Osteopontin, osteoprotegerin and musculoskeletal ultrasound findings in first-degree relatives of rheumatoid arthritis: potential markers of preclinical disease.

BACKGROUND: First-degree relatives (FDRs) of rheumatoid arthritis (RA) patients are known to have increased risk of developing the disease. The detection of altered bone metabolism in FDRs could be a predictor of the disease. Musculoskeletal ultrasound (MSUS) is known for its ability to detect subclinical joint inflammation in RA, but changes in FDRs are not yet described. We aimed to study serum Osteopontin (OPN) and Osteoprotegerin (OPG) levels in FDRs of RA patients as markers of altered bone metabolism in relation to clinical, laboratory and musculoskeletal ultrasound (MSUS) findings. METHODS: Fifty-five individuals were included, 20 had definite RA, 25 were first degree relatives (FDRs) of RA patients, and 10 healthy controls. Clinical evaluation for joint swelling/tenderness was performed for all. ESR, CRP, rheumatoid factor (RF), anti-citrullinated antibodies (ACPA), OPN, OPG, and Musculoskeletal ultrasound (MSUS) by the US7 score were evaluated. RESULTS: Osteoprotegerin was significantly higher in RA (143.89 pg/ml ± 365.47) than in FDRs (22.23 pg/ml ± 65.73; p = 0.009) and controls (6.20 pg/ml ± 12.43; p = 0.003). OPN was also higher in RA (3.66 ng/ml ± 4.20) than in FDRs (1.97 ng/ml ± 1.04) and controls (2.81 ng/ml ± 1.31), though not significant (p = 0.102). Eight of 25 FDRs (32%) had arthralgia without clinical arthritis and 17/25 (68%) were asymptomatic. FDRs with arthralgia had significantly higher ESR and CRP levels than asymptomatic FDRs (9.82 mm/h ± 4.13; p = 0.003, and 3.93 mg/l ± 3.58; p = 0.003). Osteoprotegerin was higher in FDRs than in controls, and also in those with arthralgia (51.55 pg/ml ± 114.68) than in those without (8.44 pg/ml ± 9.67), though without significant difference. OPN was higher in FDRs with arthralgia (2.09 ng/ml ± 1.19) than in asymptomatic (1.70 ng/ml ± 0.55), also without significant difference. Pathologic findings by US7 were detected in 10/25 (40%) FDRs, of which three (12%) had arthralgia and seven (28%) were asymptomatic. CONCLUSIONS: The raised OPG and lower OPN in FDRs than in controls reflect an altered bone metabolism which could precede clinical disease phase. OPN and OPG could serve as markers of altered preclinical bone metabolism in FDRs of RA. US7 score might be a useful screening tool to identify 'at-risk' individuals.

Local infliximab injection of sacroiliac joints in non-radiographic axial spondyloarthritis: Impact on clinical and magnetic resonance imaging parameters of disease activity.

OBJECTIVES: To evaluate the effectiveness of infliximab (IFX) injection into sacroiliac joints (SIJs) of non-radiographic axial spondyloarthritis (nr-axial SpA) and its impact on clinical and MRI parameters of disease activity. METHODS: Thirty-seven patients fulfilling the Association of Spondyloarthritis International Society (ASAS) criteria for axial SpA were initially studied, with disease duration not exceeding 1 year and failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs). Only SpA having active sacroiliitis on MRI without spondylitis (number = 7) were selected to receive bilateral SIJ injection of 20 mg IFX. Follow-up MRI was done at 24 weeks post-injection. Patients were clinically evaluated before, and 12 and 24 weeks after SIJ injection. Evaluation included back pain and stiffness scores, and Bath Ankylosing Spondylitis (BAS) Disease indices and C-reactive protein (CRP) levels. ASAS response criteria were also assessed. RESULTS: Twelve and twenty-four weeks after injection, there was significant decrease in back pain, stiffness, and BAS Disease Activity and Global indices. BAS Functional index, CRP, and mean bone marrow edema score of SIJs were decreased without reaching statistical significance. All patients achieved ASAS20 and five (71.4%) achieved ASAS40. CONCLUSION: SIJ injection of IFX could be a therapeutic option in early nr-axial SpA who failed to respond to NSAIDs.

Association of PTPN22 gene polymorphism and systemic lupus erythematosus in a cohort of Egyptian patients: impact on clinical and laboratory results.

To assess the possible association between the protein tyrosine phosphatases non-receptor 22 (PTPN22) gene 1858 CT polymorphism and the predisposition to systemic lupus erythematosus (SLE) in Egyptian patients and its influence on clinical and laboratory parameters. PTPN22 gene 1858 CT polymorphisms were analyzed in forty SLE patients and 20 normal controls by real-time polymerase chain reaction (PCR) technology, using the TaqMan 5-allele discrimination assay. Detailed history, clinical examination, and investigations were done to detect various organ involvement. The homozygous genotype TT was absent in both SLE and controls. The CC genotype was observed in 47.5% SLE and 80% controls; the CT genotype was found in 52.5% patients and 20% controls. The frequencies of the C and T alleles were 74 and 26% in SLE and 90 and 10% in controls, respectively. The presence of CT genotype increased the risk for developing SLE by 4.42. Renal involvement was significantly higher in SLE patients with CT (76.2%) compared to those with CC genotype (42.1%).

Role of matrix metalloproteinase-3 (MMP-3) and magnetic resonance imaging of sacroiliitis in assessing disease activity in ankylosing spondylitis.

The objective of this study is to evaluate the role of MMP-3 and MRI in assessing disease activity in sacroiliac joints of AS patients in comparison to the conventional measures Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Serum MMP-3 was measured in 30 patients who fulfilled the modified New York criteria for AS and in ten healthy volunteers. AS patients were categorized into those having high or low MMP-3 according to a cut-off value = 7.1 ng/ml. MRI of the sacroiliac joints (SIJs) was performed on all patients. SIJs were evaluated for enhancement and subchondral bone marrow edema. Results of MMP-3 and findings on MRI were correlated with multiple clinical parameters including BASDAI, ESR and CRP. Serum MMP-3 was significantly elevated in AS patients with active disease. Elevated MMP-3 levels were significantly associated with high BASDAI (P = 0.046), but not with ESR or CRP. MRI showed bone marrow edema and enhancement of SIJs in 19/30 patients with one patient showing enhancement only. These MRI findings were not correlated with MMP-3, BASDAI, CRP or ESR. In conclusion, serum MMP-3 is an objective measure reflecting clinical disease activity in AS. Bone marrow edema and enhancement detected by MRI of SIJs is another objective measure of disease activity, but are not correlated with MMP-3 or the conventional parameters as BASDAI, ESR, or CRP. Although both MMP-3 and MRI can reflect disease activity in AS they seem to be unrelated, perhaps each is reflecting a different aspect of disease activity. MMP-3 and MRI should be considered together with BASDAI in assessing disease activity and in guiding the available recommendations for initiation of biologics in AS.

MicroRNA 146a expression in rheumatoid arthritis: association with tumor necrosis factor-alpha and disease activity.

AIM: MicroRNAs (miRNAs) regulate the expression of many genes and may be involved in regulating the immune response. Expression of microRNA 146a (miRNA 146a) in peripheral blood mononuclear cells was studied by real-time polymerase chain reaction in 70 patients with rheumatoid arthritis (RA), 45 patients with knee osteoarthritis (OA), and 60 healthy controls. Disease activity of RA was assessed using disease activity score (DAS) 28 and physical disability using the Improved Health Assessment Questionnaire. RESULTS: miRNA 146a expression was significantly higher in patients with RA than in those with OA and in controls (p<0.0001) but did not differ between the latter two groups (p=0.06). Tumor necrosis factor-alpha (TNF-α) was significantly higher in RA than in OA and controls (p<0.0001) and in OA than controls (p=0.001). In patients with RA, miRNA 146a positively correlated with TNF-α (p=0.0003), erythrocyte sedimentation rate (ESR) (p=0.022), and DAS 28 (p=0.009). miRNA 146a expression did not differ between patients with RA receiving anti TNF-α and those receiving conventional therapy (p>0.05). CONCLUSION: miRNA 146a expression is upregulated in patients with RA and may be a potentially useful marker of disease activity in these patients. Lack of overexpression of miRNA 146a in the presence of increased TNF-α in OA requires further investigation.