Histocompatibility antigens in inflammatory bowel disease. Their clinical significance and their association with arthropathy with special reference to HLA-B27 (W27).
Histocompatibility (HLA) antigen phenotypes have been studied in 100 patients with ulcerative colitis, 100 with Crohn's disease, and 283 normal controls. In addition the incidence of ankylosing spondylitis, sacroiliitis, and "enteropathic" peripheral arthropathy was determined in the patients with inflammatory bowel disease (IBD). There was no significant difference in antigen frequency between patients and controls. However, the incidence of HLA-B27 was increased in the patients complicated by ankylosing spondylitis and/or sacroiliitis in both ulcerative colitis and Crohn's disease. In contrast, none of the 29 IBD patients with "enteropathic" peripheral arthropathy had B27 antigen. Furthermore, ankylosing spondylitis was found more frequently in ulcerative colitis bearing HLA-B27 compared with non-B27 patients (P less than 0-01). The same was found in Crohn's disease, although this difference was not statistically significant. In addition, 12 of 14 ulcerative colitis patients and five out of six Crohn's patients with HLA-B27 had total colitis, compared with the frequency of total colitis in non-B27 patients (P less than 0-024 and less than 0-03 respectively). The data suggest that B27 histocompatibility antigen could be a pathogenetic discriminator between the arthropathies in IBD and may be of prognostic significance with respect to extension and severity of the disease. (+info)
Alteration of descending modulation of nociception during the course of monoarthritis in the rat.
Diffuse noxious inhibitory controls (DNIC), which involve supraspinal structures and modulate the transmission of nociceptive signals, were investigated at different stages during the development of adjuvant-induced monoarthritis in the rat. After behavioral evaluation, recordings of trigeminal convergent neurons were performed in anesthetized animals with acute (24-48 hr) or chronic (3-4 weeks) monoarthritis of the ankle. Inhibitions of C-fiber-evoked neuronal responses during and after the application of noxious conditioning stimuli to the ankle were measured to evaluate DNIC. The conditioning stimuli consisted of mechanical (maximal flexion and graded pressures) and graded thermal stimuli and were applied alternately to normal and arthritic ankles. Behaviorally, the two groups of animals exhibited a similar increased sensitivity to mechanical stimuli applied to the arthritic joint (i.e., an increased ankle-bend score and a decreased vocalization threshold to pressure stimuli). However, they showed different electrophysiological profiles. In the animals with acute monoarthritis, the DNIC-induced inhibitions produced by mechanical or thermal stimulation of the arthritic joint were significantly increased at all intensities compared with the normal joint. In contrast, in the chronic stage of monoarthritis, the DNIC-induced inhibitions triggered by thermal or pressure stimuli were similar for both ankles, except with the most intense mechanical stimuli. This discrepancy between the behavioral and electrophysiological findings suggests that inputs activated during chronic monoarthritis may fail to recruit DNIC and may thus be functionally different from those activated in the acute stage of inflammation. (+info)
Sensory afferent properties of immobilised or inflamed rat knees during continuous passive movement.
We studied the sensory afferent properties of normal, immobilised and inflamed rat knees by recording the activity of the medial articular nerve (MAN). When the knee was inflamed by kaolin-carrageenan or immobilised for six weeks, MAN activity significantly increased during rest and continuous passive motion (CPM). The maximal discharge rate tended to increase depending on the angular velocity of the CPM. When the knees were then rested for one hour before again starting CPM, activity was further increased at the initial CPM cycle, the 'post-rest effect'. Analysis of the conduction velocity showed that 94% and 66% of spike units on the recorded discharge of the immobilised and inflamed knees, respectively, belonged to fine nerve fibres. Our findings show that the sensory receptors in the knee are sensitised in a similar manner by immobilisation and by inflammation, suggesting a relationship to pain. The post-rest effect may be related to a characteristic symptom of osteoarthritis called 'starting pain'. (+info)
Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice.
Cathepsins have been implicated in the degradation of proteins destined for the MHC class II processing pathway and in the proteolytic removal of invariant chain (Ii), a critical regulator of MHC class II function. Mice lacking the lysosomal cysteine proteinase cathepsin S (catS) demonstrated a profound inhibition of Ii degradation in professional APC in vivo. A marked variation in the generation of MHC class II-bound Ii fragments and presentation of exogenous proteins was observed between B cells, dendritic cells, and macrophages lacking catS. CatS-deficient mice showed diminished susceptibility to collagen-induced arthritis, suggesting a potential therapeutic target for regulation of immune responsiveness. (+info)
Effect of tripterine on collagen-induced arthritis in rats.
AIM: To study the therapeutic effect of tripterine (Tri) on collagen-induced arthritis (CIA). METHODS: Collagen type II (Col) 1.5 mg was injected intradermally to induce CIA in rats. Hind paw volumes of rats were measured with a water displacement method. The serum anti-collagen antibody was measured by an enzyme-linked immunosorbent assay. Delayed hypersensitivity was reflected by skin response to Col. Interleukin-1 (IL-1) and interleukin-2 (IL-2) activities were evaluated by [3H]TdR uptake. Joint was evaluated histologically. RESULTS: Tri 15 and 30 mg.kg-1.d-1 given i.g. to rats 3 d after the first sign of arthritis reduced inflammatory swelling, suppressed humoral and skin response to Col, inhibited IL-2 and IL-1 production, reduced pathological progression of joint. CONCLUSION: Tri has a therapeutic effect on CIA. (+info)
Body mass index, weight change, and incidence of self-reported physician-diagnosed arthritis among women.
OBJECTIVES: This study examined the relationship between body mass index (BMI), weight change, and arthritis in women. METHODS: Data were taken from the 1982-1984 National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study of 3617 women, aged 25 to 74 years. RESULTS: Women with a BMI greater than 32 at initial interview were at significantly higher risk of developing arthritis than women with a BMI of 19 to 21.9. Compared with stable-weight women with a BMI of less than 25, women who were obese at initial interview (BMI > 29) and who subsequently maintained their weight or gained more than 10% of their body weight were at significantly higher risk of developing arthritis. CONCLUSIONS: Attaining and maintaining a healthy weight may reduce the risk of developing arthritis. (+info)
HLA-B27 antigen in diagnosis of atypical seronegative inflammatory arthropathy.
Eighteen patients with an inflammatory pauciarticular peripheral arthropathy not typical of any known entity showed an asymmetrical pattern of disease, with a predilection for the lower extremities. Destructive joint changes and deformities were absent (mean follow-up 10 years). Although spondylitis and sacroiliitis were absent on x-rays, HLA-B27 antigen was found in 8 patients (44%). This antigen and similar joint symptoms are also found in other forms of arthritis. (+info)
Interferon-beta1A-induced polyarthritis in a patient with the HLA-DRB1*0404 allele.
Human interferon-alpha (IFNalpha) and IFNbeta are administered for treatment of several diseases, including viral infections, malignancies, and multiple sclerosis (MS). IFNalpha therapy has been associated with the production of autoantibodies and the development of a variety of autoimmune disorders, including polyarthritis. This report describes the development of seronegative, symmetric polyarthritis in a patient with relapsing-remitting MS, after 8 weeks of therapy with IFNbeta1a. HLA phenotyping analysis of the patient revealed the presence of HLA-DRB1*0404, an allele known to be associated with the development of rheumatoid arthritis. Therefore, IFNbeta1a may have induced arthritis in a patient who was genetically predisposed to develop arthritis on the basis of HLA determinants. The English-language literature regarding IFNalpha- and IFNbeta-induced polyarthritis is reviewed, and possible mechanisms for IFNalpha- and IFNbeta-induced autoimmunity, including the contribution of HLA determinants and nitric oxide overproduction, are discussed. (+info)