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F Jouen-Beades

Publications and source records attributed to F Jouen-Beades.

17 recordsLinked to original sources
PubMed2004

Autoantibodies recognizing citrullinated rat filaggrin in an ELISA using citrullinated and non-citrullinated recombinant proteins as antigens are highly diagnostic for rheumatoid arthritis.

The objective of the study was to determine the diagnostic value for rheumatoid arthritis (RA) of anti-filaggrin autoantibodies (autoAb) recognizing citrullinated recombinant rat filaggrin (ACRF) in community cases of very early arthritis. To evaluate the diagnostic value of ACRF, were studied sera from patients with different classified rheumatic diseases and healthy subjects (group 1, n= 422) and 314 community cases of very early arthritis (group 2) that were classified as RA (n = 176), non-RA (n = 63) and undifferentiated (n = 75) arthritides after 1 years of follow-up. ACRF were measured using a new ELISA, with results expressed as the difference between the OD value obtained on citrullinated minus that on noncitrullinated rat filaggrin (differential ACRF; dACRF). For both groups, rheumatoid factors (RF), anti-keratin autoAb (AKA) and anti-perinuclear factor (APF) were tested; for group 2, anti-CCP autoAb were also tested. Different reactivity patterns against citrullinated and noncitrullinated filaggrin were observed. Almost all sera reacting with citrullinated but not noncitrullinated filaggrin were from RA patients. Among RA and non-RA sera that recognized both forms of filaggrin, a positive result was obtained only with RA sera. For groups 1 and 2, dACRF sensitivity was 58.4% and 30.7%, and specificity for RA was 99.5% and 98.4%, respectively. In group 2, dACRF specificity for RA was better than that of RF (92.1%), APF (95.2%), AKA (96.8%) and anti-CCP (95.2%). dACRF positive predictive value was high (98.2) and close to that given by the concomitant positivity of RF and anti-CCP autoAb. Despite a high positive correlation between AKA, APF, anti-CCP and dACRF test results, they were complementary since some sera were positive for only one test. Thus, in a community setting, anti-citrullinated rat filaggrin reactivity detected by a new ELISA, whose originality is based on the difference between serum's reactivities on the citrullinated and native forms of filaggrin, had a higher diagnostic value for RA than other autoAb.

Adult↗
PubMed2004

Autoantibodies recognizing the 27 carboxy-terminal amino acids of calpastatin are associated with secondary Sjögren syndrome in systemic lupus erythematosus.

The objective of this study was to determine in systemic lupus erythematosus (SLE) the prevalence and clinical significance of anticalpastatin antibodies (ACAST), an autoantibody population previously detected in sera from patients with various connective tissue diseases. Eighty-four patients with SLE (mean age: 30 years at diagnosis, females 77) that fulfilled ACR criteria were included in the study retrospectively. Several clinical and biological data were collected. ACAST were detected by a solid-phase enzyme linked immunosorbent assay (ELISA) using as antigen a synthetic peptide corresponding to the 27 C-terminal amino acids of calpastatin (CAST-C27). The prevalence of ACAST-C27 was 13% (11/84) in SLE patients. No correlation was found between the presence of ACAST-C27 and clinical manifestations such as thrombosis and vasculitis. Furthermore, no correlation was observed with the presence ofantiphospholipid antibodies (APL). However, we found a statistically significant association between the presence of ACAST-C27 and that of secondary Sjögren syndrome (P = 0.01). The conclusion is ACAST-C27 are not associated with thrombosis in SLE patients. The association observed between ACAST-C27 and secondary Sjögren syndrome suggests that ACAST-C27 might be useful in discriminating a clinical subgroup of SLE patients.

Adolescent↗
PubMed2003

Rheumatoid factor is the strongest predictor of radiological progression of rheumatoid arthritis in a three-year prospective study in community-recruited patients.

OBJECTIVE: To evaluate the predictive value of clinical, biological and radiological parameters for the prognosis of rheumatoid arthritis (RA) in a community-recruited cohort. METHODS: Ninety-one patients (mean age 49 yr, female/male ratio 2.9) with RA of limited duration (median 2 yr), 80% recruited from the community, were prospectively enrolled in 1996 (T1) and followed until 1999 (T2). Data collected at T1 were demographic characteristics, Ritchie articular index (RAI), extra-articular manifestations, Health Assessment Questionnaire (HAQ) score, C-reactive protein (CRP) and autoantibodies (autoAbs) [rheumatoid factors (RF), detected by latex fixation test and ELISA (IgM, IgA and IgG isotypes), anti-filaggrin, detected by immunofluorescence (anti-keratin antibodies, AKA; anti-perinuclear factor antibodies, APF) and ELISA (anti-citrullinated rat filaggrin antibodies, ACRFA), anti-Sa, anti-calpastatin recognizing the 27 C-terminal fragment (ACAST-C27) and domain I (ACAST-DI), anti-cardiolipin (ACL), antineutrophil cytoplasmic antibodies (ANCA), anti-annexin V (aANX V) and anti-Ro]. Hands were radiographed at T1 and T2, and read using the Sharp method as modified by van der Heijde. The main assessment criterion was progression of radiologically detected damage between T1 and T2. RESULTS: At T1, RA activity was mild (RAI 11/78; mean CRP 14 mg/ml), with minor functional disability (HAQ 0.8/3) and mild X-ray destruction (mean total Sharp score 9.2/280). At T1, 96% of the patients were on treatment (prednisone 72%, DMARDs 95%). The latex test detected autoAb in 46% of patients, RF-IgM was detected in 51%, RF-IgA in 36%, RF-IgG in 32%, AKA in 33%, APF in 45%, ACRFA in 45%, ACAST-C27 in 14%, ACAST-DI in 5%, anti-Sa in 22%, ACL in 3%, ANCA in 28%, aANX V in 9% and anti-Ro in 2%. At T2, the mean total Sharp score was 22.9. According to univariate analysis, T1 parameters associated with the independent variable were RAI, HAQ, CRP, latex test positivity and T1 Sharp scores. Multivariate analysis retained only latex test positivity and, to a lesser degree, joint-space narrowing score as independent predictors of radiological progression. CONCLUSION: RF is the main factor that can predict radiological progression in community cases of RA of limited duration.

Adult↗
PubMed2001

Prospective X-ray densitometry and ultrasonography study of the hand bones of patients with rheumatoid arthritis of recent onset.

OBJECTIVE: Bone demineralization observed in early rheumatoid arthritis is not easily measured. To measure bone loss and to discriminate between rheumatoid arthritis and other rheumatic diseases, we used two methods: dual-energy X-ray absorptiometry and ultrasonography. METHODS: From a population-based recruitment, 32 patients with early peripheral polyarthritis (median disease duration: 4 months) were studied. Clinical, laboratory, functional, hand-bone assessments were made at the entry an at months 6 and 12. Bone X-ray densitometry measurements were made on 16 areas of the hand. Speed of sound was measured across the proximal phalanges of the four fingers. X-rays of both hands were scored according to the modified Sharp's score. At 12 months, patients were classified as rheumatoid arthritis (N = 15; 9 F) or as other rheumatic diseases. RESULTS: We found: 1) significantly decreased bone mineral density (BMD) of the whole hand, in the rheumatoid arthritis group versus the other rheumatic diseases group, at 6 and 12 months (P < 0.05); 2) no significant decrease of bone mineral density (BMD) in other areas in the rheumatoid arthritis group; 3) no significant change of ultrasounds in either group; and 4) no significant correlation between the decrease of BMD in the rheumatoid arthritis group and clinical, biological or radiologic parameters, except for IFNgamma, whose production in whole blood cell culture was lower at entry in the rheumatoid arthritis group. CONCLUSION: DEXA bone assessment in rheumatoid arthritis was able t detect bone loss in the whole hand at 6 months.

Absorptiometry, Photon↗
PubMed2001

Rheumatoid factors, anti-filaggrin antibodies and low in vitro interleukin-2 and interferon-gamma production are useful immunological markers for early diagnosis of community cases of rheumatoid arthritis. A preliminary study.

OBJECTIVE: To determine whether measurements of different autoantibodies (Ab) and cytokines are useful to distinguish very early rheumatoid arthritis (RA) from other inflammatory rheumatisms. METHODS: From a population-based recruitment, 32 patients with very early polyarthritis (median duration: 4 months) were studied. Evaluations at entry (M0), and at 6 (M6) and 12 months (M12). Ab tested: rheumatoid factors (RF) by agglutination methods and ELISA, antiperinuclear factor (APF), antikeratin Ab (AKA), anti-Sa and antinuclear Ab. Cytokine production (TNFalpha, IL2, IFNgamma, IL1beta, IL10) in whole blood cell culture (WBCC) was determined at M0. At M12, patients were classified as having RA (N = 15) or other rheumatic diseases. RESULTS: At M0, AKA/APF and anti-Sa Ab frequencies were low, 13% and 7%, respectively. While most Ab detected at M0 persisted, others appeared during follow-up, particularly APF, which rose from 13 to 40% at M12. At M6, IgM-RF was detected in two RA patients exclusively by ELISA. AKA/APF were found to be highly specific markers for RA (100% specificity). At some time during follow-up, two RF-negative RA patients were AKA-positive. In two patients, AKA and APF were present at M0 before they satisfied ACR criteria. IL2 and IFNgamma production was significantly lower (P < 0.05) for RA patients. CONCLUSION: AKA/APF and anti-Sa Ab were detected in community cases of very early RA. AKA/APF and RF detected by ELISA might contribute to an earlier diagnosis of RA. Low production of IFNgamma and IL2 in WBCC constituted a distinct immunopathological feature in very early RA patients.

Antibodies, Antinuclear↗
PubMed2001

Antibodies and vascular involvement in inflammatory joint disease: clinical relevance.

The vascular endothelium is a common target of inflammatory joint disease. Autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome can be responsible for a spectrum of vascular disorders that encompasses vasculitis, thrombosis and/or atheroma associated with the antiphospholipid syndrome, and vascular damage caused by cryoglobulin deposition. These mechanisms can coexist, particularly in lupus patients. Joint disease is sometimes the presenting manifestation in primary vasculitis. Autoantibodies are detectable in most patients with vascular involvement and inflammatory joint disease. They are not merely markers for vascular involvement: in vitro and in vivo data suggest that some autoantibodies may contribute to the genesis of endothelial lesions, together with other factors. For instance, evidence of pathogenic effects has been found for antineutrophil cytoplasmic antibody (ANCA), most notably with antimyeloperoxidase or antiproteinase-3 specificity, in small-vessel vasculitides (Wegener's granulomatosis, Churg-Strauss syndrome, and microscopic polyangiitis); for immune complexes, particularly those containing cryoglobulins, in vasculitides secondary to CTDs; and for circulating anticoagulant and anticardiolipin antibodies, above all anti-beta2-glycoprotein I, in antiphospholipid syndrome. Antibodies to annexin V, modified lipoproteins, and endothelial cells may be of interest; their clinical relevance is unclear, however, and no standardized assays are available, so thatthese antibodies are not looked for in everyday practice. When deciding which antibody tests should be performed in a given patient, the circumstances surrounding the onset of the vasculopathy should be borne in mind. In patients with previous CTD, the tests are selected based on the diagnosis. In contrast, in a patient with no previous diagnosis, a vasculopathy can be either primary or secondary to undiagnosed CTD or to antiphospholipid syndrome: consequently, a broader array of tests is needed in this situation.

Arthritis↗
PubMed2001

Autoantibodies to the 27 C-terminal amino acids of calpastatin are detected in a restricted set of connective tissue diseases and may be useful for diagnosis of rheumatoid arthritis in community cases of very early arthritis.

BACKGROUND: Calpastatin is the natural inhibitor of calpains, a protease that is overexpressed in rheumatoid synovial tissue and plays a key role in cartilage destruction. Autoantibodies to calpastatin (ACAST) were recently detected in rheumatoid arthritis (RA). Our aim was to determine their prevalence and their clinical significance. METHODS: ACAST were detected in a solid-phase enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide corresponding to the 27 C-terminal amino acids of calpastatin (CAST-C27) as the antigen. All sera reacting with this peptide also bound to purified erythrocyte calpastatin in an ELISA and/or an immunoblot assay. The frequencies and clinical significance of ACAST-C27 were assessed in sera from a well-documented population of 102 community-recruited patients (76 females; mean age 50 yr) with RA that had been evolving for <5 yr (median 2 yr) (group 1), 109 healthy blood donors, 289 patients with non-RA rheumatic disease and 88 community cases of very early (median 4 months) arthritis, i.e. 58 RA and 30 non-RA patients (group 2). RESULTS: The sensitivity of ACAST-C27 for RA was 19.5% (20/102) in group 1 and 10.3% (6/58) in group 2. These antibodies were also found in patients with anti-double-stranded DNA-positive systemic lupus erythematosus (SLE) (15.5%) and patients with anti-Ro-positive Sjögren's syndrome (18.5%). However, they were not detected in cases of rheumatism resembling early RA, i.e. peripheral spondylarthropathies. ACAST-C27 were not detected in the 30 non-RA patients of group 2. They were predominantly of immunoglobulin isotype G3 and exclusively expressed lambda chains. Among ACAST-C27-positive sera, eight out of 20 (group 1) and four out of six (group 2) were negative for rheumatoid factor and anti-keratin antibodies/antiperinuclear factor. No relationship was found between ACAST-C27 and clinical, biological or radiological findings. CONCLUSION: ACAST-C27 are detected only in a restricted set of connective tissue diseases and therefore appear to be specific for RA when antibodies that are usually associated with SLE or primary Sjögren's syndrome are negative. Because of their presence in community cases of very early RA, particularly in some seronegative forms, ACAST-C27 may be useful in discriminating recent-onset RA from the more common non-RA rheumatic diseases, such as spondylarthropathies.

Adult↗
PubMed2000

Prospective evaluation of the frequency and clinical significance of antineutrophil cytoplasmic and anticardiolipin antibodies in community cases of patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the frequencies of antineutrophil cytoplasmic (ANCA), anticardiolipin (aCLA) and anti-beta(2)-glycoprotein 1 antibodies (abeta(2)-GP1A) in rheumatoid arthritis (RA) of limited duration in patients recruited primarily from private practitioners (80%), and to attempt to correlate the presence of these antibodies with certain clinical and/or biological criteria. Patients and methods. Patients (n = 102) with RA evolving for <5 yr (mean 2.2 yr) were recruited. A home evaluation collected clinical data [Ritchie articular index, Health Assessment Questionnaire (HAQ) index, extra-articular manifestations] and blood for biological analyses [C-reactive protein (CRP), rheumatoid factor, ANCA, aCLA, abeta(2)-GP1A]. ANCA were detected by indirect immunofluorescence on neutrophils and their specificity was determined by enzyme-linked immunosorbent assay (ELISA) and confirmed by immunoblotting; aCLA and abeta(2)-GP1A were detected by ELISA. RESULTS: Patients had mild RA (Ritchie = 11/78 +/- 9.6; HAQ = 0.79/3 +/- 0.7), probably due to the recruitment procedure. ANCA, aCLA and abeta(2)-GP1A frequencies were 18.5, 7 and 0%, respectively. Titres of ANCA and aCLA were low. A perinuclear ANCA staining pattern was exclusively observed and lactoferrin was shown to be the major antigen recognized. No relationship was found between ANCA and aCLA and/or rheumatoid factor, or any clinical manifestations. ANCA were more common in RA of longer duration (cut-off: 4 yr; P = 0.05) and aCLA were correlated with the CRP level (P = 0.05). CONCLUSIONS: In RA of recent onset, ANCA and aCLA were detected at low titres and frequencies, and were not associated with any clinical manifestations. A longitudinal study is needed to determine whether their early appearance is predictive of subsequent disease severity.

Adult↗
PubMed2000

[Medium-term renal involvement in adult patients with Henoch-Schönlein purpura].

INTRODUCTION: The aim of this study was to estimate the frequency of medium-term renal involvement, in a series of adult patients with Henoch-Schönlein purpura treated in a dermatology department. PATIENTS AND METHODS: Seventeen patients with Henoch-Schönlein purpura followed from 1991 to 1997 in the department of dermatology were included in the study. Renal tests included: research of microscopic hematuria, proteinuria, plasma creatinine levels and calculated creatinine clearance which were measured during initial hospitalization and at the date of the study in May 1998. RESULTS: 10 men and 7 women (mean-age 51 years) were followed up for 39 months (6 to 79 months). Initial renal involvement was observed in 11 patients (65 p. 100). A microscopic hematuria was also observed in 9 patients (53 p. 100), a proteinuria in 6 (35 p. 100), an association of hematuria and proteinuria in 4 (23.5 p. 100). No patient had renal failure. In May 1998, only 2 patients (11.7 p. 100) had renal involvement, that consisted of proteinuria: 3.3 and 3. 9 g/d respectively, with no renal failure. DISCUSSION: The 65 p. 100 frequency of renal involvement discovered during the acute phase of HSP in our series was similar to other series mentioned in the literature, which mainly consisted of hematuria and/or proteinuria. The frequency of long-term renal involvement depends on the origin of patient recruitment. Nephrological studies have reported high levels of renal involvement, that probably overestimated the true frequency. In the present study, as well as in two other studies from a non-nephrological recruitment, the frequency of long-term renal involvement was estimated between 11 p. 100 and 16 p. 100 and was primarily persistent proteinuria. CONCLUSION: The frequency of renal involvement in the adult patient with HSP during the acute phase of the disease and after a medium-term follow-up was approximately 50 p. 100 and between 11 p. 100 to 16 p. 100 respectively.

Adult↗
PubMed1999

Expansion of circulating V gamma 9/V delta 1 T cells in a patient with a syndrome of recurrent fever: evidence for an unusual antigen-driven process leading to selection of recurrent motifs within TCR junctional loops of diverse lengths.

Polyclonal expansions of human Vdelta1 T cells have been described in diverse physiopathological situations without strong TCR structural data for an antigen-driven selection. Here, we have analyzed the phenotype and TCR repertoire of gamma delta T cells obtained from the peripheral blood of a 19-year-old patient with a syndrome of recurrent fever, which accounted for up to 40% of CD3(+) T cells and expressed predominantly Vgamma9 and Vdelta1 TCR regions and a memory phenotype. Sequence analysis of Vdelta1-Jdelta1 transcripts derived from peripheral blood lymphocytes (PBL) indicated that, while Vdelta1-Jdelta1 junctional sequences were diverse in length, all but one contained several recurrent motifs at conserved positions from both the 5'- and 3'-ends of the complementarity-determining region (CDR)3 loop. Analysis of gamma delta T cell clones derived from patient PBL demonstrated that Vgamma9(+) but not Vgamma9(-) T cell clones frequently expressed Vdelta1 chains with these characteristics and unveiled a hierarchy between the constraints imposed on the 5'- vs. the 3' motifs of the Vdelta1 CDR3 loops. These results constitute the first strong evidence for a nominal antigen-driven selection of Vdelta1 T cells in vivo and also suggest that the hierarchy of the constraints imposed by antigens respectively on the length and amino acid composition of TCR CDR3 loops differs between alpha beta and gamma delta T cells.

Amino Acid Sequence↗
PubMed1998

Flow cytometry analysis of peripheral blood lymphocytes from patients with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune disease observed in elderly subjects in which alteration of peripheral blood lymphocyte subset repartition has been described. OBJECTIVE: To evaluate peripheral blood lymphocyte subsets from BP patients and identify immunologic changes that can be assigned either to the autoimmune disease or to the ageing process. METHODS: Peripheral blood lymphocytes from 24 patients with BP and 24 age- and sex-matched healthy individuals were analyzed by flow cytometry and these results were compared to those obtained from young adults. RESULTS: This study showed: (i) the presence of T-cell lymphopenia with a decreased number of CD8+ and gdgammadelta T lymphocytes in BP patients compared with younger adult controls; (ii) a high dispersion of the results in the BP population; (iii) the absence of a significant difference of lymphocyte subset levels between BP patients and age- and sex-matched controls. CONCLUSION: This flow cytometry study suggests that the modifications of lymphocyte subpopulation values observed in BP patients are related to immunologic changes induced by age in elderly people.

Age Factors↗
PubMed1997

In vivo and in vitro activation and expansion of gammadelta T cells during Listeria monocytogenes infection in humans.

Serial flow cytometry analyses of peripheral blood mononuclear cells obtained from 8 patients infected with Listeria monocytogenes showed a higher percentage (P < 0.01) of gammadelta T cells (median, 11.7; range, 3.7 to 35.3) than did 16 age-matched uninfected controls (1.7, 0.4 to 13). Most in vivo-expanded gammadelta T cells expressed the Vgamma9 and Vdelta2 gene products and displayed a memory phenotype (CD45RO[high]), and patients' gammadelta T cells expressed significantly more (P < 0.01) activation marker HLA-DR than did controls (19.8% [median] and 0.9 to 87.6% [range] versus 2.3% and 0 to 4.7%, respectively). When peripheral blood mononuclear cells from normal donors were cultured in vitro with heat-killed Listeria cells, analysis of CD25 and HLA-DR expression on gammadelta and alphabeta T cells indicated that a high percentage of gammadelta T cells was activated early compared to alphabeta T cells. In addition, depletion of gammadelta T cells before culture abrogated the early lymphocyte proliferative response induced by the pathogen. Taken together, these results argue for the involvement of gammadelta T cells during L. monocytogenes infection in humans.

Adult↗
PubMed1996

Similarity of expression of activation markers and CD28 on gamma delta and alpha beta-receptor T cells in HIV infection.

During human immunodeficiency virus (HIV) infection, phenotypic analysis of circulating gamma delta+ T cells showed a downregulation of the CD28 surface antigen, as recently demonstrated for CD4+ and CD8+ alpha beta+ T cells. The downregulation of the CD28 molecule predominated on CD8+ gamma delta+ T cells. Moreover, an increased expression of CD38 and/or HLA-DR molecules was found on gamma delta T cells as reported for alpha beta T cells indicating that all categories of circulating T lymphocytes share similar phenotypic abnormalities in HIV-infected patients. These unique changes in the different T-cell subsets might be induced by sustained activation of the immune system or by the rapid turnover of T cells and argue for a global dysregulation of T lymphocytes during HIV infection.

ADP-ribosyl Cyclase↗
PubMed1995

During HIV infection, CD4+ CD38+ T-cells are the predominant circulating CD4+ subset whose HLA-DR positivity increases with disease progression and whose V beta repertoire is similar to that of CD4+ CD38- T-cells.

Three-color automated flow cytometry was carried out on peripheral blood CD4+ and CD8+ T-lymphocytes of 42 HIV-positive patients using tri-color anti-CD4 or anti-CD8, phycoerythrin-anti-CD38, and fluorescein-anti-HLA-DR, mAbs to elucidate further the T-cell activation hypothesis recently proposed to explain CD4+ T-cell abnormalities observed during HIV infection. CD4+ CD38+ T-cells constituted the major part of circulating CD4+ T-cells in HIV-infected patients and their HLA-DR molecule positivity increased as their disease progressed. The level of CD38 and HLA-DR expression on CD4+ T-cells was positively correlated to that of CD8+ T-cells and to the level of beta 2-microglobulin. Next, to determine whether CD38 expression was associated with a selective expansion or deletion of V beta gene-defined subsets, we compared the V beta gene frequencies between CD38+ and CD38- T-cells from HIV-infected CDC stage II patients using 13 mAbs specific to V beta families. While selective expansion of certain V beta families was observed in CD4+ and CD8+ T-cells the T-cell receptor V beta subset distribution was similar among CD38+ and CD38-, CD4+ and CD8+ T-cells, suggesting that CD38+ expression was either independent of an HIV-encoded antigen-driven process or rather indicative of T-cell immaturity. It is proposed that the phenotype of circulating CD4+ and CD8+ T-cells of HIV-infected patients is a feature of two different mechanisms: (i) an in vitro activation state responsible for increased DR expression and selective expansion of V beta gene-defined subsets, and (ii) T-cell immaturity due to an increased turnover of these cells and accounting for increased CD38 expression.

ADP-ribosyl Cyclase↗
PubMed1995

Comparison of activation marker and TCR V beta gene product expression by CD4+ and CD8+ T cells in peripheral blood and lymph nodes from HIV-infected patients.

Since lymphoid organs constitute the site of active and progressive HIV disease, analysis of their lymphocytes may provide more accurate information on T cell abnormalities than that obtained from studying peripheral blood lymphocytes. The objective of this study was to compare the expressions of activation markers and T cell receptor (TCR) V beta gene products by CD4+ and CD8+ T cells in lymph nodes (LN) and peripheral blood (PB) from healthy individuals and asymptomatic HIV-infected patients to determine whether anomalies that could be identified at the HIV replication site could support the hypothesis of T cell activation by HIV-encoded antigens or superantigens. CD4+ and CD8+ T cells in paired LN and PB obtained from six healthy controls and five asymptomatic HIV-infected individuals were analysed by flow cytometry, using anti-CD38, anti-HLA-DR and 13 anti-V beta MoAbs that cover, approximately, 45% of the T cell repertoire. Analysis of T cell activation marker expression indicated that the percentages of CD4+ and CD8+ T cells bearing CD38 or CD38 and HLA-DR molecules were higher in patients than in controls and, in patients, higher in LN than in PB. Comparison between the V beta repertoires of CD4+ and CD8+ T cells in LN and PB showed that, in each healthy individual, a limited number of V beta families expressed by CD4+ or CD8+ T cells had different repartition in LN and PB, whereas in each HIV+ patient, more V beta families exhibited different distributions and these differences recurred among certain V beta segments, such as V beta 5.3 and V beta 21 in the CD4+ T cell population and V beta 5.2/5.3, V beta 12 and V beta 21 in the CD8+ T cell population. Taken together, these data argue for a skewed TCR repertoire in HIV infection and sustained activation of T cells by HIV-encoded antigens at the site of HIV replication, and further demonstrate that a high proportion of CD4+ T cells are in an activation state that may, indirectly, participate in their functional abnormalities.

Adult↗
PubMed1992

Analysis of T cell receptors in rheumatoid arthritis: the increased expression of HLA-DR antigen on circulating gamma delta+ T cells is correlated with disease activity.

The phenotypic characteristics of peripheral blood T cells, isolated from 37 rheumatoid arthritis (RA) patients and 17 healthy controls were determined with special emphasis on gamma delta+ T cells and CD4-CD8- alpha beta+ T cells. Two- and three-colour automated flow cytometry analyses were performed using a panel of MoAbs directed against differentiation antigens and T cell receptor molecules. The results demonstrated: (i) no significant difference between the percentages of CD4-CD8- alpha beta+ T cells in patients and controls; (ii) a significant decrease of the gamma delta+ T cell level in the peripheral blood of RA patients relative to controls; (iii) phenotypic abnormalities of circulating gamma delta+ T cells in RA patients suggestive of an activation status in vivo. These abnormalities included a significant reduction in the density of the T cell differentiation antigen CD3 and an increase in the expression of HLA-DR antigen. The level of circulating HLA-DR+/gamma delta+ T cells was significantly higher in patients with active disease. HLA-DR+/gamma delta+ T cells were also present in the synovial fluid obtained from three patients with an active disease. In addition, preliminary experiments showed that the activated gamma delta+ T cells were predominantly V delta 1. Taken together, these data support the involvement of gamma delta+ T cells in the pathogenesis of RA.

Adult↗