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ID PMID Title PublicationDate abstract
17681015 Anti-arthritis effects of vitamin K(2) (menaquinone-4)--a new potential therapeutic strate 2007 Sep Vitamin K(2) (menaquinone-4, MK-4) has been reported to induce apoptosis in hepatocellular carcinoma, leukemia and myelodysplastic syndrome cell lines. The effects of MK-4 on the development of arthritis have never been addressed thus far. In the present study, we investigated the effect of MK-4 upon the proliferation of rheumatoid synovial cells and the development of arthritis in collagen-induced arthritis. We analyzed the effect of MK-4 on the proliferation of fibroblast-like synoviocytes using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The pro-apoptotic effect of MK-4 upon fibroblast-like synoviocytes was investigated with annexin V staining and DNA fragmentation and caspase 3/7 assays. Moreover, we analyzed the effect of MK-4 on the development of collagen-induced arthritis in female dark agouti rats. Our results indicated that MK-4 inhibited the proliferation of fibroblast-like synoviocytes and the development of collagen-induced arthritis in a dose-dependent manner. We conclude that MK-4 may represent a new agent for the treatment of rheumatoid arthritis in the setting of combination therapy with other disease-modifying antirheumatic drugs.
18227980 Efficacy of etanercept and complete decongestive physical therapy in bilateral lower-limb 2008 Jan A 54-y-old patient with rheumatoid arthritis (RA) and bilateral lower-limb lymphoedema is presented. Complete decongestive physical therapy (CDP) is the cornerstone of the management programme in all patients suffering from lymphoedema associated with RA, but it is not clear which therapy is the most effective in decreasing the oedema. We report on a patient with bilateral lower-limb lymphoedema associated with RA who, after receiving etanercept and CDP, showed moderate improvement. There is little information on the benefit of etanercept therapy for the extra-articular manifestations of RA. Further research is necessary to confirm the beneficial effect of etanercept and CDP.
19055603 NRAMP1 (SLC11A1) gene polymorphisms that correlate with autoimmune versus infectious disea 2009 Feb NRAMP1 gene has multiple pleiotropic effects on macrophage activation pathways. These pleiotropic effects may increase resistance to infections such as tuberculosis (TB), but may also lead to susceptibility of autoimmune diseases such as rheumatoid arthritis (RA). It has been hypothesized that allele 3 would be associated with autoimmune diseases, whereas allele 2 would be associated with infectious diseases, and genetic factors that enhanced survival in the epidemics of TB might have led to susceptibility for the development of RA. We analysed four NRAMP1 gene polymorphisms including 5' promoter (GT)(n) (rs34448891), INT4 (469 + 14G/C) (rs3731865), 3'UTR (1729 + 55del4) (rs17235416) and D543N (codon 543, Asp to Asn) (rs17235409) in 112 patients with TB, 98 patients with RA, 80 healthy controls for TB and 122 healthy controls for RA using ARMS-PCR and PCR-RFLP. We found a significant association between INT4 and RA (P = 0.004, odds ratio: 2.06, 95% CI: 1.24-3.41), but no significant differences between 5' promoter, D543N, 3'UTR polymorphisms and RA. There were no associations between NRAMP1 gene polymorphisms and TB. Similarly, no significant differences were observed between NRAMP1 polymorphisms and rheumatoid factor positivity and erosive disease in RA and localization of TB. INT4 polymorphism may be associated with RA in Turkish patients.
18260946 [Tissue dopplerography of the myocardium in diagnosis of myocardial involvement in patient 2007 Inflammatory rheumatoid damage of the heart is in most cases oligosymptomatic but it can lead to development of heart failure and cause lethal outcomes. AIM OF THE STUDY: To detect asymptomatic myocardial involvement in patients with rheumatoid arthritis (RA) with the help of tissue dopplerography (TDG) of the myocardium which allowed to evaluate velocity of myocardial movement. MATERIAL AND METHODS: TDG was carried out in 22 patients with verified RA (age 33-66, mean age 45,2 +/- 7,4 years) and in 20 healthy volunteers (age 29 - 58, mean age 44,6 +/- 8,4 years). Modules of velocities of systolic and early diastolic peaks in every left ventricular (LV) wall at basal level and at levels of upper, middle and lower thirds were calculated in all patients. RESULTS: Velocities of systolic and early diastolic peaks on some LV segments correlated with C-reactive protein and ESR (r from 0.29 to 0.46). CONCLUSIONS: Velocities of systolic and early diastolic peaks in patients with RA are diffusely lowered. A correlative relationship takes place in patients with RA between TDG parameters (velocities of systolic and early diastolic peaks) and markers of activity of systemic inflammation. This reflects participation of inflammatory process in development of asymptomatic diffuse myocardial damage in RA.
17982040 CD4+CD28null T cells in autoimmune disease: pathogenic features and decreased susceptibili 2007 Nov 15 To determine the role of expanded CD4(+)CD28(null) T cells in multiple sclerosis and rheumatoid arthritis pathology, these cells were phenotypically characterized and their Ag reactivity was studied. FACS analysis confirmed that CD4(+)CD28(null) T cells are terminally differentiated effector memory cells. In addition, they express phenotypic markers that indicate their capacity to infiltrate into tissues and cause tissue damage. Whereas no reactivity to the candidate autoantigens myelin basic protein and collagen type II was observed within the CD4(+)CD28(null) T cell subset, CMV reactivity was prominent in four of four HC, four of four rheumatoid arthritis patients, and three of four multiple sclerosis patients. The level of the CMV-induced proliferative response was found to be related to the clonal diversity of the response. Interestingly, our results illustrate that CD4(+)CD28(null) T cells are not susceptible to the suppressive actions of CD4(+)CD25(+) regulatory T cells. In conclusion, this study provides several indications for a role of CD4(+)CD28(null) T cells in autoimmune pathology. CD4(+)CD28(null) T cells display pathogenic features, fill up immunological space, and are less susceptible to regulatory mechanisms. However, based on their low reactivity to the autoantigens tested in this study, CD4(+)CD28(null) T cells most likely do not play a direct autoaggressive role in autoimmune disease.
17642229 [Biologics: current therapeutic strategies for rheumatoid arthritis]. 2007 Jul Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that causes significant morbidity and mortality. RA patients should be started with DMARD as early as possible and among multiple DMARD methotrexate (MTX) is considered the anchor drug and should be used first. However, even use of MTX often fails to control disease activity and to prevent structural damage and, thereby, more effective treatment strategies are needed. TNF-alpha plays a pivotal role in the pathological processes of RA by accumulation of inflammatory cells and the self perpetuation of inflammation, leading to cartilage and bone destruction. Biologics targeting TNF-alpha with MTX, have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously. Herein I review the evidence-based medicine that addresses these issues and document an era of anti-cytokine therapeutics which is beginning to emerge.
18568452 Comparison between resection arthroplasty alone and resection arthroplasty with arthrodesi 2008 It has been reported that nearly 90% of patients with rheumatoid arthritis (RA) have problems with their feet. Several methods of treating hallux valgus deformity in RA have previously been reported, including arthrodesis and joint resection, and good results have been observed with surgical procedures. In this report, we compare the clinical and radiological outcomes of resection arthroplasty alone (the first method) and resection arthroplasty with arthrodesis of the first MTP joint (the second method) for the treatment of forefoot deformities of RA patients. On clinical assessment, the American Orthopaedic Foot and Ankle Society (AOFAS) scale score significantly improved in both methods; however, the second method gave better results than the first method in relation to the footwear and alignment components. On radiographic assessment, in the first method there were no significant changes in the valgus angle (H-V angle) and the fifth metatarsal bone (M1/5) angle between preoperation and last follow-up. In contrast, these angles were decreased in the second method. One of the most important issues in the treatment of forefoot deformities in RA patients is to correct splaying foot deformity. We believe that the second method, which can correct splaying foot deformity, is currently the most reliable treatment method.
17694259 Diagnosis of distal radioulnar joint subluxation in patients with rheumatoid wrist by comp 2007 Subluxation of the distal radioulnar joint (DRUJ) is associated with extensor tendon rupture in patients with rheumatoid arthritis (RA). However, it remains difficult to quantitatively evaluate DRUJ subluxation in RA wrist. We devised a new method for assessing DRUJ subluxation. This study investigated whether the new method, known as the RA subluxation ratio (RASR), or a conventional method was superior for detecting extensor tendon rupture in the RA wrist. Thirty-five RA wrists and 10 wrists of healthy volunteers were scanned using computed tomography. The RA wrists were divided into a tendon rupture group and a nonrupture group. The dorsal surface of the distal radius from Lister's tubercle to the ulnar aspect of the distal radius maintains a planar surface in the RA wrist. Therefore, we defined the RASR as the extent of dorsal subluxation of the ulna relative to this plane. We quantified subluxation of the DRUJ by using the RASR or the modified radioulnar line method, and compared the two methods. The RASR was 0.440 in the rupture group, 0.333 in the nonrupture group, and 0.106 in the healthy volunteers. The RASR was significantly higher than the modified radioulnar line method in the sensitivity of diagnosing tendon rupture.
17372028 Prothymosin alpha lacking the nuclear localization signal as an effective gene therapeutic 2007 Apr 1 Prothymosin alpha (ProT) is regulated by c-Myc, an oncoprotein overexpressed in synovium of rheumatoid arthritis, and is associated with cell proliferation. However, ProT also exerts immunomodulatory activities. The growth-promoting activity of ProT can be abolished by deleting its nuclear localization signal (NLS). In this study, we showed that AdProTDeltaNLS, an adenoviral vector encoding ProT lacking the NLS, did not enhance the proliferation of synovial fibroblasts. AdProTDeltaNLS treatment abolished the up-regulation of the MIP-1alpha promoter activity induced by TNF-alpha in synovial fibroblasts. AdProTDeltaNLS suppressed macrophage chemotaxis and reduced macrophage infiltration into the ankle joints in rats with collagen-induced arthritis (CIA). Neutralization test confirmed the involvement of MIP-1alpha in macrophage chemotaxis. Administration of AdProTDeltaNLS reduced the severity of CIA in the clinical, radiographic, and histological aspects. The levels of TNF-alpha (mean +/- SEM, 1261.9 +/- 107.9 vs 2880.1 +/- 561.4 pg/mg total protein; p < 0.05), IL-1beta (56.8 +/- 8.0 vs 109.2 +/- 4.9 pg/mg total protein; p < 0.01), and MIP-1alpha (41.7 +/- 3.6 vs 55.2 +/- 1.1 pg/mg total protein; p < 0.05) in the ankle joints were lower in the AdProTDeltaNLS-treated rats with CIA than those in their control counterparts. In the AdProTDeltaNLS-treated ankle joints, matrix metalloproteinase-9 expression was decreased by 40% and infiltrating macrophages reduced by 50%. Our results demonstrate that intra-articular delivery of AdProTDeltaNLS significantly ameliorated the clinical course of CIA in rats. This study is the first to suggest that ProT lacking the NLS may have therapeutic potential for the management of rheumatoid arthritis.
16869002 Regulation of interleukin-1beta-induced chemokine production and matrix metalloproteinase 2006 Aug OBJECTIVE: To evaluate the efficacy of epigallocatechin-3-gallate (EGCG), a potent antiinflammatory molecule, in regulating interleukin-1beta (IL-1beta)-induced production of the chemokines RANTES (CCL5), monocyte chemoattractant protein 1 (MCP-1/CCL2), epithelial neutrophil-activating peptide 78 (ENA-78/CXCL5), growth-regulated oncogene alpha (GROalpha/CXCL1), and matrix metalloproteinase 2 (MMP-2) activity in rheumatoid arthritis (RA) synovial fibroblasts. METHODS: Fibroblasts obtained from RA synovium were grown, and conditioned medium was obtained. Cell viability was determined by MTT assay. RANTES, MCP-1, ENA-78, and GROalpha produced in culture supernatants were measured by enzyme-linked immunosorbent assay. MMP-2 activity was analyzed by gelatin zymography. Western blotting was used to study the phosphorylation of protein kinase C (PKC) isoforms and nuclear translocation of NF-kappaB. RESULTS: EGCG was nontoxic to RA synovial fibroblasts. Treatment with EGCG at 10 microM or 20 microM significantly inhibited IL-1beta-induced ENA-78, RANTES, and GROalpha, but not MCP-1 production in a concentration-dependent manner. EGCG at 50 microM caused a complete block of IL-1beta-induced production of RANTES, ENA-78, and GROalpha, and reduced production of MCP-1 by 48% (P < 0.05). Zymography showed that EGCG blocked constitutive, IL-1beta-induced, and chemokine-mediated MMP-2 activity. Evaluation of signaling events revealed that EGCG preferentially blocked the phosphorylation of PKCdelta and inhibited the activation and nuclear translocation of NF-kappaB in IL-1beta-treated RA synovial fibroblasts. CONCLUSION: These results suggest that EGCG may be of potential therapeutic value in inhibiting joint destruction in RA.
18668583 Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in patients with rhe 2008 Aug 15 OBJECTIVE: To determine the risk of stroke in patients with rheumatoid arthritis (RA) and risk factors associated with stroke. METHODS: We performed nested case-control analyses within a longitudinal databank, matching up to 20 controls for age, sex, and time of cohort entry to each patient with stroke. Conditional logistic regression was performed as an estimate of the relative risk of stroke in RA patients compared with those with noninflammatory rheumatic disorders, and to examine severity and anti-tumor necrosis factor (anti-TNF) treatment effects in RA. RESULTS: We identified 269 patients with first-ever all-category strokes and 67 with ischemic stroke, including 41 in RA patients. The odds ratio (OR) for the risk of all-category stroke in RA was 1.64 (95% confidence interval [95% CI] 1.16-2.30, P = 0.005), and for ischemic stroke was 2.66 (95% CI 1.24-5.70, P = 0.012). Ischemic stroke was predicted by hypertension, myocardial infarction, low-dose aspirin, comorbidity score, Health Assessment Questionnaire score, and presence of total joint replacement, but not by diabetes, smoking, exercise, or body mass index. Adjusted for cardiovascular and RA risk factors, ischemic stroke was associated with rofecoxib (P = 0.060, OR 2.27 [95% CI 0.97-5.28]), and possibly with corticosteroid use. Anti-TNF therapy was not associated with ischemic stroke (P = 0.584, OR 0.80 [95% CI 0.34-1.82]). CONCLUSION: RA is associated with increased risk of stroke, particularly ischemic stroke. Stroke is predicted by RA severity, certain cardiovascular risk factors, and comorbidity. Except for rofecoxib, RA treatment does not appear to be associated with stroke, although the effect of corticosteroids remains uncertain.
17394232 Daily health status registration (patient diary) in patients with rheumatoid arthritis: a 2007 Apr 15 OBJECTIVE: The patient perspective workshops at the Outcome Measures in Rheumatology Clinical Trials have included daily measures of health status (patient diary) and use of electronic tools for data collection in the research agenda. The objective of this study was to compare daily and weekly registrations of self-reported health status measures between personal digital assistant (PDA) and paper-pencil (PP) format regarding scores, variation, and feasibility. METHODS: Thirty-eight patients with stable rheumatoid arthritis recorded their health status during 84 days in a repeated crossover design, using PDA or PP format during four 21-day periods. Visual analog scales (VAS) for pain, fatigue, and global disease and the Rheumatoid Arthritis Disease Activity Index were scored daily; the Short Form 36 and Modified Health Assessment Questionnaire were scored weekly. RESULTS: The average scores and measures of variation of the 4 daily health status measures over 21 days did not differ significantly between PDA and PP formats in either of the 2 crossover periods. The values for the average range between the maximum and minimum values for daily measures were similar between the 2 formats, but showed considerable variation (e.g., range for pain VAS was 19-28 mm over each 21-day period). The time to complete the instruments was similar between the 2 formats. Missing daily data entries were generally low for both periods and somewhat higher for PDA. The majority of patients (82.9%) preferred using PDA. CONCLUSION: Daily assessments with PDA may be efficiently used for frequent data collection because this format performs similarly to the traditional PP format.
18821669 Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis 2008 Oct OBJECTIVE: To map the antibody response to human citrullinated alpha-enolase, a candidate autoantigen in rheumatoid arthritis (RA), and to examine cross-reactivity with bacterial enolase. METHODS: Serum samples obtained from patients with RA, disease control subjects, and healthy control subjects were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with citrullinated alpha-enolase peptides. Antibodies specific for the immunodominant epitope were raised in rabbits or were purified from RA sera. Cross-reactivity with other citrullinated epitopes was investigated by inhibition ELISAs, and cross-reactivity with bacterial enolase was investigated by immunoblotting. RESULTS: An immunodominant peptide, citrullinated alpha-enolase peptide 1, was identified. Antibodies to this epitope were observed in 37-62% of sera obtained from patients with RA, 3% of sera obtained from disease control subjects, and 2% of sera obtained from healthy control subjects. Binding was inhibited with homologous peptide but not with the arginine-containing control peptide or with 4 citrullinated peptides from elsewhere on the molecule, indicating that antibody binding was dependent on both citrulline and flanking amino acids. The immunodominant peptide showed 82% homology with enolase from Porphyromonas gingivalis, and the levels of antibodies to citrullinated alpha-enolase peptide 1 correlated with the levels of antibodies to the bacterial peptide (r2=0.803, P<0.0001). Affinity-purified antibodies to the human peptide cross-reacted with citrullinated recombinant P gingivalis enolase. CONCLUSION: We have identified an immunodominant epitope in citrullinated alpha-enolase, to which antibodies are specific for RA. Our data on sequence similarity and cross-reactivity with bacterial enolase may indicate a role for bacterial infection, particularly with P gingivalis, in priming autoimmunity in a subset of patients with RA.
18381794 Methotrexate (MTX) pathway gene polymorphisms and their effects on MTX toxicity in Caucasi 2008 Apr OBJECTIVE: Research has examined the association of folate-dependent gene polymorphisms with methotrexate (MTX) toxicity in racially homogenous patients with rheumatoid arthritis (RA). We examined the influence of MTX transporter gene polymorphisms on MTX toxicity in 2 racial groups of patients with RA. METHODS: Using a retrospective cross-validation approach, the association of polymorphisms in 6 genes in the MTX cellular pathway with MTX toxicity was examined in training and validation cohorts. The genes analyzed were ATP-binding cassette transporter B1 (ABCB1), C1 (ABCC1), C2 (ABCC2), folylpolyglutamyl synthase (FPGS), methylenetetrahydrofolate reductase (MTHFR), and thymidylate synthase (TYMS). Both cohorts included Caucasian Americans and African Americans. Statistical analyses consisted of Fisher exact tests, multivariable logistic regression models, and survival analyses. RESULTS: Four of 25 variants displayed significant associations with MTX toxicity in the training cohort. The intronic single-nucleotide polymorphism (SNP) ABCC2 IVS 23+56 T --> C was associated with alopecia in Caucasians (p = 0.035). ABCB1 1236 C --> T was associated with overall toxicity (p = 0.013); ABCC2 1249 G --> A with gastrointestinal toxicity (p = 0.009); and ABCC2 1058 G --> A with hepatotoxicity (p = 0.04) in African Americans. These 4 SNP and the MTHFR 677 C --> T variant were assessed in the validation cohort. Of these, only the MTHFR 677 C --> T SNP was associated with alopecia, and only in African Americans (p = 0.032). The ABCC2 IVS 23+56 T --> C genotype influenced toxicity-related time to discontinuation or dose decrease in the Caucasian validation cohort (p < 0.0001). CONCLUSION: In addition to SNP in folate-dependent genes, MTX transporter gene SNP may be important markers of MTX toxicity in RA. Such pharmacogenetic associations are race-specific.
17924123 [Paradoxical role of interferon-gamma in arthritis]. 2007 Nov In T cell-mediated autoimmune diseases such as rheumatoid arthritis, Th1 cells and their cytokines, especially interferon-gamma (IFN-gamma), are responsible for the induction and persistence of chronic inflammation and tissue destruction. But emerging evidence from experimental models has demonstrated that IFN-gamma also possesses unexpected anti inflammatory properties. The recent data discussed in this article indicate that beside the well-known proinflammatory efficacy, IFN-gamma may function as a master regulator of inflammation and immune responses. Such self-regulatory processes seem to play an important role in the inhibition of excessive responses and to maintain or reestablish homeostasis of the immune system.
17625968 B cell modulation in rheumatology. 2007 Aug While evidence of dysregulation of the B cell compartment was first demonstrated with the identification of autoantibodies, other functional roles of B lymphocytes in autoimmune pathogenesis have generally been underappreciated or completely overlooked. With the recent approval of the first B cell targeting agent in rheumatoid arthritis, new strategies are being developed to target B cells through a range of membrane-associated lineage-specific molecules and also by interfering with B-cell-specific pro-survival signals. B-cell-directed agents therefore provide an effective new mechanistic approach to treatment and also enable new perspectives from the dissection of the contributions of B cells in physiologic and pathologic immune responses.
18238793 Signalling, inflammation and arthritis: crossed signals: the role of interleukin (IL)-12, 2008 Jun Autoimmune diseases such as rheumatoid arthritis are the consequence of a persistent imbalance between pro- and anti-inflammatory immune mechanisms leading to chronic inflammation. The action of several cytokines is at the basis of this complex process. This review is focused on the signalling events triggered by two major groups of cytokines, namely the IL-12 and IL-17 families, which in the past few years have been shown to have a prominent role in the pathogenesis of such diseases. In particular, we will focus on the signalling cascades set in motion by such cytokines and how this may relate to the pathogenesis of human immune and inflammatory disorders as knowledge of such cascades may help in the development of novel therapeutic approaches for such diseases.
17662115 Remission by composite scores in rheumatoid arthritis: are ankles and feet important? 2007 Current treatment strategies aim to achieve clinical remission in order to prevent the long-term consequences of rheumatoid arthritis (RA). Several composite indices are available to assess remission. All of them include joint counts as the assessment of the major 'organ' involved in RA, but some employ reduced joint counts, such as the 28-joint count, which excludes ankles and feet. The aim of the present study was to determine the relevance of excluding joints of the ankles and feet in the assessment of RA disease activity and remission. Using a longitudinal observational RA dataset, we analyzed 767 patients (80% female, 60% rheumatoid factor-positive), for whom joint counts had been recorded at 2,754 visits. We determined the number of affected joints by the 28-JC and the 32-JC, the latter including ankles and combined metatarso-phalangeal joints (as a block on each side). Several findings were supportive of the validity of the 28-joint count: (a) Absence of joint swelling on the 28-joint scale had a specificity of 98.1% and a positive predictive value (PPV) of 94.1% for the absence of swelling also on the 32-joint scale. For absence of tender joints, the specificity and PPV were 96.1% and 91.7%, respectively. (b) Patients with swollen or tender joints in the 32-JC, despite no joint activity in the 28-JC, were clearly different with regard to other disease activity measures. In particular, the patient global assessment of disease activity was higher in these individuals. Thus, the difference in the joint count was not relevant for composite disease activity assessment. (c) The disease activity score based on 28 joints (DAS28) may reach levels higher than 2.6 in patients with feet swelling since these patients often have other findings that raise DAS28. (d) The frequency of remission did not change when the 28-JC was replaced by 32-JC in the composite indices. (e) The changes in joint activity over time were almost identical in longitudinal analysis. The assessment of the ankles and feet is an important part in the clinical evaluation of patients with RA. However, reduced joint counts are appropriate and valid tools for formal disease activity assessment, such as done in composite indices.
17704064 Loss-of-function mutations in the filaggrin gene: no contribution to disease susceptibilit 2008 Jan OBJECTIVES: Autoantibody formation to citrullinated (pro)filaggrin has proven to be a highly specific serological marker for rheumatoid arthritis (RA). To test the potential relevance of mutations of the filaggrin (FLG) gene for disease susceptibility and elicitation of humoural autoimmunity in RA, a case-control association study of three loss-of-function FLG variants was performed. METHODS: DNA was obtained from 282 patients with early RA (mean disease duration: 6.5 months) and from 376 control individuals. Three loss-of-function variants of the FLG gene (*R501X, *2282del4 and *3702del1) were genotyped. RESULTS: No significant differences in genotype frequencies were observed between control probands and the population of RA patients. The FLG*3702del1 allele was not identified in any of the patients nor controls, and none of the probands was homozygous or compound heterozygous. In the RA cohort, heterozygous carriers of either of the FLG variants exhibited a significantly elevated prevalence of autoantibodies to citrullinated peptides (CCP-2) (80%) compared to non-carriers (51.9%) (p = 0.018, odds ratio: 3.71 (1.20-11.46)). CONCLUSIONS: The investigated FLG variants do not confer an overall risk for the development of RA. However, loss-of-function mutations in the FLG gene may contribute to the development of humoural autoimmunity, targeting citrullinated determinants in early RA.
17601702 Analysis of expression and function of the inhibitory receptor ILT2 (CD85j/LILRB1/LIR-1) i 2007 Sep The aim of this work was to study the expression and function of the inhibitory receptor ILT2/CD85j in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). We studied 23 SLE patients as well as 17 patients with rheumatoid arthritis, 10 with fibromyalgia, and 23 healthy individuals. We found a variable level of expression of ILT2 in the PBMC from both SLE patients and controls, with no significant differences among them. However, when the expression of this receptor was assessed in cell subsets, significantly lower levels were detected in CD19+ lymphocytes from SLE patients compared with healthy controls. Functional assays performed in unfractionated PBMC, showed a significant diminished inhibitory activity of ILT2 in CD4+ and CD8+ cell subsets from SLE patients compared to either rheumatoid arthritis or fibromyalgia patients, and healthy individuals. Our results show that the PBMC from some patients with SLE show a defective expression of ILT2, and that most of them exhibit a poor function of this inhibitory receptor.