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Carlomaurizio Montecucco

Publications and source records attributed to Carlomaurizio Montecucco.

At least 19 recordsLinked to original sources
PubMed2006

High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor alpha inhibitors in rheumatoid arthritis.

OBJECTIVE: To investigate whether rheumatoid factor isotypes and anti-cyclic citrullinated peptide (anti-CCP) antibodies are related to clinical response in patients with rheumatoid arthritis treated with tumour necrosis factor alpha (TNFalpha) inhibitors. METHODS: The study was carried out on 132 patients with advanced rheumatoid arthritis refractory to disease-modifying antirheumatic drugs. Patients were treated with infliximab (n = 63), etanercept (n = 35) or adalimumab (n = 34). All patients completed 1 year of follow-up, and 126 were evaluable for clinical response according to the disease activity score (DAS) criteria. IgM, IgA and IgG rheumatoid factors and anti-CCP antibodies were assessed by ELISA both before anti-TNFalpha treatment and 1 year later. RESULTS: The DAS response was reached in 66% of evaluable patients (61% infliximab, 65% etanercept and 76% adalimumab; p = 0.354). A significant reduction in the rheumatoid factor level was reported by all treatment groups after 1 year. The frequency of positive tests for the different antibodies did not differ between responders and non-responders at baseline; however, significantly higher IgA rheumatoid factor levels were reported by the non-responder group (130.4 U/ml (interquartile range 13.8-276.7) v 24.8 U/ml (10.2-90.8); p = 0.003). A significant decrease (p<0.001) in the levels of all rheumatoid factor isotypes in the responder group was reported after 1 year of treatment, whereas anti-CCP antibody levels were not significantly affected. CONCLUSIONS: According to the clinical response, anti-TNFalpha agents seem to reduce IgM, IgG and IgA rheumatoid factor levels. More interestingly, high pretreatment levels of IgA rheumatoid factor are associated with a poor clinical response to TNFalpha inhibitors.

Adalimumab↗
PubMed2006

Etanercept maintains the clinical benefit achieved by infliximab in patients with rheumatoid arthritis who discontinued infliximab because of side effects.

OBJECTIVE: To evaluate the efficacy of switching to etanercept treatment in patients with rheumatoid arthritis who already responded to infliximab, but presented side effects. METHODS: Charts of 553 patients with rheumatoid arthritis were retrospectively reviewed to select patients who responded to the treatment with infliximab and switched to etanercept because of occurrence of adverse effects. Clinical data were gathered during 24 weeks of etanercept treatment and for the same period of infliximab treatment before infliximab was stopped. Disease Activity Score computed on 44 joints (DAS-44), erythrocyte sedimentation rate (ESR) 1st hour, Visual Analogue Scale (VAS) of pain, Health Assessment Questionnaire (HAQ), and C reactive protein (CRP) were assessed every 8 weeks. RESULTS: 37 patients were analysed. Adverse events to infliximab were mostly infusion reactions. No statistically significant difference between infliximab, before withdrawal, and etanercept, after 24 weeks, was detected in terms of DAS-44 (2.7 and 1.9, respectively), HAQ (0.75 and 0.75, respectively), ESR (21 and 14, respectively) and CRP (0.5 and 0.3, respectively). VAS pain decreased significantly after switching to etanercept treatment (40 and 24, respectively; p<0.05). CONCLUSIONS: Our study shows that etanercept maintains the clinical benefit achieved by infliximab, and suggests that a second tumour necrosis factor (TNF) alpha inhibitor can be the favourable treatment for rheumatoid arthritis when the first TNFalpha blocker has been withdrawn because of adverse events.

Adult↗
PubMed2006

Is the course of steroid-treated polymyalgia rheumatica more severe in women?

Polymyalgia rheumatica (PMR) has a marked preponderance in women. The female sex has been claimed to be a risk factor for longer-course corticosteroid therapy and to be associated with more severe systemic symptoms and lower hemoglobin levels. Eighty consecutive patients affected by PMR, seen at two tertiary referral centers, were followed-up for a mean period of 14.9 months after initiating corticosteroid treatment. At presentation, women had longer disease duration and lower hemoglobin levels (both P = 0.05) than men. In contrast, their systemic signs of PMR were less common (P = 0.01). Women were treated with a slightly higher mean daily dose of prednisone (P = 0.055), and assumed a significantly higher cumulative dosage of the drug (P = 0.01). Accordingly, the mean number of steroid-related side effects was higher among women (P = 0.003). The number of relapses during steroid treatment (P = 0.02), but not that of recurrences, was increased in women. ESR, which was raised at presentation, significantly declined during follow-up to normal values in both subgroups (P < 0.00001 by analysis of variance [ANOVA]). Its decrease was significantly more pronounced in men than in women. Hemoglobin at follow-up was significantly higher in men than in women at any given time point. In conclusion, sex is probably modulating the response to corticosteroids. This finding emphasizes the need to consider differences between males and females in the clinical and therapeutic approach to PMR patients.

Aged↗
PubMed2006

Remission, a therapeutic goal in inflammatory arthropathies? Clinical data from adalimumab studies.

In recent years, there have been major advances in the management of rheumatoid arthritis (RA), leading to the development of tumour necrosis factor (TNF) antagonists. With these agents, it is possible to arrest joint damage and, by treating early in the disease course, to prevent joint damage. It is also now thought that early treatment can achieve clinical remission in a substantial proportion of patients. With these increased expectations, a change is required in the way clinical improvement and drug efficacy is measured. The existing standard endpoint commonly used in RA clinical trials, the American College of Rheumatology (ACR) 20% response measure, is inadequate for the new goals of therapy that should be based on clinical remission and radiographic assessment.Adalimumab, a fully human anti-TNF monoclonal antibody, has been shown to be effective in achieving remission and preventing radiographic progression of joint damage in patients with RA and other inflammatory arthropathies, including psoriatic arthritis and ankylosing spondylitis. In a placebo-controlled trial in patients with early RA, combination treatment with adalimumab plus methotrexate (MTX) has been shown to be superior to either treatment alone in inducing significant clinical remission while being generally well tolerated. Compared with monotherapy, combination therapy resulted in significantly more patients (49% vs 25%; p < 0.001) remaining in clinical remission after 2 years. Suppression of joint damage assessed by the degree of inhibition of radiographic progression was also significantly higher for patients treated with adalimumab plus MTX (and with adalimumab alone) at 6 months, 1 and 2 years than for those treated with MTX alone. These data support the notion that clinical remission is a realistic therapeutic goal in patients with RA.

Adalimumab↗
PubMed2005

Multilevel examination of minor salivary gland biopsy for Sjogren's syndrome significantly improves diagnostic performance of AECG classification criteria.

The recently observed low reproducibility of focus score (FS) assessment at different section depths in a series of single minor salivary gland biopsies highlighted the need for a standardized protocol of extensive histopathological examination of such biopsies in Sjogren's syndrome. For this purpose, a cumulative focus score (cFS) was evaluated on three slides cut at 200-mum intervals from each of a series of 120 salivary biopsies. The cFS was substituted for the baseline FS in the American-European Consensus Group (AECG) criteria set for Sjogren's syndrome classification, and then test specificity and sensitivity were assessed against clinical patient re-evaluation. Test performances of the AECG classification with the original FS and the score obtained after multilevel examination were statistically compared using receiver operating characteristic (ROC) curve analysis. The diagnostic performance of AECG classification significantly improved when the cFS was entered in the AECG classification; the improvement was mostly due to increased specificity in biopsies with a baseline FS >or= 1 but <2. The assessment of a cFS obtained at three different section levels on minor salivary gland biopsies can be useful especially in biopsies with baseline FSs between 1 and 2.

Adult↗
PubMed2005

-238 and +489 TNF-alpha along with TNF-RII gene polymorphisms associate with the diffuse phenotype in patients with Systemic Sclerosis.

OBJECTIVE: To investigate possible associations of TNF-alpha and TNF-RII gene polymorphisms with diffuse or limited skin involvement phenotype in a cohort of Systemic Sclerosis (SSc) patients. METHODS: One-hundred and fourteen consecutive SSc patients attending the referral centres of three academic hospitals in Italy (University of Naples, Pavia and Udine), 56 with the diffuse (dcSSc) and 58 with limited (lcSSc) skin involvement subsets, and 170 healthy blood donors (HBDs) were included in the study. The extracted DNA was genotyped for the following polymorphisms: TNF-alpha (-238, +489) and TNF-RII (+196), using the polymerase chain reaction (PCR) and the restriction enzymes BamHI, HpyCH4 IV and NlaIII, respectively. RESULTS: The AG/AA (presence of allele A) genotypes in position -238 and the AG genotype in position +489 of the TNF-alpha gene were found significantly increased in SSc, as a whole, when compared with healthy blood donors (chi(nu=2)(2)=4.48, p=0.03 for -238 and chi(nu=2)(2)=7.82, p=0.02 for +489, respectively). The rare GG genotype in exon 6 (codon 196) of the TNF-RII gene was also found increased in SSc compared to HBDs, even though the difference did not show statistical significance (chi(nu=2)(2)=3.56, p=0.17). The strength of the association was mainly due to the dcSSc phenotype (Fisher test, p=0.04 for -238, chi(nu=2)(2)=10.07, p<0.01 for +489 and chi(nu=2)(2)=6.25, p=0.04 for the +196 TNF-RII, respectively). CONCLUSIONS: TNF-alpha and TNF-RII gene polymorphisms seem to contribute to the development of SSc and in particular to the diffuse phenotype.

Autoantibodies↗
PubMed2005

Involvement of subchondral bone marrow in rheumatoid arthritis: lymphoid neogenesis and in situ relationship to subchondral bone marrow osteoclast recruitment.

OBJECTIVE: To evaluate the presence and immunohistochemical characteristics of subchondral bone marrow inflammatory infiltrate in rheumatoid arthritis (RA) and to determine the in situ relationship between marrow inflammation and osteoclast recruitment. METHODS: Bone samples and paired synovia from 8 RA patients undergoing joint surgery were analyzed by immunohistochemistry and in situ hybridization for specific lymphoid neogenetic features, such as T and B cell composition, follicular dendritic cell (FDC) networks, peripheral lymph node addressin (PNAd)-positive high endothelial venules, and lymphoid chemokine expression. Osteoclasts were identified as multinucleated tartrate-resistant acid phosphatase (TRAP)-positive and cathepsin K-positive cells adherent to the bone surface. RESULTS: An inflammatory infiltrate with perivascular aggregates of variable size was detected in 7 (87.5%) of 8 synovial samples and in paired bone samples. Lymphoid neogenetic features typical of rheumatoid synovium were also recognized in the bone marrow. PNAd+ blood vessels were found in 4 of 8 patients, CD21+ FDC networks in 2 patients, CXCL13+ cells in 5 patients, and CCL21+ cells in 6 patients. TRAP-positive and cathepsin K-positive osteoclasts were identified on both the synovial and marrow sides of the bone surface. Bone marrow samples showing a higher degree of inflammation were characterized by a significantly increased number of osteoclasts adherent to the subchondral bone. CONCLUSION: Our data demonstrate that lymphoid aggregates with lymphoid neogenetic features are detectable on the subchondral side of the joint in established RA. Moreover, the local inflammation/aggregation process appears to be related to osteoclast differentiation on the marrow side of subchondral bone, supporting a functional role of the bone compartment in local damage.

Adult↗
PubMed2005

Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis.

CXCL13 and CCL21 have been functionally implicated in lymphoid tissue organization both in the upstream phases of lymphoid tissue embryogenesis and in ectopic lymphoid neogenesis in transgenic mice. Here, we analyzed the relationship between CXCL13 and CCL21 production and lymphoid tissue organization in rheumatoid synovitis as a model of a naturally occurring ectopic lymphoneogenesis. Through systematic analysis of mRNA and protein expression, we defined the microanatomical relationship between CXCL13 and CCL21 in progressive aggregational and structural phases of synovial inflammatory infiltrate. We provide the first direct in situ evidence that production of CXCL13 and CCL21 (rather than simply protein binding) is associated with inflammatory lymphoid tissue formation and development with the demonstration, in organized aggregates, of a secondary lymphoid organ-like compartmentalization and vascular association. Notably, the presence of CXCL13 and CCL21 (protein and mRNA) was also demonstrated in non-organized clusters and minor aggregational stages, providing evidence that their induction can take place independently and possibly upstream of T-B compartmentalization, CD21(+) follicular dendritic cell network differentiation and germinal center formation. Our data support the concept that, under inflammatory conditions, CXCL13 and CCL21 participate in lymphoid tissue microanatomical organization, attempting to recapitulate, in an aberrant lymphoid neogenetic process, their homeostatic and morphogenetic physiologic functions.

Arthritis, Rheumatoid↗
PubMed2005

Comorbid conditions in the AMICA study patients: effects on the quality of life and drug prescriptions by general practitioners and specialists.

OBJECTIVE: Osteoarthritis (OA) has been identified as the disease with the highest rate of comorbidities, which may increase the likelihood of disability. The AMICA study evaluated how the presence of a coexistent disease and/or its chronic pharmacological treatment influenced the prescription of pharmacological and nonpharmacological therapy in patients with OA. PATIENTS AND METHODS: The 2764 general practitioners (GPs) and 316 specialists (98 rheumatologists, 166 orthopedic surgeons, 52 physical medicine specialists) participating in the study were asked to enroll 10 consecutive patients with OA diagnosed according to the American College of Rheumatology clinical criteria. Information was collected regarding demographics, the clinical characteristics of OA, and previous diagnostic and therapeutic interventions. Pain intensity was assessed using a 100-mm visual analog scale (VAS); the patients were also asked to report on their quality of life and joint function, as well as the presence of any concomitant disease and/or therapy. The influence of comorbidities on the quality of life, pain, and drug prescription was evaluated. RESULTS: A total of 29,132 evaluable patients was observed (25,589 recruited by GPs and 3543 by specialists). The most frequent comorbidities were hypertension (52%), osteoporosis (21%), type II diabetes mellitus (15%), and chronic obstructive pulmonary disease (12%); myocardial infarction and/or angina pectoris were present in 6% and peptic ulcer was present in 5%. Comorbidities were more frequent in older patients and, except in the case of hypertension, were closely related to more intense pain and a decreased quality of life; they were also generally associated with worsened joint function. The presence of peptic ulcer was associated with a reduction in the prescription of nonsteroidal antiinflammatory drugs (NSAIDs) (odds ratio (OR) 0.61; confidence intervals (CI) 0.53 to 0.69) and the more frequent use of Coxibs (OR 1.15; CI 1.03 to 1.28) and simple analgesics (OR 1.42; CI 1.26 to 1.61), as well as with greater use of physical therapy. Hypertension was associated with a reduction in the prescription of physical therapy. NSAIDs and Coxibs were less frequently prescribed if the patients were on anticoagulant therapy (NSAIDs: OR 0.86; CI 0.70 to 1.06; Coxibs: OR 0.77; CI 0.64 to 0.93). Gastroprotective therapy was more frequently used in patients treated with NSAIDs, Coxibs, and analgesics, with GPs giving greater preference to proton pump inhibitors than specialists. CONCLUSIONS: Comorbidities decrease the quality of life and worsen the joint function in OA patients. Comorbidities and their treatment generally do not influence the physician's choice of OA treatment, with the exception of peptic ulcer and anticoagulant therapy, both of which were associated with a reduction in the prescription of antiinflammatory drugs. There was a preferential use of Coxibs in patients with peptic ulcer, and an underuse of gastroprotective measures in OA patients treated with NSAIDs.

Aged↗
PubMed2005

Autoimmunity in thrombotic thrombocytopenic purpura.

In the last few years, an autoimmune hypothesis for the pathogenesis of thrombotic thrombocytopenic purpura (TTP) has been proposed often, with variable success because of inconsistent supporting data. We are now aware that at least one subgroup of TTP patients does present with pathogenic autoantibodies (i.e, anti-ADAMTS13); this group consequently is a putative candidate for a curative treatment including plasma exchange (still the cornerstone of TTP treatment), together with corticosteroids or other immunosuppressants. Furthermore, for patients not responding to or relapsing following plasma exchange, the use of stronger immunosuppression (e.g., with the use of the anti-CD20 monoclonal antibody rituximab) should be considered as appropriate. Conversely, few data are actually available regarding the complex relationship between TTP and the antiphospholipid (aPL) syndrome, as well as other autoimmune diseases. Indeed, a correct differential diagnosis should be done on the basis of both different clinical presentations and autoantibody profile. At present, the presence of aPL antibodies should give evidence against a diagnosis of TTP, even though we cannot exclude that aPL antibodies may, in a minority of patients, be associated with a primary endothelial damage ultimately resulting in overt TTP.

ADAM Proteins↗
PubMed2005

Autoantibodies to heterogeneous nuclear ribonucleoproteins.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are among the most abundant proteins in the eukaryotic cell nucleus and play a direct role in several aspects of the RNA life including splicing, export of the mature RNAs and translation. To date, approximately 30 proteins have been identified. A growing body of evidence points to hnRNPs as an important target of the autoimmune response in rheumatic diseases. Autoantibodies to A and B proteins of the hnRNP complex have been detected in late 1980s in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Beyond their role as diagnostic test in clinical practice, these autoantibodies are starting to be regarded as important tools to obtain deeper insight into the pathogenesis of autoimmune rheumatic diseases. Furthermore, new anti-hnRNP antibodies have been recognized in the last ten years extending the spectrum of anti-hnRNP reactivity in different autoimmune disorders.

Animals↗
PubMed2005

Antibodies to cyclic citrullinated peptides in psoriatic arthritis.

OBJECTIVE: To determine the presence and clinical significance of antibodies to cyclic citrullinated peptides (anti-CCP) in psoriatic arthritis (PsA). METHODS: We performed a cross-sectional study on 102 outpatients (56 men) with PsA consecutively recruited from a tertiary referral center. Median disease duration was 36 months (interquartile range 21-81). All patients were investigated for peripheral joint and axial involvement, enthesitis, and dactylitis. Laboratory investigations included anti-CCP, assessed by enzyme-linked immunosorbent assay and IgM rheumatoid factor (RF). Plain radiographs of pelvis, wrists, hands, and feet were performed in all cases. RESULTS: Anti-CCP were detected in 16/102 patients, 8/68 with symmetric polyarthritis, 1/8 with asymmetric polyarthritis, 2/20 with mono-oligoarthritis, 1/2 with mutilating arthritis, and 0/4 with exclusive axial or distal interphalangeal (DIP) involvement. The male:female ratio as well as frequency of dactylitis, enthesitis, and nonexclusive axial or DIP joint involvement were similar in the anti-CCP positive and negative groups. Anti-CCP positive patients were more frequently treated with disease modifying antirheumatic drugs and showed higher number of involved joints, and higher frequency of erosive arthritis and positive RF. Using multiple logistic regression, anti-CCP (but not RF) were significantly associated with erosive arthritis (odds ratio 9.8; 95% confidence interval 1.87-51.8) and > or = 10 involved joints (17.99; 3.6-89.2). CONCLUSION: Anti-CCP can be found in a small but significant proportion of patients with a clinical picture of PsA and are associated with erosive arthritis and multiple joint involvement.

Adult↗
PubMed2005

Analysis of the apolipoprotein(a) size polymorphism in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by an increased incidence of vascular disease which is only partially explained by traditional risk factors. Previous reports suggested that the level of lipoprotein(a) [Lp(a)], a particle linked to atherothrombotic disorders, is increased in patients with SLE. However, whether there are any differences in the distribution of apolipoprotein(a) [apo(a)] phenotypes between SLE patients and healthy controls remain to be determined. To address this issue, Lp(a) levels and apo(a) isoform size were analyzed in a total of 54 patients with SLE and in 108 age- and gender-matched healthy controls. SLE patients showed Lp(a) levels [median (interquartile range): 25.3 (6.5-51.0) vs. 9.5 (4.6-25.9) mg/dl, P=0.0109)] and a percentage of subjects with at least one small-sized apo(a) isoform (< or =25 K-IV repeats) significantly higher than controls (44.44% vs. 25.92%, P=0.0277). Multiple regression analysis adjusting for age, gender, disease duration, kidney involvement, the presence of active disease, as well as the carriage of at least one small apo(a) isoform revealed that only small apo(a) phenotypes were significant predictors of Lp(a) levels in SLE patients (P=0.0001). We conclude that genetic factors related to apo(a) size are a major determinant of elevated Lp(a) levels in patients with SLE. As small apo(a) phenotypes have been related to adverse vascular effects, it is feasible that small apo(a) isoforms may be a useful biological marker in the assessment of vascular risk in patients with SLE.

Adult↗
PubMed2004

Prednisone plus methotrexate for polymyalgia rheumatica: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Steroids are the standard treatment for polymyalgia rheumatica. The efficacy of the candidate drug methotrexate has not yet been demonstrated in controlled studies. OBJECTIVE: To compare the efficacy and safety of prednisone plus methotrexate and prednisone alone in patients with polymyalgia rheumatica. DESIGN: Multicenter randomized, double-blind, placebo-controlled trial. SETTING: 5 Italian rheumatology clinics. PATIENTS: 72 patients with newly diagnosed polymyalgia rheumatica. MEASUREMENTS: The proportion of patients no longer taking prednisone, the number of flare-ups, and the cumulative prednisone dose after 76 weeks. INTERVENTION: Prednisone dosage (25 mg/d) was tapered to 0 mg/d within 24 weeks and was adjusted if flare-ups occurred. Oral methotrexate (10 mg) or placebo, with folinic acid supplementation (7.5 mg), was given weekly for 48 weeks. RESULTS: Twenty-eight of 32 patients in the methotrexate group and 16 of 30 patients in the placebo group were no longer taking prednisone at 76 weeks (P = 0.003). The risk difference was 34 percentage points (95% CI, 11 to 53 percentage points). Similar results were obtained after adjustment for C-reactive protein level and duration of symptoms in a multivariate model. Fifteen of 32 patients in the methotrexate group and 22 of 30 patients in the placebo group had at least 1 flare-up by the end of follow-up (P = 0.04). The median prednisone dose was 2.1 g in the methotrexate group and 2.97 g in the placebo group (P = 0.03). The rate and severity of adverse events were similar. LIMITATIONS: Follow-up was short, and a high dose of folinic acid and a relatively high starting dosage of prednisone were used. Ten of 72 patients (14%) discontinued treatment or were lost to follow-up. CONCLUSIONS: Prednisone plus methotrexate is associated with shorter prednisone treatment and steroid sparing. It may be useful in patients at high risk for steroid-related toxicity.

Aged↗
PubMed2004

Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment.

The aim of the present study was to investigate the effect of long-term infliximab treatment on various autoantibodies in patients with rheumatoid arthritis. Serum samples from 30 consecutive patients, who were prospectively followed during infliximab and methotrexate therapy for refractory rheumatoid arthritis, were tested at baseline and after 30, 54 and 78 weeks. At these points, median values of the Disease Activity Score were 6.38 (interquartile range 5.30-6.75), 3.69 (2.67-4.62), 2.9 (2.39-4.65) and 3.71 (2.62-5.06), respectively. Various autoantibodies were assessed by standard indirect immunofluorescence and/or ELISA. Initially, 50% of patients were positive for antinuclear antibodies, and this figure increased to 80% after 78 weeks (P = 0.029). A less marked, similar increase was found for IgG and IgM anticardiolipin antibody titre, whereas the frequency of anti-double-stranded DNA antibodies (by ELISA) exhibited a transient rise (up to 16.7%) at 54 weeks and dropped to 0% at 78 weeks. Antibodies to proteinase-3 and myeloperoxidase were not detected. The proportion of patients who were positive for rheumatoid factor (RF) was similar at baseline and at 78 weeks (87% and 80%, respectively). However, the median RF titre exhibited a progressive reduction from 128 IU/ml (interquartile range 47-290 IU/ml) to 53 IU/ml (18-106 IU/ml). Anti-cyclic citrullinated peptide (CCP) antibodies were found in 83% of patients before therapy; anti-CCP antibody titre significantly decreased at 30 weeks but returned to baseline thereafter. In conclusion, the presence of anti-double-stranded DNA antibodies is a transient phenomenon, despite a stable increase in antinuclear and anticardiolipin antibodies. Also, the evolution of RF titres and that of anti-CCP antibody titres differed during long-term infliximab therapy.

Antibodies, Anticardiolipin↗
PubMed2004

Rheumatoid arthritis in beta-thalassemic trait: clinical, serologic and immunogenetic profile.

OBJECTIVES: To investigate the clinical, serologic, radiologic and immunogenetic characteristics of rheumatoid arthritis (RA) occurring in patients with beta-thalassemic trait as compared with RA in control patients from the same geographical area. MATERIALS AND METHODS: Twenty-eight patients with beta-thalassemic trait fulfilling the American College of Rheumatology (ACR) criteria for RA were compared with a control group of twenty-eight RA patients matched for age, sex, disease duration and place of birth. Clinical and routine laboratory assessment, including anti-keratin antibodies and anti-citrullinated peptide antibodies, was carried out in the two groups. The patients were also evaluated for HLADRB1 alleles and radiologic damage. RESULTS: No differences were found with regard to clinical indexes of disease activity, laboratory parameters, and joint erosions. The immunogenetic analysis did not show any significant difference, the percentage of patients with alleles encoding for the shared epitope being similar in the two groups (61% vs. 57%). As for the extra-articular features, we found a trend for a lower prevalence of sicca syndrome in the beta-thalassemic group (14% vs. 39%; P = 0.06). Rheumatoid nodules were not found in beta-thalassemic patients while they were present in two RA patients in the control group. CONCLUSIONS: The chronic polyarthritis occurring in beta-thalassemic trait carriers can be regarded as a true RA similar to that found in Mediterranean countries, possibly characterized by a low prevalence of extra-articular features.

Age Distribution↗
PubMed2004

BAL cytokine profile in different interstitial lung diseases: a focus on systemic sclerosis.

BACKGROUND AND AIM: Fibrosing alveolitis develops in up to 80% of systemic sclerosis patients (SSc) but progression to end stage fibrosis occurs in about 15% of cases. Mechanisms leading to the process remain mostly unknown. We compared cytokine profiles of broncho-alveolar lavage fluids (BAL-f) from patients with SSc associated interstitial lung disease (SSc-ILD) (n. 34), idiopathic pulmonary fibrosis (IPF) (n. 13), stage II sarcoidosis (n. 14) and 9 controls. METHODS: Interleukin (IL) 8, monocyte chemoattractant protein 1 (MCP-1), gamma-interferon (IFN-gamma), IL12, IL18 and IL10 and transforming growth factor-beta (TGF-beta) were assessed by ELISA in concentrated BAL-f. RESULTS: Levels of IL8 and MCP-1 were significantly elevated in SSc-ILD and in IPF as compared with controls (Mann Whitney test p < 0.05), while MCP-1 values were significantly lower in SSc-ILD than in IPF. A significant correlation between neutrophils and IL8 levels (p = 0.047), as well as between eosinophils and MCP-1 levels (p = 0.004) was also observed. IFN-gamma levels were slightly higher than normal only in sarcoidosis (p = 0.06), whereas IL12 levels increased both in sarcoidosis and SSc-ILD (p < 0.05). No differences were found in IL18 and TGF-beta levels. Finally, IL10 levels were higher in SSc-ILD and sarcoidosis than in controls and IPF (p < 0.05). CONCLUSION: BAL-f cytokine profile differentiates ILD associated with SSc from IPF. The lower expression of MCP-1 and the higher expression of the anti-fibrotic IL12 and the anti-inflammatory IL10, observed both in sarcoidosis and in SSc-ILD, could account for the better prognosis of these ILDs. Further longitudinal studies are required to confirm whether a different cytokine phenotype may be considered predictive of clinical outcome in SSc-ILD.

Adult↗