Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8560190 | Serum antibodies from patients with primary Sjögren's syndrome and systemic lupus erythem | 1996 Jan | The aim of this study was to investigate the epitope recognition pattern of La(SS-B) autoantibodies in sera from patients with Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) using overlapping synthetic decapeptides on solid phase. Eighty different decapeptides with five amino acids overlap from the human La(SS-B) autoantigen were synthesized on cellulose paper using F-moc chemistry. Tests were performed with 14 SS and six SLE sera. The results showed that the immune response to the La(SS-B) oligopeptides was restricted and unique for each individual with no particular pattern typical for each of the two diseases, apart from the fact that SLE sera gave positive reaction with fewer peptides. Regions within the N- and C-termini harboured most of the positive sequences. The authors specifically addressed the possibility of a viral aetiology for disease development or autoantibody generation. In this context the most frequently recognized linear epitopes on the La(SS-B) autoantigen showed sequence similarities with proteins from a range of ubiquitous human viruses, in particular from the herpes virus group. The La(SS-B) autoantibodies may thus be generated through molecular mimicry. | |
| 8315599 | Salivary autoantibodies in HIV-associated salivary gland disease. | 1993 May | A subset of HIV-positive patients develops salivary gland disease (HIV-SGD), characterized by salivary gland enlargement and/or decreased salivary flow. While clinical symptoms are similar to Sjögren's syndrome (SS), patients with HIV-SGD lack circulating anti-SS-A/Ro and anti-SS-B/La. Occasionally, SS patients lacking circulating anti-SS-A/Ro and anti-SS-B/La have these antibodies in their saliva. Salivas from 11 patients with HIV-SGD, 13 HIV+ patients without HIV-SGD, 14 HIV-negative men controls, and 11 patients with SS were screened for autoantibodies. Five HIV-SGD salivas had antibodies recognizing the cytoplasm of a salivary cell line. No HIV+ controls showed reactivity. Ten of 11 SS patients had salivary autoantibodies, and one HIV-negative control was positive for them. Salivary anti-SS-A/Ro was present in 8/11 SS patients, and 7 also contained anti-SS-B/La. No HIV-SGD salivary samples had these specific autoantibodies. These findings suggest that while glandular polyclonal expansion occurs in both HIV-SGD and SS, different autoantibodies are produced. | |
| 1521174 | [IgG autoantibodies against cellular p72 antigen crossing with (MLV) p15-gag antigen: pres | 1992 | IgG antibodies of autoimmune SLE (Systemic Lupus Erythematosus) serum S detected a HeLa hnRNP 72 kDa protein, cross-reacting with the retroviral (MLV) p15-gag polypeptide. Since serum S disclosed a ubiquitous 72 kDa antigen in HeLa cell fractions, was prepared the so-called cytoplasmic "X fraction", enriched for the 72 kDa protein, defined here as p72. This autoantigen was detected by antibodies of HIV 1+ patients, recently of seroconverted (RSC) asymptomatic subjects, of HBV+ sera, and of primary Gougerot-Sjögren (prGS) sera. The presence of these autoantibodies in different autoimmune and infectious pathologies raises the question of the involvement of p72 in the immune processes and in the early HIV1 infection. | |
| 7979595 | Phenotypic and functional activation of alveolar macrophages, T lymphocytes and NK cells i | 1994 Sep | OBJECTIVES: Attempts to differentiate between the pathogenesis of the severe pulmonary manifestations observed in systemic sclerosis (SSc) and the mild form in primary Sjögren's syndrome (pSS) were performed by studying cell populations recovered during bronchoalveolar lavage (BAL). METHODS AND RESULTS: Two-colour flow cytometric analysis of BAL fluid lymphocytes showed a similar degree of phenotypic activation (DR+) of CD4+ and CD8+ T lymphocyte subsets and CD16+ NK cells in patients with SSc (n = 13) and pSS (n = 11) groups and healthy controls (n = 11). Alveolar macrophages expressed the CD14 antigen at significantly increased densities in patients with SSc. Alveolar macrophage activation in SSc was also suggested by increased IL-6 concentrations in neat BAL fluid and increases in macrophage production of TNF alpha and EGF in vitro. SSc patients also had increased proportions of neutrophils and eosinophils in BAL fluid. No correlations were found between any cellular subsets or cytokine levels in BAL fluid and lung status at the time of lavage in SSc or pSS patients or the subsequent course of the pulmonary function in SSc patients. CONCLUSION: It is concluded that the phenotypical activation of alveolar helper/inducer (DR+CD4+) and suppressor/cytotoxic (DR+CD8+) T lymphocytes and NK (DR+CD16+) cells is not a prerequisite for the development of lung fibrosis in SSc or bronchial hyper-responsiveness in pSS. Alveolar macrophage activation may contribute to the development of lung fibrosis in SSc. | |
| 1285896 | Target antigens of the SSA/Ro and SSB/La system. | 1992 Oct | The SSA/Ro and SSB/La antigens are polypeptides which serve as autoantigens in systemic lupus erythematosus and Sjogren's syndrome. The SSA/Ro contains two major isoforms of 60 kD and 52 kD. The former is the main native antigen while the latter is a major autoantigen in its denatured form. The SSB/La is a single phosphorylated protein of 48 kD. Recently a new protein of 46 kD, termed calregulin, was suggested as an additional component of the SSA/Ro antigens. However, extensive investigations failed to confirm its relation to the SSA/Ro system. Based on molecular techniques and cDNA cloning of these antigens, it was demonstrated that the 60 kD protein is capable of binding RNA and DNA molecules, suggesting a regulatory role in transcription for this antigen. The 52 kD polypeptide contains multiple zinc finger motifs and its sequence is homologous to the mouse rptl protein, which is a T-cell regulating peptide. The SSB/La is associated with precursors of 5S RNA and tRNA, implying that it has a role in the synthesis and maturation of RNA polymerase III transcripts. The 60 kD and 52 kD SSA/Ro components may be associated within the cell. The SSA/Ro and SSB/La may also be in complex in some points of the cell cycle. | |
| 1543196 | Increased soluble CD4 and decreased soluble CD8 molecules in patients with Sjögren's synd | 1992 Feb | PURPOSE: A new enzyme-linked immunosorbent assay for soluble CD4 (sCD4) and soluble CD8 (sCD8) molecules has been developed. We estimated the concentrations of these molecules in patients with Sjögren's syndrome and in patients with systemic lupus erythematosus (SLE) serving as a control population for non-Sjögren's inflammatory disease, since several findings suggestive of an aberration of immunocompetent cells have been reported in these autoimmune diseases. PATIENTS AND METHODS: The study population consisted of 41 patients with Sjögren's syndrome (28 cases of the primary form and 13 cases of the secondary form), 66 patients with SLE, and 43 normal individuals. Serum samples and clinical and laboratory data were collected from each patient and control. Assays of the sCD4 and sCD8 molecules were performed using an enzyme-linked immunosorbent kit developed by T Cell Science Inc., Cambridge, MA. RESULTS: The concentration of sCD4 was significantly increased in patients with both primary and secondary Sjögren's syndrome as compared with that in the control subjects. In contrast, sCD8 was significantly decreased in patients with primary disease but not in patients with secondary disease. A low or high concentration of sCD8 was significantly correlated with the presence of anti-SS-A antibody or hypocomplementemia, respectively. A similar significant correlation was noted between an increased sCD4 concentration and increased serum IgG level. In patients with SLE, the levels of both sCD4 and sCD8 were significantly increased. CONCLUSION: These observations represent the first evidence of an increased level of the sCD4 molecule and a decreased level of the sCD8 molecule and an association with immunologic abnormalities in Sjögren's syndrome. The increased and decreased levels of these soluble molecules observed may play a pathologic role in patients with Sjögren's syndrome. | |
| 8843854 | Two major autoantigen-antibody systems of the mitotic spindle apparatus. | 1996 Oct | OBJECTIVE: To characterize human autoantigen-antibody systems related to the mitotic poles and spindles. METHODS: Thirty-seven human sera with autoantibodies staining mitotic poles and spindles in indirect immunofluorescence (IIF) studies were further characterized by immunofluorescence on mitotic cells and by immunoblotting and immunoprecipitation. Clinical diagnoses meeting the American College of Rheumatology criteria were based on chart review and interview with the corresponding physicians. RESULTS: Two autoantibody systems reactive with mitotic poles and spindles were defined. Type 1 nuclear mitotic apparatus (NuMA-1) antibodies were identified in the serum of 30 patients. Interphase cells showed a fine, speckled, nuclear staining, while mitotic cells had bright staining of the rim of the centrosomes and light staining of the spindles proximal to the centrosomes. In telophase, the staining shifted from the centrosomes to the reforming nuclei. On immunoblotting, anti-NuMA-1 sera reacted with a 210-kd protein. The reactivity of these sera was identified (with the aid of reference antibodies) as the previously described NuMA antigen-antibody system. Clinical information was available for only 17 of the 30 patients with anti-NuMA-1; of these, 17 (53%) had clinical and lip biopsy findings that met the criteria for Sjögren's syndrome. NuMA-2 antibodies were found in the sera of 7 patients. Interphase cells showed no nuclear or cytoplasmic staining, but mitotic cells had brightly stained poles and spindles. At anaphase/telophase, staining shifted to the midbody and the intercellular bridge. Anti-NuMA-2 sera immunoprecipitated a protein of 116 kd. This group of patients was more heterogeneous and had both systemic and organ-specific autoimmune diseases. CONCLUSIONS: NuMA protein (here called NuMA-1) and a 116-kd protein (here called NuMA-2) are the major targets of the autoimmune response in the mitotic apparatus, since most of the selected sera (based on IIF staining of the mitotic spindles and poles) recognized 1 of these 2 antigens. | |
| 7597381 | Anticentromere antibody--clinical associations. A study of 44 patients. | 1995 | The objective of this study was to determine the clinical features of 44 patients with anticentromere antibody (ACA) positivity. We undertook a retrospective review of 44 ACA-positive patients (1 male and 43 females with a mean +/- SD age of 53.6 +/- 12.2 years). There were 25 patients with limited systemic sclerosis, 12 with Raynaud's disease, 2 with Sjögren's syndrome, 2 with systemic lupus erythematosus and 3 with polyarthritis. ACA was more frequently found in patients affected by limited systemic sclerosis with mild visceral involvement and in patients with Raynaud's disease. Moreover, ACA was detected in other connective tissue diseases that were characterized by an atypical autoantibody profile. | |
| 7517508 | A reduced level of multiple mutation in a shuttle vector passaged in Sjögren's syndrome c | 1994 Jul | Sjögren's syndrome is a systemic disorder with unknown etiology, displaying many signs of autoimmunity. Although the basic mechanism of this disease is unknown, a defect in somatic mutagenesis of antibody genes has been suggested. Using a shuttle vector plasmid, we here show that the number of vectors with multiple base changes in a marker gene was reduced in B cell lines from two patients with Sjögren's syndrome (8% in both), as compared with values reported for cell lines from normal human donors (16-27%). This finding suggests that a reduction of the rate of somatic mutagenesis may influence the development of symptoms in Sjögren patients. | |
| 7523671 | Autoimmune sera react with multiple epitopes on recombinant 52 and 60 kDa Ro(SSA) proteins | 1994 Jun | OBJECTIVE: To determine the reactivity of recombinant 52 and 60 kDa Ro(SSA) (Ro) proteins with sera from 3 subsets of patients with Ro autoantibody associated disease. METHODS: Complementary DNA (cDNA) clones that encode the human 52 and 60 kDa Ro autoantigens were isolated by the polymerase chain reaction and utilized to express recombinant glutathione S-transferase (GST) fusion proteins. Double immunodiffusion (ID) defined Ro positive autoimmune sera from 12 patients with neonatal lupus erythematosus (NLE), 16 with subacute cutaneous lupus erythematosus (SCLE) and 12 with primary Sjögren's syndrome (SS) were tested by enzyme linked immunosorbent assay (ELISA) against the recombinant 52 and 60 kDa Ro fusion proteins. RESULTS: Seventy-five percent of NLE, 56% of SCLE and 83% of SS sera reacted with the 52 kDa fusion protein. Seventy-five percent of NLE, 63% of SCLE and 83% of SS sera reacted with the 60 kDa fusion protein. Seventeen percent of NLE sera, 25% of SCLE sera and 8% of SS sera were nonreactive to both full length fusion proteins. Eight (57%) of 14 ID defined Ro negative NLE, SCLE and SS sera were reactive with both Ro fusion proteins by ELISA: ELISA studies with recombinant 52 and 60 kDa Ro protein fragments revealed at least 2 major epitopes on each Ro protein. A fragment of the 52 kDa Ro protein that contains a putative leucine zipper motif reacted with 100% of ID defined Ro positive SS sera. CONCLUSION: Our data demonstrate that the ID assay and the recombinant Ro ELISA together are more sensitive in detecting Ro antibodies than either assay alone, and that multiple epitopes are present on both Ro proteins. | |
| 8101109 | Mixed connective tissue disease and Sjögren's syndrome, accompanied by HTLV-I infection. | 1993 Mar | A 48-year-old Japanese woman with mixed connective tissue disease (MCTD) and Sjögren's syndrome (SjS) was a carrier of HTLV-I and had anti-HTLV-I antibodies in her serum. Moreover, her peripheral blood lymphocytes contained proviral DNA for the pX region of HTLV-I as detected by the polymerase chain reaction. An immunohistological study was performed on her minor salivary gland to detect gene products of HTLV-I (P19 and P28 proteins); specific staining was demonstrated only in the epithelium of the salivary ducts. HTLV-I and its associated immune dysfunction may be responsible for MCTD and SjS in this patient. | |
| 9007728 | Immune thrombocytopenia and alpha-interferon therapy. | 1996 Dec | Thrombocytopenia is often found in patients with liver diseases, especially due to congestive splenomegaly caused by portal hypertension. Immune thrombocytopenia has been described rarely, and it seems to be especially associated with hepatitis C virus, which has been described as having a particular interaction with the immune system contributing to the induction of autoimmunity. Interferons, on the other hand, because of their immunomodulatory properties, are able to induce or exacerbate autoimmune diseases. Mild thrombocytopenia is a common adverse effect of interferon therapy. Severe life-threatening thrombocytopenia is extremely rare. We report two cases of severe immune thrombocytopenia in patients with chronic hepatitis C, probably induced by alpha-interferon. Bone marrow aspirate and elevated platelet-associated IgG antibodies, determined by indirect immunofluorescence, were suggestive of immune thrombocytopenia. None of the patients had any clinical sign of autoimmune syndrome, including arthritis, serositis, Sicca syndrome, vasculitis, thyroid abnormalities and others. Cryoglobulins and rheumatoid factor were tested and were undetectable. The patients' histories of exposure to alpha-interferon and the exclusion of other causes are most consistent with drug-induced immune thrombocytopenia. After alpha-interferon withdrawal, thrombocytopenia was treated successfully with prednisolone and immunoglobulins. Response to treatment was consistent with the diagnosis of alpha-interferon-induced immune thrombocytopenia and peripheral consumption of platelets. | |
| 7704562 | Cryoglobulinaemias: a multi-centre study of the early clinical and laboratory manifestatio | 1995 Feb | In a multi-centre retrospective study, we compared clinical and laboratory data in 913 patients with cryoglobulinaemias, divided as: (i) essential cryoglobulinaemias; (ii) cryoglobulinaemias secondary to connective tissue diseases (CTD), lymphoproliferative or other haematological diseases (LPD), chronic liver diseases (CLD), and 'other diseases'. Purpura was the commonest presenting feature in all groups and was more common in essential cryoglobulinaemias (p < 0.0001). Meltzer's triad (purpura, arthralgia, weakness) was less frequent, but similarly distributed. Renal involvement was randomly distributed. Neurological impairment was less frequent in cryoglobulinaemias secondary to CLD (p < 0.002). Raynaud's phenomenon, arthritis and sicca syndrome were more frequent in cryoglobulinaemias secondary to CTD. Essential cryoglobulinaemias had a significantly higher percentage of serum complement C4 < 8 mg/dl (p < 0.004), of detectable rheumatoid factor activity (p < 0.0002), and of type II cryoglobulins (p < 0.0001). Liver involvement was evident at presentation in 32.6% of essential cryoglobulinaemias, 27.1% of cryoglobulinaemias secondary to LPD and 12.2% of cryoglobulinaemias secondary to CTD. Antibodies to hepatitis B surface (HBsAg) and core (HBc) antigens were more frequent in cryoglobulinaemias secondary to CLD; anti-HBs antibodies were randomly distributed. Antibodies to hepatitis C (HCV) were tested for in 224 patients, and prevalence was high in all the groups, but lower in cryoglobulinaemias secondary to CTD (p < 0.0001). Type II and type III essential cryoglobulinaemias differed significantly in renal involvement (p < 0.0001), cryocrit > 3% (p < 0.0001), C4 < 15 mg/dl (p < 0.001), HBsAg prevalence (p < 0.01) and purpura (p < 0.05). Despite the high prevalence of HCV markers in all groups, the role of HCV in essential cryoglobulinaemia is not well defined; HBV seems to play only a marginal role. | |
| 1409036 | [Why are diabetic patients treated at rheumatological hospitals?]. | 1992 Jan 6 | Retrospective analysis included 316 case histories of diabetic patients treated at the Silesian Rheumatology Hospital in 1987-1988. An analysis included causes of disorders, calcium-phosphorus metabolism disturbances, lipid and purine disorders. Statistical parameters were compared with the type of diabetes mellitus, duration of the disease, sex, age and obesity. There were 10% of inflammatory rheumatic disorders (6.4% rheumatic arthritis, 1.7% of rheumatoid spondylosis and 2% of other disorders) in the analysed case histories, and 32% of degenerative disorders (19% of vertebral column joints and 12.7% of other joints). Degenerative disorders were noted more frequently in patients with diabetes mellitus type 2, treated with insulin, while spondylopathies were particularly frequent in female patients of this group. Biochemical disorders in the form of hypocalcemia and hypophosphatemia, hypertriglyceridemia, hyperuricemia, signs of lesions to the liver and kidneys were more increasing with the duration of the disease and the degree of insulin-dependence. Locomotive system disorders are not related only to primary articular lesions. They depend also on diabetic neuro-vascular complications and osteopenia. | |
| 8147926 | Induction of cyclooxygenase II in human synovial microvessel endothelial cells by interleu | 1994 Apr | OBJECTIVE: To characterize the effects of interleukin-1 alpha (IL-1) on prostanoid biosynthesis by human rheumatoid synovium microvessel endothelium (HSE). METHODS: HSE cells were treated with cytokines, metabolic inhibitors, and steroids under various conditions, and prostaglandin biosynthesis was determined by radioimmunoassay. Newly synthesized cyclooxygenase (COX) was quantitated by immunoprecipitation of metabolically labeled HSE cell lysates. The effects of IL-1 on levels of messenger RNA (mRNA) for COX II were also determined. RESULTS: IL-1 induced an increase in COX activity (as assessed by prostaglandin E2 release) that was dose- and time-dependent and was blocked by cycloheximide, actinomycin D, and dexamethasone. IL-1 induced a selective increase in COX II mRNA and biosynthesis of COX II protein that was blocked by dexamethasone. CONCLUSION: IL-1 treatment of HSE cells induces COX II, as demonstrated by both Northern blotting and immunoprecipitation. The induction of COX II expression provides, at least in part, a mechanism for the pronounced increase in prostanoid synthesis observed in HSE cells following incubation with IL-1. The selective up-regulation of HSE COX II by inflammatory cytokines such as IL-1 suggests that development of specific pharmaceutical inhibitors for this novel isozyme may provide significant new therapeutic advantages in the treatment of RA. | |
| 8569187 | Chondrocyte matrix metalloproteinase-8: up-regulation of neutrophil collagenase by interle | 1996 Jan | The loss of aggrecan from articular cartilage may lead to the development of osteoarthritis (OA). Degradation products of human aggrecan, generated in vivo by enzymatic cleavages, have been identified in synovial fluid of patients with rheumatoid arthritis and OA. One matrix metalloproteinase (MMP), stromelysin (MMP-3), and an unidentified proteinase called "aggrecanase" are believed to generate these products in pathologic conditions. Thus far, only one proteinase, neutrophil collagenase (MMP-8), has been shown in vitro to be capable of cleavage of the aggrecan molecule at the "aggrecanase" site. In this study, we compare the presence and distribution of MMP-3 and MMP-8 in cartilages from two different joints of normal human donors. We determined whether mRNA for MMP-8 is expressed in normal human articular cartilage from different joints. In addition, we compared differences in MMP-8 and MMP-3 gene expression between human ankle and knee cartilage after in vitro stimulation by interleukin (IL)-1 beta. These two joints were chosen because the incidence of symptomatic and radiographic OA varies between the different joints. The knee is the most frequently involved joint, whereas the ankle (talocrural) joint is relatively rarely affected. Message for MMP-8 was detected in untreated cartilage from normal knee joints, but not in untreated cartilage of normal ankle joints. Message for MMP-3 was detectable in most of the knee and ankle cartilages. Messenger RNA expression for both MMPs could be up-regulated by IL-1 beta. The highest doses of IL-1 beta appeared to be most effective in stimulation of mRNA for MMP-3, whereas MMP-8 expression was more sensitive to lower doses of IL-1 beta. The fact that ankle cartilage with a low incidence of OA does not express MMP-8, whereas knee cartilage with a high incidence of OA does not express MMP-8, whereas knee cartilage with a high incidence of OA does constitutively express MMP-8, suggests that MMP-8 might be one of the key enzymes in the pathogenesis of osteoarthritis. This is further supported by our finding that the earliest signs of cartilage degradation were very similar to those found in IL-1 beta-treated explants. | |
| 7760867 | Silicone breast implants and the risk of connective-tissue diseases and symptoms. | 1995 Jun 22 | BACKGROUND: Silicone breast implants have been linked to a variety of illnesses, the most controversial of which are connective-tissue diseases and symptoms. To study this relation, we analyzed data from 14 years of follow-up of the Nurses' Health Study cohort. METHODS: Women who were free from connective-tissue disease in June 1976 were followed through May 31, 1990, before there was widespread media coverage of the possible association of breast implants and connective-tissue diseases. Information was collected through biennial and supplementary mailed questionnaires and blinded reviews of medical records with the use of standardized criteria. Relative risk, the measure of association, was defined as the incidence rate of connective-tissue disease among women with breast implants divided by the corresponding incidence rate among women without breast implants. RESULTS: Among 87,501 women who were eligible for follow-up, 516 were confirmed as having definite connective-tissue diseases and 1183 as having breast implants (of which 876 were silicone-gel-filled, 170 saline-filled, 67 double-lumen, 14 polyurethane-coated, and 56 of unknown type). The mean (+/- SD) period of follow-up after surgery was 9.9 +/- 6.4 years (range, 1 month to 40.5 years). Three of the patients with definite connective-tissue disease--all had rheumatoid arthritis--had implants (one silicone-gel-filled, one saline-filled, and one double-lumen). The age-adjusted relative risk of a definite connective-tissue disease among women with any type of implant was 0.6 (95 percent confidence interval, 0.2 to 2.0), as compared with women without implants. For women with silicon-gel-filled implants, the comparable relative risk was 0.3 (95 percent confidence interval, 0 to 1.9). The relative risk of self-reported signs or symptoms of connective-tissue disease for women with implants was 1.5 (95 percent confidence interval, 0.9 to 2.4); the risk of having any 1 of 41 signs, symptoms, or laboratory features of connective-tissue disease was 0.7 (95 percent confidence interval, 0.3 to 1.6). CONCLUSIONS: In a large cohort study, we did not find an association between silicone breast implants and connective-tissue diseases, defined according to a variety of standardized criteria, or signs and symptoms of these diseases. | |
| 8370391 | Selective activation of resting human gamma delta T lymphocytes by interleukin-2. | 1993 Sep | In rheumatoid arthritis and other inflammatory diseases we and others have found that gamma delta T cells express activation antigens, suggesting that they are involved in the pathogenesis of these disorders. In this study we have stimulated peripheral blood mononuclear cells from normal donors with recombinant interleukin-2 (rIL-2) to see whether such a stimulus alone could activate gamma delta T cells. Short-term exposure (24-96 h) to rIL-2 selectively stimulated the gamma delta but not the alpha beta T cells to express activation antigens (CD69, CD25 and HLA-DR). Long-term culture (2 weeks) in rIL-2-containing medium caused a selective increase in the proportion of the gamma delta T cells and a corresponding reduction of the fraction of alpha beta T cells. Limiting dilution analysis revealed that approximately 1/60 of the gamma delta T cells responded to IL-2 in contrast to only 1/250 of the alpha beta T cells. Comparison of the expression of the IL-2 receptor (IL-2R) alpha and beta chains showed that there was a similar expression of the alpha chain on gamma delta and alpha beta T cells whereas the relative density of the beta chain was more than twice as high on gamma delta T cells. Both the IL-2-induced proliferation of gamma delta T cells and the expression of activation antigens on these cells could be inhibited by an anti-IL-2R beta monoclonal antibody (mAb) but not by an anti-IL-2R alpha mAb. Expression of CD69 on gamma delta T cells was dependent neither on the presence of B cells, monocytes, nor alpha beta T cells. Finally, we found that the IL-2-induced expression of CD69 was inhibited by activation of cAMP-dependent protein kinase and by inhibition of the Src-family of the tyrosine protein kinase, but not by inhibition of protein kinase C or by activation of the CD45 associated tyrosine phosphatase. The ability of gamma delta T cells to be activated by IL-2 is a feature which they have in common with natural killer cells. Moreover, it may be possible that the expression of activation antigens on gamma delta T cells in inflammatory diseases is an epiphenomenon secondary to IL-2 produced by activated alpha beta T cells. | |
| 8392493 | Leukotriene B4-induced granulocyte trafficking in guinea pig dermis. Effect of second-gene | 1993 Jun | Leukotriene B4 (LTB4) is a proinflammatory product of arachidonic acid metabolism that has been implicated as a mediator in a number of inflammatory diseases. When injected intradermally into the guinea pig, LTB4 elicits a dose-dependent migration (chemotaxis) of neutrophils (PMNs) into the injection sites as assessed by the presence of a neutrophil marker enzyme myeloperoxidase. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-3,4-dihydro-8-p ropyl-2H-1-benzopyran-2-carboxylic acid), a first-generation LTB4 receptor antagonist inhibited the chemotactic actions of LTB4 when coadministered into the dermal site and when given orally with ED50 values of 340 ng and 1.7 mg/kg, respectively. The second-generation LTB4 receptor antagonists SC-50605 (7-[3-[2(cyclopropylmethyl)-3-methoxy-4-(4-thiazolyl)phenoxy]propoxy]- 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid) and SC-51146 (7-[3-[2(cyclopropylmethyl)-3-methoxy-4-[(methylamino)carbonyl] phenoxy]propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-propanoic acid) inhibited LTB4-induced chemotaxis when coadministered with ED50 values of 70 ng and 32 ng, respectively, and when given intragastrically with ED50 values of 0.10 and 0.09 mg/kg, respectively. SC-41930, SC-50605, and SC-51146 had oral durations of action of 5.5, 15, and 21 h, respectively. These potent, LTB4 receptor antagonists may well have application in the medical management of disease states such as asthma, rheumatoid arthritis, inflammatory bowel disease, contact dermatitis, and psoriasis, where LTB4 is implicated as an inflammatory mediator. | |
| 8094329 | Subset-specific effects of sex hormones and pituitary gonadotropins on human lymphocyte pr | 1993 Mar | Clinical observations on patients with systemic lupus erythematosus and rheumatoid arthritis and studies in murine models of autoimmune diseases suggest an important role for the sex and pituitary hormones in immune function. Estrogen and testosterone have been shown to modulate B cell functions in vitro. Prolactin (PRL) has been shown to have immunomodulatory functions. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) have homology to thioredoxin, a potentiator of T-cell growth. We therefore studied the proliferative response of peripheral blood mononuclear cells (PBMC) from normal adult males to various stimuli in the presence or absence of estradiol (E2), testosterone (Te), PRL, FSH, and LH and the effect of these hormones on T-cell subsets by flow cytometry. Unfractionated PBMC were stimulated with 1% phytohemagglutinin (PHA) (polyclonal activation), anti-CD3 (T-cell receptor stimulation), or recombinant interleukin 2 (IL-2) (late stages of activation). We assessed the effects of E2 (0.3-30 ng/ml), Te (3-300 ng/ml), PRL (2-200 ng/ml), FSH (1-100 mIU/ml), and LH (1-100 mIU/ml). E2 and Te had no consistent effect on PBMC proliferation in response to any of the stimuli. E2 significantly decreased the percentage of CD4+ cells following PHA stimulation (P = 0.022), while significantly enhancing the percentage of CD8+ cells following IL-2 stimulation (P = 0.007). Te significantly increased the percentage of CD4+ cells following IL-2 stimulation (P = 0.03). PRL enhanced proliferation in response to IL-2 and PHA without subset-specific effects. FSH and LH both enhanced IL-2-induced proliferation, particularly in physiological doses (10 mIU/ml). FSH at 100 mIU/ml significantly decreased the percentage of CD4+ cells in unstimulated cultures (P = 0.003), while it enhanced the percentage of CD8+ cells following PHA stimulation (P = 0.004). The enhancement in CD8+ cells appeared the most marked in the CD8+CD28+ subset. LH at 10 mIU/ml significantly enhanced the percentage of CD4+ cells following IL-2 stimulation (P = 0.009) and at higher doses (100 mIU/ml) enhanced the percentage of CD4+ cells following PHA stimulation (P = 0.011). Thus, sex steroids and adenohypophyseal hormones (PRL, FSH, and LH) have subset-specific effects on T-cell activation which may influence sex-related differences in immune response. |