Repeated intra-articular injection of allogeneic mesenchymal stem cells causes an adverse response compared to autologous cells in the equine model.

BACKGROUND: Intra-articular injection of mesenchymal stem cells (MSCs) is efficacious in osteoarthritis therapy. A direct comparison of the response of the synovial joint to intra-articular injection of autologous versus allogeneic MSCs has not been performed. The objective of this study was to assess the clinical response to repeated intra-articular injection of allogeneic versus autologous MSCs prepared in a way to minimize xeno-contaminants in a large animal model. METHODS: Intra-articular injections of bone marrow-derived, culture-expanded MSCs to a forelimb metacarpophalangeal joint were performed at week 0 and week 4 (six autologous; six autologous with xeno-contamination; six allogeneic). In the week following each injection, clinical and synovial cytology evaluations were performed. RESULTS: Following the first intra-articular injection, there were no differences in clinical parameters over time. Following the second intra-articular injection, there was a significant adverse response of the joint to allogeneic MSCs and autologous MSCs with xeno-contamination with elevated synovial total nucleated cell counts. There was also significantly increased pain from joints injected with autologous MSCs with xeno-contamination. CONCLUSIONS: Repeated intra-articular injection of allogeneic MSCs results in an adverse clinical response, suggesting there is immune recognition of allogeneic MSCs upon a second exposure.

Analysis of distribution and severity of inflammation in patients with osteoarthitis compared to rheumatoid arthritis by ICG-enhanced fluorescence optical imaging and musculoskeletal ultrasound: a pilot study.

BACKGROUND: In rheumatoid arthritis (RA), hand synovitis appears especially in wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. In hand osteoarthritis (OA), potential inflammatory changes are mainly present in PIP and distal interphalangeal (DIP) joints. Joint inflammation can be visualised by fluorescence optical imaging (FOI) and musculoskeletal ultrasound (US). OBJECTIVE: Comparison of the amount and distribution of inflammatory signs in wrist and finger joints of the clinically dominant hand in patients with OA and RA by FOI and gray-scale (GSUS) and power Doppler US (PDUS). METHODS: FOI and GSUS/PDUS were performed in 1.170 joints (wrists, MCP, PIP, DIP) in 90 patients (67 RA, 23 OA). Joint inflammation was graded by a semiquantitative score (0-3) for each imaging method. RESULTS: GSUS/PDUS showed wrist and MCP joints mostly affected in RA. DIP joints were graded higher in OA. In FOI, RA and OA featured inflammatory changes in the respective joint groups depending on the phase of fluorescence dye flooding. CONCLUSIONS: US and FOI detected inflammation in both RA and OA highlighting the inflammatory component in the course of OA. The different inflammatory patterns and various shapes of fluorescence enhancement in FOI may offer opportunities to distinguish and determine the inflammatory status in both diseases.

Anti­citrullinated protein antibody positivity correlates with cartilage damage and proteoglycan levels in patients with rheumatoid arthritis in the hand joints.

Objective: To investigate the factors associated with cartilage proteoglycan content in patients with rheumatoid arthritis (RA) Methods: 32 RA patients received high-field 3 Tesla Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) for determining cartilage proteoglycan content. Measurements were performed in three individual cartilage regions (medial, central, lateral) of the metacarpophalangeal joints 2 and 3. dGEMRIC values were then related to disease duration, disease activity, anti-citrullinated protein antibody (ACPA) status, rheumatoid factor status and C-reactive protein level. Results: dGEMRIC values were not significantly different between the MCP2 and MCP3 joint. Inter-class correlations were high (>0.92) for all three (medial, central and lateral) cartilage compartments. dGEMRIC values were significantly lower in RA patients with longer disease duration (≥3 years) and those with ACPA positivity than those with a short disease duration (<3 years)(p=0.034) or negative ACPA (p=0.0002), respectively. In contrast, no association between cartilage proteoglycan content and disease activity, C-reactive protein level and rheumatoid factor status was found. Conclusion: Decreased cartilage proteoglycan content in RA patients is associated with disease duration and ACPA positivity but not with the actual disease activity, CRP level or rheumatoid factor status. These data suggest that the cumulative burden of inflammation as well as ACPA are the determinants for cartilage damage in RA.

Inflammation and vascularisation markers of arthroscopically-guided finger joint synovial biospies reflect global disease activity in rheumatoid arthritis.

OBJECTIVES: To analyse whether synovial markers of the clinically dominant metacarpophalangeal (MCP) joint reflect global disease activity measures in rheumatoid arthritis (RA). METHODS: Arthroscopically-guided synovial biopsies from the dominant metacarpophalangeal (MCP) joint of 10 patients with RA (DAS28 >3.2) were stained for determination of the synovitis score, CD68, vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α). MRI and ultrasound were used to calculate the RAMRIS and US7 score respectively. Arthroscopy of the same joint was repeated in 6 patients after 6 months. RESULTS: The synovitis score significantly correlated to DAS28 (Spearman r=0.74), CRP (r=0.69), and US7 (r=0.66); sublining CD68 macrophages to CRP (r=0.6); HIF-1α to DAS28 (r=0.77), CRP (r=0.73); and VEGF to DAS28 (r=0.753) and RAMRIS (r=0.663). All patients showed a reduction of the DAS28 after 6 months (mean±SD: 5.2±1.5 vs. 2.75±1.1; p<0.05). There were three patients with a good EULAR response, and only these showed declining sublining CD68 macrophages in the control biopsy (χ2 test: LR 8.3, p=0.05). Two of the remaining patients with increasing CD68 sublining macrophages showed a deterioration of the RAMRIS. CONCLUSIONS: Some histological findings in arthroscopically-guided biopsies of the dominantly affected MCP joint reflect global disease activity measures and their changes in RA patients. Moreover, repeated MCP synovial biopsy may distinguish true responders from individuals with residual disease activity, who are not readily recognized by clinical means.

Comparison of the response to experimentally induced short-term inflammation in the temporomandibular and metacarpophalangeal joints of horses.

OBJECTIVE: To investigate the relationship between inflammatory responses of the temporomandibular joint (TMJ) and the metacarpophalangeal (MCP) joint in clinically normal horses. ANIMALS: 7 mature horses. PROCEDURES: In each horse, 1 TMJ and 1 MCP joint were injected with lipopolysaccharide (LPS; 0.0025 µg). The contralateral TMJ and MCP joint were injected with saline (0.9% NaCl) solution. Synovial fluid samples were collected from all 4 joints over 24 hours after injection. Concentrations of interleukin-6, tumor necrosis factor-α, transforming growth factor-ß, and total protein were measured via immunoassay. Horses were assessed for clinical signs of joint inflammation at each time point. RESULTS: Concentrations of interleukin-6 were not significantly different between LPS-injected MCP joints and TMJs at any time point. Transforming growth factor-ß concentrations were significantly increased in MCP joints, compared with concentrations in TMJs, at 12 and 24 hours after injection. Tumor necrosis factor-α concentrations were significantly higher in LPS-injected TMJs than in LPS-injected MCP joints at 1 and 6 hours after injection. Total protein concentration did not differ significantly between LPS-injected MCP joints and TMJs. Injection of LPS induced clinical inflammation at all time points; additionally, 2 MCP joints (but no TMJs) had an inflammatory response to injection of saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: The inflammatory response to LPS appeared to be attenuated more quickly in TMJs than in MCP joints of horses. The difference in response suggested that a lack of clinical osteoarthritis in the TMJ of horses could be attributable to a difference in cytokine response.

A paraneoplastic case of palmar fasciitis and polyarthritis syndrome.

BACKGROUND: A 58-year-old woman presented with arthritis of the small joints of her hands and rapidly progressive joint contractures. She was wheelchair bound within 2 months of the onset of her symptoms. Physical examination revealed synovitis of the small joints of her hands and palmar fasciitis. The patient had been diagnosed with pancreatic carcinoma approximately 1 year before the presentation of her rheumatic symptoms, and had undergone radical pancreatico-duodenectomy. INVESTIGATIONS: Physical examination; routine laboratory work, including full blood count and measurement of erythrocyte sedimentation rate and C-reactive protein; serological tests for rheumatoid factor, antinuclear antibodies and extractable nuclear antibodies; measurement of serum tumor markers; radiological investigations, including X-rays of her hands and feet, whole-body CT-scans and radioisotope bone scan. DIAGNOSIS: The patient's rheumatic presentation was diagnosed as a paraneoplastic syndrome associated with pancreatic carcinoma. MANAGEMENT: The patient's condition was managed with corticosteroids and methotrexate. No residual tumor or evidence of metastatic disease have been detected in the 1.5 years since the initial presentation of her rheumatic symptoms.

Manifestaciones clínicas articulares en la artritis reumatoide / Clinical articular manifestations in rheumatoid arthritis

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