Anti-C1q autoantibodies are frequently detected in patients with systemic sclerosis associated with pulmonary fibrosis.

BACKGROUND: Anti-C1q autoantibodies (autoAbs) are associated with systemic lupus erythematosus (SLE), but their presence in other rheumatic diseases has not been adequately investigated. OBJECTIVES: We aimed to assess anti-C1q autoAbs and circulating immune complexes (CICs) in systemic sclerosis (SSc). METHODS: In total 124 patients with SSc were studied; 106 were female and the median age was 59·4 years (range 25-81·4). Overall 75 (60·5%) had limited cutaneous SSc and 49 (39·5%) had diffuse cutaneous SSc. Also included were 25 patients with Sjögren syndrome (SjS), 29 with rheumatoid arthritis (RA), 38 with SLE and 53 healthy controls. Enzyme-linked immunosorbent assays with high- and low-salt buffers were used to measure anti-C1q antibodies and CICs. The former allows only anti-C1q antibody binding to C1q and the latter also allows IgG Fc to bind to C1q. RESULTS: Anti-C1q antibodies were present in 20 of 124 (16·1%) patients with SSc: five had high levels (> 80 RU mL-1 ) and 10 (50%) had moderate levels (40-80 RU mL-1 ). Anti-C1q antibodies were also present in one of 25 (4%) patients with SjS, one of 29 (3%) with RA (P < 0·05 for both) and three of 53 (6%) healthy controls (P < 0·01). Anti-C1q antibodies were detected in 13 of 38 (34%) patients with SLEs. Anti-C1q antibodies were more frequent in male than female patients with SSc (P = 0·005); this association remained after multivariate regression analysis. Anti-C1q antibody level was the most important factor in predicting the presence of pulmonary fibrosis, and the second most important in predicting pulmonary arterial hypertension. Fourteen patients with SSc (11·3%) had CICs. CONCLUSIONS: Anti-C1q autoAbs were frequently detected in patients with SSc, and their high levels predict the co-occurrence of pulmonary fibrosis or pulmonary arterial hypertension.

Acute renal failure after antibiotic-impregnated bone cement treatment of an infected total knee arthroplasty.

Antibiotic-impregnated cement is used frequently in revision procedures of infected total hip and knee arthroplasties. Local antibiotic treatment is as effective as the use of systemic antibiotics. The purpose of such treatment is to provide high tissue concentrations of antibiotics and minimize systemic toxicity, especially nephrotoxicity. Though antibiotic-impregnated cement is considered safe in terms of nephrotoxicity, two cases that have implicated aminoglycoside-impregnated cement in acute renal failure (ARF) after surgery for an infected total knee arthroplasty (TKA) have been reported [Curtis et al. 2005, Van Raaij et al. 2002]. Two more cases of postoperative ARF after use of combined tobramycin- plus vancomycin-impregnated cement, this time in total hip arthroplasty, have been recently reported [Patrick et al. 2006]. We report a case of ARF in a 61-year-old patient with a history of diabetes mellitus and hypertension after treatment of a febrile infection of a TKA with combined gentamicin- plus vancomycin-impregnated cement. The ARF could not sufficiently be attributed to other causes and though serum concentrations of antibiotics obtained from the 8th postoperative day and thereafter were far below the trough levels associated with nephrotoxicity, gentamicin and vancomycin seem to have contributed significantly to ARF in our case.

Lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) expression in human articular chondrocytes.

OBJECTIVE: To investigate the involvement of oxidized low density lipoprotein (ox-LDL) and the expression of its receptor lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) in osteoarthritis, by determining the ox-LDL in synovial fluid and the expression of LOX-1 mRNA and protein in osteoarthritic as well as normal cartilage. In addition, the effect of ox-LDL on chondrocyte viability and the effect of ascorbic acid (a well-known anti-oxidant) on LOX-1 expression were studied. METHODS: Fifteen patients were included in the study. Osteoarthritic articular cartilage was obtained from two distinct locations in the knee (n = 10) and hip (n = 5), specifically from weight-bearing and non-weight-bearing areas of the same joints. Five individuals were used as controls. mRNA and protein expression were studied by RT-PCR and immunofluorescence, respectively. Ox-LDL was measured in the synovial fluid and in paired serum samples from the patients using the ELISA method. RESULTS: Ox-LDL was detected in the synovial fluid and its receptor LOX-1 was detected in cartilage from both weight-bearing and non-weight-bearing areas, whereas no LOX-1 expression was found in normal cartilage. Ox-LDL reduced chondrocyte viability in cell cultures, while the addition of ascorbic acid to osteoarthritic chondrocytes resulted in a decrease in LOX-1 mRNA expression. CONCLUSION: The detection of LOX-1 mRNA and protein expression in osteoarthritic cartilage drawn from both weight-bearing and non-weight-bearing regions of the same patients suggest that LOX-1 may be involved in the progression and pathogenesis of osteoarthritis.

Differential expression of leptin and leptin's receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism.

OBJECTIVE: To investigate leptin's effect on cartilage metabolism and the pathophysiology of osteoarthritis (OA). METHODS: Messenger RNA (mRNA) expression and protein levels of leptin and leptin's receptor isoforms were measured by real-time reverse transcription-PCR and Western blot in osteoarthritic and normal cartilage. Osteoarthritic cartilage samples were obtained from two locations of the knee (n=11) and hip (n=6); from the main defective area (advanced OA) and from adjacent macroscopically and histological intact regions (minimal OA). Paired serum and synovial fluid (SF) leptin levels were measured. The effect of leptin was evaluated on chondrocyte proliferation, IL-1beta (interleukin-1beta), NO and metalloproteinases 9 and 13 (MMP-9, MMP-13) protein expression. RESULTS: Leptin's and leptin's receptor (Ob-Rb) expression levels were significantly increased in advanced OA cartilage compared to minimal. Leptin was significantly increased in SF than serum samples. Also, leptin had a detrimental effect on chondrocyte proliferation and induced IL-1beta production and MMP-9 and MMP-13 protein expression. Furthermore, leptin's mRNA expression in advanced OA cartilage was significantly correlated with BMI of the patients. CONCLUSION: The increased leptin levels in SF point toward a local effect of leptin in articular cartilage, while the observed intrajoint differences of leptin and Ob-Rb mRNA expression may be related to the grade of cartilage destruction. The observed production of IL-1beta, MMP-9 and MMP-13 by chondrocytes after leptin treatment indicates a pro-inflammatory and catabolic role of leptin on cartilage metabolism. Furthermore, the observed correlation of leptin's mRNA expression with BMI suggests that leptin may be a metabolic link between obesity and OA.