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ID PMID Title PublicationDate abstract
15727893 New serum biochemical markers (Coll 2-1 and Coll 2-1 NO2) for studying oxidative-related t 2005 Mar OBJECTIVE: Protein nitration is a prominent feature of inflammatory processes in the joint. We have developed immunoassays specific for a peptide of the alpha-helical region of type II collagen 108HRGYPGLDG116 (Coll 2-1) and its nitrated form 108HRGY(NO2)PGLDG116 (Coll 2-1 NO2) in biological fluids. DESIGN: Coll 2-1 and Coll 2-1 NO2 peptides were injected into rabbits. Two antisera (D3 and D37) were selected for their specificity and affinity and used to develop specific immunoassays. Coll 2-1 and Coll 2-1 NO2 were measured in sera of 242 healthy subjects (N), 67 patients with primary knee osteoarthritis (OA) and 19 patients with rheumatoid arthritis (RA). RESULTS: In healthy subjects, Coll 2-1 and Coll 2-1 NO2 concentrations were 125.13+/-3.71 nM and 0.16+/-0.08 nM, respectively. In OA and RA, Coll 2-1 and Coll 2-1 NO2 serum levels were found to be significantly increased compared to controls of the same range of age (Coll 2-1: OA: 200.80+/-8.98 nM, RA: 172.30+/-19.05 nM, normal: 126.60+/-6.70 nM and Coll 2-1 NO2: OA: 0.26+/-0.02, RA: 0.38+/-0.05, normal: 0.12+/-0.01 nM). Coll 2-1 NO2 levels were significantly more elevated in RA than in OA patients (P<0.05). As a consequence, the ratio Coll 2-1 NO2/Coll 2-1 was 1.6 times higher in RA than in OA subjects. No relationship was found between the radiological OA severity and the levels of Coll 2-1 and Coll 2-1 NO2 in serum. Coll 2-1 NO2, but not Coll 2-1, was correlated with C-reactive protein in the sera of OA and RA patients. CONCLUSIONS: The determination of both Coll 2-1 and Coll 2-1 NO2 in serum of arthritic patients seems to be a promising useful tool for the detection of oxidative-related cartilage degradation episode. Further, these markers could be helpful for monitoring the effects of anti-inflammatory or antioxidant drugs on cartilage degradation.
15515144 Adenovirus binding to cultured synoviocytes triggers signaling through MAPK pathways and i 2005 Mar BACKGROUND: Recombinant adenovirus can be administered in vivo to achieve transduction of a number of cell types including human synoviocytes. Immunogenicity of adenoviruses has limited their utility as vectors for gene delivery; however, specific mechanisms underlying the acute inflammatory response to adenovirus are not well understood. Activation of a number of signal transduction pathways occurs rapidly upon adenovirus binding to cell-surface receptors. We investigated stimulated expression of mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) in human primary synovial fibroblasts to adenovirus expressing the E. coli beta-galactosidase gene. METHODS: Cultured rheumatoid synoviocytes were exposed to transduction-competent Ad/RSVlacZ recombinant adenovirus or transduction-incompetent (psoralen/UV-irradiated) Ad/RSVlacZ. The effects on COX-2 expression, PGE(2) levels and MAPK signaling in synoviocytes were assessed using a combination of reverse-transcription polymerase chain reaction amplification and immunoblotting. RESULTS: Adenovirus treatment of synoviocytes increased levels of COX-2 mRNA and protein as well as PGE(2). Psoralen-treated transcriptionally inactive adenovirus was equivalent to untreated adenovirus for early COX-2 induction suggesting that viral genes were not required. Adenovirus treatment stimulated phosphorylation of ERK-1/-2, p38 MAPK, and JNK. Inhibition of the ERK and p38 MAPK pathways inhibited COX-2 expression and PGE(2) production. CONCLUSIONS: Taken together, these data demonstrate that a MAPK-dependent increase in COX-2 results in local prostaglandin production. These findings have clinical implications for use of adenovirus as vectors for in vivo gene delivery.
15693005 SLC22A4 polymorphisms implicated in rheumatoid arthritis and Crohn's disease are not assoc 2005 Feb OBJECTIVE: Single-nucleotide polymorphisms (SNPs) in the SLC22A4 gene encoding the organic cation transporter OCTN1 have been associated with rheumatoid arthritis (RA) in the Japanese population and with Crohn's disease in a Canadian cohort. The RA-associated and Crohn's disease-associated SNPs include, respectively, an intronic variant (slc2F2) and an exonic variant (1672T). We used a case-control approach to investigate the prevalence of these variants in a Canadian RA cohort and to determine whether RA and Crohn's disease share SLC22A4 susceptibility alleles. METHODS: Nine hundred eighteen unrelated patients with RA, 507 patients with Crohn's disease, and 623 healthy controls were genotyped for the putatively RA-associated slc2F1 and slc2F2 variants and the Crohn's disease-associated SLC22A4 1672T variant. RESULTS: Neither slc2F1 nor slc2F2 showed evidence for association with RA, the allele frequencies of these variants being significantly different in the Canadian population compared with those reported in the Japanese population, but not significantly different between patients with RA and controls. In addition, associations between the 1672T Crohn's disease risk allele and RA or between the slc2F1-A and slc2F2-T risk alleles and Crohn's disease were not detected in this study cohort, and the latter 2 alleles were not in linkage disequilibrium with the 1672T variant. CONCLUSION: These observations do not support roles for any of the previously identified SLC22A4 disease risk alleles in RA susceptibility in the Canadian population. The slc2F1/slc2F2 risk alleles were not associated with Crohn's disease nor in linkage disequilibrium with the Crohn's disease-associated 1672T variant, and accordingly, also appear to be irrelevant to Crohn's disease susceptibility in the population under study.
16362367 A hypothesis for the origin and pathogenesis of rheumatoid diseases. 2006 May It is well established that a correlation exists between rheumatoid arthritis (RA) and microbial damage. Material analyses have suggested that bacteria may be causative agents. This study was undertaken to further characterize the microbial agent responsible for pathogenesis of RA. In order to investigate whether substances in moist building materials can affect human cartilage, extracts from moist building materials were analysed for microbial components. Exposure of chondrocyte cultures to extracts in vitro showed that they were damaging the cultures. A direct correlation between strength of damage and concentration of MMP3 demonstrated that the effect was dose-dependent. High quantities of LPS were detected in the extracts. Experiments after deactivation with Polymyxin B showed that LPS are the causative agents. The present study leads to the hypothesis that LPS may bind to procollagen, as they bind to scavenger receptors. This procollagen endotoxin complex may block tropocollagen synthesis.
16121705 Technology evaluation: Belatacept, Bristol-Myers Squibb. 2005 Aug Bristol-Myers Squibb is developing belatacept, a soluble fusion protein of the B7-binding domain of CTLA4 with amino acid changes A29Y and L104E and an Ig tail, which inhibits lymphocyte co-stimulation through CD28, for the potential treatment of solid organ transplant rejection. Belatacept is currently undergoing phase III clinical trials.
17196718 Trigger wrist. 2007 Apr Trigger wrist is a relatively rare phenomenon. The pathological entities to which the term trigger wrist is applied are not well defined in the literature. We present three cases of trigger wrist as a result of flexor tendon pathology, review the literature and discuss the use of the term "trigger wrist".
16354468 Epidemiological study of patients with connective tissue diseases in Brazil. 2005 Oct To study the prevalence of connective tissue disorders and identify the epidemiological profile of the population from the northern and northeastern regions of Brazil. All patients admitted to the general medical ward at Getulio Vargas Hospital were screened through history and physical examination for the existence of known, suspected or possible connective tissue disorder. A total of 120 patients were enrolled in the study - 61 (50.8%) with systemic lupus erythematosus (SLE), 41 (34.2%) with rheumatoid arthritis (RA), 16 (13.3%) with systemic sclerosis (SS), one (0.8%) with mixed connective tissue disease (MCTD) and one (0.8%) with polymyositis (PM). Women accounted for (104) 86.7% of the participants and (83) 70.9% were non-Caucasians. The mean age was 36.8 years. Alopecia was the most frequent symptom (55/46.6%), followed by other cutaneous lesions (50/42.4%), dyspnea (47/39.8%) and chest pain (39/33.0%). The most frequent rheumatologic disorder encountered in our hospital-based study population was systemic lupus erythematosus, which is contrary to findings of the majority of studies performed in this country.
16635649 Clinical significance of lifetime mood and panic-agoraphobic spectrum symptoms on quality 2006 May BACKGROUND: Previous studies suggested that rheumatoid arthritis (RA) is associated with depressive and anxiety symptomatology. The well-being and functioning of patients with RA may be significantly influenced by subthreshold psychiatric comorbidity. Health-related quality of life (HRQoL) of patients with RA, compared with the Italian norms and patients with diabetes, was assessed by the influence of lifetime mood and panic-agoraphobic spectrum symptoms and demographic and clinical variables. METHODS: Ninety-two patients were consecutively recruited at the Department of Rheumatology at the University Hospital of Pisa, Italy. All patients met diagnostic criteria of RA according to the American College of Rheumatology. Health-related quality of life was measured using the Medical Outcomes Study 36-Item Short-Form Health Survey questionnaire (MOS SF-36). Mood and panic-agoraphobic spectra were assessed by two different structured self-report instruments: the Mood Spectrum (MOODS-SR) and the Panic-Agoraphobic Spectrum (PAS-SR), respectively. RESULTS: Patients with RA were compared, as regards the MOS SF-36 scale scores, with the Italian normative population and patients with diabetes. Compared with the Italian population, patients with RA showed significantly lower MOS SF-36 scale scores, except for role emotional. Moreover, patients with RA scored significantly lower on the role physical, bodily pain, and social functioning scales compared with patients with diabetes and higher on role emotional and mental health. A significant worsening of all MOS SF-36 scale scores was related to higher scores of the depressive domains of MOODS-SR, except for social functioning and bodily pain. A statistically significant negative association was also found between PAS-SR total score and the MOS SF-36 scales physical functioning, vitality, role emotional, and mental health. There were no statistically significant correlations between MOS SF-36 scales and the manic MOODS spectrum. In the multivariate models, the negative correlations between depressive MOODS, role emotional, and mental health were confirmed and the severity of arthritis showed a significant impact on all MOS SF-36 areas with the exception for social functioning; moreover, manic MOODS was associated with better general health. CONCLUSIONS: The present report shows that lifetime depressive spectrum symptoms negatively affects HRQoL of patients with RA and subthreshold mania improves the perception of general health. Diagnosis and appropriate clinical management of depression, including subthreshold symptoms, might enhance HRQoL in these patients.
15809977 Differential expression and response to anti-TNFalpha treatment of infiltrating versus res 2005 May Synovial macrophages play a pivotal role in the pathogenesis of chronic autoimmune arthritis by contributing to local inflammation and tissue damage and are therefore a primary target for therapeutic intervention. The aim of the present study was to investigate in more detail the relative contribution of different synovial macrophage subsets with potentially different inflammatory or anti-inflammatory functions by analysing the two most frequent forms of human autoimmune arthritis, spondyloarthropathy (SpA) and rheumatoid arthritis (RA). Both infiltrating macrophages from peripheral blood expressing myeloid-related proteins (MRP) 8 and 14, and resident tissue macrophages expressing CD163 were abundant in inflamed synovium. Whereas the global number of synovial macrophages was similar in both diseases, infiltrating macrophages were increased in the RA lining layer in contrast with resident tissue macrophages, which were more frequently observed in SpA. Soluble MRP8/MRP14 complexes, which were secreted locally in the joint during the infiltration process, were increased in the serum of arthritis patients and, in contrast with soluble CD163 shed from resident tissue macrophages, correlated well with global inflammatory parameters. Treatment in vivo with anti-TNFalpha had a rapid and pronounced effect on the infiltration of MRP-positive macrophages into tissues, as evidenced by histopathological analysis and serum MRP8/MRP14 levels. Taken together, these data support an important role for infiltrating versus resident tissue macrophages in human autoimmune synovitis and indicate that macrophage products such as soluble MRP8/MRP14 complexes are valuable biomarkers for the experimental and clinical monitoring of specific disease mechanisms in vivo.
17207389 Circannual vitamin d serum levels and disease activity in rheumatoid arthritis: Northern v 2006 Nov BACKGROUND: Greater intake of vitamin D has been associated with a lower risk of rheumatoid arthritis (RA) and low serum vitamin D together with higher prevalence of RA seem common among North European people when compared to Southern Europe. OBJECTIVES: To evaluate serum 25-hydroxyvitamin D [25(OH)D] levels in female RA patients from North (Estonia) and South (Italy) Europe and to correlate them with the disease activity score (DAS28) during winter and summer. METHODS: Fifty-four RA Italian patients (IP) and 64 RA Estonian patients (EP) were evaluated for serum 25(OH)D levels in winter and summer time, as well as for DAS28 score. Normal female controls (C) were 35 (IC) and 30 (EC) age-matched subjects, respectively. 25(OH)D concentrations were measured by a competitive radioimmunoassay. Statistical analysis was performed by "r" Pearson correlation, "t" Student with Bonferroni correction and by repeated ANOVA measures (summer and winter) with two factors (country and clinical status). RESULTS: 25(OH)D levels were found significantly higher in IP versus EP (p = 0.0116) both in winter and in summer time. Differences were observed also in controls. The variations (increase) of 25(OH)D levels between winter and summer were found significant (p = 0.0005) in both IP and EP. Differences were observed also in controls. No significant differences were found concerning 25(OH)D levels between RA patients and their controls in either country. Interestingly, a significant negative correlation between 25(OH)D and DAS28, was found in summer only in IP (r =-0.57, p < 0.0001) and in winter in EP (r =-0.40, p < 0.05). CONCLUSION: Significantly lower 25(OH)D serum levels were observed in RA patients from North versus South Europe with a circannual rhythm in winter and summer time. In addition, 25(OH)D values showed a significant correlation (negative) with RA clinical status (DAS28) in both North and South European RA patients, suggesting possible effects of vitamin D among other factors on disease activity.
15626937 Comparison of measured utility scores and imputed scores from the SF-36 in patients with r 2005 Jan PURPOSE: We sought to evaluate 3 methods for imputing utility-based outcomes from clinical trial data measured using the Medical Outcomes Study 36-Item Short Form (SF-36). SUBJECTS: Our subjects included 131 male and 505 female adults (mean age, 55.42 +/- 12.59 years) who were participating in a randomized clinical trial evaluating a new treatment of adults with rheumatoid arthritis (RA). MEASURES: Participants completed the SF-36, 2 versions of the Health Utilities Index (HUI-2 and HUI-3), the EuroQol EQ-5D, and the Health Assessment Questionnaire (HAQ). SF-36 scores were transformed to utility-based scores using 4 methods developed independently by Fryback, Nichol, and Brazier. RESULTS: All 4 imputed scores were significantly correlated with HUI-2, HUI-3, EQ-5D, and the disease-specific HAQ scores at baseline and at the end of the clinical trial period (P < 0.05). Changes in the imputed scores from baseline to end of study also were significantly correlated with corresponding changes in the measured utility scores and the HAQ score (P < 0.0001). For all imputed and measured scores, changes from baseline were associated with the clinical assessments, ACR20 and ACR50. The associations were stronger for the utility-based measures than the imputed indices. Both imputed and measured scores were sensitive to change in the clinical trial. However, mean scores for the HUI-3 and the Brazier VAS were significantly lower than for the other measures. CONCLUSION: Imputed utility-based score estimates are significantly correlated with measured utility outcomes. However, the imputed measures had more constrained variability, showed poorer correspondence to the ACR20 and ACR50 benchmarks, and predicted less than half of the variance in actual utility-based outcomes. Therefore, directly assessed, not imputed, utility-based measures should continue to be favored for cost-effectiveness analysis.
16829989 [Usefulness of anti-cyclic citrullinate peptide antibody determination in synovial fluid a 2006 Apr OBJECTIVE: To assess the role of anti-cyclic citrullinated peptide (CCP) antibody detection in synovial fluid (SF) of RA patients compared to OA patients. METHODS: We evaluated in 25 RA subjects and 14 OA patients, presenting a knee-joint effusion, the main clinical and laboratory parameters including the number of painful and/or swollen joints, Ritchie index, morning stiffness, ESR, CRP and analysis of SF obtained by therapeutic arthrocentesis. IgG anti-CCP (ELISA), rheumatoid factor (RF) and total IgG (nephelometry method) were measured in SF and paired serum samples. RESULTS: We found anti-CCP antibodies and RF in 64% (16/25) and 60% (15/25) of RA sera, respectively; 72% (18/25) of RA patients were positive for anti-CCP antibodies or RF. We found a higher SF/serum ratio for anti-CCP (p<0.004) compared to that for total IgG. The calculation of anti-CCP concentration as IgG anti-CCP (units)/total IgG (g L-1) revealed higher values in SF than in serum (p<0.046) in RA patients. Among these, correlation analysis showed that anti-CCP/total IgG values in SF correlated with the relative concentration of serum anti-CCP/total IgG (rs=0.842; p<0.00001) and serum anti-CCP antibody levels (rs=0.799; p<0.0001). We did not find any correlation between SF anti-CCP levels and the main characteristics of SF as well as the clinical or laboratory parameters. CONCLUSION: Our study give evidence for a preferential production of anti-CCP antibodies at RA joint level, confirming the pathogenetic role of these autoantibodies. Moreover, SF determination of anti-CCP, corrected for the total amount of the corresponding immunoglobulin, may be helpful as diagnostic tool in selected cases.
16838043 Selective recruitment of CXCR3+ and CCR5+ CCR4+ T cells into synovial tissue in patients w 2006 Jun The inflamed synovial tissue (ST) of rheumatoid arthritis (RA) is characterized by the selective accumulation of interferon gamma-producing Th1-type CD4+ T cells. In this study, we investigated whether the predominance of Th1-type CD4+ cells in the ST lesion is mediated by their selective recruitment through Th1 cell-associated chemokine receptors CXCR3 and CCR5. The lymphocyte aggregates in the ST of RA contained a large number of CD4+ T cells, which mostly expressed both CXCR3 and CCR5, but not CCR4. In contrast, the frequencies of CD4+ and CD8+ T cells expressing CXCR3 and CCR5 in the blood were significantly decreased in RA patients, compared with healthy controls (HC), although there was no difference in the frequencies of CCR4-expressing CD4+ and CD8+ T cells between RA and HC. CXCR3, CCR5, and CCR4 expression in blood CD4 + T cells and CXCR3 expression in CD8+ T cells were increased after interleukin-15 (IL-15) stimulation. Therefore, the distribution of Th1-type CD4+ T cells into the ST from the blood in RA may be associated with the local expression of chemokines, both CXCR3 and CCR5 ligands, and IL-15 may play a role in enhancing these chemokine receptors on CD4+ T cell infiltrates.
16583427 Extent of occupational hand use among persons with rheumatoid arthritis. 2006 Apr 15 OBJECTIVE: Occupational hand use is increasing due to increased computer use and could place persons with rheumatoid arthritis (RA) at risk for work disability. Although hand involvement in RA is typical, there is little information about occupational hand use in relation to RA. Study objectives were to describe the extent of occupational hand use by persons with RA; the types of jobs that require extensive hand use; the relationship between occupational hand use and joint pain; and the extent of occupational hand use among persons with shorter versus longer disease duration. METHODS: Cross-sectional survey data from 2,761 employed participants with RA from a US national cohort were used. Extent of occupational hand use was measured by the hand-use item from a job physical demand scale used in prior RA studies. Analyses included descriptive statistics and chi-square tests. RESULTS: The mean age was 50.6 years, 78.5% were women, 91.8% were white, and 68.8% had more than a high school education. Eighty-three percent of participants reported extensive occupational hand use. Large portions of participants in all types of jobs reported extensive hand use, 92% with administrative support jobs and 69% with operator/laborer jobs. Participants with extensive occupational hand use were more likely to have hand joint pain than those with moderate hand use (66% versus 58%; P = 0.004). Extensive hand use did not vary by disease duration (83% and 84% in participants with < or =15 and >15 years' duration, respectively). CONCLUSION: Extensive occupational hand use was ubiquitous among employed persons with RA and was associated with greater hand pain.
15864386 Tumefactive necrobiotic granulomas (nodulosis) of the pancreas in an adult with long-stand 2005 Apr Rheumatoid nodules are well-documented clinical and pathologic lesions in patients with seropositive rheumatoid arthritis (RA). The current report documents the occurrence of rheumatoid nodulosis of the pancreas in an adult woman with a 7-year history of seropositive RA who presented with upper abdominal pain and was found to have multiple masses in the body and tail of the pancreas by imaging studies. An elevated serum pancreatic polypeptide (PP) and the development of new lesions in the pancreas prompted a subsequent distal pancreatectomy. The lesions in the pancreas proved to be necrobiotic palisading and hyalinizing granulomas upon pathologic examination. Also, of interest, elevation of serum PP has been observed in patients with RA and other systemic noninfectious and infectious inflammatory disorders in the absence of a pancreatic or intestinal neuroendocrine neoplasm.
17153599 Cytotoxicity of taurine metabolites depends on the cell type. 2006 We report that the effect of Tau-Cl on the cell fate strongly depends on the cellular context. In leukemic Jurkat cells Tau-Cl (> 200 microM) triggers mitochondrial, p53-independent apoptosis and amplifies PCD induced by anti-Fas treatment. In contrast, Tau-Cl affects RA FLS in a dose-dependent manner. At the noncytotoxic (200-400 microM) concentrations it induces: (i) p53-dependent growth arrest (Kontny et al., 2005), and (ii) Bax translocation and caspase 9 activity. Although the last events are characteristic for apoptotic state, there is not execution of RA FLS apoptosis, probably due to simultaneous inhibition of caspase 3 activity and prevention of PARP degradation. The last two events suggest an excessive ATP deprivation in Tau-Cl-treated RA FLS. At sufficiently high concentrations (> or = 500 microM) Tau-Cl causes therefore necrosis of these cells. Altogether our results suggest that Tau-Cl is able to eliminate the cells with both functional (RA FLS) and mutated (Jurkat) p53 tumor suppressor. This observation is clinically relevant because Tau-Cl is used in many animal inflammatory models and its sodium salt (used in this study) has been introduced to human therapy (Gottardi and Nagl, 2002; Teuchner et al., 2005).
15996056 Importance of C-reactive protein in regulating monocyte tissue factor expression in patien 2005 Jul OBJECTIVE: To determine the relationship between plasma C-reactive protein (CRP) concentrations and monocyte tissue factor (TF) expression induced in vitro by combinations of CRP, ss2-glycoprotein I (ss2-GPI), and lipopolysaccharide (LPS). METHODS: Peripheral blood mononuclear cells (PBMC) from 26 healthy individuals and 31 patients with inflammatory rheumatic diseases (IRD) were cultured with combinations of CRP, purified or recombinant ss2-GPI, and LPS and monocyte TF procoagulant activity, TF antigen, and TF mRNA were measured. Results were examined against plasma CRP levels. RESULTS: Monocytes from patients with IRD expressed significantly more TF when stimulated with CRP compared to normal monocytes (p = 0.002). An incremental positive correlation was observed between plasma CRP levels and TF induced by CRP or ss2-GPI. Significantly more TF was induced with CRP combined with ss2-GPI, compared to ss2-GPI alone, either with costimulation or CRP priming. Conversely, when combined with LPS, ss2-GPI suppressed TF induction in a dose-dependent manner on normal PBMC but not on PBMC from patients with IRD. The loss of suppression correlated strongly with plasma CRP levels. CONCLUSION: This study shows a remarkably consistent effect of CRP on monocyte TF expression. Systemic inflammation associated with elevated plasma CRP conferred a phenotype on PBMC, whereby incremental priming with respect to TF expression (induced by CRP itself or ss2-GPI) was apparent, and ss2-GPI-mediated inhibition of TF expression induced by LPS was incrementally lost. CRP regulation of monocyte TF could contribute to the higher than expected atherosclerotic vascular disease seen in patients with IRD.
15730401 IgG subclass distribution of the rheumatoid arthritis-specific autoantibodies to citrullin 2005 Mar In the rheumatoid synovium, deiminated ('citrullinated') forms of fibrin are the major targets of IgG autoantibodies to citrullinated proteins (ACPA), the most specific serological markers of rheumatoid arthritis (RA). To further the characterization of ACPA, we determined their subclass distribution. From a previously validated highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) onto in vitro deiminated human fibrinogen - antihuman fibrin(ogen) autoantibodies (AhFibA)-ELISA - we derived and calibrated four ELISAs, using monoclonal antibodies to each of the four IgG subclasses, to determine the proportions of AhFibA subclasses in the sera. A series of 186 serum samples from RA patients was analysed. All AhFibA-positive sera contained IgG1-AhFibA, which reached the highest titres and accounted for more than 80% of AhFibA in three-quarters of the sera. One or two other subclasses were associated with IgG1 in 39% of the sera, IgG4-AhFibA being observed much more frequently and at higher titres than IgG3- or IgG2-AhFibA. IgG1 alone or IgG(1 + 4)-AhFibA were the AhFibA subclass profiles found in more than 80% of patients. AhFibA are mainly IgG1 and, to a lesser extent, IgG4. Such IgG subclass profiles may influence the effector phases of the immunological conflict between ACPA and deiminated fibrin that takes place specifically in the rheumatoid synovium and therefore may play a critical role in the self-maintenance of rheumatoid inflammation.
17195138 Histopathology of pulmonary fibrotic disorders. 2006 Dec Interstitial lung diseases encompass a broad spectrum of disorders that vary greatly in their clinical presentation, natural history, pathology, pathogenesis, prognosis, and treatment. Their correct classification requires integration of clinical, radiological, and pathological findings. Although these disorders may be well defined, interpretation of lung biopsy findings is often difficult, with surprisingly significant interobserver variability. This article reviews the histopathology of the major interstitial lung diseases, including the idiopathic interstitial pneumonias and pulmonary fibrotic disorders associated with collagen vascular diseases and smoking. In addition, the differential diagnosis of each of these disorders is discussed.
17127201 Infection and musculoskeletal conditions: Viral causes of arthritis. 2006 Dec Several viruses cause postinfectious arthritis. The disease is a typical manifestation of arthritogenic alphaviruses, rubella virus and human parvovirus B19. In addition, arthritis is not uncommon after infection by HIV, cytomegalovirus, hepatitis B virus, hepatitis C virus, or Epstein-Barr virus (EBV). Also prolonged arthritis may result from viral infections, particularly with alphaviruses and human parvovirus B19. Viruses such as EBV and B19 may have significant roles in initiating chronic arthropathies, which in some cases may be indistinguishable from rheumatoid arthritis.