Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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3262691 | Ro(SS-A) positive Sjogren's/lupus erythematosus (SC/LE) overlap patients are associated wi | 1988 Oct | Ro(SS-A) positive female Sjögren's syndrome (SS) lupus erythematosus (LE) overlap patients are a clinically and serologically homogeneous group generally demonstrating prominent subacute cutaneous lupus erythematosus (SCLE) lesions, cutaneous vasculitis, peripheral and central nervous system disease, pulmonary disease, and a low frequency of glomerulonephritis. They commonly demonstrate rheumatoid factor, hypergammaglobulinemia, antinuclear and Ro(SS-A) La(SS-B) antibody activity. This study indicates that these patients are also immunogenetically similar, sharing a statistically significant increased frequency of HLA-B8, DR3, DRW6, DQ2, and DRw52. Sixty-three percent of these SS/LE patients possess the extended haplotype (P-value 6.0 X 10(-3); RR 9.5) HLA-B8, DR3, DQ2, DRw52. One hundred percent of this SS/LE cohort was DR3 or DRw6 (P-value less than or equal to 5.0 X 10(-3); relative risk 19.1). Fifty percent of these patients were HLA DR3/DRw6 heterozygotes (P-value 1.5 X 10(-6); relative risk 31.2). Thus, HLA-DR3 and DRw6 Ro(SS-A) positive SS/LE patients may possess a similar, if not unique, DR region DNA nucleotide sequence involved in disease susceptibility or immune regulation. | |
3053745 | Human herpesvirus-6 (HHV-6, HBLV) in sarcoidosis and lymphoproliferative disorders. | 1988 Sep | Serologic studies were done to estimate the antibody prevalence against human herpesvirus 6 (HHV-6) in patients with malignant lymphomas, Sjögren's syndrome and sarcoidosis. Serologic studies showed IgG antibody titers against HHV-6 in up to 41% of patients with sarcoidosis, 50-70% with malignant lymphomas and in 36% with Sjögren's syndrome. In situ hybridization on lymph node biopsies was positive for HHV-6 genome in 1 out of 5 sarcoidosis lymph nodes. | |
3207072 | Clinical and immunological features of Sjögren's syndrome in patients with primary biliar | 1988 | Serological and pathological findings in 21 patients with primary Sjögren's syndrome (primary SS) were compared with those in 32 patients with primary biliary cirrhosis (PBC). In ELISA, anti-SS-B/La antibodies were detected in sera from 14 (67%) of the patients with primary SS, but only from 12 (38%) of those with PBC. With the Ouchterlony test, anti-SS-A/Ro antibodies were found in sera from 15 (71%) of the primary SS patients, but in no PBC patient. Of those PBC patients investigated prospectively with objective tests, four of 11 (36%) had keratoconjunctivitis sicca, and five of 15 (33%) had pathological sialometry results. In contrast, all PBC patients but one (i.e., 14 of 15 or 93%) showed evidence of focal sialadenitis. In immunochemical study of PBC patients, IgM immunoreactivity was found in the stroma, particularly adjacent to excretory ducts and acini in salivary glands (5 of 5), whereas no such IgM deposits were observed in patients with primary SS (3 of 3), nor in healthy controls (n = 20). We conclude that the frequency of anti-SS-A/Ro and anti-SS-B/La antibodies in serum is lower in PBC patients than in patients with primary SS. The incidence of focal sialadenitis is high in PBC, though only one third of the PBC patients studied here showed clinical evidence of glandular dysfunction. With immunochemical techniques, sialadenitis associated with PBC is distinguishable by its significant IgM reaction from sialadenitis in primary SS. | |
2937258 | Platelet function in patients with primary Sjögren's syndrome. | 1986 | Platelet function tests were performed in 15 patients with primary Sjögren's syndrome (SS) and in 15 normal controls. Platelet counts were within the normal range in all except two patients in whom they were only slightly decreased. P-beta-thromboglobulin was increased in several patients compared to controls, although not significantly (p less than 0.1). Platelet aggregation was enhanced in patients when measured upon stimulation with epinephrine (p less than 0.05), ADP (p less than 0.01) and collagen (p less than 0.01). No correlation was found between enhanced platelet activity and sex, age, duration of disease, extraglandular manifestations, positive ANA test, elevated P-IgG or P-immune complexes. Enhanced platelet activity in patients with primary SS is a new observation. Future studies are needed to elucidate the pathogenetic background. | |
1814527 | AIDS and Sjogren's syndrome. | 1991 | HIV infection can produce a clinical syndrome and immunologic changes similar to those seen in SS. HIV infection can occasionally result in an SS-like disease but without the formation of antibodies to Ro(SS-A) or La(SS-B). Could this mean that a retrovirus yet to be discovered is responsible for the autoimmune exocrinopathy known as SS? Evidence to date is circumstantial, based on antibodies to a retroviral protein (p24). The idea that retroviruses act in a genetically susceptible host to cause SS is a reasonable hypothesis. Syphilis and Lyme disease are both models where infectious organisms cause chronic multi-system disease. The virus of SS need not be a foreign invader but could be an endogenous retrovirus contained within our own genetic material (10, 11). More investigation is needed to exploit the research opportunities that have appeared in clinical immunology since the AIDS epidemic first appeared. | |
2665976 | Antibodies against Ku protein in sera from patients with autoimmune diseases. | 1989 Jun | Immunoaffinity-purified Ku protein was used to screen sera from patients with systemic lupus erythematosus (SLE), scleroderma, myositis and Sjögren's syndrome for anti-Ku antibodies in a quantitative immunoblot assay. Sixteen percent of the 159 studied sera were reactive with the Ku protein; significantly increased frequencies of anti-Ku antibodies were found in SLE (19%) and scleroderma (14%) sera. Patients with myositis and Sjögren's syndrome showed similar frequencies. All positive sera had antibodies to the 86 kD subunit of Ku protein; only one serum did not react with 70 kD subunit. Frequencies of other autoantibodies were compared in anti-Ku positive and negative patients. Only anti-Sm antibodies, especially in the absence of anti-nRNP, appear to be associated with the presence of anti-Ku antibodies. A strong correlation between anti-Ku antibodies and the class II HLA antigen DQw1 (89% of the positive sera) was observed, suggesting participation of MHC genes in the mounting of the anti-Ku immune response. | |
2659854 | Hypergammaglobulinemic purpura in patients with Sjögren's syndrome: a report of nine case | 1989 Mar | Nine patients with hypergammaglobulinemic purpura associated with primary Sjögren's syndrome were presented. All patients were female (mean age 45.6) and showed recurrent purpura on the lower extremities and typical findings of Sjögren's syndrome with high gammaglobulin and IgG levels, rheumatoid factors, anti-SSA/SSB antibodies (5/5) and anti-nuclear antibodies (6/9). Vasculitis was seen in 6 patients, 4 were of the mononuclear cell type and 2 of the neutrophilic cell type. Six patients had intermediate complexes between 7S and 19S shown by serum ultracentrifugation. Immunofluorescent staining showed immunoglobulin deposition along the blood vessel walls of the skin in these patients. These data suggest that hypergammaglobulinemic purpura in Sjögren's syndrome is vasculitis caused by immunologic processes. | |
2920054 | Reversal of neutropenia with methotrexate treatment in patients with Felty's syndrome. Cor | 1989 Feb | We evaluated the clinical and hematologic response to methotrexate (MTX) in 4 women with Felty's syndrome (FS) who had had neutropenia for 1-3 years. Since immune complexes or antineutrophil antibodies are implicated in the pathogenesis of the neutropenia of FS, we also measured both direct and indirect levels of neutrophil-reactive IgG. All 4 patients showed a prompt and dramatic increase in neutrophil counts within 1-2 months of starting MTX therapy. In 3 patients, the symptoms of arthritis also improved; in the fourth patient, arthritis worsened. Recurring infections ceased in 3 patients. Neutrophil-reactive IgG levels, which were elevated in all patients prior to treatment, decreased toward normal while the patients were receiving MTX therapy. We conclude that MTX is effective in treating the neutropenia of FS, in part by lowering neutrophil-reactive IgG. | |
1669586 | Macrophage containing factor XIII subunit a in salivary glands of patients with Sjögren's | 1991 Aug | Minor labial salivary glands obtained at biopsy from patients with Sjögren's syndrome were investigated by immunomorphological methods for the presence of monocyte-derived macrophages. According to our observations published earlier the immunomorphological detection of factor XIII subunit a is a useful marker for recognizing cells of monocyte/macrophage lineage. Factor XIII subunit a was detected by a highly sensitive immunoperoxidase staining, and cells containing this coagulation enzyme were characterized by double immunofluorescence stainings. Factor XIII subunit a+ cells were found to be highly accumulated at the interface of normal tissue and peritubular infiltrate. In double immunofluorescence labelling systems factor XIII subunit a+ cells were simultaneously labelled by RFD7 and Dako-antimacrophage monoclonal antibodies. They also expressed HLA-DR antigen as revealed by a reaction with RFDR2 monoclonal antibody. The results suggest that monocyte-derived tissue macrophages are present in salivary glands of patients with Sjögren's syndrome and have a characteristic distribution. It can be assumed that they have a role in the demarcation of peritubular inflammation and thus have an effect on the progression of the disease. | |
2087291 | Optic neuropathy and central nervous system disease secondary to Sjögren's syndrome in a | 1990 Dec | The authors describe a 10-year-old girl in whom optic neuropathy and central nervous system (CNS) disease developed in association with primary Sjögren's syndrome. There was angiographic evidence of cerebral vasculitis and multiple infarcts present on neuroimaging. Results of parotid biopsy, cerebrospinal fluid, and serologic analyses showed abnormalities that were consistent with the diagnosis of Sjögren's syndrome. Although the patient had optic disc pallor on initial evaluation, her color vision and acuity improved with immunosuppressive therapy, as did her other neurologic symptoms. The authors believe this represents the first reported case of optic neuropathy and CNS disease associated with primary Sjögren's syndrome in the pediatric population. The possibility of improvement in visual function with early institution of immunosuppressive therapy makes prompt diagnosis essential. | |
3261973 | Clinical course of silent thyroiditis in a patient with Sjögren's syndrome. Concomitant c | 1988 Sep | A 68-year-old woman with Sjögren's syndrome simultaneously experienced thyrotoxicosis with a marked depression of thyroid radioactive iodine uptake and systemic lupus erythematosus-like symptoms, which both resolved spontaneously. Titers of antinuclear antibody and anti-DNA antibody were most elevated when the thyrotoxicosis and systemic lupus erythematosus-like symptoms coexisted and thereafter gradually declined in response to the decrease of titers of antithyroglobulin hemagglutination antibody and antimicrosomal hemagglutination antibody. To our knowledge, no such case has been previously reported. These observations strongly suggest that thyrotoxicosis in silent thyroiditis may be induced by an autoimmune mechanism. | |
3169687 | Conjunctival biopsy in Sjögren's syndrome: correlations between histological and immunohi | 1988 Aug | We have examined conjunctival biopsies from nine primary and two secondary cases of Sjögren's syndrome. In all cases histopathological examination revealed metaplasia of the conjunctival epithelium associated with a reduced number of goblet cells and a polymorphic inflammatory cell infiltrate of the stroma. Using monoclonal antibodies with texture analysis of stained preparations we have shown that in all cases the lymphocytic infiltrate was predominantly T-cell but with substantial numbers of IgA and IgG secretory B-cells in three cases. The number of Langerhans cells present was reduced in biopsies showing the most marked degree of epithelial metaplasia. | |
2978189 | Clinical trial of ambroxol (Mucosolvan) in Sjögren's syndrome. | 1988 Aug | A clinical trial is described in which twelve patients with Sjögren's Syndrome (SS) were given a dose of 135 mg ambroxol (Mucosolvan) daily for eight weeks. Nine of the patients completed the trial. Three patients dropped out because they developed side effects (generalized rashes in two patients and stomatitis in one). The side effects, however, were mild and cleared off after cessation of treatment. Ambroxol improved sicca symptoms, especially ocular symptoms, in the SS patients, although lacrimal and salivary gland functions measured by Schirmer test or gum test were not changed. Furthermore, the treatment did not alter any chemical findings determined in the stimulated tear and saliva. Our results suggest that ambroxol is useful for the management of sicca symptoms in some patients with SS. | |
2758707 | Morphometric study of salivary glands in primary Sjögren's syndrome. | 1989 May | The relationship between structural changes of the minor salivary glands with age was evaluated by morphometric analysis in twenty patients with primary Sjögren's syndrome (prim. SS) (Group I) and in twenty sex and age-matched normal subjects (Group II). No statistically significant differences were found in the acinar tissue, intralobular ducts (ILD) and fibrous tissue between the two Groups. In contrast, there was a 5-fold increase in the volume fraction of inflammatory cells in Group 1. In both Groups the percentage of fibrous tissue and ILD increases and the percentage of acinar tissue decreases linearly with age. In Group I the increase in the volume percentage of fibrous tissue and the decrease in the volume fraction of the acinar tissue were not related to the volume percentage of inflammatory cells. These results demonstrate that in prim. SS the acinar atrophy is not related to the inflammatory process but is an age-dependent phenomenon. | |
3180538 | Salivary kallikrein in Sjögren's syndrome. | 1988 Apr | Using a chromogenic substrate (H-D-Val-Leu-Arg-pNA) salivary kallikrein levels were measured in whole saliva samples from patients suffering from Sjögren's syndrome (SS). Compared to healthy control individuals, SS patients, especially those without corticosteroid medication, exhibited significantly elevated kallikrein levels. A diurnal variation was found with the highest kallikrein activities in morning saliva. No correlation between kallikrein levels and extension of the inflammation in labial salivary glands (focus score), salivary flow rates or diagnosis (primary versus secondary SS) could be observed. A pathogenic mechanism for kallikrein in autoimmune sialadenitis is discussed. | |
3473650 | Focal lymphocytic infiltrates of salivary glands are not confined to Sjögren's syndrome. | 1986 | Focal periductal lymphocytic infiltrates of lip salivary glands (LSGs), since long considered a diagnostic hallmark of Sjögren's syndrome (SS), were found in a high proportion of patients with various connective tissue diseases, as well as in myasthenia gravis, lacking symptoms and signs of SS. | |
3296153 | A double-blind, cross-over, study of oral N-acetylcysteine in Sjögren's syndrome. | 1986 | Twenty-six patients with primary or secondary Sjögren's syndrome were treated in a double-blind, cross-over trial for a four week period with oral N-Acetylcysteine and placebo. Before treatment there were significantly elevated salivary lactoferrin levels in the patients when compared to 51 healthy controls (p = 0.0005), and significantly decreased levels of tear lysozyme when compared to 24 controls (p = 0.0003). Salivary sodium, potassium, inorganic phosphate, amylase and immunoglobulin G, A or M levels were not significantly different from control values. After treatment with N-Acetylcysteine, Sjögren's syndrome patients reported improvements in ocular soreness (p = 0.004), ocular irritability (p = 0.006), halitosis (p = 0.033) and daytime thirst (p = 0.033). N-Acetylcysteine, but not placebo improved the van Bijsterveld score (p = 0.026), but neither agent improved the Schirmer test, the tear break up time or any of the laboratory tests. These results suggest that N-Acetylcysteine may have a true therapeutic effect on the ocular symptoms of Sjögren's syndrome and be worthy of a longer study. | |
1843374 | [Noninfectious bilateral corneal ulceration associated with Sjögren's syndrome: report of | 1991 Mar | A case of noninfectious bilateral corneal ulceration in a 46 year old patient with Sjögren's syndrome is reported. The clinical evolution is commented and the available therapeutic measures for this complication are discussed. | |
3264663 | SS-B/La antigen purification, and ELISA detection of anti-SS-B/La antibodies in sera from | 1988 Nov | SS-B/La antigen was purified by immunoadsorbent columns with immunoglobulin from a patient with primary Sjögren's syndrome. Monitoring of the purification was facilitated by the fused rocket-immunoelectrophoresis technique. Technical ELISA variables for the detection of serum antibodies against the SS-B/La antigen were evaluated, and a recommended procedure is described. Prospective investigation of anti-SS-B/La antibodies in 103 blood donors and 131 patients with chronic inflammatory connective tissue diseases, including 43 patients with primary Sjögren's syndrome was performed. Anti-SS-B/La antibody concentrations were above normal in 65% of the patients with primary Sjögren's syndrome (verified by the strictly objective Copenhagen criteria for keratoconjunctivitis sicca and xerostomia) and 9% of patients with other chronic connective tissue diseases. The predictive value for primary Sjögren's syndrome among patients with increased levels of the anti-SS-B/La antibodies attending a rheumatology clinic was 78%. | |
3495872 | An analysis of polyclonal B cell activation in Sjögren's syndrome. Characterization of B | 1986 | We intended to analyze the mechanism of polyclonal B cell activation in patients with Sjögren's syndrome (SS). Peripheral blood mononuclear cells (PBMC) were grown in bulk cultures without stimulation. Four cell lines (SS-1, SS-7, SS-10, SS-14) were successfully established from SS patients but none from normal controls. All of the cell lines were B cell origin possessing B1, B4 and HLA-DR antigens on their surfaces and were positive for EB virus associated nuclear antigens (EBNA). Both SS-7 and SS-10 spontaneously produced IgM whereas SS-1 and SS-14 IgG. All the cell lines except SS-7 expressed receptors for B cell stimulatory factors (BSF). Culture supernatants of these cell lines contained multiple biological activities including those for IL-1, IL-2, IL-3 and BCGF. These data suggest that B cells are polyclonally activated in vivo presumably by EB virus in SS and these activated B cells might perturb immunoregulatory system by producing multiple lymphokines. |