arg-50, and Ile-72 in NIG2. The data accumulated at present indicate that all members of the V kappa IIIa subsubgroup are related to either AL amyloidosis or rheumatoid arthritis, whereas the V kappa IIIb proteins are related to autoimmune diseases. INTERPRETATION & CONCLUSION: These observations indicate that subgroup-specific residues might be critical for light chain pathogenesis, at least for the V kappa III proteins. Point mutations within these proteins may be another structural element controlling their conformation as well as their pathogenic aggregation.
9268497 Staphylococcal enterotoxin B induces arthritis in female DBA/1 mice but fails to induce ac 1997 Aug 1 It has been proposed that superantigens are involved in the pathogenesis of autoimmune diseases. To test the possibility of superantigens inducing arthritis in naive mice, V beta 8-reactive superantigen staphylococcal enterotoxin B (SEB) was injected into naive mice. We used female DBA/1 mice, because they were susceptible to collagen-induced arthritis (CIA), in which the pathogenic T cells were supposed to preferentially use limited V betas of T cell receptors including V beta 8. Mild monoarthritis developed in uninjected hindlimbs of mice administered with SEB in higher frequency (an average incidence of 24%) than the control phosphate-buffered saline-injected mice (4.2%). Autoimmune responses in mice administered with SEB were compared with those in mice developing CIA. However, activation of type II collagen (IIC)-reactive T cells was not detected in SEB-injected mice. Production of autoantibodies, anti-IIC antibody and rheumatoid factor was also undetected. Although exact mechanisms of pathogenesis of this arthritis remain to be known, V beta 8+ T cells were activated for a long period and the unresponsiveness of V beta 8+ T cells was not detected in this strain. From these results, we discuss the pathogenesis of arthritis induced by SEB and the possibility that superantigen may play a role in the induction of autoimmune diseases.
9498704 Autoimmune phenomena and hepatitis C virus in lymphoproliferative and connective tissue di 1997 Dec Since hepatitis C virus (HCV) infection is frequently detected in patients with lymphoproliferative or autoimmune disorders and since the virus may infect lymphocytes, the question is raised whether malignant transformation and autoimmune manifestations in the presence of HCV are HCV-related or merely fortuitous. A close association has been firmly established between HCV infection and essential type II mixed cryoglobulinemia (ECM), an indolent lymphoproliferative disorder characterized by cryoprecipitable immune-complexes (IC) that may evolve into classical non Hodgkin's lymphomas (NHL) retaining the ability to produce cryoprecipitable rheumatoid factor (RF). It is reasonable to consider HCV as one cofactor in lymphomagenesis, even if the precise pathogenetic relationship between HCV infection, the chronic presence of cryoprecipitable IC and the development of NHL have not been established yet. Several epidemiological studies have documented the ability of chronic HCV infection to favour the production of autoAb. It is not clear why only some patients with HCV infection develop autoAb, nor why the most frequent autoAb detected in HCV-infected subjects are cryoglobulins. Though a high prevalence of anti-HCV has been found in a variety of systemic and organ-specific autoimmune diseases, it is likely that several of these associations are fortuitous with the notable exception of membranoproliferative glomerulonephritis. As HCV can provoke or exacerbate inflammatory signs and cause the production of RF, it is reasonable to suspect that HCV infection may be able to trigger the development of some connective tissue diseases or to exacerbate their clinical course. Nonetheless, it is clinically prudent to conclude that the pathogenetic relationships of Sjögren syndrome, rheumatoid arthritis and polyarthritis with HCV infection are more likely to be regarded as mediated via the intermediate development of ECM.