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Biomedical subjects

Rolando Cimaz

Publications and source records attributed to Rolando Cimaz.

At least 19 recordsLinked to original sources
PubMed2006

Anti-inflammatory and immunosuppressive drugs and reproduction.

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

Adult↗
PubMed2006

Transforming growth factor beta1 in the pathogenesis of autoimmune congenital complete heart block: lesson from twins and triplets discordant for the disease.

OBJECTIVE: Clinical evidence and experimental evidence suggest that anti-Ro/La autoantibodies are necessary but not sufficient for the development of congenital complete heart block (CCHB). Maternal, fetal, and environmental factors may also contribute to heart damage in CCHB. The aim of our study was to investigate polymorphisms of transforming growth factor beta1 (TGFbeta1) and tumor necrosis factor alpha (TNFalpha) genes in twins and triplets discordant for CCHB whose mothers are anti-Ro/La positive. METHODS: We studied 2 families in which 1 of the mothers gave birth to triplets and the other gave birth to twins. Only 1 child in each family was affected by CCHB, although 1 of the triplets had incomplete heart block. We analyzed TNFalpha and TGFbeta1 polymorphisms in the 2 babies with CCHB and their siblings. TNFalpha polymorphisms at the promoter region and TGFbeta1 polymorphisms at codons 10 and 25 were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. In addition, the production of TGFbeta1 and TNFalpha by resting or mitogen-stimulated peripheral blood mononuclear cells in cell culture supernatants was evaluated by enzyme-linked immunosorbent assay. RESULTS: The profibrotic TGFbeta1 genotype was detected in the twin with CCHB but not in the healthy twin, while all of the triplets displayed the same TGFbeta1 genotype at codon 10. Peripheral blood mononuclear cells from the children with CCHB displayed higher spontaneous and mitogen-stimulated TGFbeta1 secretion than was observed in their siblings. No differences regarding TNFalpha polymorphisms and secretion of TNFalpha were observed. CONCLUSION: The results of this study suggest that, besides anti-Ro/La autoantibodies, a fetal profibrotic response might contribute to the development of CCHB, but additional pathogenic mechanism(s) are also likely to play a role.

Autoimmune Diseases↗
PubMed2006

Osteogenesis imperfecta: new treatment options.

Classic treatments of osteogenesis imperfecta for children and adults include rehabilitation therapy and orthopedic surgery. New treatments include bisphosphonates. Among them, the effects of intravenous pamidronate have been primarily evaluated in children in several open cohorts. Treatments of adult patients are not established. Several other treatments may have an effect on the fracture rate. However, further studies are needed to demonstrate an effect on fracture rate in children and adult patients. A new approach has been developed to replace mutated genes using mesenchymal stem cells and a construct, which inactivates COL1A1.

Adult↗
PubMed2006

Pediatric antiphospholipid syndrome.

APS is rare in the pediatric age, but it represents an interesting phenomenon because most of the known "second hit" risk factors such as atherosclerosis, smoking, hypertension, contraceptive hormonal treatment, and pregnancy are not present in childhood. This could also be the reason for the prevalence of some clinical manifestations rather than others in PAPS. On the other hand, the increased frequency of infectious processes in the childhood age is likely responsible for the relatively high prevalence of non-pathogenic and transient aPL. Such points raise the problem of a different diagnosis or monitoring approach in pediatric APS. Of particular interest is the special entity of neonatal APS, which represents an in vivo model of acquired autoimmune disease, in which transplacentally acquired aPL cause thrombosis in the newborn. International registries for pediatric and neonatal APS are currently in place; epidemiologic, clinical, and laboratory re-search will help to shed light on all the still obscure aspects of this fascinating but rare disorder in the very young. Finally, treatment is less aggressive overall in pediatric APS, given the reluctance to anticoagulate children over the long term. Studies on the outcome of pediatric APS and the relative risks of prolonged anticoagulation in children are necessary to determine the type and duration of anticoagulation therapy.

Adult↗
PubMed2005

Pregnancy and autoimmunity: maternal treatment and maternal disease influence on pregnancy outcome.

If a woman suffers from autoimmune disease (AD), several factors can affect pregnancy or neonatal outcome: repeated spontaneous pregnancy losses (frequently related to antiphospholipid antibodies (aPL)), neonatal lupus with complete congenital heart block (CHB) (linked to transplacental passage of IgG anti Ro/SS-A antibodies) and the disease activity itself that can affect the mother, the pregnancy and fetal outcome. If appropriately managed, the antiphospholipid syndrome (APS) is "one of the few tractable causes of pregnancy losses." A recent case control study, on babies from APS-mothers and healthy mothers, did not show any difference in the occurrence of neonatal complications. There are few data about the long-term outcome of babies born to patients with AD. We recently reported increased occurrence of learning disabilities in children born to aPL positive mothers with systemic lupus erythematosus (SLE). The modern management of pregnancy in patients with AD includes the treatment of disease flares, using drugs effective but safe for fetus. Corticosteroids and some immunosuppressive drugs can be used in pregnancy to control maternal disease. A prolonged fetal exposure to dexamethasone was reported to impair cerebral development, but we recently studied 6 children, born to patients treated with dexamathasone because of CHB, showing a normal intelligence quotient. The last 10-year experience shows that fetal exposure to antimalarial drugs should not be regarded as an important risk factor for gestational nor neonatal complications. However, information about long-term outcome of children exposed to immunosuppressive drugs "in utero" are still lacking and more efforts are needed in this research area.

Autoimmune Diseases↗
PubMed2005

The Pediatric Rheumatology International Trials Organization criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the disease activity core set.

OBJECTIVE: To validate and promulgate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile systemic lupus erythematosus (SLE). METHODS: In 2001, a preliminary consensus-derived core set of measures for evaluating the response to therapy in juvenile SLE was established. In the present study, the core set was validated through an evidence-based, large-scale data collection process that led to the enrollment of 557 patients from 39 different countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, agreement in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. RESULTS: The following clinical measures were found to be feasible and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician's global assessment of disease activity, 2) global disease activity measure, 3) 24-hour proteinuria, 4) parent's global assessment of the patient's overall well-being, and 5) health-related quality of life assessment. CONCLUSION: The members of PRINTO propose a core set of criteria for the evaluation of response to therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a patient with juvenile SLE has responded adequately to therapy.

Activities of Daily Living↗
PubMed2005

Localized scleroderma in childhood is not just a skin disease.

OBJECTIVE: Juvenile localized scleroderma is usually considered a disease that is confined to the skin and subcutaneous tissue. We studied the prevalence and clinical features of extracutaneous manifestations in a large cohort of children with juvenile localized scleroderma. METHODS: Data from a multinational study on juvenile scleroderma was used for this in-depth study. Clinical features of patients with extracutaneous manifestations were compared with those of patients who had exclusively skin involvement. RESULTS: Seven hundred fifty patients entered the study. One hundred sixty-eight patients (22.4%) presented with a total of 193 extracutaneous manifestations, as follows: articular (47.2%), neurologic (17.1%), vascular (9.3%), ocular (8.3%), gastrointestinal (6.2%), respiratory (2.6%), cardiac (1%), and renal (1%). Other autoimmune conditions were present in 7.3% of patients. Neurologic involvement consisted of epilepsy, central nervous system vasculitis, peripheral neuropathy, vascular malformations, headache, and neuroimaging abnormalities. Ocular manifestations were episcleritis, uveitis, xerophthalmia, glaucoma, and papilledema. In more than one-fourth of these children, articular, neurologic, and ocular involvements were unrelated to the site of skin lesions. Raynaud's phenomenon was reported in 16 patients. Respiratory involvement consisted essentially of restrictive lung disease. Gastrointestinal involvement was reported in 12 patients and consisted exclusively of gastroesophageal reflux. Thirty patients (4%) had multiple extracutaneous features, but systemic sclerosis (SSc) developed in only 1 patient. In patients with extracutaneous involvement, the prevalence of antinuclear antibodies and rheumatoid factor was significantly higher than that among patients with only skin involvement. However, Scl-70 and anticentromere, markers of SSc, were not significantly increased. CONCLUSION: Extracutaneous manifestations of juvenile localized scleroderma developed in almost one-fourth of the children in this study. These extracutaneous manifestations often were unrelated to the site of the skin lesions and sometimes were associated with multiple organ involvement. The risk of developing SSc was very low. This subgroup of patients with juvenile localized scleroderma should be evaluated extensively, treated more aggressively, and monitored carefully.

Autoimmune Diseases↗
PubMed2005

In vivo effects of maternal immunosuppression during pregnancy on the immune function of newborn infants.

When used in pregnancy, immunosuppressants can cross the placental barrier and enter foetal circulation, possibly affecting the immune system of the foetus. This study evaluated the immune function in eight children born by mothers with connective tissue diseases who received immunosuppressants (cyclosporine A or dexamethasone) during pregnancy and in six babies from mothers with similar diseases, but who did not receive any treatment. Judging by the cytokine production of interleukin-2 and interferon-gamma in peripheral blood mononuclear cells stimulated by phorbol-myristate-acetate (PMA) and ionomycin, immunosuppressive drugs given for rheumatic disorders during pregnancy do not induce significant immunosuppression in babies.

Connective Tissue Diseases↗
PubMed2005

Osteoprotegerin serum levels in Kawasaki disease: an additional potential marker in predicting children with coronary artery involvement.

OBJECTIVE: Emerging evidence from in vitro studies and mouse genetics attributes to osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, an important role in vascular biology. We evaluated serum levels of OPG in a group of children with Kawasaki disease (KD), before immunoglobulin (IVIG) infusion and at 3-month followup. METHODS: Fifty patients (38 boys, 20 girls, median age 3.6 yrs, range 4 mo-7.4 yrs) fulfilling criteria for the diagnosis of KD, 30 febrile controls with infectious diseases, 18 patients with juvenile systemic lupus erythematosus (JSLE), and 40 healthy controls were enrolled. All KD patients received IVIG treatment within the first 10 days of illness, and aspirin. Coronary artery abnormalities (CAA) were reported in 6 out of 58 patients; all were male and younger than 5 years. Serum OPG was measured by ELISA in patients with KD before IVIG and at 3-month followup (median time 3.2 mo, range 3-3.5). RESULTS: At baseline and at the 3-month followup, KD patients had significantly higher OPG serum levels than febrile controls (p < 0.001 and p < 0.004, respectively), JSLE patients (p < 0.0001), and healthy controls (p < 0.0001). At baseline, KD patients who developed CAA had higher OPG serum levels than those without CAA (p = 0.0001); this difference was not present at 3-month followup. The optimal OPG cutoff value of 123.2 pg/ml was a significant predictor for CAA, with a sensitivity of 100% (6/6), a specificity of 96% (50/52), and a positive predictive value of 75% (6/8). CONCLUSION: High OPG levels might be the result of compensatory production during acute and subacute phases of KD. OPG assay might be an additional clinically useful marker to monitor and differentiate patients who develop, from those who do not develop, such coronary artery abnormalities.

Biomarkers↗
PubMed2004

Neprilysin levels in plasma and synovial fluid of juvenile idiopathic arthritis patients.

OBJECTIVE: Neprilysin (neutral endopeptidase, 3:4:24:11, CD10) (NEP) is a Zn metallopeptidase linked to controlling inflammation through the degradation of neuropeptides involved in neurogenic inflammation of chronic rheumatic diseases. The aim of our study was to evaluate circulating activity and cellular expression of NEP in the plasma of 58 children with juvenile idiopathic arthritis (JIA) and 52 controls. In 20 subjects requiring local steroid injection, NEP was measured in synovial fluid. METHODS: Plasma and synovial NEP were evaluated using a fluorimetric technique. Neprilysin, expressed as the antigen CD10, was determined on circulating and synovial fluid cells as mean fluorescence intensity (MFI) and as percentage of positive cells by two-color immunofluorescence. RESULTS: Circulating NEP levels were lower in JIA patients than in controls (42.0+/-16.6 vs 76.5+/-24 pmol/ml per min, P<0.001), while synovial fluid NEP values were higher than circulating levels (241.4+/-86.2 vs 40+/-15.3 pmol/ml per min, P<0.001). In monocytes, the percentage of CD10-positive circulating cells and the MFI in JIA were lower than in controls (11.6+/-5.2% vs 41.4+/-13%, P<0.001 and 18.1+/-7.5 vs 31.2+/-5.4, P<0.05, respectively). On synovial monocytes, the percentage of CD10-positive cells and the MFI were higher than on circulating monocytes (35.2+/-14.6% vs 9.1+/-2.4%, P<0.001 and 66.4+/-5.4 vs 22.8+/-14.7, P<0.001, respectively). CONCLUSIONS: The downregulation of CD10 expression in monocytes and the reduction in NEP activity may be linked to the enzyme's role in the control of peptides involved in the inflammation. The increased levels of NEP, MFI, and CD10-positive monocytes in synovial fluid, even though in plasma, might reflect a reactive effort to control synovial proliferation.

Arthritis, Juvenile↗
PubMed2004

Lack of association between the HLA-DRB1 locus and post-streptococcal reactive arthritis and acute rheumatic fever in Italian children.

OBJECTIVE: Post-streptococcal reactive arthritis (PSReA) may be a variant of acute rheumatic fever (ARF), but there still is debate on the relationship between the 2 entities. Possible associations with HLA class II antigens of PSReA (DRB1*01) and ARF (DRB1*16) were described previously in white Americans. To confirm these findings, we studied DRB1 alleles in a group of Italian children with PSReA and ARF. METHODS: We performed low-resolution HLA-DRB1 typing by a sequence-specific primer polymerase chain reaction method in 33 children with PSReA and 25 children with ARF. We also compared the DRB1 genotypes of our patients with 200 normal subjects from the same geographic area and typed in the same laboratory with the same methods. RESULTS: The allele distributions at the DRB1 locus observed in PSReA patients, ARF patients, and controls were not significantly different from each other (chi-square test with small numbers, P = .65). The positivity for each of the 13 HLA-DRB1 alleles was compared in disease groups (PSReA and ARF) and controls, and failed to show any significant association. Comparisons of the frequency of the DRB1*01 allele among PSReA, ARF, and controls did not show any statistical differences. No significant difference in the frequency of DRB1*16 was present between ARF vs the control group, between ARF vs PSReA, and in PSReA patients when compared with controls. CONCLUSIONS: Our data do not confirm in Italian patients the previously reported associations of DRB1*01 and DRB1*16 with PSReA and ARF, respectively.

Acute Disease↗
PubMed2004

Osteoprotegerin (OPG)/RANK-L system in juvenile idiopathic arthritis: is there a potential modulating role for OPG/RANK-L in bone injury?

OBJECTIVE: To evaluate serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kB-ligand (RANK-L) in patients with juvenile idiopathic arthritis (JIA); to correlate these values with disease activity variables, radiological bone damage, and bone mass; and to correlate OPG gene polymorphisms with bone mass. METHODS: Eighty-four patients (66 girls and 18 boys) with JIA and 40 sex and age-matched controls were enrolled. Serum OPG and RANK-L were measured using an enzyme-linked immunosorbent assay. OPG genotyping was performed by polymerase chain reaction. RESULTS: Patients with JIA had significantly higher levels of serum OPG than controls (p = 0.001) and lower levels of RANK-L in comparison with controls (p = 0.0003). The OPG/RANK-L ratio in patients was higher than in controls (p = 0.004). No significant correlations were found between disease duration, erythrocyte sedimentation rate, and C-reactive protein values with either OPG or RANK-L serum levels. A significant difference in serum OPG levels (but not in RANK-L) was found between patients with and without erosions (p = 0.008). No correlation was found between OPG and RANK-L levels and bone mass (DXA Z scores). A higher prevalence of OPG CC genotype was found in both patients (65.4%) and controls (82.5%) (p = 0.006). Subjects with CC genotype had a higher lumbar spine bone mineral density (LS-BMD). CONCLUSION: We evaluated for the first time levels of OPG and RANK-L in children with JIA. The higher OPG/RANK-L ratio in JIA might be the result of a compensatory production of OPG. The presence of the T allele of the OPG gene appears to be associated with low BMD.

Arthritis, Juvenile↗
PubMed2004

Gender and ethnic origin have no effect on longterm outcome of childhood-onset systemic lupus erythematosus.

OBJECTIVE: To investigate the associations of gender and ethnic origin with longterm outcome in childhood-onset systemic lupus erythematosus (SLE). METHODS: The study cohort consisted of 51 patients (13 males and 38 females) with childhood-onset SLE followed for > or = 5 years at the British Columbia Children's Hospital in Vancouver. Fifteen patients were Caucasian, 14 Chinese, 9 East Indian, and 13 patients were of other ethnic backgrounds: none was African-American or Hispanic. Outcome measures assessed retrospectively included Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score (SDI), SLE-related death, need for dialysis or renal transplantation, and use of intensive immunosuppressive therapy. A SDI > or = 2 was assigned as poor outcome. RESULTS: The median age at diagnosis was 10.8 years and the median duration of followup was 7.2 years. Five-year survival was 100%; 10-year survival was 85.7% (12/14 patients). The median SDI score at last followup was 2.0 (range 0-9); 2.0 for male, 1.5 for female; 2.0 for Caucasian and 2.03 for non-Caucasian patients. Twenty-six out of 51 patients (51%) had poor outcome (SDI score > 2). Three female patients required dialysis: 2 had subsequent renal transplants. Thirty patients received intensive immunosuppressive therapy. The SDI scores, mortality, and need for intensive immunosuppressive therapy were not influenced by either gender or ethnic origin. CONCLUSION: The median SDI score was high for this cohort with childhood-onset SLE. In contrast to other published data, no association of male gender and/or non-Caucasian ethnicity with poor outcome was found in our study cohort.

Age of Onset↗
PubMed2003

Primary Sjögren syndrome in the paediatric age: a multicentre survey.

UNLABELLED: Primary Sjögren syndrome (SS) is very rare in childhood. We collected a series of primary paediatric SS cases from different centres. A data collection form was prepared and sent to rheumatologists who were willing to participate. Data on 40 cases of primary SS with onset before the 16th birthday were collected. Almost all patients (35/40) were females, age at onset varied from 9.3 to 12.4 years (mean 10.7 years). Signs and symptoms at disease onset were mainly recurrent parotid swelling followed by sicca symptoms. Abnormal laboratory tests were found in the majority of cases. Regarding treatment, 22 patients were treated at some time with oral corticosteroids, seven with non-steroidal anti-inflammatory drugs, and five with hydroxychloroquine; two patients needed cyclosporine and one cyclophosphamide. Follow-up varied from 0 to 7.5 years from onset, without major complications in the majority of patients. CONCLUSION: recurrent parotid swelling is a common feature of primary Sjögren syndrome in childhood and often occurs as a presenting feature. Sicca symptoms may be rarer.

Child↗