Biomedical subjects
Publications and source records attributed to J Sany.
HLA-B27 antigen is strongly correlated with ankylosing spondylitis and several other rheumatic diseases. However, data concerning frozen shoulder are contradictory. Bulgen reported an increased frequency of HLA-B27 which was not observed by Noy. We performed HLA typing of 46 French patients with frozen shoulder. We agree with Noy: frozen shoulder is not correlated with HLA-B27.
Between 1975 and 1982, 202 previously untreated patients with multiple myeloma (MM) and clinical evidence of disease progression received intensive chemotherapy every 3-5 weeks to induce remission. Treatment regimen included intermittent courses of a combination of cycle non-specific drugs (melphalan, cyclophosphamide) plus vincristine and prednisone, with or without adriamycin. Several other drugs having some efficacy in MM were used in case of primary treatment failure or in relapse. The overall median survival was 29 months, with an eight-year actuarial death-rate (related to MM) equal to 75%. Forty percent of patients had disease progression and short survival (median = 9 months, early deaths included). Fifty percent had stable or regressive disease (greater than or equal to 50 less than 99% cell mass regression) and a dramatic improvement of survival (4 years survival rate = 50% vs 0% for refractory MM p less than 10(-9]. Ten percent achieved the best remission (i.e. disappearance of the monoclonal protein, defined as greater than 99% regression and 100% of greater than or equal to 1 year plateau) with the longest survival (4 years survival rate = 80% p less than 0.02). In patients achieving a greater than or equal to 75% regression and a 1 year plateau, the remission duration was not shortened in off-treatment patients. Three types of relapse were observed: "smoldering" (13%), "slow" (49%) and "fulminant" (38%); with a major influence on survival.
Immunological parameters were studied in 25 cases of psoriatic arthropathy. We found in the peripheral blood an increase of IgA, a decrease of IgM, and low conentrations of immune complexes. Anti-gammaglobulin factors, mainly of the IgG class, were detected by indirect immunofluorescence in 55.5% of cases. The study of lymphocyte membrane markers showed a decrease of T cells as investigated by E and "active" E-rosettes, a decrease of EA gamma-rosette-forming cells, and an increase of "high avidity" EA-rosettes. Lymphocyte responses to phytomitogens were normal. There was no correlation between the clinical data and the immunolgical features.
OBJECTIVE: To determine the correlation between the pharmacokinetic (PK) parameters of methotrexate (MTX), clinical status and laboratory test results in rheumatoid arthritis (RA) patients. METHODS: 22 patients (4 M/18F, mean age: 50 +/- 12 years, mean duration of RA: 8.5 +/- 6.5 years, mean duration on MTX: 8 +/- 10 months) were included in a prospective study. The mean dose of MTX administered was 6 +/- 0.7 mg/m2 of body area/week. No patient received any nonsteroidal antiinflammatory drug (NSAID). Blood and urine samples were collected over 24 hours (9 blood samples). The MTX concentrations were assayed by fluorescence polarization immunoassay. Clinical parameters (Ritchie articular index, morning stiffness, joint pain count, joint swelling count), hematological, liver and renal function tests, and ESR were recorded. Correlations between the patients' PK parameters, laboratory tests and clinical status were carried out using Pearson's correlation coefficient test. RESULTS: A significant correlation was observed between the Ritchie articular index, morning stiffness and the area under the curve (p = 0.009 and p = 0.026, respectively). No correlation was found with the other parameters. CONCLUSION: These results suggest that when the patient's disease activity is higher, the AUC becomes more important, reflecting a greater body exposure to MTX.
Rheumatoid arthritis (RA) is a frequent disease, leading in more than 50% of cases to severe disability within 5 years of evolution, and sometimes to the premature death of the patient. It is therefore of crucial importance to diagnose, evaluate, and treat this crippling disease as soon as possible. We need accurate clinical, biological, immunological and radiographic parameters which will permit both early diagnosis and evaluation of the patient's prognosis. However, RA is a very heterogeneous disease which is sometimes considered as a clinical syndrome. The clinical heterogeneity of RA is well known; some cases are very mild and self-limiting, while others are seriously progressive and include extra-articular manifestations which can be life-threatening. There is also a biological and immunological heterogeneity of RA, depending on the presence or absence of: rheumatoid factor, high levels of serum IgA, and antinuclear, anti-Ro, antiperinuclear, or anti-stratum corneum antibodies. The association between HLA DR antigens and the severity of RA has been demonstrated in recent studies including some by our group. HLA DRB1*0401 or 0404 homozygous, or HLA DRB1*0401/0404/0408 heterozygous, or HLA DRB1*04 + HLA DRB1*0101 are associated with severe and erosive RA. Extra-articular manifestations such as nodules, vasculitis or Felty syndrome are very often observed in patients homozygous for HLA DRB1*0401 or 0404. The presence of HLA DR4 seems to be correlated with the articular erosions and not with rheumatoid factor. There is a clear need for a 'staging' of RA in order to define more homogeneous clusters of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: We set out to determine whether the ability of synovial fluids (SF) in patients with rheumatoid arthritis (RA) to facilitate the proliferation of synovial tissue-derived fibroblastic cell lines was related to the presence of growth factors and/or cytokines. METHODS: The growth factor activity of 20 RA SF was measured by their ability to induce anchorage-independent growth of the rat NRK-49F (49F) fibroblastic strain. The presence of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) was also assessed using neutralising anti-TGF-beta or anti-PDGF-AB mAbs. Cytokines were measured by functional assays or ELISA: RESULTS: We observed a correlation between growth factor activity and the IL-6 levels in SF. Both were correlated to the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in SF and serum. IL-6 (at concentrations above 10(4) U/ml), synergized with growth factors in the induction of the anchorage independent (AI) growth of 49F cells. Pretreatment of SF with a neutralising anti-IL-6 mAb substantially reduced the capacity of these SF to induce AI growth of 49F cells, confirming the growth factor activity of IL-6 in this test. In contrast, IL-6 alone or in association with PDGF, epidermal growth factor (EGF) or TGF-beta had no effect on the anchored growth of synovial tissue-derived fibroblasts, and treatment of SF with a neutralising anti-IL-6 mAb did not affect their ability to increase the growth rate of synovial tissue-derived fibroblasts. CONCLUSIONS: These results strongly suggest that IL-6 is responsible for the observed correlation between the growth factor activity of SF and inflammatory indexes such as ESR and CRP. However, neither IL-6 nor PDGF were responsible for the observed positive effect of SF on synovial fibroblastic cell lines.
The neuropeptides are involved in the immune response and in hormonal homeostasis. In this review, we analyse the interactions between the cytokine, the neuropeptide and the hormonal networks in rheumatoid arthritis (RA). We first consider pituitary-adrenal axis dysfunction in RA. An inappropriate response to cortisol in chronic inflammation has been reported, i.e., a decrease of the corticotropin-releasing-hormone (CRH) secretion by the hypothalamus. In contrast, the immunostimulant hormone prolactin (PRL) is upregulated. PRL is released by the pituitary after stimulation by neuropeptides [serotonin, thyroid-releasing-hormone (TRH), or vasoactive-intestinal-peptide (VIP)], and is down-regulated by pro-inflammatory cytokines (IL-1, IL-6). The decreased testosterone concentration observed in male RA patients is associated with HLA B 15. Thus, an altered sex hormone status and a genetic predisposition are related to HLA antigens, and increase the subject's susceptibility to the development of RA. The terminal C fibres release neurotransmitters such as substance P, neurokinin A and calcitonin-gene-related-peptide (CGRP) within the joints, and contribute to local inflammation, synoviocyte proliferation and collagenase production. The parasympathetic system may attenuate the immune response through the neuropeptide VIP. In contrast, the beta 2 adrenergic fibres of the sympathetic nervous system increase joints degradation in RA. This review presents the currently extensive knowledge regarding the immune-neuro-hormonal network, and its implication in the pathogenesis of RA.
We report the case of a patient exhibiting subacute bacterial endocarditis (SEB) associated with vasculitis and signs of nephritis. C-ANCA were present at high titer. This observation suggests that ANCA may be associated with vascular injury in SEB.
Rheumatoid pericarditis (RP) is a well known extraarticular manifestation of rheumatoid arthritis (RA). It is not frequently diagnosed despite its high reported prevalence in post-mortem studies. There have been no immunohistological studies of its presence in pericardial membranes. Here we report a complete immunohistological study of two RA patients with RP complications, using a panel of monoclonal antibodies (mAbs) for the recognition of B, T, and NK cells. Both cases showed strong and almost exclusive pericardial membrane infiltration of CD8+ T-cells which was correlated with a higher than expected similar increase in the subset of peripheral blood lymphocytes (PBL). These findings suggest an important role for CD8+ T-cells in chronic RA, especially in this extraarticular manifestation of the disease.
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We report the first case of choriocarcinoma occurring during the course of systemic lupus erythematosus (SLE). This choriocarcinoma was revealed by pulmonary metastasis associated with pulmonary hypertension secondary to neoplastic thrombi and pulmonary embolism, in parallel to a flare up of the SLE. The role of hormones in SLE is discussed.
Twenty-three per cent of rheumatoid arthritis (RA) patients show an increase of serum IgA concentrations. To determine the role of mucous-associated lymphoid tissue (MALT) in the elevation of serum IgA in RA, we studied the serum secretory-IgA (s-IgA) in 63 RA patients and in 30 healthy controls. We also analysed the secretion of circulating B cells producing IgA, which is known to reflect mucous tissue activity, in a subgroup of 15 patients with increased serum IgA concentrations, and in control patients. The mean s-IgA in the RA patients was 0.046 mg/ml +/- 0.064, versus 0.002 +/- 0.004 mg/ml in controls (not significant). Active disease defined by clinical criteria was associated with an increase in serum s-IgA (p < 0.001). Furthermore, in a subgroup of RA patients with high serum IgA levels, we found an increase in in vitro IgA production by circulating blood lymphocytes (17.39 +/- 15.2 micrograms/ml), versus RA patients with normal serum IgA levels or controls (p < 0.001). These results were not modified by LPS or PWM. Our results further support the hypothesis of primary MALT activation following environmental antigenic stimulation in RA patients.
We report the emergence of polyclonal expansion of gut lymphocyte associated tissues producing IgA in a patient with rheumatoid arthritis associated with a high serum IgA concentration. The role of IgA in rheumatoid arthritis is reviewed.
Primary agammaglobulinemia is a rare disorder which is associated with articular symptoms in 11% of patients. Septic arthritis may occur, but often patients complain of chronic oligoarthritis and have a clinical presentation similar to rheumatoid arthritis. We report 2 cases of primary agammaglobulinemia in adults, associated with non-erosive chronic arthritis. Peripheral blood lymphocyte phenotyping showed a predominance of CD8 lymphocytes with a CD4/CD8 ratio < 1. We did not find any abnormalities in cellular immunity. A histological study of the synovium showed chronic synovitis with perivascular CD8 lymphocyte infiltrates. Intravenous infusion of immunoglobulins resulted in a dramatic improvement in the arthritis in both cases. In one patient we noticed a decrease in CD8 lymphocytosis. These results suggest that CD8 lymphocytes are involved in the pathogenesis of the arthritis associated with agammaglobulinemia.
The aim of this study was to evaluate magnetic resonance images (MRI) of soft tissue abnormalities in the wrist of RA patients in the early stage of the disease. We performed magnetic resonance imaging of the wrist in 15 patients with early rheumatoid arthritis according to ACR criteria, of less than 10 months duration (mean duration 4.8 months). None of the patients had carpal bone erosions on standard radiography. MRI demonstrated abnormality of the soft tissue in 13 of the 15 cases. On coronal MRI, the sites of involvement of the synovitis were the recess of the distal ulnar (9 pts.), the distal radioulnar joint (4 pts.) and the radiocarpal joint (7 pts.). On axial MRI, tendon sheath effusion of the digital flexor was present in 3 patients. Carpal bone lacunae were present in only 4 patients. Disease activity was not associated with the extent of the synovitis on wrist MRI. Our study suggests that MRI is a sensitive method for the detection of synovitis in early RA.
CB17 SCID mice have severe combined immunodeficiency as a result of a mutation on chromosome 16 responsible for deficient activity of an enzyme involved in DNA repair. Because VDJ rearrangement does not occur, the humoral and cellular immune systems fail to mature. SCID mice do not reject human cells. They have been used to study the development of human tumors, human hematopoiesis and humoral responses in antibody-dependent organ-specific autoimmune diseases and in systemic lupus erythematosus. Studies involving grafting of synovial membrane under the renal capsule or in the subcutaneous tissue of SCID mice have provided information on the cells involved in the pathogenesis of rheumatoid arthritis. SCID mice have also been used to study adhesion molecules that play a role in the recruitment of lymphocytes in rheumatoid synovial tissue. The SCID mouse model provides new means of investigating immunologic treatments for rheumatoid arthritis.
OBJECTIVES: To study the clinical, biological and radiological characteristics of RA with a predominant increase of IgA isotype rheumatoid factor (IgA-RF) over IgM-RF. METHODS: The presence of IgA-RF was determined by a sandwich-type ELISA with an antibody against the human IgA used to capture the immunoglobulin. Associated RF activity was revealed with a peroxidase-conjugated human IgG Fc fragment. Forty-nine RA patients were studied, of whom 19 had an increase in IgA-RF (38%). The control group comprised 30 RA patients without IgA-RF. RESULTS: None of the patients had isolated IgA-RF. In the selected 19 RA patients, the OD of IgA-RF (0.971 +/- 0.62 U) was higher than the IgM-RF (mean OD: 0.675 +/- 0.522 U). A statistically significant correlation was found between IgA-RF and IgM-RF (r = 0.64, p < 0.0001). No correlation was noted between the IgA concentration and the IgA-RF titer. The two groups were comparable for age, disease duration, sex ratio and previous DMARD use. We observed that patients with RA associated with increased IgA-RF more often had the sicca syndrome, but no other extra-articular features. RA patients with IgA RF also had more erosive disease: the mean Larsen score at the hand and wrist was 76 (SD = 68) versus 54 (SD = 60) in the controls, p < 0.02. Replacement surgery for the hip or knee was necessary in 47% of the RA patients with IgA-RF, versus 13% in the controls, p < 0.01. No association of IgA-RF with disease activity was noted. CONCLUSION: Our study showed that RA patients with a predominant increase of IgA-RF had a more erosive disease and a high frequency of associated sicca syndrome.
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