Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
8022761 Identification of autoantibodies to a pancreatic antigen in patients with idiopathic chron 1994 May A serum autoantibody to a pancreatic antigen was identified in patients with idiopathic chronic pancreatitis and Sjögren's syndrome by radioimmunoassay and Western immunoblotting. Antigen from porcine and human pancreas extracts was partially purified using a monoclonal antibody, SP3-1, which recognizes the antigen in duct cells of various exocrine organs. Solid phase radioimmunoassay of the pancreatic antigen showed a positive result in 6 of 20 patients with idiopathic chronic pancreatitis (30%), 3 of 11 patients with Sjögren's syndrome (27%), and 1 of 15 patients with alcoholic chronic pancreatitis (7%). Among seven patients with stone-related chronic pancreatitis, six patients with autoimmune thyroiditis, and 14 normal controls, none showed evidence of autoantibodies to the pancreatic antigen. Western immunoblotting showed that serum antibody commonly reacted with a 60-kD molecule of either porcine or human pancreatic antigen, with which SP3-1 also reacted. These results show the existence of the autoantibodies to pancreas, especially to an antigen expressed in ductal cells of exocrine glands, in idiopathic chronic pancreatitis and Sjögren's syndrome, and suggest the possibility of an autoimmune mechanism in the pathogenesis of idiopathic chronic pancreatitis.
8171386 [Rheumatologic manifestations of chronic myelomonocytic leukemia. Presentation of 2 cases] 1993 Dec We describe two patients with chronic myelomonocytic leukemia (CMML) and associated rheumatic manifestations. The first patient presented an acute seronegative arthritis one month before the diagnosis of CMML and another bout one month after the diagnosis had been made. No specific cause was found after complete laboratory and roentgenographic studies. The second patient was diagnosed of Sjögren's Syndrome two years before the CMML became apparent. Although immunologic abnormalities are frequently observed in CMML, after a thorough bibliographic research we have found scarce reports describing associated rheumatic conditions.
1445454 Restricted junctional usage of T cell receptor V beta 2 and V beta 13 genes, which are ove 1992 Nov OBJECTIVE: To analyze the clonality of T cell receptor (TCR) V beta 2- and V beta 13-positive T cells, which are predominantly expressed in the lips of patients with Sjögren's syndrome (SS). METHODS: The junctional sequences of complementary DNA clones encoding TCR V beta 2 and V beta 13 genes were determined by the polymerase chain reaction. Forty-one V beta 2 and 45 V beta 13 clones established from the lips of 3 SS patients were sequenced. RESULTS: The V beta 2/J beta 2.3 pair was enriched in 2 of the 3 patients (44% and 46% of the clones, respectively), and the V beta 13/J beta 2.1 sequence was dominant in 2 of the 3 (23% and 45%). These pairs were not used preferentially in peripheral blood lymphocytes from the same patients. CONCLUSION: Infiltrating V beta 2- and V beta 13-positive T cells from the lips of all 3 patients with SS were polyclonal, but the junctional usage of cells from 2 lip samples was restricted, compared with cells from peripheral blood. This suggests that not all expanded cells from the lips of SS patients are stimulated by superantigens.
1340971 [HTLV-I clinical pathological spectrum]. 1992 Aug HTLV-I has been revealed as the etiological factor of the Tropical Spastic Paraparesis (TSP) and of the T-cell leukemia-lymphoma of the adult (ATLL). Recently, it has also been associated to some forms of polymyositis, polyarthritis, polyneuropathies, Sjögren's syndrome, thrombocytopenia and lympho-alveolitis. The clinical and pathological spectrum of this retrovirus is analyzed taking into account the Chilean cases and those reported by the international medical literature.
9592266 [Sialochemistry in nonneoplastic diseases of parotid gland: immunoglobulins and electrolyt 1996 Jul The concentration and total value of immunoglobulins (SIgA, IgG) and electrolytes (sodium, potassium, chlorine, calcium and phosphorus) in mixed saliva were examined in 28 patients with Sjögren's syndrome (SS), 25 with chronic obstructive parotitis (COP), 32 with sialadenosis and 32 normal controls. The results showed that in SS group, total saliva flow rate was decreased: concentration of SIgA, IgG, electrolytes was significantly elevated; but total value of SIgA, IgG, electrolytes was markedly decreased. Decreased total value of sodium, potassium, chlorine and calcium was revealed in COP group. Elevated concentration and total value of phosphorus was found in sialadenosis group. This study indicates that examination of total value of immunoglobins and electrolytes has greater value than that of concentration. The possible mechanism of changes observed is discussed.
8531345 [Analyses of T cell clonality in mice with autoimmune sialoadenitis]. 1995 Oct T cells are believed to be deeply involved in the pathogenesis of organ-specific autoimmune diseases. However, it remains unknown whether antigen-specific immune responses occur at the inflammatory sites in vivo. As a model of human Sjögren's syndrome, we investigated the T cell clonality of mice with autoimmune sialoadenitis, i.e. IQI/Jcl-(Saegusa et al), thymus grafted (TG) nude-(Taguchi et al), and MRL/lpr-SCID (Hayashi et al) mice; using RT-PCR-SSCP method. As a result, accumulations of distinct T cell clones were demonstrated in the salivary and lacrimal glands in these mice, without V beta restriction. Moreover, a part of the accumulating clones were commonly detected among multiple glands, suggesting the existence of a common and specific immune response probably toward autoantigen(s) expressed on the affected glands.
8092039 Color Doppler sonography of salivary glands. 1994 Oct OBJECTIVE: We used color Doppler sonography to evaluate the vascular anatomy of the salivary glands and to analyze physiologic changes that occur during salivary stimulation in normal subjects and the flow alterations that occur in diseased glands. SUBJECTS AND METHODS: The vascular appearance of the three major salivary glands was examined in healthy volunteers (n = 24); in patients with chronic autoimmune diseases, including Sjögren's syndrome (n = 23) and salivary sarcoidosis (n = 2); and in a variety of benign (n = 49) and malignant (n = 13) nodules. Physiologic changes were assessed in healthy volunteers by means of a stimulation test with lemon and were quantified with color images and spectral analysis. Tumor vascularity was graded on a four-step analog scale of 0 to (+3) and classified as either peripheral or hilar, depending on the distribution of vessels. RESULTS: In the control subjects, color Doppler imaging accurately reflected the complex vascular anatomy of the salivary glands and showed dramatic changes occurring in parenchymal vessels during lemon stimulation as a result of the intense hyperemia associated with the secretion of saliva. Sjögren's syndrome and sarcoidosis showed a diffuse hypervascular pattern when morphologic changes of salivary parenchyma were seen on gray-scale sonograms. Benign tumors showed a lower grade of vascularity than did malignant tumors. All but one of the hypovascular nodules graded as 0 (n = 8) and + (n = 23) were benign. Conversely, eight of 11 nodules labeled with the highest grade of tumor vascularity (+3) were malignant. When the pattern of tumor flow signals was peripheral, it could be considered specific enough to aid in diagnosing pleomorphic adenoma. Peak systolic velocities greater than 60 cm/sec were never detected in benign tumors and were seen in only 44% of malignant tumors. CONCLUSION: Color Doppler sonography is a promising technique for analyzing the vascularity of the salivary glands and for characterizing some pathologic conditions. Our experience suggests that color Doppler sonography can provide additional diagnostic information in patients with chronic inflammatory diseases or suspected malignant tumors and can help in differentiating pleomorphic adenomas from other salivary gland tumors.
8057118 Sensory conduction study in chronic sensory ataxic neuropathy. 1994 Aug Sensory conduction was studied in six patients with chronic sensory ataxic neuropathy of an idiopathic type and associated with Sjögren's syndrome. Motor nerve conduction velocities were normal in most cases, but sensory nerve potentials could not be evoked in a routine peripheral nerve conduction study. Cortical and cervical somatosensory evoked potentials (SEPs) and evoked potentials from Erb's point were barely recorded by median nerve stimulation at the wrist. When the median nerve was stimulated at more proximal points, clear potentials were recorded from Erb's point, but cortical SEPs were still hardly elicited. Thus the sensory nerves are centrally and peripherally involved in this condition, and the involvement is more prominent in the distal portion in the peripheral nerve. These findings suggest that central-peripheral distal axonopathy is a process involved in this illness and that the dorsal root ganglia may be primarily involved, in accord with previous pathological studies.
8069731 [Interrelationship between Epstein-Barr virus and Sjögren's syndrome]. 1994 Feb We designed a specific primer of EB virus Bam W fragment and EBV DNA sequence by using the polymerase chain reaction (PCR) to amplify the EBV DNA sequences and then performing the hybridization analysis (dot blot and Southern transfer) with a gamma 32P end-labelled internal oligonucleotide probe. There was a significantly higher positive rate of 24% (7/29) for the labial glands of Sjögren's syndrome patients than 68% (20/29) for gamma 32P Bam W probe. In situ DNA hybridization, with (alpha 35S) DCTP labelled EBV DNA probe, the EBV genomes were demonstrated in the labial glands of the Sjögren's syndrome patients (16/28). Moreover, the elevated content of EBV DNA was identified in those with more severe destruction of labial glands. We conclude that EBV has a normal site of latency at salivary glands in a nonpathogenic state, and may be reactivated in Sjögren's syndrome patients and play a role in the pathogenesis of this disease. The great sensitivity of PCR and the ability to analyze very small tissue biopsies (fresh or paraffin-embedded) make this technique applicable to clinical diagnosis.
1377917 Peptide-containing nerves in labial salivary glands in Sjögren's syndrome. 1992 Jul OBJECTIVE: The presence and spatial distribution of peptide-containing nerves in labial salivary glands from 10 Sjögren's syndrome patients were compared with those in salivary glands from 7 healthy controls. METHODS: Immunoperoxidase staining was used to demonstrate vasoactive intestinal peptide (VIP)-immunoreactive (IR) fibers, postganglionic sympathetic fibers containing the C-flanking peptide of neuropeptide Y (CPON), and sensory fibers containing calcitonin gene-related peptide (CGRP) and substance P. RESULTS: Acini, intralobular ducts, small arteries, and postcapillary veins were richly innervated by VIP-IR fibers, whereas CPON-, CGRP-, and substance P-IR fibers were restricted to blood vessels. Peptide-containing nerves were found surrounding, but not in the middle of, the highly inflamed mononuclear cell areas. CONCLUSION: This topologic distribution suggests involvement of VIP-IR fibers in vascular, motor, and secretory components of the reflex salivary secretion, whereas the distribution and the vasoactive actions of CPON, CGRP, and substance P suggest a role in the regulation of the salivary gland circulation, and thus of transcapillary flow. Excessive release may contribute to a neurogenic inflammation. Local depletion and absence of trophic neuropeptide stimuli may contribute to acinar atrophy.
7605264 Salivary beta 2-microglobulin in NZB/WF1 mice. 1995 Apr Unstimulated parotid and submandibular/sublingual saliva from New Zealand black/WF1 (NZB/WF1) mice as collected by microcapillary (1 microliter), and the content of beta 2-microglobulin (beta 2-MG) determined by a sandwich enzyme immunoassay. Salivary beta 2-MG contents of control C57BL/6 and NZB/WF1 mice (45 weeks of age) were 0.68 +/- 0.18 micrograms/ml and 1.42 +/- 0.21 micrograms/ml (mean +/- SD), respectively, from the parotid gland and 0.62 +/- 0.17 micrograms/ml and 1.34 +/- 0.21 microliters/ml, respectively, from the submandibular sublingual glands. However, the concentration of beta 2-MG was not increased in the NZB/WF1 mice at 5 and 20 weeks of age. Saliva from NZB/WF1 mice (45 weeks old) was fractionated by micro two-dimensional gel electrophoresis; it exhibited both qualitative and quantitative changes in protein composition in comparison to the two-dimensional at 5 weeks of age. These observations parallel those in saliva from patients with Sjögren's syndrome.
7543002 Snake-like chromatin in conjunctival cells of normal elderly persons and of patients with 1995 Feb The aim of this study was to investigate the prevalence of snake-like chromatin in the nuclei of conjunctival cells of normal elderly persons, and to compare with findings in patients with connective tissue diseases other than primary Sjögren's syndrome and in age-matched patients with primary Sjögren's syndrome. Thirty-nine per cent of the eyes of normal controls contained snake-like chromatin. Snake-like chromatin has almost never been found in young normals, and the results of this study therefore raise the question of whether age may be a contributing factor. Snake-like chromatin was as frequent in patients with other connective tissue diseases as in patients with primary Sjögren's syndrome, and no correlation to the presence of keratoconjunctivitis sicca was found in this group. The presence of snake-like chromatin was significantly correlated to increased cell size (N/C ratio) and low goblet cell density. A marked correlation between snake-like chromatin and low values of break-up time was found in normals, whereas no correlation was found to the other standard tests for dry eye.
8371602 Chronic inflammatory meningoencephalitis should not be mistaken for Alzheimer's disease. 1993 Sep We describe two patients with a chronic encephalopathy that clinically resembled dementia but that resolved after oral administration of high-dose corticosteroid therapy. Both patients had serologically documented Sjögren's syndrome, a diagnosis that was further supported by biopsy of a salivary gland in one. Neither patient had radiologic evidence of vasculitis of the central nervous system. In one patient, meningeal and brain biopsy specimens showed perivascular inflammatory lymphocytic infiltrates. Chronic inflammatory meningoencephalitis is a treatable cause of chronic encephalopathy that should be clinically distinguished from dementia associated with Alzheimer's disease.
8246404 [Local use of cyclosporin in nonbacterial corneal ulceration]. 1993 May The authors present the results of local use of cyclosporin solution in 6 patients with corneal ulcerations occurring in Sjögren disease, rheumatic disease and after corneal transplantation. The ulceration was healed in all patients. The cyclosporin, locally applied, has no side effects and may be an efficient way in the treatment of some immunological diseases of cornea.
1620982 A case of bronchiolitis obliterans organizing pneumonia associated with primary Sjögren's 1992 Bronchiolitis obliterans organizing pneumonia (BOOP) developed in association with primary Sjögren's syndrome in a 69-year-old female. She died of diffuse alveolar damage superimposed on BOOP in spite of corticosteroid therapy.
8003068 Comparative inhibitory effects of bucillamine and D-penicillamine on the function of human 1994 Jun OBJECTIVE: Clinical trials have suggested that the efficacy of bucillamine (BUC) in rheumatoid arthritis (RA) may be superior to that of D-penicillamine (DP), although the basis of the differences remains unclear. Previous studies have revealed that BUC has unique immunomodulatory effects that depend upon its capacity to form an intramolecular disulfide (BUC-ID). We therefore examined the effects of BUC-ID on the in vitro function of human B cells and T cells compared with those of DP, at their pharmacologically attainable concentrations. METHODS: IgM production was induced in highly purified B cells from healthy donors by stimulation with Staphylococcus aureus Cowan 1 (SAC) plus interleukin-2 (IL-2) or with immobilized anti-CD3-activated CD4+ T cells. Interferon-gamma (IFN gamma) production was induced in CD4+ T cells by stimulation with immobilized anti-CD3. RESULTS: BUC-ID suppressed IgM production induced by SAC+IL-2 as well as that induced by immobilized anti-CD3-activated CD4+ T cells, whereas DP suppressed the latter more markedly than the former. DP (3 micrograms/ml) significantly suppressed IFN gamma production by immobilized anti-CD3-stimulated CD4+ T cells, but not IgM production induced by SAC + IL-2 stimulation. By contrast, BUC-ID (0.3 microgram/ml) significantly suppressed IgM production induced by SAC + IL-2, but not T cell IFN gamma production. Of note, BUC-ID did not suppress IL-6 production by SAC-activated B cells. CONCLUSION: These results indicate that the target cells of BUC and DP in vivo might be different, with the former inhibiting the function of B cells and the latter that of T cells. The data suggest the possibility that BUC may have a different effect in RA patients compared with the effect of DP, and may be effective in patients who do not respond to DP.
7740132 [Butel's isoelastic hip prosthesis. A limited prospective study]. 1994 INTRODUCTION: A limited prospective study was undertaken at the Centre Hospitalier de l'Université Laval to assess the outcome of 21 isoelastic prostheses described by Butel. MATERIAL AND METHODS: The femoral component consisted of a one-piece forged stainless steel stem with four metallic rods ranging in diameter from 11 to 18 mm, in 1 mm increments. The two lateral and medial rods, 20 cm in length, were linked distally. The 2 mm gap between the medial and lateral rods was obliterated at insertion, allowing the component to be firmly seated in the femoral canal. Twenty-one Butel isoelastic prostheses were inserted in 20 patients (14 men and 6 women with an average age of 51 years). The preoperative diagnosis was aseptic total hip prosthetic loosening in three cases, rheumatoid arthritis in five cases, avascular necrosis in six cases and degenerative arthritis in six cases. A standard postero-lateral approach was used in all cases. Postoperatively, the patients were mobilized immediately, with partial weight bearing on the affected side for six weeks. RESULTS: Follow-up ranged from 24 to 34 months with an average of 28 months. One patient, who developed a late infection, was excluded from the study. Nineteen patients with 20 prostheses were reviewed clinically and roentgenographically by independent observers in the absence of the senior author. Clinically, the patients rated 11 to 58 on the preoperative Harris scale with an average of 34 while they rated 39 to 96 postoperatively with an average of 67. Eight patients were below 70 on the Harris scale postoperatively and were rated unsatisfactory. Eleven patients complained of postoperative thigh pain which was still present in three patients after two years. None complained of pain related to the acetabular component. On roentgenograms, prosthetic seating seemed to be inadequate in 14 cases but with good clinical results in 9 cases. Seating seemed to be adequate in six cases but with an unsatisfactory outcome in three cases. DISCUSSION: The concept of isoelasticity is that the implant and bone should deform as one unit. However, clinical results of an implant must be validated by investigators who are not developers of their own implant. The results in this series do not corroborate with those reported by Butel. A number of technical problems occurring at or after surgery precluded the safety, efficacy and durability of the surgical procedure and its successful outcome. A substantial incidence of thigh pain was found in this series. This has also been noted by a variety of authors using femoral designs with a large intramedullary rod which has less torsional stability than a flat wedge shaped femoral implant. CONCLUSION: The isoelastic prosthesis used in this series did not fulfill the expectations and was considered marginal in regards to quality and efficiency.
7980677 Inhibition of human fibroblast adhesion by cartilage surface proteoglycans. 1994 Nov OBJECTIVE: Recent studies from our laboratory have identified the nonaggregating, collagen-binding proteoglycans, fibromodulin (FM) and decorin, and fibronectin (Fn) and albumin, noncovalently bound at the articular surface of cartilage. The present studies were designed to investigate the interactions between these cartilage macromolecules and the underlying collagen matrix and their role as a barrier to cell adhesion in intact articular cartilage. METHODS: Cell adhesion studies were carried out with human skin fibroblasts incubated on the articular surface of bovine cartilage explants and on collagen-coated and/or Fn-coated plastic surfaces. Interactions of collagen and Fn with either FM or decorin were studied by radioimmunoassay of the same surfaces, using specific antibodies. RESULTS: The present studies show that 1) Fn is immunologically detectable at the intact articular surface of cartilage; 2) fibroblast adhesion to Fn is inhibited by cartilage surface extract proteins and by purified FM, but not by purified decorin; 3) FM has binding affinity for Fn; 4) FM interferes with the binding of a monoclonal antibody specific for the cell-binding domain of Fn; and 5) FM and decorin inhibit collagen-dependent fibroblast adhesion. CONCLUSION: These results indicate that the small proteoglycans at the normal articular surface may act as a barrier to cell adhesion. Since protective cartilage surface proteins break down readily after the induction of acute arthritis in experimental animals, and in rheumatoid cartilage specimens, it is postulated that proteolytic degradation of the surface proteoglycans may be responsible for increasing cell adhesion to, and subsequent pannus invasion of, articular cartilage in inflammatory arthritis.
7528671 Role of the CD40-CD40 ligand interaction in CD4+ T cell contact-dependent activation of mo 1994 Dec Most studies of the induction of cytokine synthesis in monocytes have employed an exogenous triggering agent such as lipopolysaccharide. However, in nonseptic inflammatory responses (e.g. rheumatoid arthritis) monocyte activation occurs as a result of T cell-generated signals. In previous reports, we and others have demonstrated that contact-dependent T cell-generated signals are capable of contributing to macrophage activation. We have shown that plasma membranes from anti-CD3 activated purified peripheral CD4+ T cells (TmA) but not from resting CD4+ cells (TmR) induce monocytes to synthesize interleukin (IL)-1 in the absence of co-stimulatory cytokines. Studies to determine the expression kinetics of the molecule(s) unique to activated CD4+ T cells which interact with monocytes to induce IL-1 revealed that optimal expression occurred at 6 h post activation. This matched the previously reported kinetics of expression of CD40 ligand (CD40L) on activated peripheral T cells, implicating the CD40-CD40L interaction as a candidate for the initiator of the IL-1 signaling event. The ability of TmA to induce IL-1 synthesis in resting monocytes could be markedly reduced by addition of a monoclonal anti-CD40L antibody, 5c8. In addition, a monoclonal anti-CD40 IgM (BL-C4) proved dramatic in its ability to induce resting monocytes to synthesize IL-1. In summary, these results demonstrate that the CD40-CD40L interaction provides a critical component of CD4+ T cell contact-dependent activation of monocyte IL-1 synthesis.
8961909 Analysis of cognitive and psychological deficits in systemic lupus erythematosus patients 1996 Dec OBJECTIVE: To examine cognitive and psychological functioning in relation to antiribosomal P protein autoantibodies in patients with systemic lupus erythematosus (SLE) who had no previous history of central nervous system disease (non-CNS SLE). METHODS: Comprehensive neuropsychological and psychological tests were administered to 51 non-CNS SLE patients, 29 rheumatoid arthritis (RA) patients, and 27 healthy controls. RESULTS: Twenty-nine percent of the non-CNS SLE patients, 31% of the RA patients, and 11% of the control subjects were classified as cognitively impaired. Similar reductions in intelligence, attention, and fluency were detected in the non-CNS SLE and RA patients compared with controls. The non-CNS SLE patients showed a distinct deficit in learning compared with the RA and control groups. Forty-two percent of the non-CNS SLE patients demonstrated psychological distress, compared with 7% of the RA patients and 6% of the controls. In the patient groups, neither cognitive dysfunction nor psychological distress was associated with disease activity or prednisone dosage. Elevated serum levels of autoantibodies to ribosomal P protein were not associated with either psychological or cognitive abnormalities. CONCLUSION: These results suggest that certain cognitive deficits in non-CNS SLE patients may not be specific to the immunopathology of SLE. In contrast, it is possible that deficits in learning, as well as psychological distress without major psychiatric pathology, may be subtle manifestations of CNS lupus.