Luis Carreño

The aim of this study was to examine the extent to which infliximab (IFX) serum levels impact disease activity in rheumatoid arthritis (RA) patients. In this cross sectional study, serum samples were taken prior to drug infusion from 60 RA patients who had been undergoing IFX therapy > 12 months as a first line of biological treatment. Patient IFX levels were tested and then associated with clinical disease activity. Three DAS28 cut-off points, 3.2 (p=0.005). DAS28 and IFX serum levels were shown to have an inverse correlation. Undetectable IFX serum levels were associated to RA patients presenting DAS28>3.2 meaning that DAS28 <3.2 may be useful to clinicians to evaluate patient response to drug therapy.

The complement system plays a fundamental role in mediating the activity of rheumatoid arthritis (RA). Biologic therapy can reduce native complement component levels and its activation. We aimed to study the relation of Doppler ultrasound (US) synovitis versus clinical synovitis with changes in native complement component levels in RA patients on biologic therapy. This was a cross-sectional study. Ninety-seven consecutive patients with RA on biologic therapy for at least 3 months were recruited. Clinical, laboratory and Doppler US assessments were performed. The Disease Activity Score in 28 joints (DAS28), Simplified Disease Activity Index (SDAI) and a 12-joint US assessment were carried out. Synovitis was semiquantitatively scored in B-mode and power Doppler (PD) mode. A significant decrease in native complement (i.e. C3 and C4) and C-reactive protein (CRP) levels was observed. This was highly significant for C3 decrease (p<0.0005), and C4 decrease (p<0.0005). Synovitis detected by PD US showed significant negative association with C3 change (p<0.008), where patients with higher C3 change were more likely to have PD US inactive status on assessment. Our results suggested that disease inactive status determined by PD US but not by clinical assessment can be related with decrease in complement in RA patients treated with biologic therapy.

The aim of this paper is to assess the usefulness of measuring serum levels of adalimumab (ADL) and anti-ADL antibodies in 57 patients with rheumatoid arthritis (RA) treated with ADL for at least 3 months in daily practice. All patients received concomitant disease-modifying anti-rheumatic drug (DMARD). Receiver-operator characteristics (ROC) analysis was used to obtain the cut-off value of ADL for low disease activity (DAS28-ESR ≤3.2). Anti-ADL antibodies were detected in 4 (7%) patients with a mean (SD) DAS28 score of 4.6 (0.9). Patients with positive anti-ADL antibodies had significantly lower levels of ADL and higher DAS28 scores than those with negative antibodies. Patients with DAS28 ≤3.2 as compared with patients with DAS28 >3.2 showed significantly better SDAI score, higher serum concentrations of ADL and none of them showed anti-ADL antibodies. The cut-off of serum level of ADL for DAS28 11.3 mg/L. Patients in the medium group were closed to clinical remission (median DAS28 2.7) and patients in the high group were on clinical remission (DAS28 2.1). Serum levels of ADL should be maintained >4.3 mg/L. In patients with ADL levels >11.3 mg/L, a decrease of the dose of ADL or an increase in the interval between doses may be planned. The presence of anti-ADL antibodies was associated with a loss of clinical efficacy of ADL.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease uncommon in children, clinically characterized by recurrent parotitis at the onset, which is a common disorder in childhood, most of them of infectious origin. Juvenile pSS diagnosis is based on clinical symptoms and presence of autoantibodies, after exclusion of infectious or lymphoproliferative diseases. However, salivary gland ultrasound (SGU) shows typical features of pSS that can add useful information for the diagnosis of this disorder. We describe three patients who presented with recurrent parotitis in which characteristic autoantibodies and typical SGU pattern allow us to make the diagnosis of juvenile pSS. We suggest that in children with recurrent parotitis SGU and autoantibodies should be routinely performed.

Cutaneous polyarteritis nodosa (CPAN) is a form of necrotizing vasculitis of small and medium-sized arteries. It is limited to the skin and has a recurrent and chronic course, possibly associated with fever, arthralgia, myalgia and neuropathy, but without visceral involvement. We report the clinical case of a 7-year-old male patient with CPAN refractory to treatment with high doses of corticoids and cyclophosphamide, who was successfully treated with the TNF-α (tumor necrosis factor-alpha) inhibitor, etanercept, in monotherapy.

Objective: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease that may not always be related to the presence of traditional cardiovascular risk factors. The aim of this study was to determine if anti–cyclic citrullinated peptide (anti‐CCP) antibodies are associated with cardiovascular disease in patients with RA.Methods: Anti‐CCP antibodies were determined by enzyme‐linked immunosorbent assay in the earliest serum sample available from 937 patients with a diagnosis of RA. We studied the relationship between anti‐CCP antibodies with traditional cardiovascular risk factors and cardiovascular events.Results: We found positive anti‐CCP antibodies (>25 units/ml) in 672 patients (71.7%). There was no association between the anti‐CCP antibodies and cardiovascular risk factors such as smoking, hypertension, dyslipidemia, being overweight, or diabetes mellitus. However, patients who had positive anti‐CCP antibodies experienced more frequent ischemic heart disease (6.5% versus 2.6%; odds ratio [OR] 2.58, 95% confidence interval [95% CI] 1.17–5.65) and had higher mortality rates (11.2% versus 6.8%; OR 1.72, 95% CI 1.01–2.91). Similar results were obtained when we considered anti‐CCP titers 20‐fold higher (>500 units/ml). Multivariable analysis showed that ischemic heart disease is independently associated with positive anti‐CCP antibodies (OR 2.8, 95% CI 1.19–6.56; P = 0.009).Conclusion: Anti‐CCP antibodies in patients with RA are independently associated with the development of ischemic heart disease.

Introduction: Genome-wide association studies of rheumatoid arthritis (RA) have identified an association of the disease with a 6q23 region devoid of genes. TNFAIP3, an RA candidate gene, flanks this region, and polymorphisms in both the TNFAIP3 gene and the intergenic region are associated with systemic lupus erythematosus. We hypothesized that there is a similar association with RA, including polymorphisms in TNFAIP3 and the intergenic region. Methods: To test this hypothesis, we selected tag-single nucleotide polymorphisms (SNPs) in both loci. They were analyzed in 1,651 patients with RA and 1,619 control individuals of Spanish ancestry. Results: Weak evidence of association was found both in the 6q23 intergenic region and in the TNFAIP3 locus. The rs582757 SNP and a common haplotype in the TNFAIP3 locus exhibited association with RA. In the intergenic region, two SNPs were associated, namely rs609438 and rs13207033. The latter was only associated in patients with anti-citrullinated peptide antibodies. Overall, statistical association was best explained by the interdependent contribution of SNPs from the two loci TNFAIP3 and the 6q23 intergenic region. Conclusions: Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus.

Anti-Sa antibodies have been described to be a highly specific marker for rheumatoid arthritis (RA). We demonstrate the existence of 2 different subsets of anti-Sa antibodies, only one of which is specific for RA. Our objective was to purify the Sa antigen, and to achieve partial characterization of these proteins. Saline extract and mitochondrial extract from human placenta were used as antigenic sources. Antigens were purified by immunoaffinity chromatography and studied by ELISA and immunoblotting. Three antigenically active bands of 68, 50, and 46 kDa were purified from the saline extract by immunoaffinity chromatography. Two other bands of 29 and 10 kDa that do not react with anti-Sa antibodies were obtained as well. The 68 kDa band was purified from a mitochondrial extract. These bands are not the same as other known mitochondrial autoantigens such as M2, M4, or M9. The amino terminal sequence of the 68 kDa Sa band is DEPKXEVP. The sequence of the 68 kDa Sa band is not compiled in the databases we searched, as either aminoterminal or internal sequence. Antibodies to 50/46 kDa anti-Sa bands detected by immunoblotting were highly specific for RA, while the 68 kDa antigen reacted in ELISA with sera from patients with RA and systemic lupus erythematosus, the latter showing a marked increase in features of RA. Antibodies directed against the 68 and 50/46 kDa Sa bands fluctuated with time, the 50/46 kDa anti-Sa antibodies present during the active period of the disease, and the 68 kDa anti-Sa antibodies during the remission period. At least 2 subsets of autoantibodies are present in anti-Sa sera, one directed against a 68 kDa Sa protein and another to the typical 50/46 bands of the Sa system.