Antiphospholipid antibodies in systemic lupus erythematosus: Clinical and laboratory associations in 111 patients

Summary An enzyme linked immunosorbent assay (ELISA) was used to evaluate the prevalence and disease associations of antibodies to a range of negatively charged phospholipids in 111 patients with systemic lupus erythematosus (SLE). The frequency of one or more isotypes of different antiphospholipid antibodies (APLs) was similar (range 33%–45%). When individual isotypes were considered alone there was considerable variation (range 5%–32%). There were significant associations between thrombosis, thrombocytopenia, and central nervous system (CNS) disease but not abortion with elevated APL. Strong associations were found between raised anti-ds-DNA (Farr assay) and a positive direct Coomb's test with raised APL. Thus, APLs are common in SLE and are associated with discrete clinical and laboratory features. However, detection of antibodies to a range of negatively charged phospholipids added little clinically useful information to that obtained by measuring anticardiolipin antibody (ACL) alone. We cannot recommend the use of APLs other than ACL for routine testing.     

Anti-Clq affinity isolated circulating immune complexes correlate with extra-articular rheumatoid disease

Summary Circulating immune complexes (CIC) were isolated from sera of 35 patients with rheumatoid arthritis (RA) by a two-step method using 2% polyethylene glycol precipitation and anti-C1q affinity chromatography. By this method CIC were exclusive to 19 patients with vasculitis, nodules, or Sjögren's syndrome. Levels of CIC did not correlate with the severity of synovitis but reflected the extent of extra-articular disease. Furthermore, in four patients with persistent severe synovitis observed over a period of 4 to 16 months, the levels of CIC paralleled changes in extra-articular disease. Despite such additional evidence, whether the relationship between CIC and tissue injury is causative or consequential remains unresolved.     

Regulation of adhesion molecule expression by human synovial microvascular endothelial cells in vitro

Objective. To examine the in vitro expression of E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1), ICAM-2, vascular cell adhesion molecule 1 (VCAM-1), and platelet–endothelial cell adhesion molecule 1 (PECAM-1) by synovial microvascular endothelial cells (SMEC) in comparison with microvascular neonatal foreskin endothelial cells (FSE) and macrovascular human umbilical vein endothelial cells (HUVE). Methods. Cultured endothelial cells were treated for 4 hours with medium alone or tumor necrosis factor α (TNF α). The expression of endothelial adhesion molecules was evaluated by flow cytometry, cell enzyme-linked immunosorbent assay, and Northern blot analysis. Results. SMEC continuously expressed E-selectin under basal culture conditions, whereas FSE and HUVE did not. TNF α treatment of rheumatoid arthritis (RA) SMEC resulted in sustained peak expression of E-selectin for up to 24 hours, which subsequently declined but remained elevated even at 72 hours. In contrast, peak E-selectin expression in FSE and HUVE occurred between 4 hours and 16 hours after TNF α treatment and then declined to near basal levels by 24–48 hours. SMEC expressed significantly higher levels of ICAM-1 compared with HUVE under basal culture conditions. There was no difference between SMEC, FSE, and HUVE in the expression of P-selectin, VCAM-1, ICAM-2, or PECAM-1. Northern blot analysis demonstrated that the levels of E-selectin expression by TNF α-stimulated endothelial cells correlated with their respective messenger RNA levels. Conclusion. Regulation of E-selectin and ICAM-1 expression in RA synovial endothelium is different from that in neonatal foreskin and human umbilical vein endothelium. The augmented expression of adhesion molecules in RA synovial endothelium may facilitate the recruitment of leukocytes to this site.     

Temporal processing deficits in remediation-resistant reading-impaired children

There is considerable interest in whether a deficit in temporal processing underlies specific learning and language disabilities in school-aged children. This view is particularly controversial in the area of developmental reading problems. The temporal-processing hypothesis was tested in a sample of normal children, 9-11 years of age, and in a sample of age-matched children with reading impairments, by assessing temporal-order discrimination. Five different binary temporal-order tasks were evaluated in the auditory and visual sensory modalities. Other basic discrimination abilities for single auditory stimuli were also assessed, including just noticeable differences (JNDs) for frequency and intensity and a simple threshold detection task. In these tasks, the temporal dimension was the duration of the individual stimuli (20 and 200 ms). All data were obtained using forced- choice psychophysical methods, either in a single-track adaptive format or using psychometric functions. The results from these experiments showed that children with reading impairments had deficits in temporal-order discrimination, but these effects were not modality specific. These same children also had significantly elevated frequency and intensity JNDs and their performance on these tasks were not dependent on stimulus duration. No group differences were observed on the threshold detection task, and the derived measurements of temporal integration (i.e. the threshold difference between the 20- and 200-ms stimuli) were considered normal, averaging 11.7 dB. As a whole, discrimination deficits observed in the reading-impaired group only occurred with suprathreshold stimuli. The deficits were neither modality specific nor temporal (duration) specific.     

Augmented lymphocyte binding to cultured endothelium in psoriasis.

Lymphocyte binding to cultured human umbilical vein endothelial cells was evaluated using a modified centrifugation binding assay in 15 patients with psoriasis and compared with three patients with atopic dermatitis, 11 patients with rheumatoid arthritis and 28 normal controls. Patients with psoriasis demonstrated 61% augmented lymphocyte binding compared with normal controls (P < 0.0001), which was not explained by differences in age and sex or an effect of psoriatic sera. In serial studies of six patients, this difference was found to be reversible with treatment and clinical improvement. Lymphocytes from patients with atopic dermatitis demonstrated decreased binding to endothelium (P < 0.005), while those from patients with rheumatoid arthritis were not different from normal controls. This is the first skin disease described in which augmented lymphocyte binding to endothelium occurs, and may represent a mechanism by which lymphocytes are targeted to psoriatic skin.     

Immunosuppressive drugs and corticosteroids in the treatment of rheumatoid arthritis

Rheumatoid arthritis is the most common form of severe inflammatory arthropathy affecting patients at a relatively early age. Although there are a number of drugs which significantly reduce pain and swelling, few alter the development of erosions and progression of joint destruction. A significant number of patients with rheumatoid arthritis develop this progressive disability and will require treatment with corticosteroids or immunosuppressive agents. In this article the use of immunosuppressive drugs and corticosteroids in the treatment of aggressive rheumatoid arthritis is reviewed. Controlled clinical trials have shown that a number of these drugs can play a significant role in reducing pain and swelling and might possibly alter the disease course in rheumatoid arthritis. Side effects of these agents, including the potential for oncogenesis, still pose major problems in their long term use. The risks and benefits of immunosuppressive and corticosteroid drug therapy must be balanced in each patient to whom they are prescribed and reviewed at frequent intervals.     

Quantitation and detection of isotypes of anti-SS-B antibodies by ELISA and Farr assays using affinity purified antigens. An approach to the investigation of Sj?gren's syndrome and systemic lupus erythematosus

Affinity purified SS-B was characterized as a protein with immunoreactive polypeptides of 40K and 29K. A modified Farr assay and an enzyme linked immunosorbent assay (ELISA) were 100- to 1,000-fold more sensitive than immunodiffusion and showed an association with the systemic manifestations of primary sicca syndrome and Sj?gren's syndrome with systemic lupus erythematosus. The ELISA was sufficiently sensitive to detect class specific antibodies in saliva and lymphocyte culture supernatants.