SJOGREN'S SYNDROME: ASSOCIATION WITH TYPE-1 DIABETES MELLITUS

This study of 102 unselected type-1 diabetic patients has shownthat sicca symptoms affect 55% of the patients, although sometimesonly during hyperglycaemic phases. While these symptoms mightbe attributable to the diabetes, the frequency of antinuclearantibodies in those suspected of having Sjögren's (25%by HEp-2) and particularly anti-Ro antibodies (32% by ELISA)reinforces the suspicion that Sjogren's syndrome may underlietheir presence. KEY WORDS: Sicca syndrome, Autoantibodies, Anti-Ro, Hyperglycaemia, Immunoglobulins, Rheumatoid factor     

FcγRIIa polymorphism in systemic lupus erythematosus (SLE): no association with disease

An allotypic variant of FcγRIIa, FcγRIIa-HR (FcγRIIa-R131), has been shown in vitroto reduce the capacity of phagocytic cells to bind and internalize IgG-containing immune complexes. Our aim was to determine whether this allotypic variant was associated with susceptibility to SLE and the development of lupus nephritis, as previous studies have suggested. FcγRIIA genotype analysis was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 215 Caucasoid, 70 Afro-Caribbean, and 46 Chinese patients with SLE, and in 259, 77, and 49 ethnically matched controls, respectively. Distribution of FcγRIIa genotypes between the patients and ethnically matched controls was not significantly different in the three populations studied. No association between the FcγRIIa-HR allotype and nephritis was found. Our results suggest that the FcγRIIa-HR allotype is not a major factor predisposing to the development of SLE, or to lupus nephritis.     

PREVALENCE OF SELF-REPORTED DEPRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS

The prevalence of self-reported depressive symptoms was investigatedin a case-control study of patients with rheumatoid arthritis(RA) attending an out-patient clinic at the Middlesex Hospital.Patients selected their own controls, matched for age and sex.Previous attempts to measure depressive symptoms in RA havesuffered from measurement error due to criterion contamination,where psychological symptoms augment depressive scores. A totalof 163 patients (77% of the sample) and 115 matched pairs completedthe Hospital Anxiety and Depression Scale (HADS). The resultsIndicated that RA patients are more depressed and anxious thancontrols. The prevalence of depression above the cut-point was15%. This figure is comparable to other reports adjusted forcriterion contamination, but is lower than that of other studieswhich employ ‘contaminated’ tools. The depressionscale of the HADS appeared to be relatively free of criterioncontamination. Subject to further reliability testing, the HADSmay be a practical screening tool for practitioners to assesspatients in need of psychological interventions. KEY WORDS: Depression, Rheumatoid arthritis, Criterion contamination     

ANTI-DNA ANTIBODIES IN THE PRIMARY ANTIPHOSPHOLIPID SYNDROME (PAPS)

Primary antiphospholipid syndrome (PAPS) is considered a distinctentity from SLE and patients with PAPS are generally regardedas being dsDNA antibody negative. Levels of IgG and IgM ss andds DNA antibodies were measured by ELISA in 30 patients whofulfilled the criteria for the diagnosis of PAPS. We comparedthese patients with 20 normal controls and seven patients withidiopathic SLE. We also examined all the sera for anti-nuclearantibodies by Hep-2 cells and for dsDNA antibodies by Crithidia. We found that 16 patients with PAPS had antibodies to ss and/ordsDNA. Only three of the 16 positive patients had both IgG andIgM anti-DNA antibodies. Twelve patients had anti-nuclear antibodies,but only two were weakly positive for dsDNA antibodies by Crithidiaimmunofluorescence. Eleven out of 30 patients with PAPS hadIgM anti-dsDNA antibodies compared to two out of the seven SLEpatients. The PAPS patients with anti-DNA antibodies were clinicallyindistinguishable from the PAPS patients without antibodiesagainst DNA. Our results show that 53% of patients with PAPS had antibodiesto DNA which supports the view that PAPS and SLE are probablyoverlapping disorders. KEY WORDS: ELISA, Primary antiphospholipid syndrome, Anti-DNA antibodies     

INSIDIOUS LOSS OF RENAL FUNCTION IN PATIENTS WITH ANTICARDIOLIPIN ANTIBODIES AND ABSENCE OF OVERT NEPHRITIS

Circulating anticardiolipin antibodies are associated with recurrentthrombosis, fetal loss and thrombocytopenia. We have identifiedfour patients with SLE or lupus-like disease who have high circulatinglevels of ACLA, repeated thrombosis and evidence of renal disease.Their clinical signs and symptoms of lupus activity were minimal,yet all had renal insufficiency with GFR 50 ml/min or less despiteno history nor evidence of overt nephritis (proteinuriat<0.5g/day and no haematuria). Renal biopsy specimens showed focalischaemic lesions with no evidence of active lupus nephritis.We describe a new lesion of renal ischaemia secondary to non-inflammatoryvascular pathology associated with circulating ACLA. KEY WORDS: Anticardiolipin antibody, Lupus nephritis, SLE, Renal dysfunction     

GENETIC ANALYSIS OF TAP2 IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS FROM TWO ETHNIC GROUPS

The aim of this study was to determine whether the TAP2 (Transporterassociated with Antigen Processing 2) locus is involved in susceptibilityto systemic lupus erythematosus (SLE). We adopted the interethnicapproach to overcome problems in the analysis resulting fromlinkage disequilibrium. The TAP2 gene polymorphisms of the codonscorresponding to amino acid positions 379, 565 and 665 wereinvestigated by amplification refractory mutation system polymerasechain reaction (ARMS-PCR) in 186 patients (151 white Europeans,35 Afrocaribbeans) and 183 controls (79 white Europeans, 104Afrocaribbeans). In the European SLE patients, the frequencyof the TAP2 type V-A-TA was marginally lower compared with thecontrol group (31% vs 42%), with negative linkage disequilibriumbetween this TAP2 type and DR3 probably accounting for the difference.For the European SLE patients, we confirmed a significant associationof DR3 with disease status [odds ratio = 4.16, 95% confidenceinterval (CI), 2.08–8.39] and in the patients with DR3there was a significantly high frequency of the TAP2 type V-A-T-.In the Afrocaribbean SLE patients, any associations of diseasestatus with TAP2 phenotype were the inverse of those in theEuropean patients. Thus, in these patients the frequency ofV-A-TA was higher than in controls (46% vs 26%, OR = 2.4, 95%CI 1.01–5.74), while the frequency of V-A-T- was lower(26% vs 40%, not significant). Despite possible sampling error,the lack of a difference in TAP2 status between cases and controlswithin ethnic groups and, if anything, an inverse associationacross ethnic groups, makes it unlikely that the TAP2 polymorphismstudied here is of primary relevance to SLE susceptibility. KEY WORDS: MHC, TAP2, SLE, Interethnic     

Review article: gastroduodenal bicarbonate secretion

The gastroduodenal epithelium is covered by an adherent mucus layer into which bicarbonate is secreted by surface epithelial cells. This mucus-bicarbonate barrier is an important first line of defence against damage by gastric acid and pepsin, and has been demonstrated in all species including human. Similar to gastric acid secretion, regulation of gastric and duodenal bicarbonate secretion can be divided into three phases: cephalic, gastric and duodenal. In humans, sham-feeding increases bicarbonate secretion in both the stomach and duodenum which is mediated by cholinergic vagal fibres in the stomach, but seems to be noncholinergic in the duodenum. Gastric distention and luminal acidification increases gastric bicarbonate production. Whereas there are no data relating to the gastric phase of human duodenal bicarbonate secretion, in animals, food and acid in the stomach independently stimulate duodenal bicarbonate output. To date, the duodenal phase of human gastric bicarbonate secretion has not been studied, but data from animals reveal that duodenal acidification augments bicarbonate secretion in the stomach. In all species tested, direct acidification of the duodenum is a potent stimulant of local bicarbonate production. In humans, the pH threshold for bicarbonate secretion is pH 3.0. Mediation of gastroduodenal bicarbonate secretion is provided by a variety of agonists and antagonists, tested mainly in animals, but some have been evaluated in humans. Prostaglandins of the E class and VIP are major factors that control bicarbonate secretion. Bicarbonate secretion, and the mucus-bicarbonate layer in general, is adversely effected by ulcerogenic factors such as aspirin, NSAIDs, bile salts, and cigarette smoking. Furthermore, duodenal ulcer patients have an impairment in bicarbonate production within the duodenal bulb, at rest and in response to stimulation. These findings indicate that the mucus-bicarbonate barrier is an important first line of defence in the pathogenesis of peptic ulcer disease.     

DETECTION OF AUTOANTIBODIES TO THE 90 kDa HEAD SHOCK PROTEIN IN SYSTEMIC LUPUS ERYTHEMATOSUS AND OTHER AUTOIMMUNE DISEASES

Expression of the highly conserved 90 kDa heat shock protein(Hsp90) is elevated in the peripheral blood mononuclear cellsof approximately 25% of patients with SLE. Conflicting datahave been published about the frequency of antibodies to Hsp90with the previous methodology using a complex Western blot system.We now describe an ELISA to measure autoantibodies to Hsp90and Hsp70 in SLE patients, healthy controls and patients witha variety of autoimmune rheumatic diseases, IgG and IgM antibodieswere elevated in 26 and 35% of SLE patients, respectively. Theseresults show autoantibodies to Hsp90 (but not Hsp70) are elevatedin a significant proportion of patients with SLE (P<0.025)compared to healthy controls; and that those with raised antibodylevels were more likely to have renal disease and a low C3 level(P<0.02). KEY WORDS: Heat shock protein 90, Autoantibodies, Systemic lupus erythematosus, Autoimmunity, Myositis     

Immunoglobulin Deposition in Skeletal Muscle in Primary Muscle Disease

Using direct Immunofluorescence the deposition of lgG, IgM,IgA, Clq and C3 was studied on muscle biopsies from 39 patientswith polymyositis/dermotomyositis, 21 patients with musculardystrophy, 57 other disease controls and volunteers. Three stainingpatterns were observed, sarcolemma/basement, but not blood vesselwall or intrafibrous. Sarcolemma/basement membrane staining,but not blood vessel wall or intrafibrous staining, occuredmore frequently (p < 0.05) in the polymyositis/dermatomyositisgroup compared with the two other disease groups. Immunoglobulindeposition was usefull in distinguishing myopathic from neuropathicdisorders, Grouping the patients into those with connectivetissue disease and those without, sarcolemma/basement membraneand blood vessel wall staining were shown to distinguish thetwo groups (p < 0.05). An analysis of the historical abnormalitiesin the polymyosities/dermatomyositics group was performed andrelated to immunoglobulin/complement deposition. Fibre damsge,rather than the presence of a mononuclear perivasular infiltrate,was shown to be the best correlate with each of the three Stainingpatterns. Immunoglobulin and/or complemet deposition in skeletalmuscle is an abnormal finding and the results described supportthe nation that the humoral abnormalities may be detected frequentlyin polymyositis/dermatomyositis. In addition, the inabilityto distinguish polymuositis/dermatomyositis from muscular dystrophylimits the potential value of direct immunofluoresence as adiagnostic tool.