IntroductionConventional or biologic disease-modifying anti-rheumatic drugs (DMARDs) are the mainstay of treatment for systemic autoimmune disease (SAD). Infectious complications are a major concern in their use.ObjectiveTo evaluate the clinical benefit of sublingual mucosal polybacterial vaccines (MV130 and MV140), used to prevent recurrent respiratory and urinary tract infections, in patients with SAD and secondary recurrent infections following conventional or biologic DMARDs.MethodsAn observational study in SAD patients with recurrent respiratory tract infections (RRTI) and/or recurrent urinary tract infections (RUTI) was carried out. All patients underwent mucosal (sublingual) vaccination with MV130 for RRTI or with MV140 for RUTI daily for 3 months. Clinical evaluation was assessed during 12 months of follow-up after the first dose, i.e., 3 months under treatment and 9 months once discontinued, and compared with the previous year.ResultsForty-one out of 55 patients completed 1-year follow-up. All patients were on either conventional or biologic DMARDs. A significant decrease in the frequency of RUTI (p<0.001), lower respiratory tract infections (LRTI) (p=0.009) and upper respiratory tract infections (URTI) (p=0.006) at 12-mo with respect to the previous year was observed. Antibiotic prescriptions and unscheduled medical visits decreased significantly (p<0.020) in all groups. Hospitalization rate also declined in patients with RRTI (p=0.019). The clinical benefit demonstrated was concomitant to a significant increase in both anti-S. pneumoniae IgA and IgG antibodies following MV130 vaccination.ConclusionsSublingual polybacterial vaccines prevent recurrent infections in patients with SAD under treatment with immunosuppressant therapies, supporting a broad non-specific anti-infectious effect in these patients.
Systemic lupus erythematosus (SLE) is characterized by autoantibody production of unknown origin. Since T-B cell interaction is a key event to produce antibodies, we investigated this interaction through study of CD69, CD40 ligand (CD40L) and CD23 expression (three very early activation antigens). Peripheral blood mononuclear cells (PBMC) from inactive lupus patients were studied following culture with either medium alone, anti-CD3 monoclonal antibody (mAb), recombinant interleukin-4 (rIL-4) or phorbol myristate acetate (PMA)+/-ionomycin. Analysis of CD23 expression on lupus B cells in basal conditions and after anti-CD3 challenge of PBMC, a reflection of cognate interaction between T and B cells, was clearly defective. Conversely, CD23 expression on lupus B cells following non-cognate T cell signals (rIL-4) was preserved. CD69 and CD40L expression was also impaired in lupus T cells following anti-CD3 challenge. Nonetheless, activation by means of PMA and/or ionomycin was preserved both in T cells (CD69 and CD40L expression) and in B cells (CD23 expression). These results indicate that B cells from inactive lupus patients display a normal early response to direct B-cell stimuli. Conversely, T-dependent B-cell stimuli are clearly defective in SLE patients in remission. These results indicate that T-B cognate interaction related to defective T cell activation located between surface membrane and protein kinase C (PKC)/ionomycin function is an intrinsic characteristic of these patients.
We describe a 67-year-old white woman with a long-standing active rheumatoid arthritis who refused treatment. Chest roentgenograms performed in 2000 revealed a pulmonary nodule in the mid-left lung. Progression of the nodule was followed annually by computerized tomography (CT). In the last CT in 2002, we observed multiple nodules in both lungs in the absence of lymph gland involvement. The patient was operated by video-thoracoscopy to resect one of the pulmonary nodules. Pathological examination of the excised tissue revealed amyloid A-type (AA) amyloidosis. Although pulmonary amyloidosis is rare in patients with systemic AA amyloidosis, we recommend that this possibility be considered when confronted with a patient with these characteristics.
Eleven newly-diagnosed GCA patients were included in a prospective open study and treated with high initial prednisone doses, a quick-tapering CS schedule and weekly oral MTX for two years. It took a mean of 14 weeks to reach a 10 mg/day dose of prednisone and 29.8 weeks until steroid withdrawal. The mean cumulative dose of prednisone was 3.4 g. Two patients relapsed and five developed CS side effects. No serious MTX side effects were observed. Our results suggest that MTX is safe and could be useful in the therapy of GCA.
The study was performed in 78 (23 men, mean age 60-9 years, 95% confidence interval 58-8-63) Spanish patients with RA diagnosed according to the 1987 revised ACR-criteria.5 All patients had received second line therapy. No patient had liver and/ or kidney disease or had taken drugs known to interfere with the metabolic rate of DBQ6 in at least the previous six weeks. The study was approved by the Local Ethical Committee.The control group was composed of 837 healthy subjects (391 men, mean age 26-3 years, 95% CI 25-6-26-9) not taking any drugs.The oxidative phenotype of DBQ was determined by giving a 10 mg Declinax tablet at 22-00 hours. Urine of the following eight hours was collected. DBQ and its main metabolite, 4-OH-DBQ, was measured by chromatography7 and metabolic ratio (MR = excreted DBQ/excreted 4-OH-DBQ) was calculated. Subjects with MR <12 6 (LoglO <1 1) were classified as EM and those with MR >12-6 were classified as PM of DBQ.' Four patients (5 13%) and 42 controls (5 03%) were PM of DBQ (no significant difference). No differences were observed when comparing MR values by gender. When analysing separately EM subjects of both groups (figure), LoglO of MR values were normally distributed (Kolmogorov-Smirnov test) and were significantly lower (p<0-001, U Mann-Whitney's test) in controls (mean = -0-295, SD = 0 427) than in patients (mean = -0-085, SD = 0 388), indicating a higher hydroxylating ability in the control group.No relationship exists between oxidative phenotype of DBQ and the risk of developing RA. Nevertheless, the EM phenotype includes two genotypes: homo and heterozygotes for the dominant-functioning wildtype allele. Heterozygotes carry one of the three existing non-functioning mutant recessive alleles, A, B or D.2 Homozygote EMs tend to have lower values for MR than heterozygote EMs,2 indicating that they are more efficient oxidisers than heterozygote EMs, suggesting a gene-dose effect. Nevertheless, there is a broad overlap of LoglO of MR values between both EM genotypes (figure) that makes it impossible to classify individually EMs as homo or heterozygous only in the basis of their values for MR.Our results suggest that there is an excess of heterozygote EMs patients with RA. The mean age in our control group was much lower than in patients, but age does not influence the metabolic rate of DBQ in otherwise healthy subjects.'" Many patients were taking NSAIDs and/or low dose prednisone when they were phenotyped, but these drugs do not seem to modify the oxidation of DBQ.'We conclude that the possible excess of any recessive-mutant allele(s) of the CYP2D6 gene we have detected among patients with RA should be confirmed by using genotyping procedures to establish which, if any, allele is linked to the risk of RA. Controls in
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