Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2439101 | Rheumatoid factor and immune networks. | 1987 | Rheumatoid factors represent a normal component of the immune network. The autoantibodies promote complement fixation and clearance of immune complexes. They amplify the avidity of polyclonally induced IgG. Genes related to the primary structure of rheumatoid-factor light chains are widely distributed in the human population and have been conserved during the evolution and dispersion of the species. Products of these genes may be detected with anti-idiotypic antibodies against synthetic peptides corresponding to individual hypervariable regions on rheumatoid-factor light chains. Such anti-peptide antibodies provide unique reagents for analyzing the genetics of immunoglobulins in outbred populations. Precursors of rheumatoid factor are abundant among immature B lymphocytes. Some of these cells may tend to localize to mucosal surfaces, where they are stimulated directly by pathogenic microorganisms with polyclonal B cell-activating properties. Synthesis of rheumatoid factor regularly accompanies all secondary immune responses but is usually transient. Production of the autoantibody is T-cell dependent. The T cells may recognize antigen in an IgG-antigen immune complex that is processed and presented by B-cell precursors of rheumatoid factor. Rheumatoid factor-associated light-chain idiotypes are rare in serum IgG and on IgG myeloma proteins. They are common among monoclonal IgM proteins and on the surface of the malignant B cells from patients with chronic lymphatic leukemia. The rheumatoid factors that are produced by patients with mixed cryoglobulinemia, or primary Sjogren's syndrome can share idiotypic antigens with monoclonal rheumatoid factors. Rheumatoid factor synthesis in the diseases may reflect an abnormal proliferation of B-cells that is not antigen-driven and that can degenerate into malignancy. The rheumatoid factors in patients with rheumatoid arthritis are diverse and almost certainly represent the outcome of antigen-induced, T cell-dependent mechanisms. The antigens that drive the T cells have not been identified but could represent exogenous microorganisms, self components, or idiotypic antigens that fortuitously interact with rheumatoid factors. | |
| 1909589 | Suppression of bacterial cell wall-induced polyarthritis by recombinant gamma interferon. | 1991 Mar | Group A streptococcal cell wall fragments (SCW) induce erosive polyarthritis, characterized by synovial cell hyperplasia and intense mononuclear cell infiltration, in susceptible rats. Because of the known antiproliferative and immunomodulatory effects of interferon (IFN), we evaluated the effect of systemically administered alpha, beta and gamma IFN on the evolution of these destructive lesions. Treatment with gamma IFN not only reduced the acute response, but had an even greater suppressive effect on the chronic mononuclear cell-mediated destructive phase of the disease (articular index 10.2 +/- 1.2 for SCW only versus 3.8 +/- 0.7 for SCW + gamma IFN; p less than 0.01). Treatment with gamma IFN was more effective in the suppression of the arthritis than alpha, beta IFN. Histopathologic evaluation of the joints demonstrated that gamma IFN-treated animals had significantly fewer inflammatory cells, and less synovial hyperplasia and erosions than the SCW controls. gamma IFN suppression of mononuclear cell prostaglandin synthesis and synovial fibroblast proliferation was consistent with its anti-arthritic effects. These data indicate that the pathophysiology of SCW-induced erosive polyarthritis is subject to regulatory control by gamma IFN and that the mechanisms of suppression may be relevant in the treatment of rheumatoid arthritis. | |
| 2383162 | Ceftriaxone therapy of chronic inflammatory arthritis. A double-blind placebo controlled t | 1990 Aug | To determine whether chronic inflammatory arthritis may respond to antibiotic therapy (implying a bacterial origin), we conducted a placebo-controlled, double-blind study. Sixty patients with inflammatory arthritis and antibody titers to Borrelia burgdorferi 1:64 or more were randomized to receive placebo (n = 20) or 2 g/d of ceftriaxone intravenously (n = 40) for 2 weeks. Two of 20 placebo- and 19 of 40 antibiotic-treated patients improved. At 1 month, the placebo-treated patients could elect to receive ceftriaxone. Altogether, 58 patients were treated with ceftriaxone and followed up for 13 to 24 months. Improvement was noted in 27 of the 58 antibiotic-treated patients. Patients with a wide diversity of inflammatory arthritis were studied. Response to ceftriaxone was seen in all groups, including 5 of 12 with rheumatoid arthritis, 5 of 8 with psoriatic arthritis, 3 of 5 with vasculitis, and 14 of 33 with less well-differentiated chronic inflammatory arthritis. In 16 of the 27 who responded to the antibiotic, the arthritis worsened 6 to 18 months after the initial response to ceftriaxone. Previous improvement of arthritis after oral antibiotic was a better predictor of response to ceftriaxone than either duration of disease or Lyme antibody titer. Side effects to ceftriaxone were frequent and included diarrhea (29/60) and acute allergic reactions (9/58). We conclude that some patients may have an occult bacterial infection underlying their chronic inflammatory arthritis, and may respond to antibiotic therapy. The response to ceftriaxone in patients with even weakly reactive Lyme titers encourages further prospective placebo-controlled studies of antibiotics in various subsets of chronic arthritis. | |
| 1973354 | The in vitro effects of methotrexate on peripheral blood mononuclear cells. Modulation by | 1990 Jul | The mode of action of low-dose methotrexate (MTX) in rheumatoid arthritis (RA) is unclear. The effects of MTX are mediated primarily through inhibition of dihydrofolate reductase, resulting in a dose-dependent inhibition of purine and pyrimidine synthesis. Other folate-dependent metabolic pathways might be secondarily affected. One such pathway is the regeneration of methionine from homocysteine, with subsequent formation of the methyl donor S-adenosylmethionine (SAM) and polyamines, which are important in cell-mediated immune reactions. To assess whether MTX inhibits SAM and polyamine synthesis in lymphocytes, pokeweed mitogen-stimulated mononuclear cells from healthy donors were incubated with MTX. This resulted in decreased proliferation and IgG, IgM, and IgM rheumatoid factor synthesis. However, addition of folinic acid, methionine, SAM, or spermidine resulted in reversal of the MTX-mediated inhibition. These data suggest that MTX inhibits the folate-dependent pathway of methionine regeneration, thereby inhibiting SAM and polyamine synthesis. Since RA lymphocytes have increased concentrations of polyamines, the beneficial effects of MTX in RA may be related to its potential ability to reduce polyamine synthesis. | |
| 3596631 | [Functional Fc receptor defect of granulocytes in a patient with Sjögren's syndrome]. | 1987 Apr | A patient with Sjögren's syndrome exhibited markedly impaired stimulation of her granulocytes via Fc-receptors (FcR), four other stimuli elicited a normal chemiluminescent response. Unexpectedly, granulocytes of the control bore 39,000, of the patient, however, 86,000 FcR/granulocyte. | |
| 3351695 | Determinants of low serum concentrations of salicylates in patients with Kawasaki disease. | 1988 Apr | The mechanisms leading to the previously reported difficulties in achieving therapeutic serum concentrations of salicylates in Kawasaki disease were studied in eight children, once during the acute (febrile) phase and again during the nonfebrile (subacute) phase of the disease. Salicylate bioavailability was impaired during the acute phase of the disease (47.7% +/- 6.6%), and increased significantly thereafter to 75.1% +/- 9.3%. During the febrile phase there was a significant correlation between salicylate bioavailability and steady-state serum concentrations. Salicylate renal clearance was significantly higher during the febrile phase (14.45 +/- 2.5 mL/kg.h), compared with the nonfebrile phase (7 +/- 1.6 mL/kg.h, P less than 0.05). The change in salicylate clearance could be explained by decreased protein binding in the acute phase (82.5% +/- 1.9%) with substantially more free salicylates caused by significantly lower serum albumin concentrations. Changes in urine metabolites during the acute and subacute phases were consistent with the changes in dose administered (100 mg/kg in the acute phase vs 10 mg/kg in the subacute phase). The pattern of metabolites excreted in the urine of children with Kawasaki disease receiving 100 mg/kg was similar to that in children with juvenile rheumatoid arthritis receiving the same dose. | |
| 2952952 | [Treatment of Felty's syndrome accompanied by agranulocytosis using high-dose corticoids. | 1987 Apr 4 | Three cases of severe Felty's syndrome (neutrophils 80/mm3 in 2 cases and 800/mm3 in one) with enlarged spleen (1 case) and leg ulcer (2 cases) were treated with high doses of corticosteroids (methylprednisolone 1 g by intravenous infusion over 3 hours, on 3 consecutive days). In all 3 patients a dramatic result was obtained, the granulocytes returning to normal values in 24 to 48 hours. In 2 cases, an early relapse (1 month) required a second course in high dosage; after a follow-up of 36 and 8 months respectively, the number of granulocytes remains stable under prednisone 5 to 10 mg/day. The third patient was improved by one single course of infusions and remains stable after 18 months. It must be noted that one patient had previously been treated with plasma exchange and another with corticosteroids without any significant result. | |
| 3627703 | Lacrimal proteins in Sjögren's syndrome. | 1987 | Tear protein electrophoresis results are studied in a group of 5 patients suffering from Sjögren's syndrome. Decreased globulin fraction and severe diminution of post-gamma protein fraction are the main alterations of lacrimal protein in this disease. | |
| 1994866 | Bronchial hyperresponsiveness to methacholine in patients with primary Sjögren's syndrome | 1991 Jan | The prevalence of bronchial hyperresponsiveness (BHR) to methacholine inhalation in a consecutive series of 21 patients with primary Sjögren's syndrome was studied prospectively. Slight to severe BHR was seen in 12/20 (60%) of the patients. Ten of 12 patients with BHR (83%) had a non-productive cough, wheezing, or intermittent breathlessness. Bronchial hyperresponsiveness was more common in patients with extraglandular symptoms (10/14, 71%) than in those with only glandular symptoms (29%). Spirometrically 29% (6/21) of the patients had 'small airways' disease', and all those had BHR. Of 6/21 (29%) who had diffuse interstitial lung disease, two had BHR. Three of the four patients with obstructive lung function were challenged with methacholine and two of them had BHR. Only two patients with BHR had normal spirometry findings. The data showed that respiratory disease--mostly mild or moderate but even severe bronchial hyperresponsiveness--is commonly seen in patients with primary Sjögren's syndrome. | |
| 1651095 | Radiolabelled semisolid test meal clearance in the evaluation of esophageal involvement in | 1991 | Esophageal involvement by scleroderma is frequent. Investigation by manometry or radiography is invasive and nonphysiological. Scintigraphy of the clearance of small radiolabelled liquid boluses in the supine position, while sensitive and noninvasive, may also be nonphysiological and does not allow the simultaneous determination of gastric emptying. We thus studied the esophageal clearance of a semisolid test meal ingested in the upright position. Forty-seven patients with scleroderma and 24 with Sjogren's syndrome were compared with ten normal controls and ten patients with gastric emptying abnormalities but no esophageal involvement. Results of scintigraphy were also correlated with manometry and contrast radiography. Quantitative evaluation of esophageal tracer retention at ten minutes postingestion was: (mean +/- SD), 2.8 +/- 1.0% in normals, 2.9 +/- 0.9% in gastric dysmotility, 4.8 +/- 2.9% in Sjogren's syndrome, and 22.3 +/- 25.0% in scleroderma; similar results were found at 20 and 60 minutes. The T 1/2 of gastric emptying was 47.1 +/- 5.7 minutes in normals, 95.9 +/- 25.3 minutes in gastric dysmotility, 62.9 +/- 19.5 minutes in Sjogren's syndrome, and 52.9 +/- 13.5 minutes in scleroderma. We conclude that esophageal clearance of a semisolid test meal is a sensitive index of esophageal dysmotility and correlates well with results from manometry and contrast radiography but is noninvasive and quantifiable. The simultaneous measurement of gastric emptying is also possible in many cases. | |
| 2148613 | [Relationship between autoimmune diseases and personality traits in women]. | 1990 Dec 22 | The personality traits of 40 women with non organ-specific dysimmune diseases were studied by means of a questionnaire devised to evaluate behavioural components including 48 items divided into 8 different patterns. The patients fell into 3 groups. Group I comprised 20 women with collagen diseases, including systemic lupus erythematosus (n = 8), scleroderma (n = 4), Sharp's syndrome (n = 4), polymyositis (n = 3) and Shulman's syndrome (n = 1). Group II was made of 10 women with either primary (n = 6) or secondary (n = 4) Sjögren's syndrome. Group III consisted of 10 women with vasculitis. Results were compared with those obtained in a control population of 41 women without dysimmune disease. At the time of examination the mean daily dose of prednisone was 10.5 mg. All 40 patients differed from the control group by their unobtrusiveness, self depreciation (P less than 0.01), hyperconformability and excessive kindness (P less than 0.02). Additional traits were a tendency towards contradiction and intolerance in patients with Sjögren's syndrome and a lack of agressiveness combined with a feeling of inferiority in patients with vasculitis. These results confirms that patients with dysimmune disease are psychologically fragile and suggest that the possibility of psychotherapy should be examined in these patients. | |
| 2752662 | [A case of Sjögren's syndrome with mononeuritis associated with high levels of circulatin | 1989 Mar | A 32-year-old woman with Sjögren's syndrome accompanied by mononeuritis of right lower extremity was described. She admitted Shinshu University Hospital with the chief complaints of Raynaud's phenomenon and generalized lymphadenopathy. One year before admission Raynaud's phenomenon of right hand was first noticed. One month later she complained of a gritty sensation in the eyes and severe dryness of the mouth. On admission, she had systemic lymphadenopathy. Neurological examination revealed decreased light touch and pinprick sensations and decreased deep tendon reflexes in right lower extremity. Lip biopsy revealed marked mononuclear cell infiltrates around the salivary glands. Laboratory data included IgG 3,007 mg/dl, circulating immune complexes 1,200 micrograms AHGeq/ml (Raji-cell ELISA), anti-nuclear antibody 2,560X (speckled pattern) and anti-SSA antibody 256X. The levels of total protein, IgG and immune complexes were increased in the CSF of this patient. Sural nerve biopsy revealed a decreased number of large myelinated fibers and perivascular lymphocyte infiltration of vasa nervorum. Direct immunofluorescent staining showed deposition of IgG and C3 in the endoneural vessel walls. The increased level of immune complexes were decreased in the sera of the patient, accompanied by remission. These results suggest that immune complexes may be involved in the pathogenesis of a mononeuritis associated with Sjögren's syndrome. | |
| 11039042 | Sialographic images of pathological changes in the mouse parotid gland. | 1988 Jan | In order to correlate pathological changes of mouse parotid glands with their sialographic images, we conducted studies on mice with known pathological changes: mice with Stensen's duct ligated, NZB mice with a systemic auto-immune disease, and aged mice. The sialographic images were found to be specific for the pathological changes: The glands after ligation of Stensen's duct were characterized by dilated, large excretory ducts with a reduced system of peripheral ducts; the glands of NZB mice showed lobular leakage of the contrast medium from small excretory ducts; and the glands of aged mice showed a great reduction in the ductal system. It is concluded that sialography yields useful information on the pathological changes of the ductal systems in the mouse parotid gland. | |
| 3532967 | Cyclosporin A (CyA) in primary Sjögren's syndrome: a double blind study. | 1986 Sep | The efficacy and toxicity of cyclosporin A (CyA) were studied in a blind fashion in 20 patients with primary Sjögren's syndrome (pSS). The dose of CyA or placebo was 5 mg/kg of body weight daily. Among the 20 patients, 10 received CyA and 10 placebo. The two groups were matched for age, sex, and disease duration. Patients treated with CyA improved in subjective xerostomia in comparison with patients treated with placebo. Subjective xerophthalmia and recurrent parotid gland enlargement did not differ in the two groups. No change in Schirmer's test and stimulated parotid flow rate was observed in either group. In contrast, the histopathological lesion of patients treated with CyA remained unchanged in most of the patients, while in the placebo treated group the lesion deteriorated. Laboratory parameters did not change before or after treatment in either group. The only clinical side effect observed in the CyA treated group was hypertrichosis. | |
| 2693062 | Xerostomia and glossodynia in patients with autoimmune disorders. | 1989 Oct | Xerostomia presents a difficult challenge for the clinician to manage and a serious problem for the afflicted patient. Patients with dysfunctional or hypofunctional salivary or lacrimal glands suffer considerably both emotionally and physically. Because of the ever-increasing geriatric population, health practitioners can expect to encounter a substantial number of patients with xerostomia or salivary gland disorders. Early detection and appropriate management will improve the quality of these patient's lives. | |
| 2799300 | A follow-up study of the progress of keratoconjunctivitis sicca and response to treatment | 1989 | Thirty-four patients with Sjögren's syndrome were retrospectively examined in order to evaluate longitudinal alterations in objective ocular disease parameters and their possible relation to systemic bromhexine treatment. Twenty-three patients (68%) were initially found to respond to peroral bromhexine treatment and were subsequently treated with this agent in addition to tear substitutes. The other 11 patients (32%) were considered bromhexine non-responders and were treated with topical agents only. The bromhexine non-responders had a significantly (p less than 0.02) more reduced tear gland function, evaluated by the Schirmer-1 test, than the responder group. At the end of the follow-up period the conjunctival surface cells were significantly (p less than 0.02) more damaged in the bromhexine non-responders than in the responders. The bromhexine non-responders improved in both break-up time and van Bijsterveld score in the course of time while the responders improved in the van Bijsterveld score only. No differences as regards extraglandular disease manifestations, serological abnormalities or treatment with other systemic agents were found between the bromhexine responders and non-responders. | |
| 3369771 | Magnetic resonance imaging of cerebral lesions in patients with the Sjögren syndrome. | 1988 Jun | Thirty-eight patients with the primary Sjögren syndrome, 16 with active neuropsychiatric manifestations and 22 without clinical evidence of central nervous system involvement had magnetic resonance (MR) imaging. Eight patients had focal neurologic deficits (6 of these also had psychiatric, or cognitive dysfunction), and 8 had psychiatric or cognitive abnormalities alone. Magnetic resonance imaging showed abnormal results in 12 of 16 (75%; 95% CI, 48 to 93) patients with active central nervous system disease (67 focal lesions predominantly within the subcortical and periventricular white matter), and in 2 of 22 (9%; 95% CI, 1 to 29) patients without clinical evidence of central nervous system disease (P less than 0.0001). Seven of eight patients with focal neurologic deficits and 5 of 8 patients with psychiatric or cognitive dysfunction alone had abnormal results on MR imaging. Magnetic resonance imaging was more sensitive in the subgroup with focal deficits, (sensitivity, 88%; 95% CI, 44 to 97) than computerized axial tomography or cerebral angiography. Magnetic resonance imaging detects focal cerebral lesions in patients with the Sjögren syndrome and central nervous system involvement, including patients with psychiatric and cognitive dysfunction alone. | |
| 3033239 | Reversal of depressed neutrophil superoxide production in Felty's syndrome after gold ther | 1987 Feb | Six patients with Felty's syndrome were reevaluated after a course of chrysotherapy. In 5 patients, white cells and absolute neutrophil counts had returned to normal. In 4 of these, there was significant concomitant improvement in neutrophil function as assessed by the ability of cells to generate superoxide radicals. | |
| 3490010 | [Antinuclear antibodies in Sjögren's disease and syndrome]. | 1986 | A study was made of the presence of antinuclear antibodies to Ro, La, nDNA, RNP and Sm in 18 patients with Sjögren's disease (SD) and in 13 patients with Sjögren's syndrome (SS). Anti-Ro and/or anti-La were revealed in 12 SD patients (67%) and in 3 SS patients (23%, P less than 0.05) only. Anti-nDNA and anti-RNP were detected in 39 and 15% of the SS patients respectively and were undetectable in the SD patients. Anti-Ro and/or anti-La were detected in all SD patients, III degree activity, and associated with the presence of Raynaud's syndrome, recurring nonerosive arthritis and the absence of adequate therapy. Anti-Ro only were detected in 44% of the SD patients only and in none of the SS patients. Higher values of ESR, RF and CIC were revealed in the SD patients with anti-La and especially anti-Ro. | |
| 3218469 | Keratoconjunctivitis sicca in patients with primary Sjögren's syndrome. A longitudinal st | 1988 Oct | Thirty-four patients, all fulfilling the Copenhagen criteria for Primary Sjögren's Syndrome, were examined retrospectively in order to evaluate possible longitudinal alterations in Schirmer-1-test results, Rose-bengal score, break-up time and level of ocular score. Twenty-three of the patients were characterized as Bromhexine responders according to their initially positive response to systemic treatment (16 mg x 3 daily) and 11 patients were Bromhexine non-responders. All patients were treated with tear substitutes during the entire observation period of 27 to 76 months (mean 53 months), and all eye examinations were carried out by the same ophthalmologist. The responder group had, both in the start as well as at the end of the observation period, a better ocular status compared to the non-responder group. The latter group had a significantly (P less than 0.02) lower Schirmer-1-test at the start and at the end of the period, and a significantly (P less than 0.02) higher Rose-bengal score at the end of the period. Moreover, the responder group improved in Rose-bengal score (P less than 0.001), whereas the non-responder group improved both in break-up time (P less than 0.05) and Rose-bengal score (P less than 0.05). The use of a score combining results from all three tests, i.e. the ocular score, seems to be a useful tool when evaluating longitudinal variations i dry eye states. Considerable variation was seen between successive results of each ocular test, also in the periods without systemic treatment. |