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The aim of this study was to determine whether NK cell receptor (NKR) expression could modulate cytotoxicity of oligoclonal CD8+ T cells present in the synovial fluid (SF) of HLA-B27-reactive arthritis (ReA) patients, especially in a TCRBV1 population shared among different patients and cytotoxic toward HLA-B27. A CD8+ T cell line, two TCRBV1 lines and clones were isolated from the SF of an HLA-B27+ ReA patient, and tested with mAb specific for Ig-like (KIR2DL1, KIR2DL2, KIR3DL1 and ILT2) and CD94 C-type lectin NKR. Transcripts for NKG2 subunits (NKG2A-2E) associated with CD94 were also evaluated. Function was tested in a 51Cr-release cytotoxic assay. We found stable but distinct levels of CD94/NKG2 complexes at the surface of T cell lines and clones. Different NKG2 members could be associated with CD94, either inhibitory (NKG2A/B) or activating (NKG2C). The inhibitory ILT2 receptor could also be differently expressed, but other Ig-like NKR were negative. Functionally, one TCRBV1 line and clones with a high CD94/NKG2A expression did not lyse B27+ targets. Another TCRBV1 line with the same TCRBV1 rearrangement had a low expression of CD94/NKG2A, but expressed NKG2C transcripts and was cytotoxic toward HLA-B27. HLA-B27 is a ligand for ILT2 and we observed an inhibitory effect of ILT2 engagement on B*2705 targets in blockade experiments. Altogether, these data indicate a high degree of heterogeneity in the expression of NKR by intrasynovial CD8+ T cells which could modulate their cytotoxicity and play a role in the control of this HLA class I-associated autoimmune disease.

Interleukin 1alpha (IL-1alpha) has been implicated in the pathogenesis of infectious, auto-immune and inflammatory diseases. Polymorphisms in the genes encoding IL-1alpha, IL-1beta and the IL-1 receptor antagonist (ILRN) molecules have been associated with several inflammatory diseases. As the marker D2S160 has been characterized as a candidate locus for Ankylosing Spondylitis (AS) after a genome-wide scan, and since this locus is located approximately 0.3 cM telomeric to the IL-1 gene cluster, we hypothesized that these cytokines might be good candidates for Spondylarthropathies (SpA). Therefore we tested this hypothesis using the transmission disequilibrium test (TDT) in 37 families representing 217 subjects from three intragenic IL-1 gene cluster polymorphisms, the IL1B Taq I, the ILRN 2nd intron, and the IL1A Nco I, taking HLA B27 status into account or not. In conclusion, by means of intra-familial TDT analysis we found no linkage or intra-familial association between SpA and the three IL-1 gene-cluster polymorphisms in SpA multiplex family material., (Copyright 2001 Academic Press.)

Spondyloarthropathies constitute a group of autoimmune diseases of special interest because of their tight association with the MHC class I molecule HLA-B27 and the bacterial triggering of some clinical forms called reactive arthritis (ReA). One current hypothesis is the presentation by HLA-B27 of a so-called arthritogenic peptide to T cells. To better focus on the relevant T cell populations within the joint, we performed an extensive beta-chain T cell repertoire analysis of synovial fluid compared with PBL in seven patients, four of whom were characterized as having ReA triggered by Yersinia enterocolitica, Chlamydia trachomatis, or Shigella sonnei. Analysis of the size diversity of the beta-chain complementarity-determining region 3 (CDR3) allowed us to evaluate the degree of T cell clonality in the samples. Oligoclonal T cell expansions were frequently observed in the joint. In one patient, CDR3 amino acid sequences of major expansions using two different BV genes were identical. One dominant T cell expansion and several CDR3 amino acid sequences were identical in two different patients. Furthermore, one sequence was identical with a sequence reported independently in a Salmonella-induced ReA patient. Together, these data indicate a surprisingly high degree of conservation in the T cell responses in recent-onset ReA triggered by different micro-organisms. A CD8+ synovial line expressing shared clonotypes was established and reacted toward several B*2705 lymphoblastoid cell lines, therefore supporting a molecular mimicry phenomenon at the T cell level in the disease mechanism.

The appearance of systemic lupus erythematosus (SLE) after thymectomy (or thymomectomy) is presented in four patients together with a comparative review of additional reports found in a Medline search for the years 1966-94 in the English and French literature. Fourteen women and two men of average age of 39 years (range 11-66 years) at presentation, developed SLE after thymectomy (11 patients) or thymomectomy (five patients). Half developed SLE within 3 years after surgery (range 3 months to 18 years). The most common SLE manifestation was polyarthritis occurring in 15 of 16 patients either at presentation or during the first year. Other frequent manifestations included skin rashes, fever, cytopenias and pleuritis. Two rare manifestations of SLE, optic neuritis and transverse myelitis, were reported in two patients. Thymic hormone activity was measured in one patient and was undetectable compared with normal controls. HLA studies in eight patients showed the combination of A1, B8 in four. In conclusion, the appearance of SLE after thymectomy or thymomectomy appears to be more than a coincidence. It may provide insights into the pathogenesis of SLE.

Although osteoarthritis is characterized by a uniform pattern of clinical and radiological manifestations, it is a syndrome that can be produced by a variety of causative factors. Rare causes of osteoarthritis can be categorized as follows: 1) systemic metabolic disorders due to known biochemical and/or genetic abnormalities, such as hemochromatosis, ochronosis, Wilson's disease, Ehlers-Danlos syndrome (and probably the "idiopathic" joint hypermobility syndrome), sickle cell anemia, and thalassemia; 2) endocrine disorders, such as acromegaly, whose joint manifestations are now well-known, and hypothyroidism; 3) Paget's disease of bone, osteopetrosis (which induces changes in bone elasticity), and other systemic bone diseases; 4) dysplasias, which form a vast group including familial polyepiphyseal dysplasia, spondyloepiphyseal dysplasia congenita (especially its milder forms), Stickler's syndrome, osteo-onychodysplasia, Kniest's dysplasia, trichorhinopharyngeal syndrome, and a group of diseases that affect the epiphyses; 5) endemic forms of osteoarthritis, e.g., Mselini disease, Kashin-Beck disease, and Malnad disease, which are unknown in western Europe but have been reported to affect thousands of individuals in endemic areas. All these disorders are usually responsible for premature osteoarthritis, whose presentation sometimes bears the imprint of the causative abnormality but can be identical to that of common osteoarthritis. The effects of toxic substances (Kashin-Beck disease) or genetically-determined collagen II abnormalities (epiphyseal dysplasias) may explain the occurrence of these rare forms of premature osteoarthritis.

Experimental results suggest that substance P (SP) may play an important role in pain and inflammation in rheumatic diseases. Measurements of SP-like immunoreactivity (SPLI) were performed in synovial fluid (SF) and synovial tissue from 40 patients with rheumatoid arthritis (RA) or osteoarthritis (OA). High levels of SPLI were found in the SF of patients with RA compared with OA. Conversely, SPLI content in synovial tissue was higher in OA than in RA, suggesting that there is an active secretory process of SPLI into the SF in RA, thus depleting SPLI stores in the synovium. Our data support the involvement of SP in the perpetuation and exacerbation of inflammation in RA, and may also explain some clinical features of this disease.

"Camptocormism" in the elderly is an acquired kyphosis which increases during walking and is totally reducible in dorsal horizontal position in two thirds of cases. The authors report 16 cases of camptocormism in patients with a mean age of 76 (12 women, 4 men). Camptocormism was accompanied in 5 cases by an extrapyramidal syndrome, in 3 cases by articular chondrocalcinosis, in 1 case by giant cell arteritis and in 1 by rheumatoid arthritis. There was no inflammatory syndrome and muscle enzymes were raised in only 4 cases. Electromyogram of the paravertebral muscles was pathological in 5 cases, with neurogenic changes in 4 cases and a myogenic type tracing in one. CT scan or magnetic resonance imaging showed evidence in all cases of atrophy with fatty involution of the paravertebral muscles. Biopsies of the paravertebral muscles revealed moderate mononuclear cell infiltrates in 4 cases with similar abnormalities in peripheral muscles. Corticosteroids had a beneficial effect in 11 cases out of 13 and the most prolonged results were seen after bolus doses of methylprednisolone. These findings suggest that camptocormism in the elderly could be linked to inadequacy of the paravertebral muscles or, in certain cases, to interstitial myositis.

This retrospective study involved 60 patients (7 men, 53 women) with rheumatoid arthritis (RA) and given methotrexate between 1985 and 1990. The mean time that RA had been present was 12 years and more than half of the patients had received more than 3 types of general treatment in the past. The mean total duration of MTX was 17.3 months, with a total dose of 790 mg. The efficacy of MTX was confirmed by a significant improvement in clinical and laboratory parameters. Treatment was withdrawn permanently in 21 cases (35% of patients). Adverse reactions, responsible for two thirds of treatment withdrawals (14/21) occurred in most instances during the first year of treatment. Hepatic toxicity was commonest. Two cases of aplasia were reported as well as 3 cases of pneumonitis, one fatal. These involved two cases of secondary infection and one of pneumonitis directly imputable to MTX. Withdrawals for inefficacy were rare, occurring in less than 10 p. cent of patients. Treatment continuation rates were 77 p. cent at 1 year, 66 p. cent at 18 months, 55 p. cent at 2 years, 42 p. cent at 3 years and 32 p. cent at 4 years. MTX is effective treatment for RA but is not free of adverse reactions, sometimes potentially fatal. Prolonged monitoring is necessary because of the sometimes delayed onset of adverse reactions.

In 3 patients who developed acute arthritis of the knee 3 months to 5 years after insertion of a total condylar prosthesis, it was possible to formally exclude an infectious cause. A number of cytological and histological arguments confirm that these were cases of foreign body arthritis (polyethylene debris and metal dust). These cases of arthritis responded to local steroid treatment combined with a Yttrium synoviorthesis, in the absence of any antibiotic treatment. The synoviorthesis was performed in order to eliminate the real foreign body granuloma which develops and which can contribute to the loosening of these prostheses.

This paper deals with mitochondria microcrystal deposition in some human inflammatory rheumatism and in experimental arthritis. Hydroxyapatite microcrystals were observed in Ankylosing Spondylitis (AS) and Reiter Syndrome (RS) but never in rheumatoid synovitis nor in chondrocalcinosis synovitis. In Rat and Rabbit experimental arthritis, they were always seen in mitochondria as in AS and RS and never in lysosomes. This fact suggests mitochondrial abnormalities in calcium metabolism, which may be a consequence of synovial inflammation in a susceptible host.

The aim of this paper is to describe clinical pattern and pathogenesis of spontaneous chronic polyarthritis observed in Swiss goats. Roentgenograms, histologic findings, ultrastructural study and microprobe analysis of synovium samples show apatite microcrystal deposit ion. Thus this spontaneous goat disease may be related to apatite microcrystal deposit ion disease in man, so called crystallopathic-hydroxyapatite rheumatism.

In inflammatory rheumatism treated by gold therapy synoviocytes A are stuffed with gold salt deposits leading to a therapeutic thesaurismosis. These deposits are localized in lysosomes, then called aurosomes. However they may be rarely near collagen fibers or free, particularly in ankylosing spondylitis synovitis. Their structural morphological aspect is the same in several human rheumatic diseases and in rabbit experimental arthritis whatever the gold salt used. In such deposits, microprobe analysis shows gold and sulphur. This latter is probably given by the cell. Therapeutic effect of gold salts may imply the effect of the thiol moiety and the gold metal one.

This paper deals with the paramyxovirus-like intranuclear inclusions observed in giant cells tumours of bone (GCTB). Twenty-one (49%) of 43 cases of GCTB (1977-1985), either fresh and/or cultured, show these ultrastructural inclusions. Fifty samples of various bone lesions in which giant cell lesions occurred, including aneurysmal cysts, hyperparathyroidism, osteoblastoma, human and rat osteopetrosis, GCT of tendon sheaths, and non skeletal granuloma were used as controls. These, together with 20 samples of normal bone (osteoclasts) did not contain intranuclear or intracytoplasmic viral inclusions.

This paper deals with the various crystalline aspects of the ceramide trihexoside (CTH) inclusions, in the synovial tissue essentially. A basic classification is proposed and uncommon examples are illustrated. Image processing confirms the membrane-like structure of CTH inclusions and corroborates the proposed classification.

Image analysis and Fourier transformation of the various nuclear immunofluorescence patterns observed while detecting antinuclear antibodies allow an objective and quantitative definition of the fluorescence. They also point out various IF types hidden by the main pattern, without having to dilute the test serum. They make obvious the difference between speckled and reticular patterns, and reveal the existence of intermediate states. The usual nuclear IF patterns (homogeneous, ring, nucleolar, reticulated, speckled and diffuse) may be grouped, according to their photo emission, into nuclear and subnuclear patterns. The first group includes homogeneous, annular and passive nucleolar IF. The second group is composed of speckled, reticulated, mixed, and active nucleolar IF. Alternatively, these aspects may be grouped into three types: homogeneous nuclear IF (homogeneous and ring), heterogeneous nuclear IF (speckled, reticulated and mixed) and nucleolar IF (active or passive). Diffusion can affect or not these aspects and does not apply to a special type or pattern. Image analysis and the study of the image spatial spectrum lead to automated recognition of the IF types, and later on, to the discrimination of antinuclear antibodies.

Articular inflammatory involvement may be the first sign of gluocecerebrosidase deficiency (Gaucher's disease). Electron microscope study shows specific synovial storage lesions which explain arthritic manifestations. Furthermore presence of mitochondrial microcrystals, (apatite?), suggest microcrystal pathogenesis of Gaucher's arthritis.

Articular manifestations may be the onset of genetic alpha galactosidase deficiency (Fabry's disease). Ultrastructural study shows typical osmiophilic lamellar inclusions of trihexosylceramides in synoviocytes, capillaries and adipocytes. Furthermore microcrystals identical to those seen in Gaucher's disease and type II hyperlipoproteinemia were observed in mitochondria and free in cytoplasm. These data suggest a microcrystalline pathogenesis of these arthropathies, as in gout and chondrocalcinosis, and what we have generally called crystallopathic arthropathies.

We are reporting a case of multicentric reticulo-histiocytosis which is exceptional because of its gravity and the diversity of the clinical lesions: huge subcutaneous nodules, bone destruction in the spine responsible for spondylolisthesis, pulmonary fibrosis, acute pericarditis, laryngeal compression requiring a permanent tracheostomy. From ultrastructural observations, various hypotheses to explain the intra-macrophagic accumulation of membrane granules and lipids are discussed.

Trituration-aspiration-infiltration of calcifications of the shoulder region is a method applied for treatment of intractable calcifying periarthritis. A television screen is used to guide the needle until it is in contact with the calcifications provoking the symptoms. Trituration and aspiration of the calcified lesions is followed by saturation with prolonged released corticoids of 41 shoulders treated, recovery or improvement was noted in 70% after one month, results being rated as excellent in 19 patients followed up for 3 months.

The activity of cyanide-sensitive and cyanide-insensitive superoxide dismutase (CNs- and CNi-SOD) was measured in polymorphonuclear neutrophils isolated from the blood of patients with ankylosing spondylitis (A.S.) or adults with rheumatoid arthritis (R.A.). Our purpose was to detect alterations in the protecting activity of these enzymes that might cause rheumatic lesions secondary to superoxide anion generation in the inflammatory loci. There was no difference in total SOD activity (CNs + CNi) in either A.S. or R.A. when compared to the control group. In contrast, CNi-SOD activity decreased in R.A. and A.S. and CNs-SOD activity rose significantly in A.S. only. None of the changes observed in SOD activity correlated with patient's age, erythrocyte sedimentation rate, clinical evolution of the disease or the drug doses administered. It is concluded that the reduced activity of CNi-SOD might be partly responsible for the reduced protection of the joints against oxygen-free radicals in patients with A.S. or R.A. Other factors however appear to have greater effects on the clinical evolution of these diseases.

The ceramide trihexoside inclusions, which characterize Fabry-Anderson disease, have been studied using electron microscopy and digital image processing. Results are given showing the various apparent periodicities of the inclusion lamellae and the orientation, perpendicular to the lamellae or oblique, of the ceramide molecular component.

This paper dealt with the case of a 53 years old man, affected by a chronic renal failure as the initial symptom of a primary oxalosis and treated by hemodialysis three years ago. Two years after the onset of renal failure, the left knee was painful and swollen but no cartilage or bone joint lesion was observed. Presence of intra synovial calcium oxalate crystals suggests that this arthropathy may be related to the primary oxalosis. However the role of other calcium salts under identification evidenced by synovial electron microscopy (apatite ? pyrophosphate ?) is discussed.

An application of the Fourier Transform Process to the Fabry inclusion study has been made. The study, which rests upon five tissues and eight persons, brings out a new low frequency stratification. Various degrees of freedom exist for the basic molecule association. The periods are given for the three fundamental directions of the inclusion.

The authors report a case of the Gougerot-Sjögren syndrome with rheumatoid arthritis, of particular interest because of lymphocytic proliferation. This was initially confined to the broncho-pulmonary tissues with histological appearances of pseudo-lymphoma, a diagnosis supported by clinical regression with immunosuppressive drugs, over a 5 years period. This difficult diagnosis needs histological, biochemical and clinical confirmation and, the very existence of this entity is debatable. The occurrence of a malignant lymphoma of the small intestine in the same patient a few years later is an argument in favour of the hypothesis that the pseudo-lymphoma was an intermediary pre-malignant stage of B-lymphocytic proliferation.

The authors report three cases of type IIa hypercholesterolemia in which ultrastructural observation of the synovial fluid revealed the presence of frothy cells and microcrystals. A questionnaire-based retrospective investigation amongst a population of 201 patients followed-up for type IIa essential hypercholesterolemia revealed the presence of joint disorders in 92 cases (45.8%). The condition sometimes affected a single joint (17.4%), but was generally polyarticular (82.6%), affecting the large joints. Joint pain was reported in 38 cases (41.3% of the patients presenting joint disease and 18.9% of the group as a whole) and predominantly affected the arms. Acute arthritis (54 cases) occurred preferentially in the legs. In 35 cases (38% of the joint-disease cases and 17.4% of the population as a whole) this resulted in acute rheumatic fever. Nineteen of these cases were unspecified forms of arthritis (20.7% amongst the joint-disease sufferers and 9.5% of the population). This analysis, combined with ultrastructural studies of the synovial fluid from 3 patients, establishes the existence of hypercholesterolemic rheumatism amongst heterozygotes as well as amongst homozygotes.

Thanks to an elaborated mathematical approach, based on statistics and signal processing, the chronological changes of the Erythrocyte Sedimentation Rate (ESR) of young healthy subjects, considered from a collective point of view, have been discriminated into genuine and well-defined rhythms. These rhythms are tied up either to natural (year, season) or 'social' (month, week, holidays) cycles, or to some other causes, still unknown and possibly intrinsic (such is probably the case of a 26.5-day strongly marked period). The solar induced time variation strictly obeys a frequency modulation law, the relative amplitude of which is 10 per cent. Two axes of symmetry are found, centered on 8 August and 8 February. The rhythm is roughly in accordance with seasons. The modulation frequency is maximum at summer time. Oscillations of the ESR are observed during the week and the month. Fridays and the last fortnight of each month appear to be low ESR time.

This paper deals with diagnosis value of synovium electron microscopic study in inflammatory and metabolic rheumatism. Detection in synovium of hydroxyapatite, Ca pyrophosphate and other biological crystals often need the use of EM. It is also a good diagnosis tool in inherited lipid and glucid metabolism disorders and to establish an anatomic correlation between the osteo-articular localization and the systemic disease. Furthermore EM is able to detect stigmata of previous treatment such as chrysotherapy, immune complexes deposits in tissues, amyloidosis fibrils and even viral or bacterial material.

A case of chronic, corticosteroid-responsive arthritis affecting particularly one ankle in a patient with type IV hyperlipoproteinaemia is reported. After gout or inflammatory rheumatism of another nature had been excluded, and following synovial fluid examination and synovial membrane biopsy, a diagnosis of type IV hyperlipoproteinaemia rheumatism was made. At electron microscopy, the synovial membrane showed numerous large spumous cells and a peculiar appearance of the capillary vessels.