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T W J Huizinga

Publications and source records attributed to T W J Huizinga.

At least 55 records · Page 3Linked to original sources
PubMed2003

Association between polymorphisms in the human chemokine receptor genes CCR2 and CX3CR1 and rheumatoid arthritis.

Cell trafficking into the rheumatoid synovium is thought to play an important role in the inflammation seen in rheumatoid arthritis. Chemokine receptors play a central role in this process, and several common variants are known, including the CCR2 variant, CCR2-64I, and two variants of the CX3CR1 gene, V249I and T280M. All three variants result in functional amino acid substitutions. We studied the association of these chemokine receptor variants with susceptibility to and severity of rheumatoid arthritis in two Dutch patient populations; 282 consecutive rheumatoid arthritis patients from a rheumatology outpatient clinic, and a cohort of 101 female rheumatoid arthritis patients, followed closely for a 12-year period, from whom hand and feet X-rays taken at three year intervals were scored and analyzed in this study. Although there was a trend towards increased severity of disease in patients carrying CX3CR1 variants, this was not independent of known risk factors. We found no evidence for a significant independent role for the CCR2 and CX3CR1 variants in the susceptibility to or severity of rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2003

Discovery of distinctive gene expression profiles in rheumatoid synovium using cDNA microarray technology: evidence for the existence of multiple pathways of tissue destruction and repair.

Rheumatoid arthritis (RA) is a heterogeneous disease. We used cDNA microarray technology to subclassify RA patients and disclose disease pathways in rheumatoid synovium. Hierarchical clustering of gene expression data identified two main groups of tissues (RA-I and RA-II). A total of 121 genes were significantly higher expressed in the RA-I tissues, whereas 39 genes were overexpressed in the RA-II tissues. Among the 121 genes overexpressed in RA-I tissues, a relative majority of nine genes are located on chromosome 6p21.3. An interpretation of biological processes that take place revealed that the gene expression profile in RA-I tissues is indicative for an adaptive immune response. The RA-II group showed expression of genes suggestive for fibroblast dedifferentiation. Within the RA-I group, two subgroups could be distinguished; the RA-Ia group showed predominantly immune-related gene activity, while the RA-Ib group showed an additional higher activity of genes indicative for the classical pathway of complement activation. All tissues except the RA-Ia subgroup showed elevated expression of genes involved in tissue remodeling. These results confirm the heterogeneous nature of RA and suggest the existence of distinct pathogenic mechanisms that contribute to RA. The differences in expression profiles provide opportunities to stratify patients based on molecular criteria.

Arthritis, Rheumatoid↗
PubMed2003

Cartilage degradation and invasion by rheumatoid synovial fibroblasts is inhibited by gene transfer of TIMP-1 and TIMP-3.

Matrix metalloproteinases (MMPs) are believed to be pivotal enzymes in the invasion of articular cartilage by synovial tissue in rheumatoid arthritis (RA). Here, we investigated the effects of gene transfer of tissue inhibitors of metalloproteinases (TIMPs) on the invasiveness of RA synovial fibroblasts (RASF) in vitro and in vivo. Adenoviral vectors (Ad) were used for gene transfer. The effects of AdTIMP-1 and AdTIMP-3 gene transfer on matrix invasion were investigated in vitro in a transwell system. Cartilage invasion in vivo was studied in the SCID mouse co-implantation model for 60 days. In addition, the effects of AdTIMP-1 and AdTIMP-3 on cell proliferation were investigated. A significant reduction in invasiveness was demonstrated in vitro as well as in vivo in both the AdTIMP-1- and AdTIMP-3-transduced RASF compared with untransduced SF or SF that were transduced with control vectors. in vitro, the number of invading cells was reduced to 25% (P<0.001) in the AdTIMP-1-transduced cells and to 13% (P<0.0001) in the AdTIMP-3-transduced cells (% of untransduced cells). Cell proliferation was significantly inhibited by AdTIMP-3 and, less, by AdTIMP-1. In conclusion, overexpression of TIMP-1 and TIMP-3 by Ad gene transfer results in a marked reduction of the invasiveness of RASF in vitro and in the SCID mouse model. Apart from the inhibition of MMPs, a reduction in proliferation rate may contribute to this effect. These results suggest that overexpression of TIMPs, particularly TIMP-3 at the invasive front of pannus tissue, may provide a novel therapeutic strategy for inhibiting joint destruction in RA.

Adenoviridae↗
PubMed2003

Autoantibodies against mannose-binding lectin in systemic lupus erythematosus.

In systemic lupus erythematosus (SLE), autoantibodies directed against complement components of the classical pathway, especially against C1q, are associated with severe disease and are of prognostic value for flares of lupus nephritis. Mannose-binding lectin (MBL), the recognition unit of the MBL pathway of complement activation, has structural similarities to C1q. Deficiencies of MBL have been shown to predispose to the development of SLE and to influence the course of the disease. We hypothesized that the presence of autoantibodies to MBL, analogous to autoantibodies to C1q in patients with SLE, may contribute to disease development. The occurrence of anti-MBL autoantibodies was assessed by enzyme-linked immunosorbent assay (ELISA) of 68 serum samples from 20 patients with SLE and in serum from 70 healthy controls. Levels of antibodies directed against MBL were significantly higher in patients with SLE compared to healthy subjects. No significant difference was found between patients with active disease compared to those with inactive disease. While the occurrence of anti-C1q autoantibodies was associated with renal involvement, no such relationship was found for anti-MBL autoantibodies. A significant correlation was found between anti-MBL and anti-C1q antibody levels. The level of anti-MBL antibodies was negatively correlated with MBL-complex activity of circulating MBL. Anti-MBL autoantibodies were of the immunoglobulin G (IgG) isotype and the binding site of IgG anti-MBL was located in the F(ab')2 portion. We conclude that anti-MBL are present in sera from SLE patients and influence the functional activity of MBL.

Adult↗
PubMed2003

Matrix metalloproteinases-3, -8, -9 as markers of disease activity and joint damage progression in early rheumatoid arthritis.

OBJECTIVE: To analyse the relation between systemic levels of pro-MMP-3, -8, and -9 matrix metalloproteinase (MMP) activity in alpha(2) macroglobulin (alpha(2)M)/MMP complexes and the progression of joint destruction in patients with recent onset rheumatoid arthritis (RA). METHODS: 109 patients with RA of recent onset were entered into this longitudinal study. Patients were followed up for two years; clinical data, blood samples, and radiographs were obtained at baseline and at 1 and 2 years. Serum levels of MMPs were measured by sandwich ELISA and MMP activity assays. RESULTS: During the two years joint damage progressed from 0 to 10 (median Sharp score, p<0.001). Stable levels of pro-MMP-3 and a significant decrease in the levels of pro-MMP-8 and -9 and alpha(2)M/MMP complexes were seen throughout the two years. Regression analysis showed that serum pro-MMP-3 levels at disease onset were independently associated with the progression of joint damage (B=0.7, 95% CI 0.3 to 1.1, p=0.001). Based on the rate of joint destruction, patients were divided into two subgroups: patients with mild and severe joint damage progression. The pro-MMP-3 levels were significantly higher in the group with severe compared with mild disease at all times. Levels of pro-MMP-8 and -9 were decreased in both groups, whereas alpha(2)M/MMP complex levels decreased in the group with mild disease only. CONCLUSION: Serum levels of the MMPs studied are associated with disease activity, but serum pro-MMP-3 levels at the onset of disease are also predictive of joint damage progression.

Adult↗
PubMed2003

HLA class II is associated with distal interphalangeal osteoarthritis.

OBJECTIVE: To investigate whether there is an association between HLA class II and distal interphalangeal osteoarthritis (DIP OA). METHODS: The study group consisted of consecutive patients with and without DIP OA aged between 40 and 70 years. DIP OA was diagnosed by radiology. These patients were referred to an "Early Arthritis Clinic" (EAC) with different types of arthritis at an early stage. Patients with rheumatoid arthritis, systemic lupus erythematosus, spondyloarthropathies, and psoriatic arthritis were excluded for the purpose of this study. DNA typing for HLA-DR and x ray examination of the hands were performed at enrollment in the EAC. To establish whether the study group was representative of the Dutch population, a population based study in Zoetermeer (n=3243) for the prevalence of DIP OA and blood donors in the Leiden area (n=2400) for the HLA-DR antigen frequencies were used as references. RESULTS: Fifty five patients (33%) of the total study group (n=166) had DIP OA. The prevalence of DIP OA and frequency of the HLA-DR alleles were similar to those of the two reference groups. Within the study group an association between DIP OA and HLA-DR2 and DR4 with respectively odds ratios of 2.4 (95% confidence interval (CI) 1.1 to 5.0) and 0.3 (95% CI 0.1 to 0.7) was found. No association was found between other HLA-DR alleles and DIP OA. CONCLUSION: The study group is a representative sample of the Dutch population. The HLA-DR2 allele was more common in patients with DIP OA. Furthermore, an inverse relation was observed between DIP OA and HLA-DR4. The results confirm findings from other investigations implicating HLA-DR2 as a risk factor in the development of DIP OA.

Adult↗
PubMed2003

Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis.

OBJECTIVE: To study factors associated with toxicity, final dose, and efficacy of methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Data were used from a randomised clinical 48 week trial on 411 patients with RA all treated with MTX, comparing folates and placebo. Logistic regression was used to study the relation between baseline variables and various dependent factors, including hepatotoxicity (alanine aminotransferase >/=3 x upper limit of normal), MTX withdrawal, final MTX dose >/=15 mg/week, and MTX efficacy. RESULTS: Addition of folates to MTX treatment was strongly related to the lack of hepatotoxicity. Next to this, high body mass index was related to the occurrence of hepatotoxicity. Prior gastrointestinal (GI) events and younger age were related to the adverse event, diarrhoea. Hepatotoxicity and GI adverse events were the main reason for MTX withdrawal, which in turn was associated with the absence of folate supplementation, body mass index, prior GI events, and female sex. Renal function (creatinine clearance >/=50 ml/min) was not associated with toxicity. Reaching a final dose of MTX of >/=15 mg/week was related to folate supplementation and the absence of prior GI events. Efficacy of MTX treatment was associated with low disease activity at baseline, male sex, use of non-steroidal anti-inflammatory drugs (NSAIDs), and lower creatinine clearance. CONCLUSIONS: MTX toxicity, final dose, and efficacy are influenced by folate supplementation. Baseline characteristics predicting the outcome of MTX treatment are mainly prior GI events, body mass index, sex, use of NSAIDs, and creatinine clearance.

Adult↗
PubMed2003

A neuroimaging follow up study of a patient with juvenile central nervous system systemic lupus erythematosus.

BACKGROUND: The course of central nervous system systemic lupus erythematosus (CNS-SLE) is largely unknown. New imaging techniques are available to assist in monitoring the disease course. OBJECTIVE: To report a case of juvenile CNS-SLE, in which magnetic resonance imaging (MRI) was used to assess disease activity. CASE REPORT: A 10-year-old female patient with SLE presented with convulsions; MRI and computed tomography (CT) of the cerebrum disclosed abnormalities. Despite adequate treatment, two years later she had a generalised convulsion, and MRI showed new lesions. MR spectroscopy (MRS) indicated neuronal loss, inflammation, and metabolically compromised tissue; magnetisation transfer imaging (MTI) showed an increase in whole brain lesion load. After exclusion of a malignancy, CNS-SLE was the most likely diagnosis, and cyclophosphamide pulses were administered. Initially, multiple sclerosis (MS)-like lesions regressed, but despite maximal immunosuppressive drugs, new lesions formed and disappeared. When immunosuppressive drugs had been stopped for six months MRI showed improved lesions and MTI histograms. DISCUSSION: In this case report, the anatomical substrate, metabolic aspect, neuroimaging, and clinical course of MS-like lesions in a child with CNS-SLE are described. The way in which radiological techniques can support clinical decision making in this young patient with progressive CNS-SLE is illustrated.

Child↗
PubMed2003

Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis.

BACKGROUND: Glucocorticoids induce hypercholesterolaemia, a cardiovascular risk factor, in patients with diseases other than rheumatoid arthritis (RA), but the data in RA are contradictory. OBJECTIVE: To determine the effects of antirheumatic treatment, including prednisolone (combination) therapy on total and high density lipoprotein (HDL) cholesterol levels in RA, taking disease activity into account. METHODS: HDL cholesterol and total cholesterol levels were determined in:(a) established RA (b) two cohorts with early active RA, (c) a previously conducted 56 week trial among patients with early RA comparing the value of intensive combination therapy (that included glucocorticoids) with sulfasalazine alone (COBRA trial). RESULTS: In established RA total cholesterol levels were only slightly raised, irrespective of disease activity. However, HDL cholesterol was significantly higher in patients in remission than in patients with active disease. In contrast, in active early RA at baseline total cholesterol was low normal: between 4.6 and 5.1 mmol/l in the different populations. The level of HDL cholesterol was highly dependent on the duration of storage. In both COBRA groups total cholesterol increased by a mean of 0.6 mmol/l. HDL cholesterol increased by more than 50% after treatment, leading to an improvement of the total cholesterol/HDL ratio (atherogenic index). This increase (and index improvement) was much more rapid in the group receiving combination treatment. A similar pattern was seen in the 2001 cohort with early RA. In all the groups with active disease HDL and total cholesterol levels correlated inversely with disease activity. CONCLUSION: In established, but especially in early RA, disease activity is accompanied by atherogenic lipid levels. This dyslipidaemia can be rapidly reversed by aggressive antirheumatic treatment including glucocorticoids.

Adult↗
PubMed2002

Evidence for additional genetic risk indicators of relapse-onset MS within the HLA region.

BACKGROUND: Human leukocyte antigen (HLA)-DR2 carriership is associated with an increased risk for MS. Genome searches using microsatellite markers have consistently shown that additional genetic factors contribute to susceptibility for MS. OBJECTIVE: To identify loci within the HLA region that predispose to relapse-onset MS independently of HLA-DR2. METHOD: A case-control study involving 159 patients with definite relapse-onset MS and 273 control subjects was conducted. Six highly polymorphic microsatellite markers encoded within the HLA-C to DR region, that is, D6S1014, D6S273, TNFa, MIB, C1_2_5, and C1_3_2, three single-nucleotide tumor necrosis factor (TNF) promoter gene polymorphisms at positions -238, -308, and -376, and HLA-DR2 carriership were typed. RESULTS: These data confirmed the well-known association between the HLA-DR2 haplotype and relapse-onset MS, yielding an odds ratio (OR) of 3.6 (95% CI: 2.4 to 5.4; p < 0.0001). Multivariate analyses revealed that C1_3_2*354 was also associated with an increased risk for developing relapse-onset MS independently of HLA-DR2 (OR: 2.0; 95% CI: 1.2 to 3.1; p = 0.004). This allele is encoded within an ancestral haplotype that is highly linked to HLA-DR3. The joint effect of this ancestral haplotype and HLA-DR2 resulted in an OR of 8.7 (95% CI: 2.7 to 29; p < 0.0001) to develop relapse-onset MS. In addition, a protective risk factor was found: carriers of TNFa*107 had a 0.5-fold lower risk to develop relapse-onset MS (95% CI: 0.3 to 0.9; p = 0.026). CONCLUSION: Within the HLA region, other loci besides HLA-DR2 haplotype modulate susceptibility for relapse-onset MS.

Adult↗
PubMed2002

Early and aggressive treatment of rheumatoid arthritis patients affects the association of HLA class II antigens with progression of joint damage.

OBJECTIVE: The presence of certain HLA class II antigens is strongly associated with the progression of joint destruction in rheumatoid arthritis (RA). Such antigens may be more effective than other class II antigens in inducing the formation of autoreactive T cells after presentation of (auto)antigens. We investigated whether early and aggressive treatment with disease-modifying antirheumatic drugs could modify this relationship. METHODS: We analyzed data from 2 studies of patients with early RA treated according to different strategies. The first study consisted of 2 cohorts, one (n = 109; median disease duration before treatment 4 months) was treated according to the pyramid strategy (initial nonsteroidal antiinflammatory drugs, followed by chloroquine [CQ] or sulfasalazine [SSZ] when necessary), and the other (n = 97; median disease duration before treatment 2 weeks) was immediately treated with CQ or SSZ. The second study comprised 155 patients (median disease duration 4 months) from the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial, in which patients were randomly assigned to combination treatment with step-down prednisolone, methotrexate (MTX), and SSZ (n = 76) or with SSZ alone (n = 79). Prednisolone and MTX dosages were tapered and stopped after 28 and 40 weeks, respectively. The extent of joint damage was measured by the modified Sharp method. RESULTS: In the pyramid treatment cohort, the median increase in Sharp score after 2 years was 12 in patients positive for the shared epitope (SE) and 1 in SE- patients. In the immediate treatment cohort, the median increase was 3 in SE+ patients and 2 in SE- patients. In the SSZ group of the COBRA study, the median increase in Sharp score after 1 year was 11 in DR4+ patients and 3 in DR4- patients. In the combination treatment group, the median increase was 4 in DR4+ patients and 2 in DR4- patients. Significance was confirmed by multiple regression using log-transformed scores. CONCLUSION: Early and aggressive antirheumatic drug treatment affects the association of HLA class II alleles with progression of joint damage in RA.

Adult↗
PubMed2002

Association of global brain damage and clinical functioning in neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To investigate the relationship between quantitative estimates of global brain damage based on magnetization transfer imaging (MTI) and cerebral functioning, as measured by neurologic, psychiatric, and cognitive assessments, as well as disease duration in patients with a history of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: In a clinically heterogeneous group of 24 female patients (age range 19-65 years, mean age 35 years) with a history of NPSLE, the correlation values of several volumetric MTI measures and an estimate of cerebral atrophy, neurologic functioning (Kurtzke's Expanded Disability Status Scale [EDSS]), psychiatric functioning (the Hospital Anxiety and Depression Scale [HADS]), and cognitive functioning (cognitive impairment score [CIS] derived from the revised Wechsler Adult Intelligence Scale), as well as several measures of disease duration were assessed using Pearson's correlation coefficient. RESULTS: Quantitative volumetric estimates of global brain damage based on MTI and a measure of global brain atrophy correlated significantly with the EDSS, HADS, and CIS scores. No significant correlation was found between the quantitative estimates of global brain damage and the measures of disease duration. CONCLUSION: The results of this study demonstrate that volumetric MTI parameters and cerebral atrophy reflect functionally relevant brain damage in patients with NPSLE. Furthermore, the absence of a linear relationship between disease duration and results of volumetric MTI measures and atrophy suggests a complicated pattern of accumulating brain damage in patients with NPSLE.

Adult↗
PubMed2002

Relationship of polymorphisms of the Interleukin-1 gene cluster to occurrence and severity of rheumatoid arthritis.

Interleukin-1 (IL-1) has been implicated in the pathogenesis of rheumatoid arthritis (RA). We investigated whether IotaL-1 gene locus polymorphisms are associated with susceptibility to or severity of RA. Genotyping for IL-1alpha, IL-1beta and IL-1Ra single nucleotide polymorphisms (SNPs) performed in a cross-sectional group of 312 consecutive RA patients (RA-group 1) and a cohort of 94 incident female RA patients (RA-group 2) revealed that the rare IL-1RN + 2017 C allele was significantly increased in RA compared to controls (n = 245). A retrospective analysis in RA-group 1 showed no significant associations between IL-1 genotypes and disease severity. A prospective study in RA-group 2 demonstrated that the extent of joint destruction over 12 years was higher in patients genotyped heterozygous for the IL-1 A + 4845, IL-1B + 3953 and IL-1RN + 5111 SNPs compared to homozygous wildtype patients, although differences did not reach statistical significance. These data indicate that the IL-1RN + 2017 polymorphism is associated with susceptibility to RA.

Alleles↗
PubMed2002

Polymorphisms in or near tumour necrosis factor (TNF)-gene do not determine levels of endotoxin-induced TNF production.

Innate differences in tumour necrosis factor (TNF) production have been associated with susceptibility for and outcome of inflammatory diseases. Several studies have tried to identify whether polymorphisms in or near the TNF gene or other markers on the short arm of chromosome 6 (6p21) are related to differences in TNF production. Data on these associations are conflicting. Therefore, we conducted a study among 129 healthy individuals in which TNF production was determined upon stimulation with endotoxin in whole blood cultures. TNFa microsatellite, TNF single nucleotide polymorphisms at position +489, -238, -308 and -376 typing was performed. The data revealed that alleles of TNFa microsatellite and carriership of TNF polymorphisms were not related to TNF production. We conclude that the genes determing the differences in endotoxin-induced TNF production have not been yet identified.

Adult↗
PubMed2002

Invasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10.

BACKGROUND: Matrix metalloproteinases (MMPs) have a pivotal role in the destruction of cartilage in rheumatoid arthritis (RA), which is mediated by the fibroblast-like synoviocytes (FLS). OBJECTIVE: To examine the in vitro invasiveness of synoviocytes obtained from inflamed joints of patients with arthritis in relation to the expression of MMP 1-14, 17, 19, cathepsin-K, the tissue inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2 by FLS. METHODS: FLS were derived from 56 patients (30 with RA, 17 with osteoarthritis (OA), and nine with avascular necrosis (AVN)). Invasive growth of FLS through an artificial matrix (Matrigel) was measured in a transwell system. The number of cells that migrated through the matrix were counted. Proliferation rate was determined by counting the FLS after seven days of culturing. Expression of MMPs, cathepsin-K and TIMPs was investigated with reverse transcriptase-polymerase chain reaction and related to the expression of a household gene, beta-actin. RESULTS: FLS from RA showed greater invasive growth than FLS from OA and AVN. The median number of cells that grew through the matrix membrane was 4788 for RA, significantly higher than the number for OA, 1875 (p<0.001) and for AVN, 1530 (p=0.014). The median rate of proliferation of RA FLS was 0.27 per day compared with OA 0.22 per day (p= 0.012) and AVN 0.25 per day, but there was no correlation between the rate of proliferation and invasive growth in vitro. FLS from RA and OA that expressed MMP-1, MMP-3, or MMP-10 were significantly more invasive (median number of invasive cells: 3835, 4248, 4990, respectively) than cells that did not express these MMPs (1605, p=0.03; 1970, p=0.004; 2360, p=0.012, respectively). There was also a significant relationship between the expression of MMP-1 and MMP-9 and the diagnosis RA (both p=0.013). The expression levels of mRNA for MMP-1 and MMP-2 correlated with the protein levels produced by the synoviocytes as measured by an enzyme linked immunosorbent assay (ELISA). CONCLUSION: FLS of RA invade more aggressively in a Matrigel matrix than OA and AVN FLS; this is not because of a higher rate of proliferation of RA FLS. The significant correlation between the expression of MMP-1, MMP-3, and MMP-10 and invasive growth in a Matrigel transwell system suggests that these MMPs play a part in the invasive growth of FLS obtained from patients with RA.

Aged↗
PubMed2002

Elevated IL-16 levels in patients with systemic lupus erythematosus are associated with disease severity but not with genetic susceptibility to lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by several immunological abnormalities. The pathogenic importance of T cells in this disease is well established. Interleukin-16 (IL-16) is a cytokine which is mainly produced by CD8+ T cells and induces chemotaxis of CD4+ T cells and monocytes. IL-16 levels have been shown to be elevated in SLE patients in a cross-sectional study, but the mechanism is unknown. To explore whether the increased IL-16 levels are associated with genetic background or the disease itself, we investigated the IL-16 level in healthy first-degree family members of SLE patients and SLE patients who were followed over time with regard to disease activity. We observed high IL-16 levels in SLE patients with severe disease compared to SLE patients with non-severe disease and healthy controls. Furthermore, IL-16 levels in first-degree relatives were not different from those in healthy controls. These results suggest that high IL-16 levels are associated with severity of SLE, but not with genetic susceptibility to SLE. Finally, we followed the disease activity of SLE patients over time, which showed significant correlation between the SLE disease activity index and IL-16, ESR and the complement components C3, C4 and CH50. In conclusion, these results implicate an association of IL-16 with SLE.

Adult↗
PubMedDate not supplied

Adenoviral-mediated gene transfer to the synovial tissue.

In various animal models gene transfer to the synovial tissue has been shown after intraarticular injection of adenoviral vectors. Safety of the transfer of therapeutic genes to the synovial tissue depends on multiple factors, including the mode of administration, the vector and the gene used, and the immune system of the host. In this article, data on the biodistribution and induction of inflammation after the intraarticular administration of adenoviral vectors are summarized and discussed. The ultimate goal of gene therapy will be the injection of a vector that has a specific target cell. Such a goal will require major improvements in the currently available delivery systems or the development of novel vectors. In this article new strategies are proposed in which gene transfer efficiency to the synovial tissue increases, whereas simultaneously the effect of neutralization of the adenoviral vector by the synovial fluid is circumvented.

Adenoviridae↗