Diagnostic value of anti-cyclic citrullinated peptide antibodies to detect rheumatoid arthritis in patients with Sjögren's syndrome.
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Adult↗
Biomedical subjects
J P van de Merwe
Publications and source records attributed to J P van de Merwe.
A hampered chemoattractant-induced cytoskeletal rearrangement in granulocytes of patients with unexplained severe chronic and relapsing infections of the upper and lower airways. In vitro restoration by G-CSF exposure.
Granulocytes play a major role in host defense against bacterial infections. Severe inborn defects in granulocyte function are associated with fulminant bacterial infections in early childhood. Subtle disturbances in granulocyte function might contribute to an enhanced susceptibility to bacterial infections in adulthood. We investigated chemoattractant (N-formyl-methionyl-leucyl-phenylalanine, fMLP and casein) induced cytoskeletal rearrangements (polarization) of blood granulocytes in 77 adults with chronic and recurrent therapy-resistant infections of the upper and lower airways. These infections could not be explained by B- and/or T-cell defects or local anatomic abnormalities. Besides polarization, chemotaxis of blood granulocytes was measured in 33 patients, as well as granulocyte superoxide production in eight patients. The chemoattractant-induced cytoskeletal rearrangement in patient blood granulocytes was significantly lower as compared to healthy control values with both fMLP and casein as stimuli. About two-thirds of the patients showed a defective polarization response to fMLP. Granulocyte colony-stimulating factor (G-CSF) when added in vitro corrected the defective polarization responses; responses in the normal range were not enhanced. The chemotactic motility of patient blood granulocytes was also slightly, but significantly lowered. However, it did not correlate to the lowered polarization. Granulocyte superoxide production was comparable in patients and in healthy controls. Our data thus show that subtle abnormalities in chemoattractant-induced cytoskeletal and motile function of blood granulocytes are frequent in patients with severe therapy-refractory bacterial infections of the upper and lower airways.
Adult↗
Cost analysis of regular and filgrastim treatment in patients with refractory chronic rhinosinusitis.
In this double blind randomized placebo controlled clinical trial of filgrastim in chronic sinusitus, we analyzed costs of a 24-week interval in which filgrastim was administered. Since we hypothesized that the scheduled preventive visits within the trial might cause savings as compared to the regular situation in which these patients have a strong tendency to visit the outpatient clinic immediately in case of complications, direct medical costs within the trial were also compared to costs of regular treatment. The difference in costs between both trial groups was driven by the filgrastim costs (Euro 5108). If filgrastim costs were left out of consideration, no significant difference in direct medical costs remained between the filgrastim and placebo groups (Euro 2904 and Euro 2765, respectively). Indirect medical costs also showed no significant differences. Within a regular situation, costs of a 24-week interval were Euro 896. As filgrastim treatment had already been shown not to improve the quality of life, its cost-effectiveness in these patients can only be favourable in case of major clinical improvements. Furthermore, scheduled preventive visits in chronic sinusitis patients appear not to cause savings as compared to the situation in which patients are only seen in case of recurrences.
Adult↗
Retinal vasculitis occurring with common variable immunodeficiency syndrome.
PURPOSE: To report severe retinal vasculitis causing decreased vision in three patients with the common variable immunodeficiency syndrome. METHOD: Case report. Three patients with common variable immunodeficiency syndrome developed decreased vision secondary to retinal vasculitis. Fluorescein angiography was performed in all three patients. Peribulbar injections were given in one patient, and two patients were treated with oral steroids and cyclosporin. RESULTS: All three patients were young and had classic common variable immunodeficiency syndrome. Bilateral retinal vasculitis and diffuse retinal edema were present in all three patients, and two patients had retinal neovascularization in the absence of ischemia. No evidence of intraocular infection was present, and none was detected systematically. Visual acuity decreased in five of the six eyes and was responsive to treatment in only one patient (both eyes). CONCLUSION: Retinal vasculitis may be another autoimmune manifestation of common variable immunodeficiency syndrome.
Capillary Permeability↗
Two different types of sialoadenitis in the NOD- and MRL/lpr mouse models for Sjögren's syndrome: a differential role for dendritic cells in the initiation of sialoadenitis?
Sjögren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal glands. In these glands, focal lymphocytic infiltrates develop. Little is known about the initiation of this autoimmune disease. Antigen-presenting cells (APC) such as dendritic cells (DC) can play a role in the initiation of autoimmunity. To date, no data on the presence of DC in Sjögren's syndrome are available. Several mouse strains, the nonobese diabetic (NOD) and the MRL/Ipr mouse, can be used as models for Sjögren's syndrome. We compared the development of sialoadenitis in the submandibular glands (SMG) of NOD and MRL/Ipr mice with particular focus on the presence of APC. DC, macrophages, T cells, and B cells in the SMG were studied by means of immunohistochemistry, after which positively stained cells were quantified. NOD-severe combined immunodeficiency (SCID) mice were used to study the presence of APC in the SMG in the absence of lymphocytes. Before lymphocytic infiltration, increased numbers of DC were detected in the SMG of NOD mice compared with those numbers in control mice and MRL/Ipr mice, which suggests that DC play a role in the initiation of sialoadenitis in NOD mice. In the SMG of NOD mice, lymphocytic infiltrates organized in time. In MRL/Ipr mice, however, lymphocytic infiltrates were already organized at the time of appearance. This organization was lost over time. In conclusion, two types of sialoadenitis are described in two mouse models for Sjögren's syndrome. Differences exist with regard to early events that may lead to the development of sialoadenitis and to the composition and organization of inflammatory infiltrates. It is possible that different types of sialoadenitis also exist in humans and that the pathogenetic process in both the early and late phases of the autoimmune reaction differs among patients.
Animals↗
Professional antigen presenting cells in minor salivary glands in Sjögren's syndrome: potential contribution to the histopathological diagnosis?
Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the salivary and lacrimal glands. We have shown that dendritic cells (DC) infiltrate the submandibular gland of the nonobese diabetic (NOD) mouse, a mouse model for Sjögren's syndrome, before lymphocytic infiltration, suggesting that these antigen-presenting cells (APC) may play a role in the initiation of Sjögren's syndrome. In later stages, DC and macrophages also form an important part of the infiltrate of the NOD sialoadenitis. To find out if DC and macrophages form part of the infiltrate in Sjögren's syndrome as well, and to determine whether they may be useful in the histopathological diagnosis of Sjögren's syndrome, we studied their presence in minor salivary glands (MSG) of patients with Sjögren's syndrome and patients with focal lymphocytic sialoadenitis (FLS), but without clinical or serological criteria of Sjögren's syndrome. Immunohistochemistry was applied, followed by semiquantitative analysis. DC and macrophages were present in all MSG; however, there were clear differences in marker expression between Sjögren's syndrome and FLS, on the one hand, and control tissue, on the other hand. CD1a+ DC and RFD9+ macrophages were mainly observed in MSG in which a focal lymphocytic infiltrate was present. In fact, the diffuse presence of single CD1a+ DC and RFD9+ macrophages correlated closely with the presence of a focal lymphocytic infiltrate in the MSG. This indicates that these cells could be of help during the evaluation of a MSG. Because the detection of APC is technically less cumbersome than a focal score, this parameter may perhaps replace the focal score in the histopathological diagnosis of Sjögren's syndrome. This study therefore prompts further investigation focusing on the presence of CD1a+ and RFD9+ cells in the MSG of a large cohort of patients.
Adult↗
The effect of intranasal and inhaled corticosteroids in healthy volunteers on the number of circulating lymphocytes and lymphocyte subsets.
BACKGROUND: There has been an increasing interest in the potential systemic effects of inhaled corticosteroids. METHODS: The effect of locally inhaled corticosteroids in the nose and lung on blood lymphocytes was measured in two studies. In the first study, budesonide (BUD) (200 and 800 microg), fluticasone propionate (FP) (200 and 800 microg), and placebo were administered in the nose, and BUD (1600 microg) and FP (1500 microg) were inhaled into the lungs in a blinded, randomized fashion by 12 healthy volunteers. Blood samples were taken before and 4 h after the administration of the drug, and total lymphocyte count and different subpopulations were determined. In the second study, 15 healthy volunteers were randomized to BUD (1600 microg), FP (1600 microg), or placebo inhaled into the lungs. Blood samples were taken before and 4, 8, 24, 48, and 148 h (=7 days) after inhalation of the medication. RESULTS: Neither the nasal applications nor the inhalation of FP (1500 microg/1600 microg) showed significant differences in total lymphocyte count or different subpopulations between baseline and 4 h after the administration. In both studies, a significant reduction was found in the total lymphocyte count, B cells, T cells, and the CD4+ and the CD8+ fractions 4 h after application of BUD 1600 microg. CONCLUSIONS: Nasal application of BUD or FP in doses up to 800 microg do not induce lymphopenia. BUD 1600 microg inhalation in the lung reduces lymphocytes and their subfractions. Further studies have to be done to determine whether the results obtained in this study in healthy volunteers will also be found in patients with diseased mucosa and whether there is any correlation with adverse effects such as growth inhibition or osteoporosis.
Administration, Inhalation↗
Serological markers to differentiate between ulcerative colitis and Crohn's disease.
AIM: To assess prospectively the value of three serological tests for differentiating between ulcerative colitis and Crohn's disease, used either alone or combined. METHODS: Coded serum samples from 63 patients with ulcerative colitis and 67 patients with Crohn's disease were analysed. Detection assays for the presence of perinuclear antineutrophil cytoplasmic antibodies (pANCA), serum agglutinating antibodies to anaerobic coccoid rods, and specific IgG antibodies against a Kd-45/48 immunological crossreactive mycobacterial antigen complex (ImCrAC) were studied. Sensitivity, specificity, pre- and post-test probabilities, likelihood ratios, and predictive values of each of these serological tests were determined. RESULTS: The sensitivity and specificity of the pANCA test for the diagnosis of ulcerative colitis were 61 and 79%, respectively. The serum agglutination test for anaerobic coccoid rods had a sensitivity of 42% and a specificity of 89% for a diagnosis of Crohn's disease. The sensitivity of specific IgG antibodies against Kd-45/48 ImCrAC in diagnosing Crohn's disease was 70% and specificity 60%. Although 100% specificity was achieved by combining all three tests in a small group of patients with Crohn's disease (n = 20), combining two or more tests had no additive clinical value. No correlation was found between the presence of any one of these antibodies and disease activity, duration, or localisation of disease. Surgery or medical treatment did not influence the presence of antibodies or the antibody titre. CONCLUSIONS: The value of these tests in the differential diagnosis between ulcerative colitis and Crohn's disease is limited, but the high predictive values and specificities of different tests for both diseases suggest that these tests may be of help in studying disease heterogeneity and in defining different subgroups of patients with different pathogenesis.
Antibodies, Antineutrophil Cytoplasmic↗
Hemiparkinsonism in a patient with primary Sjögren's syndrome. A case report and a review of the literature.
A 55-year-old woman presented with hemiparkinsonism on the left side. Clinical features suggested primary Sjögren's syndrome. Eye tests and a salivary gland biopsy confirmed this diagnosis. Magnetic resonance imaging of the brain showed distinct linear lesions of increased intensity on the T2-weighted images in the right striatum and globus pallidum. Treatment with prednisone and azathioprine did not give any improvement of the neurological symptoms. To date, hemiparkinsonism in association with primary Sjögren's syndrome has not been reported.
Azathioprine↗
CD5+ B lymphocytes and other lymphocyte subsets in primary Sjögren's syndrome.
CD5+ B cells and other lymphocyte subsets were analyzed by flow cytometry in patients with primary Sjögren's syndrome (pSS), in healthy subjects (HS) and in patients with various control diseases. When compared with HS, patients with pSS were found to have similar levels of CD5+ B cells and decreased levels of CD8+ T cells (P = 0.0003). When compared with patients with various other diseases, however, the number of CD5+ B cells in pSS was more than twice as high (P = 0.0002), whereas no difference was found between numbers of CD8+ T cells. When the number of CD5+ B cells was expressed as a percentage of total B cells, the results obtained were similar to those with absolute numbers. Determination of lymphocyte subsets may be used as a diagnostic aid for Sjögren's syndrome in selected patients with suspected immunological diseases of unknown type.
Adolescent↗
Chronic arthritis induced in rats by cell wall fragments of Eubacterium species from the human intestinal flora.
To investigate arthritis-inducing properties of Eubacterium species, which are major residents of the human intestinal flora, cell wall fragments (CWF) of several Eubacterium strains were prepared and tested in an animal model. After a single intraperitoneal injection in the rat, CWF of E. aerofaciens, E. contortum, and E. lentum induced a chronic polyarthritis. E. limosum and E. tortuosum CWF induced an acute self-limiting joint inflammation, whereas E. rectale CWF failed to do so. The rhamnose contents of the isolated CWF were not related to their arthritis-inducing properties. Paradoxically, the sensitivity of CWF to lysozyme digestion, which is regarded as a parameter for the clearance of CWF in tissues, appeared to be positively correlated with the ability of Eubacterium CWF to induce chronic joint inflammation. Our findings show the diversity in arthritis-inducing properties among different species of the anaerobic genus Eubacterium and underline the importance of the anaerobic intestinal flora in the induction of joint inflammation.
Animals↗
Serum antibodies to peptidoglycan-polysaccharide complexes from the anaerobic intestinal flora in patients with Crohn's disease.
Soluble peptidoglycan-polysaccharide complexes (PPC) isolated from feces of a healthy subject shared antigens with 22 out of 40 anaerobic intestinal bacteria and, therefore, these could be considered as flora derived. IgG, IgA and IgM antibodies against PPC were found in sera from healthy subjects, patients with Crohn's disease (CD) and other patients. In sera of CD patients with agglutinating antibodies to 4 anaerobic intestinal bacteria (used as an aid for diagnosis of CD) IgG and IgA levels to PPC were higher than in CD patients without these antibodies.
Antibodies, Bacterial↗
Cell wall fragments from major residents of the human intestinal flora induce chronic arthritis in rats.
To investigate the involvement of human intestinal flora in joint inflammation, cell wall fragments of 9 anaerobic gram positive bacteria of the human fecal flora were prepared and tested for arthropathic properties in the rat. A single intraperitoneal injection of cell wall fragments from Eubacterium aerofaciens or Bifidobacterium species induced persistent chronic arthritis, in contrast to those from Eubacterium rectale, Clostridium species and Lactobacillus leichmanii. The results show that cell wall fragments of major residents from the human fecal flora can induce chronic arthritis in the rat and support the hypothesis that normal human intestinal flora plays a role in the induction of arthritis in man.
Animals↗
Induction of chronic arthritis in rats by cell wall fragments of anaerobic coccoid rods isolated from the faecal flora of patients with Crohn's disease.
Crohn's disease and ulcerative colitis are accompanied by seronegative arthritis in about one fifth of the cases. In the present study, cell wall fragments from major residents such as Eubacterium, Coprococcus and Peptostreptococcus species, isolated from the faecal flora of patients with Crohn's disease, were tested for properties to induce chronic arthritis in Lewis rats. Cell wall fragments from Eubacterium contortum strains Me44 and Me47 were found to induce chronic arthritis; Peptostreptococcus productus strain C 18 cell wall fragments induced acute self-limiting arthritis. Coprococcus comes strain Me46 cell walls, on the other hand, were found to be lethal to the majority of rats inoculated, whereas those which survived did not develop acute or chronic arthritis. The results indicate that intraperitoneal injection of a single dose of cell wall fragments from bacteria that are major residents of the human anaerobic faecal flora can induce chronic inflammatory joint disease in the rat.
Animals↗
Antibodies to Coprococcus comes in sera of patients with Crohn's disease. Isolation and purification of the agglutinating antigen tested with an ELISA technique.
Previous studies showed that agglutinating antibodies to Coprococcus comes, an anaerobic Gram-positive coccoid rod isolated from the faecal flora of patients with Crohn's disease, are more frequently found in sera of Crohn patients than in ulcerative colitis patients and healthy subjects. Isolation of the antigen may be useful in developing a more sensitive and specific diagnostic test. The present study describes first a method to improve the presentation of the relevant agglutinating antigen by the bacterium and second, the purification by column chromatography of a relatively crude antigen extract of C. comes described previously by Hazenberg et al. (1). Comparative results with the agglutination reactions and ELISA technique of extensive series of patients with Crohn's disease and healthy subjects have shown that the agglutinating antigen of C. comes has been isolated. Although the present ELISA technique cannot replace the simple and reliable agglutination reaction for screening purposes, the purified antigen will allow further immunological studies and it is to be hoped that a deeper insight into pathogenesis of the disease will be gained.
Agglutination Tests↗
Culturing and extraction of Coprococcus comes, absorption of serumagglutinins by soluble fractions and relation between agglutinins and antibodies in sera of patients with Crohn's disease.
Agglutinating antibodies to Coprococcus comes and three other obligately anaerobic coccoid rods from the intestinal flora are used in the diagnosis of Crohn's disease. Further studies on the pathogenetic role as well as the development of more sensitive and specific methods for detecting antibodies require extraction of the antigen fractions. Culturing methods to obtain C. comes with optimal antigen presentation and isolation of soluble antigen fractions were therefore developed. Hot water extraction of whole cells and subsequent removal of proteins with trichloroacetic acid provided a fraction that absorbed serum agglutinins, was useful for an enzyme-linked immunosorbent assay and induced agglutinating antibodies in rats.
Agglutination Tests↗
Reversible binding of polymyxin B and neomycin to the solid part of faeces.
Previous studies have shown that polymyxin B and neomycin were bound to the solid part of human faeces. In the present study, the faecal binding of polymyxin B and neomycin was studied, using a wide range of concentrations of drugs and faecal dilutions. Up to 25 mg of polymyxin B and 15 mg of neomycin could bind to 1 g of faeces but the binding was found to be reversible. With faeces of rats it was found that polymyxin B was mainly bound to the non-bacterial part of faeces, whereas neomycin was bound to the bacterial as well as the non-bacterial part. The implications of the reversible binding of antibiotics to intestinal contents for selective decontamination are discussed.
Animals↗
Binding to and antibacterial effect of aztreonam, temocillin, gentamicin and tobramycin on human faeces.
Aztreonam, temocillin, gentamicin and tobramycin were studied for their effect on the human faecal flora in vitro and for their usefulness for selective decontamination (SD) of the gastrointestinal tract. The sensitivities of the obligately anaerobic flora and the Gram-negative facultatively anaerobic bacteria were determined and the ratio was expressed as SD factor. The high SD factor of the flora from most subjects for aztreonam and tobramycin indicates that the drugs are useful for SD in contrast to temocillin and gentamicin. Binding to and subsequent release of tobramycin from faeces are presumed to facilitate the maintenance of adequate concentrations in the intestine despite the discontinuous intake.
Aztreonam↗