Complement Expression and Activation in Osteoarthritis Joint Compartments

Objective: To investigate complement(C) factors(F) and their activation fragments expression in OA joint tissues. Design: Immunohistochemistry and quantitative imaging were performed to analyze C3, C4, and CF (factor) B expression on osteochondral biopsies (43 patients) collected during arthroplasty. Isolated chondrocytes and synoviocytes, cartilage and synovial tissues obtained from surgical specimens of OA patients (15 patients) were cultured with or without IL-1\u3b2. Real time PCR for CFB, C3, and C4 was performed. Culture supernatants were analyzed for C3a, C5a, CFBa, and terminal complement complex (TCC) production. Results: In osteochondral biopsies, C factor expression was located in bone marrow, in a few subchondral bone cells and chondrocytes. C3 was the most expressed while factor C4 was the least expressed factor. Gene expression showed that all C factors analyzed were expressed both in chondrocytes and synoviocytes. In chondrocyte cultures and cartilage explants, CFB expression was significantly higher than C3 and C4. Furthermore, CFB, but not C3 and C4 expression was significantly induced by IL-1\u3b2. As to C activation factors, C3a was the most produced and CFBa was induced by IL-1\u3b2 in synovial tissue. TCC production was undetectable in isolated chondrocytes and synoviocytes cell culture supernatants, whereas it was significantly augmented in cartilage explants. Conclusion: C factors were locally produced and activated in OA joint with the contribution of all tissues (cartilage, bone, and synovium). Our results support the involvement of innate immunity in OA and suggest an association between some C alternative pathway component and joint inflammation

Increased serum vascular cell adhesion molecule (VCAM)-1 levels in patients with erosive hand osteoarthritis

Un numero sempre crescente di evidenze sottolinea l\u2019importante contributo dell\u2019angiogenesi nell\u2019ambito dei meccanismi che inducono le modificazioni articolari caratteristiche dell\u2019osteoartrosi (OA). Nei pazienti con OA, alcune molecole correlate al processo angiogenetico, quali vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1) e fibroblast growth factor-2 (FGF-2) sono espresse a livello articolare e possono avere un ruolo non solo in relazione all\u2019angiogenesi, ma anche all\u2019omeostasi cartilaginea. Questo studio si propone di valutare i livelli circolanti di VEGF, VCAM-1 e FGF-2 in pazienti con OA della mano affetti da forma erosiva (OA-E) e non-erosiva (OA-NE) e di determinare le eventuali associazioni con il danno articolare valutato tramite analisi radiologica convenzionale. Sono stati analizzati, con metodo ELISA, i sieri di 146 pazienti con OA-E, di 148 pazienti con OA-NE e di 148 soggetti di controllo (CN). I livelli circolanti di sVCAM-1 nei pazienti con OA-E sono risultati pi\uf9 elevati rispetto a quelli evidenziati nei CN; non sono state dimostrate differenze tra i pazienti con OAE e i pazienti con OA-NE. L\u2019analisi di VEGF e FGF-2 non ha evidenziato differenze significative tra pazienti con OA e CN, inoltre non sono emerse correlazioni tra i livelli circolanti di VEGF, sVCAM-1 e FGF-2 e parametri radiologici e clinici. I dati ottenuti, dimostrando un aumento dei livelli circolanti di sVCAM-1 nei pazienti con forma erosiva di OA della mano, caratterizzata da una peggiore decorso e maggiore aggressivit\ue0, aggiungono nuove informazioni circa la possibilit\ue0 di identificare sVCAM-1 come biomarcatore di severit\ue0 di malattia

Systemic inflammation and antibodies to citrullinated peptides in hand osteoarthritis.

none9OBJECTIVES: To investigate systemic inflammation and autoimmune response to citrullinated peptides in patients with erosive and non erosive 'lone' hand osteoarthritis (HOA) with no hip/knee involvement and their relationship with radiographic structural damage. METHODS: Sera were obtained from a total of 99 patients with HOA (52 patients with erosive HOA and 47 patients with non-erosive HOA) and from 50 control subjects (NC). Hand radiographs were obtained from all patients and scored for joint damage according to the Kellgren-Lawrence and the Kallman scores. Serum levels of high-sensitivity CRP (hsCRP), IL-6, pentraxin-3 (PTX-3), anti-CCP and anti-modified citrullinated vimentin (MCV) antibodies were evaluated by a sandwich ELISA. RESULTS: Circulating levels of inflammatory biomarkers hsCRP, IL-6 and PTX3 were not significantly different in the two groups of patients with erosive and non-erosive HOA compared to NC and no significant difference was seen between non-erosive and erosive HOA. Anti-CCP positivity was detected respectively in 1 patient (2.1%) with non-erosive HOA and 1 patient (1.9%) with erosive HOA. Anti-MCV antibodies were present in 4 patients (8.5%) with non-erosive HOA, and 4 patients (7.7%) with erosive HOA. In the control group, one subject (2%) was positive for anti-CCP and 2 subjects (4%) had anti-MCV antibodies. Significant correlation was obtained only between body mass index and hsCRP concentration (r=0.4071; p<0.0001). No correlation between inflammation markers/autoantibodies and disease duration and radiological scores was found. CONCLUSIONS: Our study underlines the lack of systemic inflammation and autoimmunity in 'lone' HOA and confirms the association between BMI and CRP levels.noneDolzani P.; Assirelli E.; Pulsatelli L.; Addimanda O.; Mancarella L.; Peri G.; Mantovani A.; Facchini A.; Meliconi R.Dolzani P.; Assirelli E.; Pulsatelli L.; Addimanda O.; Mancarella L.; Peri G.; Mantovani A.; Facchini A.; Meliconi R

Systemic inflammation and antibodies to citrullinated peptides in hand osteoarthritis

OBJECTIVES: To investigate systemic inflammation and autoimmune response to citrullinated peptides in patients with erosive and non erosive 'lone' hand osteoarthritis (HOA) with no hip/knee involvement and their relationship with radiographic structural damage. METHODS: Sera were obtained from a total of 99 patients with HOA (52 patients with erosive HOA and 47 patients with non-erosive HOA) and from 50 control subjects (NC). Hand radiographs were obtained from all patients and scored for joint damage according to the Kellgren-Lawrence and the Kallman scores. Serum levels of high-sensitivity CRP (hsCRP), IL-6, pentraxin-3 (PTX-3), anti-CCP and anti-modified citrullinated vimentin (MCV) antibodies were evaluated by a sandwich ELISA. RESULTS: Circulating levels of inflammatory biomarkers hsCRP, IL-6 and PTX3 were not significantly different in the two groups of patients with erosive and non-erosive HOA compared to NC and no significant difference was seen between non-erosive and erosive HOA. Anti-CCP positivity was detected respectively in 1 patient (2.1%) with non-erosive HOA and 1 patient (1.9%) with erosive HOA. Anti-MCV antibodies were present in 4 patients (8.5%) with non-erosive HOA, and 4 patients (7.7%) with erosive HOA. In the control group, one subject (2%) was positive for anti-CCP and 2 subjects (4%) had anti-MCV antibodies. Significant correlation was obtained only between body mass index and hsCRP concentration (r=0.4071; p<0.0001). No correlation between inflammation markers/autoantibodies and disease duration and radiological scores was found. CONCLUSIONS: Our study underlines the lack of systemic inflammation and autoimmunity in 'lone' HOA and confirms the association between BMI and CRP levels

Imbalance between angiogenic and anti-angiogenic factors in sera from patients with large-vessel vasculitis

OBJECTIVES: To investigate serum levels of a panel of angiogenic inducers (VEGF, FGF-2, Angiopoietin 1, -2, soluble VCAM-1) and inhibitors (angiostatin, endostatin, pentraxin-3) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK), in order to gain further insights into the molecular mechanisms driving angiogenesis dysregulation in large-vessel vasculitis (LVV). METHODS: Sera were obtained from 33 TAK patients and 14 GCA patients and from two groups of age-matched normal controls (NC). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Angiogenic and anti-angiogenic factor serum levels were evaluated using commercial ELISA kits. Pentraxin 3 (PTX3) serum levels were evaluated by non-commercial ELISA, as already described. RESULTS: Among the angiogenic factors, only VEGF serum levels were significantly higher in TAK patients compared to NC. No difference was found between angiogenic factor levels in GCA patients compared to those detected in NC. Anti-angiogenic factor (Angiostatin, Endostatin, PTX3) serum levels were significantly higher in both GCA and TAK patients compared to NC. Significant associations were observed between VEGF and PTX3 levels and disease activity evaluated using PET scan and clinical indices. Cluster analysis based on PET scan scores in TAK patients showed significant ordered differences in VEGF and angiostatin serum levels. Indeed, we noted a progressive increase of VEGF and angiostatin from NC to the cluster including patients with the highest and more diffuse scan positivity. CONCLUSIONS: Our overall results demonstrate a circulating molecular profile characterised by a prevailing expression of anti-angiogenic soluble factors