Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2039494 | Inhibition of the oxidative burst response of N-formyl peptide-stimulated neutrophils by s | 1991 May 15 | Strong binding of the acute phase protein serum amyloid-A (SAA) to human neutrophils was found using flow cytometry. This binding was shown to be functionally relevant with respect to the oxidative burst reaction assayed on N-formyl peptide-stimulated neutrophils by the intracellular oxidation of non-fluorescent dihydrorhodamine to fluorescent rhodamine 123. The results show reduction of the oxidative burst response by isolated SAA (and recombinant SAA2). Inhibition was also demonstrated by acute phase as compared to normal human serum. This inhibitory effect was abolished by the purified monoclonal anti-amyloid A antibody mc29, strongly suggesting that SAA counteracts neutrophil responses to cytokines or bacterial products. This newly recognized function of SAA may help to prevent oxidative tissue destruction. | |
| 2451818 | On the adverse reactions and efficacy of long-term treatment with flupirtine: preliminary | 1987 | In order to investigate the efficacy and safety of long-term treatment with flupirtine in patients with chronic pain, in particular arthrosis and arthritis, a study was planned which, when completed, will encompass the treatment of 200 patients over a 12-month period. The present paper is a preliminary report of this ongoing study. The report deals with 104 patients: 55 of whom completed the 12-month treatment period and a 2-week follow-up phase, during which flupirtine was replaced by placebo in order to be able to detect drug-withdrawal effects. Forty nine patients withdrew from the study. Most of the patients were suffering from degenerative rheumatic arthrosis or inflammatory rheumatic arthritis. The average daily dosage was 300 mg. The incidence of drop-outs was highest in the first months with hardly any patients withdrawing in the last six months. Fifteen patients dropped out because of side effects (dizziness, nausea, sleep disturbances, and headache). Ten patients dropped out because of ineffectiveness, seven because of side effects plus ineffectiveness, and three because of side effects and other reasons. The remaining 14 patients dropped out because of other or non-medical reasons. For the 55 patients who completed the study, the analgesic took effect within 45 minutes to 2 hours, the duration of effect was 4-6 hours. Three-quarters of the patients responded to the drug, one-quarter did not. The analgesic effect remained constant during the 12-month treatment, as did the average number of capsules taken per month. There was no evidence that tolerance developed. The most frequent side effects were drowsiness (9% of patients), dizziness (11%), dry mouth (5%) and pruritus (9%). The withdrawal symptom scale completed every month during treatment (to determine baseline values) and every day throughout the 2-week placebo post-treatment phase showed no changes in the median. The mean value increased during the withdrawal phase, however, indicating that the symptomatology was more pronounced in some subjects. After withdrawal, the non-specific symptoms increased to a greater extent than symptoms from the opiate scale. The symptoms were present throughout the withdrawal phase. If the withdrawal phenomena had corresponded to the flupirtine's terminal half-life, then the symptoms ought to have been present mainly in the first few days. There was a slight trend for lowering systolic blood pressure but no changes in diastolic blood pressure or heart rate, nor changes in the ECG or laboratory analysis that could be related to flupirtine. These preliminary data suggest that flupirtine is safe when given for a period of one year. | |
| 3133431 | Hydrallazine-induced Sjögren's syndrome. | 1988 Apr | 4 years after initiation of therapy with hydrallazine hydrochloride (for treatment of hypertension), a 60-year-old male patient developed clinical features of Sjögren's syndrome, with immunological features of drug-induced systemic lupus erythematosus. In addition, the patient described rheumatoid arthritis-like symptoms and had reduced lacrimal and parotid salivary flow, but lacked the typical features of Sjögren's syndrome on labial gland biopsy. 1 year after discontinuation of hydrallazine therapy, the clinical parameters returned to normal. | |
| 2033916 | [Human anti-murine immunoglobulin antibodies as disturbing factors in TSH determination]. | 1991 Mar 18 | Monoclonal murine antibodies are increasingly used for immunotherapy and in vivo diagnostic procedures such as immunoscintigraphy. The therapeutic or diagnostic reagent however, is a foreign antigen, which may induce host reactivity. This may interfere with the therapeutic or diagnostic reagent in vivo, resulting in a loss of efficacy or the necessity to increase dosages. In addition, there is an important interference to in vitro immunoassays detecting specific antigens utilizing murine monoclonal antibodies. In the present study, sera of patients who had undergone a therapeutic trial using 140 mg of an anti-CD4 antibody, were investigated. Human anti-murine-immunoglobulin-antibodies (HAMA) were detected 2-3 weeks after treatment was started and reached maximal amounts of 0.8 micrograms/ml after a single and 2 micrograms/ml after a repeated treatment course. Parallely raised values of TSH were found in sera containing HAMAs of more than 0.3 micrograms/ml. Elevations of TSH levels up to 13 microU/ml were most pronounced after a repeated trial of the murine antibody and were detectable up to 20 weeks. | |
| 2624351 | Age and sex specific reference serum selenium levels estimated for the Italian population. | 1989 | The association between the concentration of selenium in serum and the risk of degenerative processes of the cardiovascular apparatus or of neoplastic disease remains still uncertain. An inaccurate selection of the study populations, and above all the lack of age, sex and area of residence specific reference values could have contributed to create confusion on the biological relevance of selenium in human diseases. In our present work the serum selenium levels for the Italian population have been studied, adopting standardized methods. The study population (4201 adult subjects and 1217 children) was derived from samples of populations previously enrolled in epidemiological preventive programs. The mean observed values for the various adult populations examined varied between 87 and 93 micrograms/l and resulted approximately 5 micrograms/l higher than the mean observed values in ten European countries. The mean observed values for the paediatric population (less than 15 years of age) were slightly lower (78-83 micrograms/l). A decreasing trend of the values with age, above 60 years, especially in males, has been observed. No significant difference has been observed for sex and geographic area of residence. A preliminary study of the variations of the serum selenium levels during certain diseases has shown a sharp reduction in children with phenylketonuria and undergoing dietary restrictions, in subject with active systemic Lupus erythematosus, and in certain neoplasias. | |
| 3052964 | Anti-idiotypic antibodies in autoimmune diseases. | 1988 Apr | The variable region (V region) of an antibody, the part of the molecule that binds to antigen, is itself antigenic and can elicit anti-V region antibodies when injected into animals of a different or even of the same species. The antigens of the V region constitute its idiotype, and they are defined by anti-idiotypic antibodies in polyclonal antisera or by monoclonal anti-idiotypic antibodies. An idiotype actually consists of multiple antigenic determinants, each of which is an idiotope. The antigenic determinants or idiotopes can reside in the heavy chain component of the V region, in its light chain component, or they may consist of a surface made up of parts of both chains. The idiotype of an antibody is, therefore, a way to describe by serological means the variable region of an antibody molecule. Originally, idiotypes were defined by heterologous antisera made, for example, by immunizing a rabbit with a monoclonal human myeloma protein. After extensive absorption with normal human immunoglobulins, such antisera were found to bind only to the V region of the immunizing myeloma immunoglobulin. Thus, idiotypes were originally thought to be unique markers of individual antibodies (hence their name). However, it is now known that different antibodies can share the same, or similar, idiotype. Even antibodies with different antigen-binding specificities can share the same idiotype if they use the same heavy or light chain in forming their V regions. Such antibodies constitute parallel sets. Thus, idiotypes can be: private (confined to a particular immunoglobulin molecule), public (shared by different antibodies), or cross-reactive (different idiotypes containing similar antigenic structures).(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2826055 | Human rheumatoid synovial and normal blood dendritic cells as antigen presenting cell--com | 1987 Oct | Rheumatoid dendritic cells (DC) from synovial membrane and synovial fluid and normal dendritic cells from peripheral blood were compared with autologous monocytes concerning accessory activities for T cell antigen responses. Purified protein derivative of tuberculin (PPD), herpes simplex virus type 1 antigen (HSV) and Chlamydia trachomatis antigen were used as antigens. The dendritic cells were shown to be efficient antigen presenting cells for the various antigens and were much more potent than monocytes. The DC were strongly positive for major histocompatibility complex (MHC) class II antigens. The T cell responses both to bacterial and viral antigens induced by DC could all be inhibited by monoclonal antibodies against HLA-DQ and HLA-DR antigens. Dendritic cells may thus play an important role as accessory cells in presenting antigens for T cells in the context fo class II MHC molecules in the rheumatoid inflammation. | |
| 2870830 | Uptake of fatty acids and their mobilization from phospholipids in cultured monocyte-macro | 1986 May | Prostaglandins (PG) and related eicosanoids which derive from essential fatty acids are important mediators and modulators of inflammation. Macrophages (M phi), which derive from peripheral blood monocytes (PBM), are prominent cells in the synovium of patients with rheumatoid arthritis (RA), and are a major source of synovial PGE2. In addition, fresh and cultured PBM from RA patients produce more PG than normal control cells. When allowed to mature in culture PBM exhibit many characteristics of macrophages (M-M phi). We examined uptake by M-M phi of eicosanoid precursor fatty acids (FA), their incorporation into cellular phospholipid (PL), and mobilization of FA after cell stimulation. Cultured M-M phi from treated and untreated RA patients (RA M-M phi) took up significantly more linoleic acid (LA), dihomogammalinolenic acid (DHLA) and arachidonic acid (AA) than M-M phi from normal volunteers (N M-M phi). The enhanced uptake of FA observed in 12-day cultures of RA M-M phi was similar to uptake seen in normal human peritoneal macrophages (PM phi). After uptake FA were incorporated mainly into phosphatidylcholine (PC). M-M phi from untreated RA patients incorporated a smaller proportion of [14C]LA into PC (37.0 +/- 12.7% of total PL label) than normal cells (86.0 +/- 4.2%), and a greater proportion of [3H]AA into PC (57.1 +/- 7.1%) than normals (23.9 +/- 6.9%). Stimulation of M-M phi with calcium ionophore A23187 resulted in significantly greater hydrolysis of LA and AA from PC in RA M-M phi from both treated and untreated patients than from PC in N M-M phi. The data indicate that M-M phi from RA patients mature more rapidly in vitro than M-M phi from controls as uptake of FA by RA M-M phi increases with duration of culture and by 12 days in culture equals uptake by normal human peritoneal M phi. Also, RA M-M phi exhibit differences from N M-M phi in uptake, PL distribution, and hydrolysis of eicosanoid precursor FA. Such changes in FA metabolism might influence cell function and inflammatory responses. | |
| 3318423 | Endoscopic studies of nabumetone in patients with rheumatoid arthritis. A comparative endo | 1987 Oct 30 | Gastric tolerance to 1 g of nabumetone administered in a single nightly dose was assessed in two trials in patients with rheumatoid arthritis. Gastroscopy and histology of mucosal biopsy specimens were performed before and after the end of treatment in both trials. Trial 1 was an open study that compared the effects of 1 g of nabumetone at night with those of naproxen (dose, 500 mg twice daily) and indomethacin (dose, 50 mg three times daily) in 41 hospitalized patients. After three weeks of treatment, nabumetone was significantly better tolerated than naproxen or indomethacin. Trial 2 was a randomized trial with 24 patients per group that compared 1 g of nabumetone given at night with 250 mg of naproxen given in the morning and 500 mg given at night for a period of three months. This single-blind study revealed that the number of patients with microscopic or macroscopic mucosal lesions was significantly smaller following intake of nabumetone. Concerning efficacy, as judged clinically by a rheumatologist, treatment with nabumetone was superior as well. | |
| 1689581 | Monoclonal antibody 6B6.6 defines a cross-reactive kappa light chain idiotope on human mon | 1990 Feb | Mouse monoclonal antibody (MAb) 6B6.6 was raised against a cross-reactive idiotope (CRI) present on the light chains of 2 human IgM paraproteins with rheumatoid factor (RF) activity. The MAb inhibited the IgG-binding activity of these proteins, and thus appears to react with an epitope located at or near the RF-binding site. Enzyme-linked immunosorbent assay (ELISA) and Western immunoblotting studies indicate that the 6B6.6 CRI is associated with kappa IIIa sub-subgroup light chains, is not related to the Wa, Po, and Bla RF cross-idiotypic specificities, and is clearly distinct from the kappa IIIb-associated CRI detected by MAb 17.109. Using an ELISA, we detected 6B6.6 CRI in 59% of 107 sera and 48% of 50 synovial fluids from patients with seropositive rheumatoid arthritis (RA). However, the quantities of CRI-positive RF were small, and the amount of CRI-positive RF did not correlate with the amount of IgM-RF. The 6B6.6 CRI was shown to occur primarily in the IgM fraction of RA sera by both chromatographic studies and isotype-specific ELISA, although small quantities appeared to be associated with IgA and IgG in some sera. The presence of 6B6.6 CRI on both monoclonal and polyclonal RF is consistent with the view that both are derived, at least in part, from a common gene pool. However, its occurrence in relatively low levels suggests that the number of germline genes encoding for RF is large or that extensive mutation occurs in the course of RF expression in RA. | |
| 3492318 | Anti-idiotypic antibodies to anti-DR in patients with rheumatoid arthritis. | 1987 Feb | Rheumatoid arthritis (RA) sera were evaluated for anti-idiotypic (anti-id) antibodies to HLA-DR antigens (anti-DR) using an ELISA method with murine monoclonal anti-DR antibody-coated microtiter plates incubated serially with either normal or RA sera and peroxidase-conjugated goat anti-human IgG (Fc specific). Specificity was examined using other monoclonal antibodies including anti-Leu 3a, OKM5, OKT8, anti-cytochrome c, and anti-breast tumor antigen. Significant binding of 11/33 (33%) RA to anti-DR was found compared with 0/44 normals (P less than 0.001). Two groups were identified: RA sera reacting with anti-DR and anti-Leu 3a and sera which did not bind to anti-DR but bound to irrelevant monoclonal antibodies. Anti-DR reactivity was differentiated from anti-Leu 3a by competitive inhibition studies. Binding of whole sera and IgG from RA patients to anti-DR was significantly inhibited by DR+ cell extract. The same extract was not inhibitory after selective removal of DR antigen by adsorption on an anti-DR-Sepharose column. These data suggest that anti-id antibodies are directed against the antigen-binding site of id. We conclude that some RA patients have anti-id antibodies potentially involved in immunoregulation of anti-DR antibodies. | |
| 1721835 | Epitope specificity and MHC restriction of rheumatoid arthritis synovial T cell clones whi | 1991 Oct | CD4+ T cell clones specific for the mycobacterial hsp 65 were obtained from synovial fluid of a DR4 homozygous rheumatoid arthritis (RA) patient. A stimulatory epitope was defined using both deletion mutants of the mycobacterial hsp 65 and synthetic peptides and proved to be in a highly conserved region of the molecule. Despite this, however, there was no recognition by these clones of either the recombinant human homologue of mycobacterial hsp 65, P60, nor of a synthetic peptide containing an amino acid sequence from P60 corresponding to the epitope defined in the mycobacterial hsp 65. When the pattern of HLA restriction shown by the hsp-65-specific T cell clones was investigated, all clones tested proved to be restricted by HLA-DP rather than the more usual HLA-DR. Inhibition experiments suggested that this restriction also applied to the polyclonal synovial T cell response to hsp 65, but not to other antigens. Exclusive restriction of T cell recognition of an antigen by HLA-DP has not been reported previously, and strongly suggests that in this case the T cell repertoire for recognizing hsp 65 in the context of DR4 is deficient. Such an association between DR4 and the inability to respond to an immunodominant bacterial antigen may have implications for the pathogenesis of RA. | |
| 1691192 | Detection of high levels of heparin binding growth factor-1 (acidic fibroblast growth fact | 1990 Apr | The synovium from patients with rheumatoid arthritis (RA) and LEW/N rats with streptococcal cell wall (SCW) arthritis, an experimental model resembling RA, is characterized by massive proliferation of synovial connective tissues and invasive destruction of periarticular bone and cartilage. Since heparin binding growth factor (HBGF)-1, the precursor of acidic fibroblast growth factor (FGF), is a potent angiogenic polypeptide and mitogen for mesenchymal cells, we sought evidence that it was involved in the synovial pathology of RA and SCW arthritis. HBGF-1 mRNA was detected in RA synovium using the polymerase chain reaction technique, and its product was immunolocalized intracellularly in both RA and osteoarthritis (OA) synovium. HBGF-1 staining was more extensive and intense in synovium of RA patients than OA and correlated with the extent and intensity of synovial mononuclear cell infiltration. HBGF-1 staining also correlated with c-Fos protein staining. In SCW arthritis, HBGF-1 immunostaining was noted in bone marrow, bone, cartilage, synovium, ligamentous and tendinous structures, as well as various dermal structures and developed early in both T-cell competent and incompetent rats. Persistent high level immunostaining of HBGF-1 was only noted in T-cell competent rats like the disease process in general. These observations implicate HBGF-1 in a multitude of biological functions in inflammatory joint diseases. | |
| 3480088 | ARAMIS today: moving toward internationally distributed databank systems for follow-up stu | 1987 Sep | The American Rheumatism Association Medical Information System (ARAMIS) is a consortium of North American rheumatic disease data banks. Founded in 1974, it has grown to include more than 16 centers, 22,000 patients, 140,000 patient encounters, and 80,000,000 observations. Traditionally, data storage and computer programs have resided on the IBM "2"-370 system at Stanford University. Distant peripheral centers have entered and retrieved data and performed analyses using proprietary long distance telephone networks. With growth, ARAMIS has placed strong emphasis on data quality and epidemiological soundness. "Core" groups at Stanford specifically address issues of quality control, biostatistics, health care economics, outcome assessment, study design, and administration. Advances in microcomputers and software has led ARAMIS to begin a migration from mainframe computing to distributed systems using IBM PC/XT/AT type computers and the Medlog software system. Substantial cost savings have been noted with distributed processing. The ability to easily transfer data and software forms a groundwork for international data banks and data exchange, but common vocabulary and common quality control procedures are essential for effective international cooperation and exchange. | |
| 3268205 | Age differences in coping with chronic illness. | 1987 Jun | We examined the correlation between age and six coping strategies in a sample of 151 middle-aged and older chronically ill adults. Coping strategies included cognitive restructuring, emotional expression, wish fulfilling fantasy, self-blame, information seeking, and threat minimization. Older adults were less likely to use emotional expression or information seeking than were middle-aged adults in their efforts to cope with the illness. These strategies were related to age even when numerous illness characteristics (e.g., physical limitations) were used as control variables. Interaction effects showed that older adults who perceived their illnesses as highly serious were less likely than were others to cope by seeking information, reconstruing their illness as having positive aspects, or engaging in wishfulfilling fantasies, and more likely to cope by simply minimizing the illness's threat. Consideration of related research studies suggests that the age differences in emotional expression may be due to age-related shifts in the types of stresses experienced, whereas the age differences in information seeking may be more strongly linked to cohort phenomena. | |
| 3263864 | Comparison of the in vivo inflammatory activities after intra-articular injection of natur | 1988 Nov 1 | Comparison has been made of the in vivo pro-inflammatory activities or procine natural and human recombinant alpha and beta interleukin 1 (IL-1) after injection into the knee joints of rabbits. Both forms of pig IL-1 and human IL-1 were separately equiactive in vitro in stimulating rabbit synovial fibroblasts and articular chondrocytes to synthesize prostaglandin E2 (PGE2). Injection of IL-1 into the rabbit knee joint was not associated with swelling of the joint nor with the appearance of PGE2 in the synovial fluid. However, all preparations of IL-1 induced a dose-dependent increase in inflammatory leukocytes in the synovial lining and joint cavity. In addition, both the alpha and beta forms of IL-1 from both species caused loss of proteoglycan from the matrix of articular cartilage. This study demonstrates that both genetically distinct forms of IL-1 have the same range of inflammatory actions within the joint and that they have similar potencies in these respects. | |
| 1718638 | Aberrant T-regulation in rheumatoid arthritis and IgA nephropathy affects CD5+ and CD5- B | 1991 Nov | T-suppressor function and T-helper function in healthy adults, elderly patients with non-immune diseases, and patients with rheumatoid arthritis (RA) and IgA nephropathy (IgAN) were titrated by adding graded concentrations of CD8+ cells to autologous CD8-depleted peripheral blood mononuclear cells (PBMC), or CD4+ cells to CD8- 4- PBMC, respectively. Following culture with pokeweed mitogen (PWM), numbers of CD5+ and CD5- immunoglobulin-secreting cells were determined using a combination of rosetting with anti-CD5-coated Dynabeads and reverse haemolytic plaque formation (Jones, 1990). Of 11 RA patients studied, eight had slightly reduced suppressor activity for CD5+ and CD5- IgM-secreting cells, and three with active disease and high serum levels of C-reactive protein, could not suppress IgG, IgA or IgM secretion by either B subset. Helper activity for both CD5+ and CD5- B cells was slightly but significantly increased in RA patients. One of eight patients with IgAN could not suppress IgG, IgA or IgM production by CD5+ or CD5- B cells, and all IgAN patients required strikingly fewer CD4+ cells for PWM-induced activation of CD5+ and CD5- B cells than controls. It was concluded that in two immunologically mediated diseases in which some patients have raised numbers of circulating CD5+ B cells, aberrant T-regulation affects CD5+ and conventional CD5- B cells equally. | |
| 2013419 | Ranitidine in the treatment of non-steroidal anti-inflammatory drug associated gastric and | 1991 Mar | In a multicentre study the effect of ranitidine on healing non-steroidal anti-inflammatory drug (NSAID) associated peptic ulcers was compared in a group of patients who had stopped NSAID treatment with another group who continued with NSAID treatment. A total of 190 patients with confirmed ulcers were randomised to continue or stop NSAID treatment. All patients in addition received ranitidine 150 mg twice daily. Patients were endoscopically monitored at four, eight, and 12 weeks. Gastric ulcers at eight weeks had healed in 63% of those taking NSAIDs compared with 95% of those who had stopped NSAID treatment. For duodenal ulcer the healing rates at eight weeks were 84% in the group continuing NSAIDs compared with 100% in those who stopped NSAIDs. The differences in healing rates were statistically significant for both gastric ulcer (p = 0.001) and for duodenal ulcer (p = 0.006). At 12 weeks, 79% of gastric ulcers and 92% of duodenal ulcers were healed in the group continuing with NSAIDs. All patients with gastric and duodenal ulcers who stopped taking NSAIDs were healed at 12 weeks. The study shows that ranitidine 150 mg twice daily effectively heals NSAID associated peptic ulcers. Healing is more successful when NSAID treatment stops but even if these drugs are continued, substantial healing rates are achievable. | |
| 3092343 | A prospective study of high-frequency auditory function in patients receiving oral neomyci | 1986 | Orally administered, neomycin is reported to cause ototoxicity rarely. Most reports on hearing loss due to oral neomycin have been case studies. One prospective study of a pediatric sample demonstrated a significant loss of hearing in the frequency range of 2 to 8 kHz in 9 of 17 children. To our knowledge there are no published prospective studies on this type with adult samples and therefore little is known of the true incidence or nature of ototoxicity from oral neomycin. This prospective study presents the results of long-term use of oral neomycin in 30 adult subjects. Hearing sensitivity was serially monitored in the frequency range 250-20,000 Hz. Two of the 30 subjects subsequently revealed ototoxicity. Thus the results of this investigation suggest that clinical use of oral neomycin implies relatively little risk of ototoxicity. | |
| 1663752 | The B cell repertoire in rheumatoid arthritis. I. Frequency of EBV-inducible circulating p | 1991 Aug | The frequency of B cell precursors producing antibodies against various autoantigens (Fc fragment of IgG, F(ab')2 fragment of IgG, type II collagen, cytoskeleton filaments and insulin) was determined in patients with rheumatoid arthritis (RA) using immortalization of peripheral blood B cells by the Epstein-Barr virus (EBV) and limiting dilution analysis. Equally large numbers of B cell precursors producing IgM-rheumatoid factors (RFs) were present in the peripheral blood of seronegative and seropositive RA patients and of controls. On average, 1 out of 15,000 B cells could be induced by EBV to secrete IgM-RFs, which represents 0.5-1% of the EBV-induced proliferating clones. By cloning or somatic hetero-hybridization of EBV cell lines derived from patients and controls, we obtained two types of monoclonal RFs: one polyreactive, reacting with Fc but also with the other autoantigens tested, and the other monoreactive, reacting with Fc only and that previously had only been found in the RA B cell repertoire. Moreover, patients and controls had similar numbers of circulating B cell precursors secreting IgM antibodies against other autoantigens that might be regarded as specific targets of RA (F(ab')2 fragment of IgG and type II collagen), and against cytoskeleton filaments that are targets of natural autoantibodies, increased in RA. The frequencies of EBV-induced B cells producing antibodies against all these autoantigens were of the same order of magnitude as the frequency of EBV-induced B cells producing RFs. The patients also possessed a similar number of precursors producing antibodies against insulin, an autoantigen irrelevant to the pathogenesis of the disease, taken as control. These data tend to demonstrate no abnormality in the autoantibody repertoire of B cells activable by EBV in RA, especially those secreting RFs. In vitro spontaneous RF secretion by circulating B cells was observed in seropositive RA patients but not in seronegative patients and in the controls tested. We enumerated the number of B cells spontaneously secreting RFs in seropositive RA patients and found that it correlated with the serum RF titer, but not with the number of RF-secreting B cells activated by EBV. The mean frequency values of B cells secreting RFs either spontaneously or after EBV infection were of the same order of magnitude, showing that the expanded population of in vivo-activated B cells was not (at least partially) infectable by EBV. This raised the possibility that EBV triggers a repertoire which may not reflect the status of B cells secreting autoantibodies in autoimmune diseases. |