Measurement of whole unstimulated salivary flow in the diagnosis of Sjögren's syndrome.

The criteria for a clinical diagnosis of Sjögren's syndrome remain controversial and vary widely from study to study. With respect to the oral component it is considered necessary to use some form of objective test, but many of those available are not suitable for use in a busy clinical situation. The purpose of this study was to evaluate a simple method for measuring the whole unstimulated salivary flow. Twenty five patients with Sjögren's syndrome, 69 young control subjects, 20 age matched normal older control subjects and 20 patients with rheumatoid arthritis without Sjögren's syndrome had their salivary flows measured. Whole unstimulated salivary flows in the young control subjects were higher than in all other groups. Patients with primary Sjögren's syndrome had lower flows than either the older controls or the rheumatoid patients. Among the patients with Sjögren's syndrome 52% had a flow of 0.1 ml/min or less compared with only 8% of age matched controls. The positive predictive value of this low flow was 81%. It is concluded that whole unstimulated salivary flows of 0.1 ml/min or less are highly specific for xerostomia. When interpreted in the context of all the clinical findings whole unstimulated salivary flows are useful for diagnosing the oral component of Sjögren's syndrome.

Brief exercise induces an immediate and a delayed leucocytosis.

Haematological profiles were measured: (1) before and for 5 h 30 min after 30 min sports (squash, swimming, jogging); and (2) before, during and for 2 h 30 min after 30 min cycle ergometry at workloads which required rates of oxygen consumption that were between 48% and 84% of maximal. In both instances exercise induced an immediate leucocytosis (owing to rises in both neutrophils and lymphocytes) which subsided rapidly at the finish of exercise and was followed by a delayed neutrophilia of greater magnitude which peaked at approximately 3 h after the start of exercise. Changes in plasma catecholamines and cortisol recorded during and after exercise (cycle ergometry only) support the hypothesis that the immediate leucocytosis during brief exercise is attributable to elevated catecholamine levels, whereas the delayed neutrophilia is due to raised cortisol levels.

Rapid clearance of the lupus antigen Sm is delayed by autoantibody: a possible mechanism of autoimmunity perpetuation.

Sm ribonucleoprotein complex was immunopurified and labelled with 125I. After i.v. injection into normal mice 125I-Sm was cleared with a half life of less than 3 min, mainly to the liver (54% at 15 min). With time there was a progressive reduction in liver uptake (13.3% at 1 h), and this was associated with the appearance of increasing amounts of trichloroacetic acid soluble 125I in serum, suggesting complete Sm catabolism. Injection of 125I-Sm as a preformed immune complex with human anti-Sm antibody was associated with slower antigen removal from the circulation (half life 15 min), more gradual liver uptake (27% at 1 hr), and less degradation products in the serum than after injection of antigen alone. These data suggest that release of 125I-Sm into the circulation is followed by specific organ uptake and antigen degradation. In the form of an immune complex, the rapid removal mechanism is impaired, and antigen persists in the circulation in an undegraded form. Simultaneous production of anti-Sm antibody and Sm antigen release following tissue destruction could lead to amplification of any primed immune response as a result of autoantigen drive in systemic lupus erythematosus.

Spontaneous atlantoaxial subluxation: an unusual presenting manifestation of Reiter's syndrome.

A male Sikh presented with spontaneous neck pain. Plain cervical radiography showed gross atlantoaxial subluxation (AAS). Computed tomography showed soft tissue anterior to a subluxed odontoid peg. A diagnosis of atlantoaxial tuberculosis was considered. Confirmation of this would have required a trans-oral anterior cervical biopsy. Despite the paucity of other rheumatic symptoms a diagnosis of Reiter's syndrome with spondylitis was made, and the only surgical procedure required was posterior fusion of C1 and C2, with resultant spinal stability and pain relief. This is the first report of Reiter's syndrome presenting with AAS.

Sarcoidosis in a patient presenting with clinical and histological features of primary Sjögren's syndrome.

A patient presenting with bilateral enlargement of parotid and lacrimal glands, xerostomia, and keratoconjunctiva sicca, whose labial biopsy specimen showed changes consistent with Sjögren's syndrome, is described. The patient was initially misdiagnosed as having primary Sjögren's syndrome (SS). Subsequent investigations, however, performed to exclude an associated lymphoma or sarcoidosis, showed histological changes of the latter. The possibility that early infiltrates of the salivary glands in sarcoid may mimic those of SS is discussed.

Demonstration of an unidentified 48 kD polypeptide in circulating immune complexes in rheumatoid arthritis.

Circulating immune complexes (CIC) were isolated from 25 patients with rheumatoid arthritis (RA) by anti-C1q affinity chromatography. The components were detected by silver stained sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gels and identified by the Western blot. The CIC were composed of 20 different polypeptides, including albumin, immunoglobulin, complement, and acute phase reactants. Two components (molecular weight 48 kD and 45 kD respectively) remained unidentified. The 48 kD polypeptide was found in CIC from six out of 14 patients (43%) with extra-articular RA, but from none of eight patients with vasculitic complications of other connective tissue diseases. All immunoreactants were more frequently found in the patients with extra-articular features of RA. Although these results emphasise that most CIC in RA are composed of endogenous proteins, the 48 kD polypeptide is a candidate for an extrinsic antigen in RA.

Anti-C1q affinity isolated circulating immune complexes correlate with extra-articular rheumatoid disease.

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.

A seroepidemiological study of cytomegalovirus and Epstein-Barr virus in rheumatoid arthritis and sicca syndrome.

Antibodies to cytomegalovirus (CMV) and Epstein-Barr virus capsid antigen (EBVCA) were examined in 41 patients with rheumatoid arthritis (RA), 26 patients with primary sicca syndrome, and 26 healthy subjects of similar age and sex. IgG antibody titres to EBVCA and CMV were similar in all three groups, apart from a trivial increase of antibodies to EBVCA in RA. False positive IgM anti-CMV antibodies detected in serum from one patient with sicca syndrome and 20 patients with RA were shown to be due to rheumatoid factors. These data did not support recent suggestions that patients with these diseases showed exaggerated immunological responses to either virus and emphasised the need to incorporate adequate laboratory and disease controls when seroepidemiological studies are performed on sera containing rheumatoid factors and autoantibodies.

MRL mice show an age-related impairment of IgG aggregate removal from the circulation.

The fate of heat-aggregated human IgG (HAGG) was examined in young and old autoimmune MRL-lpr/lpr and MRL-+/+ mice and compared to BALB/c mice of different ages. Following iv injection of [125I] HAGG the older MRL-lpr/lpr and MRL-+/+ mice showed impaired hepatic and splenic uptake of this material. In addition the clearance rate of HAGG was significantly slower in the older MRL-lpr/lpr mice (t1/2 = 50 min) when compared to younger controls (t1/2 = 13 min) although this age-related retardation of clearance was not observed in the MRL-+/+ mice. No difference was seen in the clearance rate or organ uptake studies of the two age groups of BALB/c mice. Catabolic studies using trichloracetic acid suggested that the HAGG was catabolized to smaller fragments with time but not to such a great extent in the older diseased animals, again no age-related difference was seen in the BALB/c mice. Our studies suggest that with age both autoimmune strains of MRL mice show some saturation of the mononuclear phagocytic system (MPS) and that this process is more obvious in the MRL-lpr/lpr mice. MPS saturation may play a role in the pathogenesis of autoimmune disease in these mice.

Specific autoantibody slows the rapid plasma clearance of 125I-SS-B (La) in mice.

In BALB/c mice the plasma clearance of intravenously (i.v.) injected 125I-SS-B (La) (T 1/2 = 3 min) is markedly delayed when complexed in vitro to specific autoantibody (T 1/2 = 60 min) and is associated with diminished hepatic and renal uptake. The in vivo behaviour of 11S 125I-SS-B-IgG-anti-SS-B complexes was similar to that of 20-30S 125I-heat-aggregated IgG. The presence of anti-SS-B antibodies in systemic lupus erythematosus and Sjögren's syndrome could similarly result in persistence of SS-B containing immune complexes and provide a mechanism which may perpetuate autoimmunity.

Tissue uptake and catabolic studies of 125I SS-B (La) injected into mice.

The radiolabeled soluble cellular antigen 125I SS-B (La) has a plasma half-life of 3 min following iv injection into BALB/C mice. Uptake by Kupffer cells (KC) and proximal renal tubular (PRT) cells was demonstrated by autoradiography (ARG). That trichloracetic acid (TCA)-soluble products of 125I SS-B appeared in plasma within 1 min of iv injection suggests rapid in vivo breakdown. Activated peritoneal macrophages (APM) degraded 125I SS-B in a time- and cell-dose-dependent fashion. These findings suggest that the plasma clearance and catabolism of 125I SS-B may be dependent on its interaction with phagocytic cells. This rapid antigen elimination may protect against harmful autoantibody responses.

In vivo fate of 125I SS-B (La) injected into mice.

The fate of the radiolabelled soluble cellular antigen SS-B (La) was compared with that of other 125I-labelled proteins of known molecular weight (MW) and electrostatic charge, following i.v. injection into BALB/c mice. The plasma half-life of 125I-SS-B was 3 min, while that of 125I-bovine serum albumin (similar MW and electrostatic charge) was 270 min. 125I-heat-aggregated IgG (MW greater than 1 x 10(6)) and 125I-7S human IgG (MW 168,000) had plasma half-lives of 40 min and greater than 300 min, respectively. Liver and kidney showed preferential uptake of 125I-SS-B, followed by a rapid decrease in radioactivity. During this time low MW, trichloroacetic acid (TCA) soluble, material appeared in urine. This suggests a specific uptake mechanism followed by a catabolic phase. These studies demonstrate that normal mice remove 125I-SS-B rapidly from the circulation and then degrade it. This rapid antigen elimination may protect against the induction of potentially harmful autoantibody responses.

Measurement of radiographic joint space in the rheumatoid knee: correlation with obesity, disease duration, and other factors.

A new and highly reproducible method for measuring radiographic joint space in the rheumatoid knee is described. The joint space was measured in radiographs of the knees of 120 patients with rheumatoid arthritis and correlated by computer analysis with age, sex, duration of disease, erosions, degenerative change, therapy and Quetelet's index (an index of obesity). Narrowing of both compartments of the knee correlated significantly with the duration of disease. Narrowing of the lateral, but not medial, compartment showed some degree of correlation with obesity as measured by Quetelet's index, but this did not achieve significance. The presence of erosions was associated with marked narrowing of joint space which frequently occurred early in the course of the disease; three-quarters of the patients showing even moderate erosions had at least one knee compartment narrowed to 2 mm or less and in half of these the changes had occurred in less than 10 years. Joint space narrowing also correlated strongly with degenerative change which was, however, remarkable for its infrequency.