微波和磁疗治疗膝关节骨性关节炎300例

1临床资料①对象:本组骨性关节炎患者300(男130,女170)例,年龄36～78(56±1.0)岁,病程1 mo～10 a,其中左膝120例,右膝112例,双膝68例.临床表现为关节疼痛、僵直、活动受限,偶尔会关节肿胀、关节腔积液.X线表现为关节间隙变窄,关节软骨下骨质致密,骨密度增高,骨小梁有断裂,髁间嵴变尖及髌骨后缘和外侧缘增生形成骨刺[1].     

BAFF, APRIL, TWE-PRIL: who's who?

BAFF and APRIL are two members of the TNF superfamily that have co-stimulatory activity on B cells and contribute to autoimmunity. While BAFF is processed at the cell surface, APRIL is processed inside the cell by a furin-convertase and is able to perform its function only as a soluble factor. However, APRIL can be expressed as a cell surface fusion protein with TWEAK called TWE-PRIL. BAFF can also exist as a soluble molecule and can be detected in human serum. Whether the biological functions controlled by membrane-bound BAFF differ from those triggered by soluble BAFF is unclear. In addition to this complexity, DeltaBAFF, an alternative splice isoform of BAFF shows different properties. BAFF can also, in autoimmune disease form heterotrimers with APRIL but the control and function of these heterotrimers remain unclear. In order to understand the function of these molecules we need to elucidate the complexity of the various forms of these members of the TNF family.     

Does the BAFF dysregulation play a major role in the pathogenesis of systemic lupus erythematosus?

Given the prominent role currently assigned to B lymphocytes in systemic lupus erythematosus, it is not surprising that the B cell activity factor belonging to the tumor necrosis factor family (BAFF) is involved in its pathogenesis. This cytokine is produced in excess, and inserted into its receptors on the surface of circulating B cells. Up-regulation of BAFF is most likely to lead to breach of tolerance by aberrant survival of B cells directed to the self. Trials aimed at blocking BAFF have thus been set out. Yet the results are awaited.     

Changes in glycosylation of immunoglobulins in primary Sjögren's syndrome

Serum IgG and IgA are glycoprotein and significant glycoform abnormalities have been established in primary Sj?gren's syndrome. The proportion of asialylated IgG is abnormally high in the patients, whereas IgA1 and IgA2 appear to be over-sialylated. This peculiarity might explain the defective binding of IgA to asialoglycoreceptors. Furthermore, the activity of alpha 2,6 sialyl transferase is higher in the IgA-producing B cells from the patients than in the controls, whereas the alpha 2,3 sialyl transferase operates in the former cells but not in the latter. The mechanism of this enzyme dysregulation warrants elucidation.     

The binding of some human antiendothelial cell antibodies induces endothelial cell apoptosis.

The pathogenic role of antiendothelial cell antibodies (AECA) remains unclear. They are frequently associated with antibodies to anionic phospholipids (PL), such as phosphatidylserine (PS), which is difficult to reconcile with the distribution of PL molecular species within the plasma membrane. Since it is already known that PS is transferred to the outer face of the membrane as a preclude to apoptosis, the possibility exists that apoptosis is initiated by AECA. AECA-positive/anti-PL antibody-negative sera from eight patients with systemic sclerosis (SS) and 21 control patients were evaluated. Endothelial cells (EC) were incubated with AECA and the exposure of PS was established through the binding of annexin V. Hypoploid cell enumeration, DNA fragmentation, and optical and ultrastructural analyses of EC were used to confirm apoptosis. Incubation of EC with AECA derived from six of eight patients with SS led to the expression of PS on the surface of the cells. This phenomenon was significantly more frequent in SS (P < 0.04) than in control diseases. The redistribution of plasma membrane PS preceded other events associated with apoptosis: hypoploidy, DNA fragmentation, and morphology characteristic for apoptosis. Apoptosis-inducing AECA did not recognize the Fas receptor. We conclude that AECA may be pathogenic by inducing apoptosis.     

Chronic lymphocytic leukemic (CLL) cells secrete multispecific autoantibodies

A subset of B cells expressing the CD5 marker, a 67 KD molecule, has been implicated in the pathogenesis of autoimmune disease. To study the immunoglobulin repertoire of CD5+ B cells we investigated chronic lymphocytic leukemic (CLL) cells, since the majority of the malignant clones express CD5. CLL were induced to secrete their IgM in vitro by phorbol 12-myristate 13-acetate (PMA) and the supernatants screened for binding to a panel of autoantigens. Twelve out of 14 CLL clones were autoreactive, binding to Fc of IgG, ssDNA, dsDNA, histones, cardiolipin, or cytoskeletal components. Many also bound to more than one antigen tested for, showing multispecificity. Our data suggest that a high proportion of CD5+ B cells are programmed to secrete multispecific autoantibodies.     

Increased N-linked glycosylation leading to oversialylation of monomeric immunoglobulin A1 from patients with Sjögren's syndrome

Increased serum immunoglobulin A (IgA) level is a common finding in primary Sjögren's syndrome (pSS). IgA might not be properly eliminated because of an abnormal glycosylation. We reported previously that IgA₁ from patients with pSS was oversialylated. We extend this finding by showing that monomeric IgA₁ contains more sialic acid (SA) in patients than in controls, as determined by enzyme‐linked immunosorbent assay (ELISA) and Western blot with Sambucus nigra agglutinin (SNA), a lectin specific for SA. To localize this excess of SA on the N‐ and/or O‐linked oligosaccharides, we analysed them separately, using N‐ and O‐linked oligosaccharide profiling kits based on fluorophore‐assisted carbohydrate electophoresis. N‐linked, but not O‐linked, oligosaccharides of patients' IgA₁ were oversialylated, and this seemed to be linked to an excess of SA on the same number of polysaccharides as normal IgA₁. To localize the abnormality to the Fab and/or Fc fragments, monomeric IgA₁ was digested with protease, separated and transferred to nitrocellulose, where SA was identified by SNA. Both Fab and Fc fragments appeared to be oversialylated. Oversialylation of N‐linked oligosaccharides of IgA₁ from patients with pSS might prevent the recognition of IgA by receptors that are responsible for their clearance, resulting in an excess of serum IgA and related immune complexes.