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Anti-Ro(SS-A) 52 kDa and 60 kDa specificities in undifferentiated connective tissue disease
No full textAutoantibodies to Ro(SS-A) may recognize two different polypeptides, of 52 kDa and 60 kDa, respectively. We used an ELISA with purified human recombinant antigens to conduct a detailed analysis of the specificities of anti-Ro(SS-A) antibodies from 170 patients with definite diagnoses (systemic lupus erythematosus [SLE], n = 55; primary Sjogren's syndrome [PSS], n = 39; systemic sclerosis, n= 9; rheumatoid arthritis [RA], n = 10) or undifferentiated connective tissue disease (UCTD, n = 57). Most of the patients with SLE or PSS had both anti-52 kDa and -60 antibodies; isolated anti-60 kDa antibodies were found in 13% of the SLE patients and in none of the PSS patients, whereas high titers of anti-52 kDa were more common in the PSS than in the SLE patients. In the UCTD patients, the anti-Ro(SS-A) profile showed no significant correlations with clinical features but was associated with the clinical outcome. Over the mean follow-up of five years, definite SLE developed in four of the five UCTD patients with isolated anti-60 kDa vs only one of the remaining 52 patients (P < 0.0001); progression to PSS was seen in seven of the 34 patients with both anti-52 kDa and anti-60 kDa vs none of the remaining 23 patients (P= 0.03); none of the 12 patients with isolated anti-52 kDa developed a definite connective tissue disease. Conclusion. Our study suggests that analysis of anti-Ro(SS-A) specificity may provide useful information far predicting the course of UCTD
Rheumatoid arthritis and renal light-chain deposition disease : long-term effectiveness of TNF-a blockade with etanercept
No full textA 68-year-old woman diagnosed with erosive rheumatoid arthritis (RA) was treated with intramuscular methotrexate 15 mg weekly and oral prednisone 5 mg daily. A favorable outcome of 6 years was followed by RA flare and nephrotic syndrome (NS). Renal biopsy revealed non-amyloid light-chain deposition disease. Laboratory analysis and bone marrow biopsy excluded monoclonal protein and plasma cell dyscrasia. Addition of subcutaneous etanercept, 25 mg twice weekly allowed rapid control of both arthritis and NS. To date, after over 7-year follow-up, RA is in clinical remission, 24-h albuminuria is consistently below 0.5 g, and serum creatinine is 0.9 mg/dl
Autoantibodies to RNA-polymerases in Italian patients with systemic sclerosis
No full textObjective To assess the frequency and clinical correlates of the systemic sclerosis-related autoantibodies to RNA polymerases in Italian patients. Methods Sera from 115 patients with systemic sclerosis (SSc) and 10 patients with systemic sclerosis-overlap syndromes recruited from a single center in northern Italy were investigated for antibodies to RNA polymerase I, II, and III by means of immunoprecipitation using S-35-labeled HeLa cell antigen extract. Twenty-five normal volunteers and 91 patients with different connective tissue diseases were studied as a control group. Results Antibodies to RNA-polymerases were found in 14/115 SSc patients (12.1%). None of the normal controls and none of the patients with other connective tissue diseases, including overlap syndromes, were positive. Antibodies reacting with RNA-polymerase I and III (+/- RNA-polymerase II) were found in 9/115 patients (7.8%) and were mutually exclusive with respect to other scleroderma-related autoantibodies. Isolated anti-RNA polymerase H. reactivity was found in 5 patients and was associated with anti-topoisomerase I antibodies in 4 cases. Anti-RNA-polymerase I and III antibodies were associated with diffuse cutaneous involvement and male gender Only two patients from our series had scleroderma renal crisis, and one of them had anti-RNA polymerase antibodies. Conclusions Anti-RNA-polymerase antibodies appear to be less frequent in Italian patients than in Caucasian patients from the United Kingdom or USA. This might be associated with the lower frequency of scleroderma renal crisis
Long term treatment of rheumatoid arthritis with rituximab.
Get PDFB cells play an important role in the pathogenesis of rheumatoid arthritis (RA). Rituximab is a chimeric monoclonal antibody that depletes B-cells by binding to the CD20 surface antigen that has been approved for the treatment of RA. Its efficacy has been clearly demonstrated by different clinical trials and, recently, in long-term observational studies. The use of rituximab in clinical practice has highlighted its efficacy and safety over more than 5 years of treatment, as well as to try to understand the timing for retreatment of patients relapsing after a good initial response
Serious infections during anti-TNFalpha treatment in rheumatoid arthritis patients
No full textThe objective was to estimate the incidence of serious infections in the patients treated with anti-TNFalpha agents for rheumatoid arthritis (RA) recorded in the Lombardy Rheumatology Network (LORHEN) registry. The study inclusion criteria were met by 1064 of the 1114 patients with long-standing RA, 519 treated with infliximab, 303 with adalimumab, and 242 with etanercept; their mean age was 55.8 years and the mean duration of RA 9.4 years. Seventy-three patients (6.9%) experienced a total of 74 serious infections, an incidence rate for all treatment courses of 35.9 per 1000 patient-years (95% confidence interval [95% CI] 27.66-44.13). Most were lower respiratory tract (34.2%) or skin and soft tissue infections (20.5%). Of the 1064 patients, the 790 treated with anti-TNFalpha after March 2002 underwent screening tests for LTBI; five patients developed active tuberculosis. Three patients died of septic shock. The type of anti-TNFalpha agent did not seem to affect the incidence or site of the infections. Both univariate and multivariate analyses identified age at the start of anti-TNFalpha treatment (p=0.008), baseline erythrocyte sedimentation rate ([ESR] p=0.014), and the concomitant use of corticosteroids (p=0.029) as significant predictors of infections. There was no statistically significant difference in risk between the anti-TNFalpha agent
Infections and treatment of patients with rheumatic diseases
No full textGlucocorticoids (GCs) have many complex quantitative and qualitative immunosuppressive effects which induce cellular immunodeficiency and Increase host susceptibility to various viral, bacterial, fungal and parasitic infections. As cortisol secretion is inadequate in chronic immune/inflammatory conditions, and current therapies have the aim of providing adequate (low) compensatory doses, the timing of GC administration, such as during the nocturnal turning-on phase of tumour necrosis factor (TNF) secretion, can be extremely important. The use of the lowest possible GC dose, at night, and for the shortest possible time should therefore greatly reduce the risk of infections. Infection is a major comorbidity in rheumatoid arthritis (RA), and conventional disease-modifying anti.-rheumatic drugs (DMARDs) can increase the risk of their occurrence, including tuberculosis. TNF-alpha plays a key role in the pathogenesis of RA, and the data concerning infections in RA patients treated with anti-TNF agents are controversial. Patients and physicians should vigilantly monitor for signs of infection when using anti-TNF agents. Recombinant gene technologies now make it possible to produce protein drugs that are almost identical to naturally occurring human polypeptides, including antibody (Ab) constructs; unfortunately, all human biological agents are potentially immunogenic. An increasing number of recent studies have demonstrated the safety of influenza and pneumococcal vaccines administered to patients with systemic lupus erythematosus (SLE) or RA. These vaccinations are generally immunogenic (i.e., capable of inducing a protective level of specific antibodies) but may not induce an adequate response in a substantial proportion of patients
Safety of tumor necrosis factor α blockers in hepatitis B virus occult carriers (hepatitis B surface antigen negative/anti-hepatitis B core antigen positive) with rheumatic diseases
Get PDFOBJECTIVE:
To assess the safety of anti-tumor necrosis factor alpha (anti-TNFalpha) therapy on the course of hepatitis B virus (HBV) infection in carriers of antibodies to hepatitis B core antigen (anti-HBc) affected by chronic inflammatory arthropathies.
METHODS:
From January 2001 to December 2008, HBV markers were determined before the first administration of anti-TNFalpha agents in all 732 patients affected by inflammatory arthropathies treated with anti-TNFalpha at 2 outpatient rheumatologic clinics in Northern Italy. Anti-HBc-positive patients were prospectively evaluated and HBV markers and HBV DNA were assessed every 6 months, in case of aminotransferase elevation, and at the end of the study.
RESULTS:
At the time of recruitment, 72 patients were anti-HBc carriers, 5 of whom were positive for hepatitis B surface antigen (HBsAg) and not included in the study. The ratio of men:women was 26:41 and the mean +/- SD followup was 42.52 +/- 21.33 months. Of the patients, 25 were treated with infliximab, 23 with etanercept, and 19 with adalimumab. Fifty-one patients were treated also with methotrexate, 52 with nonsteroidal antiinflammatory drugs, and 43 with prednisone (3 with a dosage >7.5 mg/day). All anti-HBc patients were HBV DNA negative at the first observation. During followup, no patient presented HBV reactivation with viral load increase and no patient became HBsAg positive.
CONCLUSION:
Anti-HBc positivity in HBsAg-negative patients is a sign of previous HBV infection and does not indicate chronic hepatitis. In these patients, anti-TNFalpha therapy appears to be quite safe, as no HBV reactivation was found in our study. Nevertheless, careful monitoring is necessary
Anti-tumor necrosis factor-α response in rheumatoid arthritis is associated with an increase in serum soluble CD30
No full textOBJECTIVE:
Patients with rheumatoid arthritis (RA) display high serum concentrations of soluble CD30 (sCD30), which correlate with counter-regulatory activity of CD30+ T cells in the inflamed joint. To verify the contribution of this T cell subset to disease remission, sCD30 levels were analyzed longitudinally in patients with active RA following infliximab therapy.
METHODS:
Infliximab plus methotrexate were started in 39 patients with active RA, while 20 patients with inactive disease, controlled by stable doses of methotrexate, acted as controls. Serial evaluations of sCD30 concentrations and disease activity indexes were performed throughout 38 weeks.
RESULTS:
sCD30 levels were higher in patients than in healthy controls. Rapid infliximab-induced decrease in disease activity was associated with an overall increase of sCD30 levels. In contrast, levels remained stable in controls. An inverse correlation between sCD30 levels and Disease Activity Score 28 was observed from the 22nd week of infliximab treatment. Analysis of sCD30 levels according to American College of Rheumatology response showed, after an initial general enhancement of sCD30 concentrations, a persistent increase of sCD30 in responders, but not in nonresponders.
CONCLUSION:
sCD30 serum levels are enhanced by tumor necrosis factor-a (TNF-a) blockade in patients with active RA and inversely correlated with disease activity, but only after some weeks of treatment. Of interest, a sustained increase of sCD30 is present only in subjects with evidence of persistent clinical response to anti-TNF-alpha. As sCD30 serum levels mirror antiinflammatory activity of joint T cells, the present data may suggest a role of synovial counter-regulatory CD30+ T cells in the induction of infliximab-mediated remission in RA
Body iron status in critically ill patients: significance of serum ferritin.
No full textSerial measurements of blood haemoglobin, serum iron, serum transferrin, total iron-binding capacity, transferrin per cent saturation and serum ferritin were determined in 51 post-operative critically ill patients to investigate body iron status in severely stressed patients. The results showed decreased blood haemoglobin, serum iron, serum transferrin and transferrin saturation compared to an increase in serum ferritin levels. These results indicate that there is inadequate availability of iron to tissues (secondary to rearrangement of body iron to the advantage of the iron storage compartment), which is often present in severely critically ill patients. A positive correlation was found between the initial (ferritin) levels and SAPS (r = 0.41, p less than 0.01). In addition, the increase of ferritin concentration parallels a worsening of the clinical status in severely ill patients. This is due to enhanced release by the macrophage system. From this, we consider serum ferritin as an acute-phase protein and a useful marker of the severity of the clinical status. It appears to be useful in predicting the patient's outcome, but is not reliable in evaluating iron stores in stressed patients
Perivascular fibrosis and IgG4-related disease: a case report
Get PDFImmunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibroinflammatory condition which can potentially involve any organ. Some characteristic histopathologic features with lymphoplasmacytic infiltrate, an increased number of IgG4+ cells, storiform fibrosis and obliterative phlebitis are the mainstay for diagnosis. Serum IgG4 levels often increase. We report the case of a patient with perivascular fibrotic lesions involving the aortic arch and the splenic hilum, with a surgical biopsy-proven diagnosis of IgG4-related disease. The patient is now undergoing a low-dose corticosteroid maintenance therapy without evidence of new localizations of the disease. This case highlights the need for increasing awareness and recognition of this new, emerging clinical condition
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