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ID PMID Title PublicationDate abstract
8849369 Activation of transcription factor NF-kappa B in human synovial cells in response to tumor 1996 Feb OBJECTIVE: To examine whether nuclear factor kappaB (NF-kappaB) is activated in cultured synovial cells in response to tumor necrosis factor alpha (TNFalpha) and to investigate the correlation between NF-kappaB activation and synovial cell proliferation. METHODS: Activation of NF-kappaB was detected by electrophoretic mobility shift assay. The transcription of several NF-kappaB-dependent genes was evaluated by reverse transcriptase polymerase chain reaction and transient expression assay using human immunodeficiency virus-long terminal repeat chloramphenicol acetyltransferase. Proliferative activity was determined by measurement of 3H-thymidine incorporation. RESULTS: Stimulation of synovial cells with TNFalpha activated NF-kappaB and subsequent transcription of several genes. Treatment of synovial cells with N-acetyl-L-cysteine (NAC), an antioxidant agent, inhibited TNFalpha-induced NF-kappaB activation and transcription. Moreover, NAC also inhibited synovial cell proliferation induced by TNFalpha. CONCLUSION: Our results suggest that NF-kappaB plays a pivotal role in synovial cell activation by TNFalpha. Thus, suppression of NF-kappaB could be a potential therapeutic modality for synovitis such as that of rheumatoid arthritis.
8520712 A connective tissue disease screening questionnaire for population studies. 1995 Jul To develop a technique to screen populations for potential connective tissue disease (CTD), we mailed a 30-item questionnaire to 253 randomly selected patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease (MCTD), or Sjögren's syndrome and to 340 randomly selected control subjects. The response rate after four mailings was 71% for case subjects and 54% for control subjects. Test-retest reliability for detection of any CTD was 0.82. Sensitivity for specific CTDs was 83 to 96% and specificity was 83 to 93%. The positive predictive value for any CTD (assuming an overall prevalence of 1.3%) was 5.5%; negative predictive value was 99.7%. The CTD Screening Questionnaire has high sensitivity and specificity for screening large populations.
7807105 Taperloc femoral component. A 2-6-year study of the first 100 consecutive cases. 1994 Oct The first 100 consecutive patients who underwent insertion of the Taperloc (Biomet, Warsaw, IN) femoral stem were prospectively studied with a mean follow-up period of 3.8 years (range, 2-6 years). Two of the original 100 patients were lost, giving a 98% follow-up rate. The diagnoses included osteoarthritis (76 patients), avascular necrosis (19), rheumatoid arthritis (3), chrondrolysis (1), and post-traumatic arthritis (1). The mean age at surgery was 56 years (range, 25-79 years), mean weight was 78 kg (range, 45-127 kg), and the female to male ratio was 29:71. Charnley pain and function scores were 3.0 and 2.8 before surgery and 5.5 and 5.4 after surgery. Thigh pain was present in 2% of the patients at the final follow-up evaluation. There were no revisions. Radiographic signs of bone-ingrowth fixation (calcar atrophy, spot welds) were seen in 92 of 94 components (98%). No component had complete demarcation of the porous-coated zones. Fifty-two of 94 patients were able to be matched for age, sex, weight, diagnosis, and length of follow-up period with a series of patients who received a contemporary cemented total hip. In this matched subset, the Charnley pain and function scores were 5.6 and 5.5 for the cementless Taperloc stem and 5.7 and 5.5 for the cemented control group; this is not a significant difference. These data indicate a clinical performance equivalent to a matched group of contemporary cemented total hip arthroplasties.
8140094 Structure-activity studies of human tumour necrosis factors. 1994 Jan The mechanism by which tumour necrosis factors (TNF and lymphotoxin, also called TNF alpha and TNF beta respectively) exert their cytotoxic activity on many malignant cells, remains largely unknown. Furthermore, the broad array of differentiation (gene induction) and mitogenic activities towards many primary cells is still a subject of intensive investigation. TNF is an important mediator in inflammation, immune responses and infection-related phenomena and these activities contribute to the severe toxicity seen when TNF is used as an anticancer agent. The first step in the mechanism of action is the specific binding of the ligand to its receptors and dissection of the molecular mechanism involved in this interaction is the subject of this review. The reasons for the interest in this aspect are obvious: first, the development of strong antagonistic TNF analogues can be useful in dampening the potentially lethal or debilitating effects of an overproduction of the cytokine (as in septic shock or rheumatoid arthritis). Secondly, since two distinct TNF receptors exist, construction of TNF muteins that distinguish between both types may lead to derivatives of this pleiotropic agent with a more restricted biological activity pattern. Ideally, one would like to develop a TNF mutant that has retained its cytotoxic action on tumour cells without inducing the deleterious systemic toxicity. Such an optimized TNF molecule could become a potent anticancer agent.
8252715 Serum phospholipases A2 in inflammatory diseases. 1993 Dec Phospholipase A2 (EC 3.1.1.4; PLA2) is detected in serum by determination of either the catalytic activity of the enzyme or the concentration of the enzyme protein by immunoassays. The most sensitive methods for determining PLA2 catalytic activity are radiometric assays, with a substrate of synthetic phospholipid (e.g., phosphatidylcholine or phosphatidylethanolamine) containing a 14C- or 3H-labeled fatty acid at the sn-2-position. Membranes of autoclaved Escherichia coli grown in the presence of radioactive oleic acid may also be used as a substrate. The released fatty acids are separated from the unreacted substrate and quantified by liquid scintillation counting. PLA2 catalytic activities are increased in serum in sepsis, acute pancreatitis, peritonitis, multiple injuries, rheumatoid arthritis, and other arthropathies. Immunoassays--radioimmunoassay, enzyme-linked immunosorbent assay, or time-resolved fluoroimmunoassay--are based on the use of either polyclonal or monoclonal antibodies to purified PLA2s. Specific assays have been developed for both pancreatic group I PLA2 (PLA2-I) and nonpancreatic group II PLA2 (PLA2-II). The cellular source of PLA2-I in serum is the pancreatic acinar cell. Increased serum PLA2-I values have been reported in acute pancreatitis, pancreatic cancer, and abdominal trauma. Increased PLA2-II values are found in conditions involving inflammation, e.g., sepsis, infections, acute pancreatitis, various forms of arthritis, cancer, complications of pregnancy, and postoperative states. Good correlations have been found in serum samples between the catalytic activity of PLA2 and the concentration of PLA2-II but not PLA2-I. PLA2-II may represent an acute-phase protein. The cellular source of the PLA2-II in serum is unknown; it is present in large amounts in cartilage and Paneth cells, prostatic gland cells, seminal fluid, lacrimal gland cells, and tears, but cannot be demonstrated by immunohistochemical or immunochemical methods in inflammatory cells.
8489536 AI/LEARN/Rheumatology. A comparative study of computer-assisted instruction for rheumatolo 1993 May OBJECTIVE: To assess the effectiveness of AI/LEARN/Rheumatology, a computer-controlled interactive videodisc system for teaching. METHODS: We assessed improvement in knowledge about rheumatic diseases, using a pretest and posttest in a control year and a treatment year. The subjects were medical students and postgraduate trainees taking the rheumatology elective. The control year used traditional lectures and the standard rheumatology curriculum. The treatment year used AI/LEARN/Rheumatology in place of lectures on rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis. RESULTS: The trainees showed significant improvement in knowledge in both the control year and the treatment year (P < 0.0001 for both). The average time spent using AI/LEARN/Rheumatology was similar to the time spent in lectures (3 hours). The number of patient consultations in which trainees participated was lower in the treatment year than in the control year; however, the adjusted posttest scores using the pretest as a covariate tended to be higher in the treatment year (P = 0.10). Analysis of covariance of the adjusted posttest scores for the treatment year only showed that the trainees who spent more time using AI/LEARN/Rheumatology learned more (r = 0.57). Trainees felt that AI/LEARN/Rheumatology was the most helpful educational experience of the elective. CONCLUSION: AI/LEARN/Rheumatology is an effective means of teaching about the rheumatic diseases. It has many advantages: availability for independent study, effective use of trainee's time, and liberation of faculty time from lectures. Trainees enjoyed using AI/LEARN/Rheumatology.
8431210 Suppression of interleukin-2 and interleukin-2 receptor biosynthesis by gold compounds in 1993 Feb OBJECTIVE: To further investigate the mechanism of action of gold compounds by studying their effects on interleukin-2 (IL-2) and IL-2 receptor (IL-2R) biosynthesis. METHODS: We cultured phytohemagglutinin- or anti-CD3 antibody-activated normal peripheral blood mononuclear cells (PBMC), as well as the erythroleukemic K562 cell line, in the presence of gold sodium thiomalate or auranofin. Tritiated thymidine incorporation assays, cytotoxicity assays, immunofluorescence analysis, enzyme-linked immunosorbent assay, Northern blot, and RNA dot-blot hybridization were used. RESULTS: Gold compounds, at concentrations attainable in vivo, inhibited the proliferation of normal PBMC, with no evidence of direct cytotoxicity. This inhibitory effect was associated with a dose-dependent suppression of both IL-2 and IL-2R messenger RNA accumulation. In contrast, the same concentrations of gold compounds failed to inhibit the spontaneous proliferation of the IL-2-independent K562 cells. CONCLUSION: Our findings suggest an IL-2/IL-2R-mediated mechanism for suppression of lymphocyte proliferation by gold compounds, which might account for the immunomodulatory effects of gold in patients with rheumatoid arthritis.
1353962 Inhibition of human phospholipase C by aurothiomalate and (triethylphosphine) gold complex 1992 Mar The effect of several gold complexes on the activity of phospholipase C from human blood platelets was studied in vitro. Aurothiomalate and auranofin--2 agents used for the chrysotherapy of rheumatoid arthritis--, gold chloride, (triethylphosphine)gold chloride, and 5 newly synthesized (triethylphosphine)gold complexes dose-dependently inhibited the enzyme with IC50 values between 0.8 mumol/l ((triethylphosphine)gold chloride) and over 100 mumol/l (auranofin). None of the compounds affected phospholipase A2 from human polymorphonuclear leukocytes at concentrations up to 100 mumol/l. Inhibition of phospholipase C by (triethylphosphine)gold chloride, aurothiomalate, and compound 3 was not significantly different at substrate concentrations of 20 and 100 mumol/l phosphatidylinositol, suggesting that these gold complexes do not inhibit phospholipase C by competing with the substrate. After confirming the Ca2+ dependence of the human platelet phospholipase C by demonstrating inhibition by the Ca2+ chelators EDTA and EGTA--but no inhibition by the Zn2+ chelator 1,10-phenanthroline--the inhibition of the enzyme by (triethylphosphine)gold chloride, aurothiomalate, and compound 3 was studied at 3 different concentrations of Ca2+ in the range of 0.2 to 2 mmol/l. Inhibition by (triethylphosphine)gold chloride was not affected by changes of Ca2+, whereas inhibition by aurothiomalate and compound 3 was markedly suppressed by increasing the Ca2+ concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
1600345 Endothelial heterogeneity and the acquired immunodeficiency syndrome: a paradigm for the p 1992 Feb Vascular disorders comprise a wide range of diverse disease entities. Correspondingly, vessels, and even more so the endothelial which line them, show a remarkable extent of heterogeneous differentiation, e.g. between the blood vascular and lymphatic systems, along the length of the vascular trees, and in the microvascular beds of various organs. The most important morphologic criterion to discriminate between endothelia is continuity (continuous endothelial cell layer and well-formed basement membrane) versus discontinuity (intra- or intercellular gaps and/or reduced or missing basement membrane). Most blood vascular endothelia are of the continuous type, while most sinusoidal and lymphatic endothelia are discontinuous by these criteria. Antigen expression corroborates these morphologic data in that CD31, CD34, and 1F10 antigen are exclusively expressed in continuous endothelia, while MS-1 antigen is preferentially expressed in non-continuous sinusoidal endothelia. In contrast, no specific marker has as yet been described for lymphatic endothelia. Endothelial heterogeneity substantially contributes to the pathogenesis of vascular disorders. For example, in patients with acquired immunodeficiency syndrome the same infectious agent may cause either bacillary angiomatosis (a lobular capillary proliferation) or peliosis (sinusoidal dilatation, endothelial denudation, and development of blood-filled cysts) depending on whether the affected organs have predominantly continuous endothelia or noncontinuous sinusoidal endothelia. Moreover, in Kaposi's sarcoma, it is still an open question of whether the lesion is derived from blood vascular or lymphatic endothelia (Kaposi's sarcoma cells in situ do not express the von Willebrand factor+, PAL-E+, 1F10+ phenotype of mature, resting blood vascular endothelia). It is also unresolved how endothelia of either type may be differentially induced to dedifferentiate and how they are recruited into the lesion. Clearly, knowledge about endothelial heterogeneity is still too incomplete to identify the actual mechanisms and molecules that govern the pathogenesis of vascular disorders (including still others than those mentioned here such as atherosclerosis, diabetic angiopathy, and rheumatoid arthritis) affecting distinct endothelia. Further efforts in antigenic phenotyping and in cell and molecular biology of heterogeneously differentiated endothelia should be made to improve this state of affairs.
8870111 Cyclooxygenase 1 and 2 in rheumatic disease: implications for nonsteroidal anti-inflammato 1996 Aug OBJECTIVES: Prostaglandin synthase (cyclooxygenase) is now known to exist in two separate isoforms, termed prostaglandin synthase 1 and 2 (or COX1 and COX2). This has prompted a dramatic increase in research regarding the contribution of these isoforms to inflammatory disease and their relationship to the efficacy and safety of nonsteroidal anti-inflammatory drugs (NSAIDs). The emerging picture is that COX1 is responsible for maintaining prostaglandin synthesis in the gastric mucosa, platelets, and kidney, whereas COX2 is responsible for prostaglandin production in inflamed tissues, including rheumatoid arthritis (RA) synovium. This review examines the validity of the hypothesis that NSAIDs exhibiting selectivity for COX2 demonstrate an improved safety and efficacy profile when compared with NSAIDs exhibiting selectivity for COX1. METHODS: Literature on the efficacy and safety (gastric, renal, and hemostatic) of various NSAIDs are compared with published data on their relative COX1 and COX2 in vitro specificity. RESULTS: No differences in clinical efficacy are evident between NSAIDs exhibiting preferential activity for either COX1 or COX2. NSAIDs representing the extremes in terms of selectivity for COX1 or COX2 do exhibit some differences with respect to gastric, renal, and hemostatic safety; those exhibiting a preferential action on COX2 are generally less toxic than those exhibiting a preferential activity on COX1. Exceptions do exist. CONCLUSIONS: There is some support for the hypothesis that NSAIDs exhibiting a preferential action on COX2 are safer than those exhibiting a preferential activity on COX1, but there exists no support for improved efficacy. A strict correlation does not exist between the COX1 and COX2 specificity and the gastric, renal, and hemostatic toxicity of NSAIDs. This lack of correlation is believed to stem from the fact that both the safety and efficacy of NSAIDs may result from mechanisms distinct from prostaglandin inhibition. Preferential COX2 activity can reduce the level of toxicity for a given NSAID but may not be sufficient to overcome toxicities resulting from other mechanisms.
1374588 Expression of vascular cell adhesion molecule-1 in fibroblastlike synoviocytes after stimu 1992 May Rapid expression of mRNA encoding vascular cell adhesion molecule-1 (VCAM-1) was induced by tumor necrosis factor (TNF) in fibroblast-like cells obtained from synovial tissue. Both alternatively spliced forms of VCAM-1 mRNA were detected by polymerase chain reaction in TNF-stimulated fibroblast-like synoviocytes. Western blotting analysis showed that two distinct proteins, reactive with an anti-VCAM-1 anti-sera, were expressed by 2 hours of TNF stimulation in both synoviocytes and human umbilical cord vein endothelial cells (HUVEC). The majority of HUVEC and synoviocytes displayed VCAM-1 surface expression after several hours of TNF stimulation. In contrast, dermal fibroblasts upregulated intercellular adhesion molecule-1 (ICAM-1) but not VCAM-1 expression in response to TNF. These results indicate that VCAM-1 and ICAM-1 expression can be differentially regulated and suggest tissue specific regulation of VCAM-1 expression. Furthermore, these findings may provide an explanation for the chronic retention and activation of long-lived lymphocytes and monocytes, which express VLA-4 (the receptor for VCAM-1), in the synovium in rheumatoid arthritis.
7880124 PPD and hsp65 induced monoarthritis initiates spontaneous recurrent flares in Lewis rats. 1995 Jan OBJECTIVES: To investigate the time course of a monoarthritis induced with the purified protein derivative of tuberculin (PPD) or a recombinant 65 kDa heat shock protein (rhsp65) in two different strains of sensitised rats. METHODS: Wistar and Lewis rats, sensitised with heat killed Mycobacterium tuberculosis in oil, were challenged intraarticularly with PPD or rhsp65 and monitored for six weeks. Inflammation was assessed by joint swelling, histology, and radiographic studies. RESULTS: Sensitised Lewis rats injected with PPD or rhsp65 showed a chronic response with recurrent spontaneous flares, while Wistar rats showed one inflammatory episode. CONCLUSIONS: The Wistar strain response to PPD resembles a transient reactive arthritis, while the response of the Lewis strain mimics the relapsing nature of rheumatoid synovitis, providing an interesting model to determine dominant immunopathogenic mechanisms.
1395130 Markers of inflammatory activation: upregulation of complement receptors CR1 and CR3 on sy 1992 Nov Expression of the C3 receptors CR1 and CR3 was investigated on neutrophils from paired peripheral blood and synovial fluid samples from 34 patients with inflammatory joint disease (21 patients with rheumatoid arthritis (RA) and 13 patients with other articular diseases (OAD)). Using monoclonal antibodies (anti-CD35, anti-CD11b) and immunofluorescence flow cytometric analyses the percentages of positively labeled cells and the relative fluorescence intensities (as a measure of receptor number) were determined. CR1 and CR3 were found to be present on the majority (> 85%) of circulating neutrophils from normal subjects, RA and OAD patients, and on synovial fluid neutrophils from both patient groups. A strong correlation between neutrophil CR1 and CR3 expression was observed in peripheral blood samples from normal subjects (r = 0.81; P = 0.001), RA (r = 0.79; P = 0.001), and OAD patients (r = 0.83; P = 0.001); in each case the levels of CR3 expression were approximately twice those recorded for CR1. Both CR1 and CR3 expression was upregulated on synovial fluid neutrophils compared with that observed on the corresponding peripheral blood cells. Mean percentage increases observed were: RA patients: CR1, 16.5% (P < 0.001) and CR3, 28.7% (P < 0.001); and OAD patients: CR1, 4.1% and CR3, 26.9% (P = 0.001). Correlation of serum and synovial fluid IL-6, IL-8, and immune complex levels with neutrophil CR1 and CR3 expression failed to demonstrate any significant relationship between the concentrations of these soluble factors and receptor expression. Upregulation of CR1 and CR3 receptors, reflecting neutrophil activation within the inflamed joint, is a consistent finding in patients with inflammatory arthropathies.
8610975 Oral tolerance in experimental autoimmune encephalomyelitis. 1996 Feb 13 In work performed by a number of laboratories, it has become quite clear that the oral administration of autoantigens exerts a profoundly suppressive effect on the development and long-term clinical course of autoimmune disease. Specific peptide sequences derived from the autoantigens are similarly suppressive. An interesting sidelight to emerge from specificity studies is that oral administration of a self-protein or peptide sequence (i.e., rat MBP peptide administered to a rat) is markedly less tolerogenic than oral administration of a non-self or even closely related sequence (guinea pig MBP peptide administered to a rat). The dose of oral antigen is now known to play a critical role in determination of the mechanism of oral tolerance, with low doses of antigen causing active suppression with concomitant release of TGFbeta1. Studies outlined here suggest that oral administration of higher antigen doses (e.g., 20 mg MBP to rats or mice) results in deletion of specific antigen-reactive T lymphocytes. This conclusion stems from the fact that injections of IL-2 could not reverse high-dose tolerance while reversing low-dose oral tolerance. Moreover, feeding MBP to MBP-TCR transgenic mice caused trafficking of transgenic cells to the intestine followed by a profound depletion of transgene-positive cells and reduction in proliferative function in all peripheral lymphoid organs. Oral tolerance has proven to be of therapeutic benefit in other animal models of autoimmune disease as well, including uveitis, collagen-induced arthritis, adjuvant arthritis, thyroiditis, myasthenia gravis, and diabetes. Initial human trials in multiple sclerosis, rheumatoid arthritis, and uveitis show promising results.
7923322 Patient compliance with tenoxicam in family practice. 1994 May This study evaluated factors that may influence patient compliance and also confirmed tolerability and efficacy of tenoxicam in routine clinical practice. Compliance in 1809 patients was evaluated over a 4-week period by physician pill-counts, patient assessment cards, and, for a subpopulation, by electronically monitored pill vials. In addition, physicians documented patient improvement and side effects after 2 weeks and after 4 weeks of therapy; patients reported satisfaction with therapy and side effects on a weekly basis. A total of 399 physicians provided data on 1809 patients, of whom 84.3% had osteoarthritis, 12.6% had rheumatoid arthritis, and 3.2% had ankylosing spondylitis. The typical patient was a woman (64.9%), white (91.2%), in her 50s (mean age, 57.9 years), with a duration of osteoarthritis of at least 1 year (72.3%). High and similar compliance rates were achieved by patients regardless of age, gender, or diagnostic category. Patient and disease characteristics were similar between compliant and noncompliant patients. Most patients (81.1%) experienced improvement of symptoms after 4 weeks of treatment. A low incidence of side effects (12.6%) was reported, with no significant differences observed among patients with respect to age, gender, or diagnostic category. Product characteristics, such as tolerability, efficacy, and dosing regimen, are more significant factors of compliance than patient or disease characteristics. Tenoxicam's tolerability and clinical effectiveness were confirmed in patients with arthritis in routine clinical practice settings.
1728999 Imaging of the hip joint. Computed tomography versus magnetic resonance imaging. 1992 Jan The authors reviewed the applications and limitations of computed tomography (CT) and magnetic resonance (MR) imaging in the assessment of the most common hip disorders. Magnetic resonance imaging is the most sensitive technique in detecting osteonecrosis of the femoral head. Magnetic resonance reflects the histologic changes associated with osteonecrosis very well, which may ultimately help to improve staging. Computed tomography can more accurately identify subchondral fractures than MR imaging and thus remains important for staging. In congenital dysplasia of the hip, the position of the nonossified femoral head in children less than six months of age can only be inferred by indirect signs on CT. Magnetic resonance imaging demonstrates the cartilaginous femoral head directly without ionizing radiation. Computed tomography remains the imaging modality of choice for evaluating fractures of the hip joint. In some patients, MR imaging demonstrates the fracture even when it is not apparent on radiography. In neoplasm, CT provides better assessment of calcification, ossification, and periosteal reaction than MR imaging. Magnetic resonance imaging, however, represents the most accurate imaging modality for evaluating intramedullary and soft-tissue extent of the tumor and identifying involvement of neurovascular bundles. Magnetic resonance imaging can also be used to monitor response to chemotherapy. In osteoarthrosis and rheumatoid arthritis of the hip, both CT and MR provide more detailed assessment of the severity of disease than conventional radiography because of their tomographic nature. Magnetic resonance imaging is unique in evaluating cartilage degeneration and loss, and in demonstrating soft-tissue alterations such as inflammatory synovial proliferation.
8519280 Recombinant human type II phospholipase A2 lacks edema producing activity in rat. 1993 Apr 22 The rat paw edema-inducing, acute inflammatory activity of four snake venom phospholipase A2S (PLA2) (Naja naja, Naja mocambique mocambique, Crotalus atrox and recombinant Naja naja naja) and of recombinant human type II PLA2 (rh-PLA2) found in rheumatoid synovial fluid, were compared after a bolus subplantar injection. The snake venom-derived PLA2s, including the recombinant Naja naja naja, were potent inducers of paw edema. On the other hand, when given in similar amounts (protein and/or enzymatic activity), the rh-PLA2 did not produce paw edema. Furthermore, the addition of Naja naja PLA2, blood plasma from rats with adjuvant arthritis or the E. coli-based enzymatic incubation mixture used to measure PLA2 activity to the injection mixture containing rh-PLA2, did not result in paw edema-inducing activity. These results suggest that the lack of paw edema-inducing activity of rh-PLA2 may be due to significant structural differences between snake venom PLA2s and human PLA2 which allow snake venom PLA2s, but not the human group II PLA2, to express inflammatory activity as measured by paw edema in rat induced by a bolus injection.
8305809 Comparison of serological tests for the detection of antibodies against Chlamydia trachoma 1993 Nov In cases of reactive arthritis, a suspected Chlamydia trachomatis infection is often detected by serological methods. However, mostly tests with genus-specific antigens are used, neglecting the fact that antibodies against Chlamydia pneumoniae are highly prevalent in the adult population. Therefore we tested sera of 129 patients with various rheumatological disorders and of 18 healthy persons in parallel with a genus-specific test (IPAZYME) and with the species-specific microimmunofluorescence test for C. trachomatis and C. pneumoniae antibodies. The data showed that 55% of the 64 IPA-positive results were caused by antibodies (IgG) against Chlamydia pneumoniae, only 6% by anti-Chlamydia trachomatis IgG and 20% by both specificities. For IgA antibodies, the percentages were 44%, 12.5% and 12.5% respectively. In 12 IPA-positive cases, the MIF showed no reaction. 58% of all 147 sera tested with MIF had IgG antibodies against C. pneumoniae, 5% had anti-C. trachomatis IgG and 8% IgG against both species. The percentages for IgA were 29%, 2% and 2%, respectively. IgM positivity in MIF disappeared after absorption with rheumatoid factor absorbent. No significant differences were found between the various groups of patients. The data suggest that due to the high prevalence of anti-C. pneumoniae antibody, genus-species tests cannot be used as screening tests for the serological diagnosis of C. trachomatis infections.
1376123 Restricted epitope recognition by precipitin-negative anti-La/SS-B-positive sera. 1992 Jun OBJECTIVE: To determine whether anti-La/SS-B-positive sera that are precipitin negative show a distinct B cell epitope pattern. METHODS: Serum reactivity was tested with recombinant La/SS-B fusion proteins. RESULTS: Among the 18 precipitin-negative anti-La/SS-B-positive sera, reactivity was confined to the full-length recombinant protein (La33.3) in 8 (44%); 5 of 18 (28%) reacted only with La33.3 and with the first 107 N-terminal amino acids (LaA), and 4 (22%) reacted with La33.3, LaA, and the middle region of the La molecule (LaC; amino acids 111-242). One serum reacted with La33.3 and LaC. None of the 18 precipitin-negative sera was positive on a carboxy-terminal fragment (LaL2/3; amino acids 346-408). In contrast, all 26 precipitin-positive anti-La/SS-B-positive sera reacted with La33.3, LaA, and LaC, and 92% reacted with LaL2/3. Rheumatoid factor and serum IgG levels were significantly lower in the precipitin-negative group, providing further evidence of a distinct serologic subset. CONCLUSION: The restricted epitope recognition by these sera may explain the lack of precipitin formation and may represent an early autoantibody response to La/SS-B.
8188366 Mycoplasma arthritidis-derived superantigen induces proinflammatory monokine gene expressi 1994 Jun Soluble factors produced by Mycoplasma arthritidis play an important role in the pathology of arthritis in rodents, which closely resembles human rheumatoid arthritis. At least one of the products of these microorganisms, M. arthritidis-T cell mitogen (MAM), has biological activities in common with superantigens. These superantigens activate T cells in a V beta-restricted fashion, and this response is strictly dependent on the presence of major histocompatibility complex (MHC) class II-positive cells. In the present study, we have examined the ability of MAM to induce proinflammatory monokine (interleukin 1 beta [IL-1 beta] and tumor necrosis factor alpha [TNF-alpha]) gene expression in the THP-1 monocytic cell line. Treatment of these cells (which express a very low level of HLA-DR molecules) with gamma interferon (INF-gamma) induced HLA-DR, -DQ, and -DP molecules and enabled them to respond to MAM in a dose-dependent manner, resulting in an increase in the level of steady-state mRNA for IL-1 beta and TNF-alpha. Stimulation of the U937 monocytic cell line (MHC class II-negative even after INF-gamma treatment) with MAM did not induce either IL-1 beta or TNF-alpha transcription. Moreover, MAM adsorption on Raji (MHC class II-positive) cells resulted in the loss of its cytokine-inducing activity to induce monokine gene expression. These findings demonstrate clearly that MAM induces monokine gene expression following interaction with MHC class II molecules. Pretreatment of INF-gamma-treated THP-1 cells with the transcription inhibitor actinomycin D prevented the induction of monokine mRNA, whereas cycloheximide superinduced mRNA after stimulation with MAM. Finally, our results, obtained with protein tyrosine kinase inhibitors and antiphosphotyrosine Western blotting (immunoblotting), indicate that protein tyrosine kinase is involved in MAM-induced IL-1 beta and TNF-alpha gene expression in the THP-1 monocytic cell line. The capacity of MAM to induce proinflammatory cytokine transcription in monocytes via MHC class II molecules can be one pathway of MAM contribution to autoimmune diseases.