Associations of MHC class II alleles in Norwegian primary Sjögren's syndrome patients: implications for development of autoantibodies to the Ro52 autoantigen.
Sj?gren's syndrome (SS) is a chronic autoimmune disease characterized by dryness of the eyes and mouth. Currently, the highly polymorphic major histocompatibility complex (MHC) genes are the best documented genetic risk factor for the development of autoimmune disease. We examined the MHC class II alleles DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1 in a group of Norwegian pSS patients and compared with a group of healthy controls. Because a number of studies have shown that some of the MHC class II alleles are not associated with the disease as a whole, but rather to the development of autoantibodies, anti-Ro52 autoantibodies in serum were measured and compared to MHC class II allele status. A clear association with pSS was detected for the DRB1*0301 and DRB3*0101 alleles, but these alleles were more closely associated with the presence of anti-Ro52 autoantibodies than with pSS itself. Moreover, the DQA1*0501 and DQB1*0201 alleles were only associated with the presence of anti-Ro52 autoantibodies. This study shows that the production of anti-Ro52 autoantibodies in pSS is associated with the DRB1*0301, DRB3*0101, DQA1*0501 and DQB1*0201 alleles which are in strong linkage disequilibrium.
Calprotectin (L1) is a major granulocyte and monocyte protein which is released during activation of these cells. The plasma level of L1 is thought to reflect disease activity in rheumatoid arthritis (RA). In our cross sectional study of 70 patients with RA, L1 had significant correlations with erythrocyte sedimentation rate (r = 0.50), C-reactive protein (r = 0.58), orosomucoid (r = 0.62), platelet count (r = 0.42), leukocyte count (r = 0.33) and IgM rheumatoid factor (r = 0.32); and with the following clinical variables: number of swollen joints (r = 0.24), grip strength (r = -0.22), PIP joint circumferences (r = 0.33) and a combined global assessment score (r = 0.24). L1 was higher in seropositive (median 14,861 micrograms/l) than seronegative patients (median 10,487 micrograms/l) (p less than 0.03).
In our prospective controlled study, a total of 185 patients with polymyalgia rheumatica (PMR) and temporal arteritis (TA) diagnosed during 1978-83 and their 925 matched controls were cross checked with the data files at the Cancer Registry of Norway at the end of 1987. Malignancy was registered in 27 patients (14.6%) and 131 controls (14.2%) between 1953 and the end of 1987. Malignancy was registered in 16 (24.6%) of the patients with biopsy demonstrating arteritis temporalis. The hazard rate for developing malignancy after diagnosis for the whole patient population was not significantly different from the controls. The hazard rate for developing malignancy in patients with positive biopsy, however, was 2.35 times higher than in the controls (p = 0.036) and 4.40 times higher than the rest of the patient population (p = 0.007) (Cox proportional hazards model). The general long interval between diagnosis of PMR and/or TA and registration of malignancy (mean 6.5 years) is not consistent with a paraneoplastic mechanism.
Health care in a department of rheumatology was evaluated by interviewing 15 patients by a person not associated with the department. The patients' evaluation of the health care was then further evaluated by 264 former patients and the staff. There was a considerable mismatch between the patients' and staff's rating of the problems. The patients' feedback was then used systematically to choose between alternative methods of organising and providing the health care, and the effect of this was then re-evaluated by the patients.
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Comment In: Tidsskr Nor Laegeforen. 1995 Aug 20;115(19):2437-87667867
Rheumatoid arthritis is a serious disease associated with increased morbidity and mortality, and requires adequate routines for therapy and follow-up examination. This article presents the work of the Norwegian Society for Rheumatology to improve the quality of the therapeutic assessment of patients with rheumatoid arthritis in Norway. The process of reaching an agreement involved a large number of rheumatologists. The final meeting included a variety of activities, plenary lectures, workshops, group discussions and opinion polls. A literature search through Medline was provided continuously. Agreement was achieved on a programme for monitoring therapy with disease-modifying antirheumatic drugs, which was to comprise visits to the physician and laboratory tests. This programme was later voted on and affirmed by the Annual Meeting of the Norwegian Society for Rheumatology. Proposals were issued regarding endpoint measures to assess progression of the disease. These proposals can be expected to improve the quality of treatment and management of patients with rheumatoid arthritis, both in primary health care and in the specialized rheumatological health service.
Broegelmann Research Laboratory, Center for Medical Genetics and Molecular Medicine, Institute of Medicine, Haukeland University Hospital, Bergen, Norway. anne.bolstad@gades.uib.no
OBJECTIVE: To screen for polymorphisms in the apoptosis regulating Fas and Fas ligand (FasL) genes in patients with primary Sjögren's syndrome (SS), and to explore associations with susceptibility to the disease. METHODS: Polymorphisms in Fas and FasL of 70 patients with primary SS and 72 controls were determined by polymerase chain reaction combined with the restriction enzyme fingerprinting single strand conformation polymorphism technique, verified by automatic sequencing and natural or amplification created restriction site tests. RESULTS: Polymorphisms were found in both Fas and FasL, but only some of the Fas polymorphisms were found in statistically significant differences between patients and controls. Patients displayed a higher frequency of the G/G genotype at position -671 than the controls, and the -671 G allele frequency for primary SS was increased compared to controls. A higher frequency of the C allele at position IVS2nt176 and IVS5nt82 was also found. Of note, the nucleotide variants in intron 2 and intron 5 were associated. CONCLUSION: We describe the positions and frequencies of several polymorphisms in the genes encoding Fas and FasL in patients with primary SS. None caused any amino acid change. Three Fas alleles, of which one is located in the promoter area, showed significant although modest differences between patients and controls.
The prevalence of thyroid antibodies in 100 patients with rheumatoid arthritis in Northern Norway was studied. The serological data were compared with those from a major population survey in the same area. Compared to the prevalence in the normal population, the present study demonstrates that patients with rheumatoid arthritis have a higher prevalence of antibodies to both thyroid microsomal antigen and thyroglobulin.
Photosensitivity is one of the major clinical features of Systemic Lupus Erythematosus (SLE), and is considered to be implicated in the disease pathogenesis. We studied seasonal variations of SLE disease activity at latitude 70 degrees North where there is no sunlight in the winter time, in contrast to 24 h daily sunlight in the summer (midnight sun). The associations between the level of plasma melatonin in June and December with disease manifestations were also studied. Twenty-one SLE patients were examined each month for 1 y, and disease activity was assessed by laboratory parameters as well as clinical disease activity parameters SLEDAI and doctor's global assessment. Melatonin levels were quantified by a RIA-assay. There was no significant change of clinical measures or laboratory parameters of disease activity from one month to the next during the one year, except photosensitive rashes. January was the only month without SLE-flares or arthritis, in contrast to rest of the year. The levels of plasma melatonin were highest in December for seven patients and highest in June for one patient (P
The purpose of this study was to determine the total and cause-specific mortality in rheumatoid arthritis (RA) patients compared to a control population in northern Norway. One hundred and eighty-seven patients with RA and 930 population controls matched for age, gender and municipality were followed until death or for a maximum of 17 years. The total mortality in RA patients was twice that of their controls (MRR = 2.0, 95% CI = 1.6-2.5). Patients possessing serum rheumatoid factors did not have a higher relative mortality than the seronegative patients. There was no statistically significant increased mortality from cancer or cardiovascular diseases. Indications for a higher death rate in RA patients than in controls were found for infection and sudden death.
In its classical form, Wegener's granulomatosis (WG) is characterized by acute granulomatous vasculitis of the upper and lower respiratory tract together with glomerulonephritis, and when untreated, mortality is high. The use of cyclophosphamide and prednisolon has improved the prognosis dramatically, while azathioprine and trimetoprim-sulfamethoxazole are of limited therapeutic value in these patients. Only 1/3 of subacute and chronic cases show renal impairment, and the prognosis is better in limited Wegener's granulomatosis without renal disease than in the classical form. This case-report and review takes up various new aspects of diagnosis, treatment and prognosis.
