Rheumatoid Arthritis: Lunardi C

Gerli R, Lunardi C, Pitzalis C. · No affiliation provided · Rheumatology (Oxford). · Pubmed #12468812 links to  free full text

This publication has no abstract.

Lunardi C, Tinazzi E, Bason C, Dolcino M, Corrocher R, Puccetti A. · Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona, Verona, Italy. · Autoimmun Rev. · Pubmed #18700174 No free full text.

Abstract: Human parvovirus B19 infection is responsible for a wide range of human diseases ranging from mild erythema infectiosum in immunocompetent children to fetal loss in primary infected pregnant women and aplastic anemia or lethal cytopenias in adult immunocompromised patients. Since persistent viral infection is responsible for an autoimmune response and clinical symptoms can mimic autoimmune inflammatory disorders, parvovirus B19 is the object of intense efforts to clarify whether it is also able to trigger autoimmune diseases. Indeed the virus has been implicated as the causative or the precipitating agent of several autoimmune disorders including rheumatoid arthritis, systemic lupus, antiphospholipid syndrome, systemic sclerosis and vasculitides. Molecular mimicry between host and viral proteins seems to be the main mechanism involved in the induction of autoimmunity. By means of a random peptide library approach, we have identified a peptide that shares homology with parvovirus VP1 protein and with human cytokeratin. Moreover the VP peptide shares similarity with the transcription factor GATA1 that plays an essential role in megakaryopoiesis and in erythropoiesis. These new data sustain the role played by molecular mimicry in the induction of cross-reactive (auto)antibodies by parvovirus B19 infection.

Gerli R, Pitzalis C, Lunardi C. · Department of Clinical and Experimental Medicine, Section of Internal Medicine and Oncological Sciences, Center for the Study of Rheumatic Diseases, University of Perugia, Perugia, Italy. · Isr Med Assoc J. · Pubmed #12455188 links to  free full text

This publication has no abstract.

Gerli R, Lunardi C, Vinante F, Bistoni O, Pizzolo G, Pitzalis C. · Section of Internal Medicine and Oncological Sciences, Department of Clinical and Experimental Medicine, Center for the Study of Rheumatic Diseases, University of Perugia, I-06122, Perugia, Italy. · Trends Immunol. · Pubmed #11286706 No free full text.

Abstract: CD30 has been proposed to identify Th0/2-type clones. However, the in vivo relevance of this finding is still a matter of debate, as high serum levels of soluble CD30 have been found in both Th1- and Th2- dominated disorders. Among these, rheumatoid arthritis represents a condition where the Th1 predominance is combined with the presence of CD30(+) T-cell activity, particularly in specific stages of the disease. This article discusses the hypothesis that CD30(+) T cells might play a counter-regulatory role at sites of inflammation in Th1-mediated conditions, such as rheumatoid arthritis.

Gerli R, Lunardi C, Bocci EB, Bobbio-Pallavicini F, Schillaci G, Caporali R, Bistoni O, Pirro M, Pitzalis C, Montecucco C. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. · J Rheumatol. · Pubmed #18061981 No free full text.

Abstract: OBJECTIVE: Patients with rheumatoid arthritis (RA) display high serum concentrations of soluble CD30 (sCD30), which correlate with counter-regulatory activity of CD30+ T cells in the inflamed joint. To verify the contribution of this T cell subset to disease remission, sCD30 levels were analyzed longitudinally in patients with active RA following infliximab therapy. METHODS: Infliximab plus methotrexate were started in 39 patients with active RA, while 20 patients with inactive disease, controlled by stable doses of methotrexate, acted as controls. Serial evaluations of sCD30 concentrations and disease activity indexes were performed throughout 38 weeks. RESULTS: sCD30 levels were higher in patients than in healthy controls. Rapid infliximab-induced decrease in disease activity was associated with an overall increase of sCD30 levels. In contrast, levels remained stable in controls. An inverse correlation between sCD30 levels and Disease Activity Score 28 was observed from the 22nd week of infliximab treatment. Analysis of sCD30 levels according to American College of Rheumatology response showed, after an initial general enhancement of sCD30 concentrations, a persistent increase of sCD30 in responders, but not in nonresponders. CONCLUSION: sCD30 serum levels are enhanced by tumor necrosis factor-a (TNF-a) blockade in patients with active RA and inversely correlated with disease activity, but only after some weeks of treatment. Of interest, a sustained increase of sCD30 is present only in subjects with evidence of persistent clinical response to anti-TNF-alpha. As sCD30 serum levels mirror antiinflammatory activity of joint T cells, the present data may suggest a role of synovial counter-regulatory CD30+ T cells in the induction of infliximab-mediated remission in RA.

Navone R, Lunardi C, Gerli R, Tinazzi E, Peterlana D, Bason C, Corrocher R, Puccetti A. · Department of Clinical and Experimental Medicine, University of Verona, Policlinico GB Rossi, Piazzale LA Scuro 10, Italy. · J Autoimmun. · Pubmed #16249071 No free full text.

Abstract: Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration and tissue damage mainly confined to the salivary and lacrimal glands, resulting in dryness of mouth and eyes. Since different epithelial cells of exocrine and non-exocrine tissues are primarily affected, an autoimmune reaction against antigens commonly expressed in epithelial cells is believed to play a pathogenic role. To identify novel autoantigen targets associated with the systemic involvement in SS, we screened a random peptide library with pooled IgG immunoglobulins derived from patients with primary SS. Among the identified peptides, one was recognized by the majority of patients' sera, but not by sera of normal donors and of patients with other autoimmune diseases. The peptide showed homology with an Epstein-Barr Virus (EBV) derived protein and with tear lipocalin, a protein highly expressed in tears and saliva, and with alpha-fodrin, a cytoskeleton protein considered an important autoantigen target in SS. Anti-peptide antibodies affinity purified from patients' sera recognize the viral protein, tear lipocalin and alpha-fodrin. Our findings suggest that EBV infection may be linked to the pathogenesis of SS and that tear lipocalin can be considered a novel and yet unidentified autoantigen in SS.

Beri R, Peterlana D, Puccetti A, Simeoni S, Garzotti P, Biasi D, Caramaschi P, Tinazzi E, Lunardi C. · Sezione di Medicina Interna, Dipartimento di Medicina Clinica e Sperimentale, Policlinico G.B. Rossi, Universita di Verona. · Recenti Prog Med. · Pubmed #15929613 No free full text.

Abstract: We studied HLA-DRB1 alleles in 101 patients with rheumatoid arthritis (RA) and 229 normal subjects by polymerase chain reaction and sequence-specific oligonuclotide hybridization. We observed a statistically significant association between HLA-DR4 and RA (p = 0,0088). This association was not observed for the DR1 status. No particular DR4 suballeles were preferentially expressed in patients. Allele *0102 was more frequent in RA patients (p = 0.0084), while *0103 in controls (p = 0.000047). No difference was observed for the presence of early erosions and extra-articular features in patients with no, one or two RA associated alleles and among share epitope positive and negative patients.

Peterlana D, Puccetti A, Beri R, Ricci M, Simeoni S, Borgato L, Scilanga L, Cerù S, Corrocher R, Lunardi C. · Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona, 37134 Verona, Italy. · J Rheumatol. · Pubmed #12966589 No free full text.

Abstract: OBJECTIVE: To amplify both NS1 and VP genes of Parvovirus B19 DNA in synovial membrane (SM) and serum obtained from patients with rheumatoid arthritis (RA) and to analyze whether the presence of viral DNA is correlated with synovitis. METHODS: DNA obtained from 30 SM and 24 serum samples from RA patients was analyzed using single round-polymerase chain reaction (PCR) and nested PCR for both VP and NS1 genes of parvovirus B19. Twenty-four SM and serum samples from sex and age matched subjects with osteoarthritis (OA) or joint trauma served as controls. RESULTS: The first round PCR was negative for NS1 in RA samples. After nested PCR, NS1 was detected in the SM of 6/30 patients and of 10/24 controls and in the serum of 4/24 patients and controls. Nested PCR for the VP gene detected viral DNA in the SM of 7/30 patients with RA and of 7/24 of the controls and in the serum of 5/24 patients and of 2/24 controls. Altogether parvovirus DNA was found in the SM of 11/30 (36.6%) patients and of 12/24 (50%) controls and in the serum of 8/24 (33.3%) patients with RA and of 5/24 (20.8%) controls. CONCLUSION: Our results suggest that the amplification by nested PCR of both NS1 and VP genes is necessary to define the presence of viral DNA in tissue samples and confirm that the presence of parvovirus B19 DNA is similar in RA and control SM, suggesting that simple detection of viral DNA is not sufficient to confirm a link between the virus and RA.

Gerli R, Bistoni O, Russano A, Fiorucci S, Borgato L, Cesarotti ME, Lunardi C. · Department of Clinical and Experimental Medicine, Section of Internal Medicine and Oncologic Sciences, Rheumatology Unit, University of Perugia, Italy. · Clin Exp Immunol. · Pubmed #12197898 links to  free full text

Abstract: T-cell cytokines play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). Their detection in the joint, however, is impaired by the complex network present in the synovium. Although many synovial T cells show signs of previous activation, only a few express interleukin (IL)-2 receptor, marker of recent activation. The aim of this study was to analyse the cytokine production by in vivo activated (IL-2R +) T cells from RA at different stages of the disease. For this purpose, T cells were isolated from peripheral blood and synovial fluid of four patients with active RA, two at the onset of the disease, one in the early phase during treatment, one in long-lasting chronic phase. One patient was studied at the onset of the disease and 52 months later. Cells were initially expanded with a low dose of IL-2, cloned and analysed for cytokine production. The results showed a strong predominance of T helper (Th) 1 clones in the blood and a slight prevalence of Th0 clones in the joint of all the four patients. Interferon-gamma and IL-2 production was higher in the long-lasting RA, whereas IL-4 synthesis was prevalent in early RA. Enrichment in IL-10-producing clones was present only in the joint of the untreated patients. The longitudinal study confirmed the differences in cytokine production between early and late phases of disease. These data confirm that RA is mainly a Th1-driven condition. However, in vivo activated synovial T cells produce also Th2-type anti-inflammatory cytokines, such as IL-4 and IL-10. The synthesis of both cytokines is a feature of the very early phase of RA, although the selective recruitment of IL-10-producing T cells is quickly lost.

Sartoris S, Brendolan A, Degola A, Testi MG, Chignola R, Scarpa A, Scardoni M, Contreas G, Pinelli L, Lunardi C, Beri R, Pera C, Ferrara GB, Riviera AP, Tridente G, Andrighetto G. · Dipartimento di Patologia, sezione di Immunologia, Facoltà di Medicina e Chirurgia dell'Università di Verona, Verona, Italy. · Hum Immunol. · Pubmed #10825588 No free full text.

Abstract: Qualitative and/or quantitative alterations in the expression of the MHC class II molecules affect the onset and maintenance of the immune response and may be the basis of a wide variety of disease states, such as autoimmunity and immunodeficiency.CIITA is a major physiological regulator of the expression of MHC class II genes. The availability of CIITA ap- pears generally essential for MHC class II gene expression, and hence its own transcriptional regulatory mechanisms result of fundamental importance for a correct homeostasis of the immune response. Therefore, it is possible to hypothesize that variability at the CIITA-encoding locus, AIR-1, could constitute an additional source of susceptible traits to autoimmune diseases. Mutations at AIR-1/CIITA promoters could modulate expression of CIITA. Variations in CIITA expression could influence the qualitative and quantitative expression of MHC class II molecules at cell surface. We have analyzed sequence variation at AIR-1/CIITA promoters by PCR-SSCP in 23 IDDM and 30 RA patients compared to a sample of 19 unaffected normal controls and 16 unaffected IDDM family members, for a total of 88 Caucasian subjects from the Northeast of Italy. No sequence difference was found at the four AIR-1/CIITA promoters between autoimmune patients and normal controls. Moreover, the promoters resulted invariant within the entire group of 88 subjects analyzed, comprising patients and controls. This finding suggests a possible selective advantage in maintaining CIITA upstream regulatory sequences invariant.

Gerli R, Pitzalis C, Bistoni O, Falini B, Costantini V, Russano A, Lunardi C. · Department of Clinical and Experimental Medicine, Section of Internal Medicine and Oncological Sciences, Center for the Study of Rheumatic Diseases, University of Perugia, Perugia, Italy. · J Immunol. · Pubmed #10754341 links to  free full text

Abstract: High serum levels of soluble CD30 (sCD30) have been reported to better predict the response to second line therapy in rheumatoid arthritis (RA). It is believed that sCD30 is released by CD30+ T cells present in the RA synovium. However, both the mechanism of recruitment to the joint and the functional role of this T cell subset in the pathogenesis of the disease remain unknown. This study confirmed higher levels of sCD30 in the serum and synovial fluid (SF) of RA patients compared with normal controls. However, analysis of mRNA and cell surface CD30 expression showed that CD30+ T cells are detectable in the SF, but not in the synovial membrane. In contrast, T cells expressing the CD30 transcript, but not the surface molecule, were found in the peripheral blood of both RA and normal controls. CD30 surface expression was up-regulated by adhesion and migration through endothelium in vitro and in a delayed-type hypersensitivity model in vivo. Although the great majority of fresh or cloned CD30+ T cells from SF produced both IFN-gamma and IL-4, CD30 expression strictly correlated with IL-4 synthesis in synovial T cell clones. In addition, CD30+ T cell clones also produced high amounts of the anti-inflammatory cytokine IL-10. On this basis, we would like to propose that synovial CD30+ cells may play a role in the control of the inflammatory response. Serum sCD30 may reflect such cell activity and, therefore, explain the previously demonstrated correlation between high sCD30 serum levels and positive response to therapy.

Gerli R, Bistoni O, Lunardi C, Giacomelli R, Tomassini C, Biagini P, Pitzalis C. · Department of Clinical and Experimental Medicine, Section of Internal Medicine and Oncological Sciences, Centre for the Study of Rheumatic Diseases, University of Perugia, Italy. · Rheumatology (Oxford). · Pubmed #10587561 links to  free full text

Abstract: OBJECTIVE: To evaluate whether serum levels of the soluble form of CD30 (sCD30) correlate with disease activity in early rheumatoid arthritis (RA) and may have prognostic value in predicting the response to disease-modifying anti-rheumatic drugs (DMARDs). METHODS: The levels of sCD30 and C-reactive protein (CRP) were measured in the serum of 14 untreated subjects with early RA, before and during treatment with hydroxychloroquine, for a follow-up period of 8 months. At the end of the study, patients were also evaluated for their response to DMARDs. RESULTS: An inverse correlation between sCD30 and CRP serum values was demonstrated at baseline, but not during the follow-up. Patients who responded to DMARD therapy had higher sCD30 basal levels than non-responders. CONCLUSIONS: The evaluation of sCD30 serum levels in early RA may reflect the attempt by CD30+ T cells to downmodulate inflammation and may be a useful marker to predict a good response to DMARDs.