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H J Haga

Publications and source records attributed to H J Haga.

At least 19 recordsLinked to original sources

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Age of Onset↗

Reproduction and gynaecological manifestations in women with primary Sjögren's syndrome: a case-control study.

BACKGROUND: The impact of primary Sjögren's syndrome (pSS) on reproduction and gynaecological manifestations has seldom been explored. AIM OF STUDY: Assess gynaecological aspects, gynaecological interventions, and use of contraceptives in a population of pSS-patients versus controls. METHODS: In a case-control study, 58 pSS-patients and 157 controls answered a self-administered questionnaire, covering demographic data, reproductive events, gynaecological problems, and gynaecological interventions. RESULTS: Significantly more patients than controls reported episodes of amenorrhoea lasting for more than 3 months, and more patients suffered from menorrhagia/metrorrhagia compared with controls (54.5% versus 35.7%; p = 0.012). Complaints of vaginal dryness were common among the patients (52.9% versus 28.3%; p = 0.005). Endometriosis was reported to occur more frequently in the patients (8.5% versus 2.1%; p = 0.03), and 6.3% of pSS-patients reported having undergone surgical intervention for endometriosis versus 0.7% of the controls (p = 0.009). Positive information about surgery for endometriosis correlated with the presence of the autoantibodies anti-SSA (r = 0.322; p = 0.008) and anti-SSB (r = 0.313; p = 0.01). Among the pSS-patients, 5.9% had chosen not to have children due to the disease, but there was no indication of reduced fertility as judged by the number of pregnancies. CONCLUSION: Patients with pSS reported more gynaecological problems than controls, including vaginal sicca symptoms, endometriosis, several episodes of amenorrhoea, and menorrhagia/metrorrhagia.

Adult↗

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Adolescent↗

Total mortality is increased in rheumatoid arthritis. A 17-year prospective study.

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.

Adult↗

Associations of MHC class II alleles in Norwegian primary Sjögren's syndrome patients: implications for development of autoantibodies to the Ro52 autoantigen.

Sjögren'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.

Alleles↗

Clinical utility of diagnostic tests for rheumatoid factor.

OBJECTIVE: To investigate and compare the accuracy and usefulness of diagnostic tests for rheumatoid factor (RF). METHODS: In a cross-sectional study sera derived from patients admitted to the Section of Rheumatology were tested for presence of RF using either nephelometry or the Waaler test. Diagnostic sensitivity and predictive values of the tests were calculated and compared. The accuracy of the tests was compared using receiver-operating characteristics (ROC) methodology. RESULTS: Good agreement was found between the tests (kappa approximately 0.7). At cut-off 19 IU/mL nephelometry showed the highest sensitivity (82.4%) and specificity (95.9%) for rheumatoid arthritis (RA). In comparison, the Waaler test had a sensitivity of 60.3% and specificity of 95.9% at cut-off titer 128. The tests showed nearly equal performance characteristics when predicting SS. CONCLUSION: Although both tests exhibit good performance characteristics, nephelometry has a higher accuracy when predicting RA and SS. The common practice of using both tests for detection of RF is not recommended.

Cross-Sectional Studies↗

HLA markers and clinical characteristics in Caucasians with primary Sjögren's syndrome.

OBJECTIVE: To explore the association between HLA genotypes and clinical and immunological characteristics in Caucasians with primary Sjögren's syndrome (pSS). METHODS: HLA genotyping for DRB1, DQA1 and DQB1 was carried out in 62 single case patients with pSS and 64 healthy controls. The specific amino acid residues at DQA1 position 34 (DQalpha-34Q) and DQB1 position 26 (DQbeta-26L) in addition to the DQ-DI (AA59-AA69) motif were deterrmined. Subsequently, the relative contribution of individual HLA markers to clinical and immunologic characteristics of pSS was assessed by group comparisons. RESULTS: No significant associations were seen between HLA markers and histopathological or clinical features of pSS. Significant positive associations with HLA Class II markers were restricted to the formation of different autoantibodies. Formation of an anti-Ro/SSA and anti-La/SSB autoantibody response was positively associated with DRB1*03, DQB1*02 and DRB1*03/DRB1*15-DQB1*02/DQB1*0602 heterozygosity. Patients positive for anti-La/SSB also showed a strong positive anti-La/SSB association with DQA1*0501. Considering the contribution of individual DQA1 and DQB1 amino acids and sequence motifs to the formation of anti-Ro/SSA and anti-La/SSB autoantibodies, a dose dependent positive influence was detected for DQalpha-34Q and DQbeta-26L. For DQbeta-DI, the largest difference between patients and controls was seen for the presence of a single copy of this motif after selecting patients with either anti-Ro/SSA or anti-La/SSB autoantibodies. CONCLUSION: The association of HLA Class II markers with pSS may concern the anti-Ro/La response rather than the disease itself. The strongest contributors to the formation of an anti-Ro/La response included components of the DRB1*03-DQB1*02-DQA1*0501 haplotype also encompassing the transethnically-associated DQbeta-DI motif. In addition, the dose dependent contribution of DQalpha-34Q and DQbeta-26L argue for a recessive contribution of HLA-DQ to the formation of an anti-Ro/La response. Given the prominent associations with DRB1*03 and the complex dose dependent interactions at HLA-DQ, a joint contribution of HLA-DR and DQ is likely to be relevant for the formation of anti-Ro/La autoantibodies in patients with pSS.

Antibodies, Antinuclear↗

Fine mapping of the SLEB2 locus involved in susceptibility to systemic lupus erythematosus.

We have previously reported linkage of systemic lupus erythematosus to chromosome 2q37 in multicase families from Iceland and Sweden. This locus (SLEB2) was identified by linkage to the markers D2S125 and D2S140. In the present study we have analyzed additional microsatellite markers and SNPs covering a region of 30 cM around D2S125 in an extended set of Nordic families (Icelandic, Swedish, and Norwegian). Two-point linkage analysis in these families gave a maximum lod score at the position of markers D2S2585 and D2S2985 (Z = 4.51, PIC = 0.65), by applying a "model-free" pseudo-marker linkage analysis. Based on multipoint linkage analysis in the Nordic families, the most likely location of the SLEB2 locus is estimated to be in the interval between D2S125 and the position of markers D2S2585 and D2S2985, with a peak multipoint lod score of Z = 6.03, assuming a dominant pseudo-marker model. Linkage disequilibrium (LD) analysis was performed using the data from the multicase families and 89 single-case families of Swedish origin, using the same set of markers. The LD analysis showed evidence for association in the single-case and multicase families with locus GAAT3C11 (P < 0.0003), and weak evidence for association was obtained for several markers located telomeric to D2S125 in the multicase families. Thirteen Mexican families were analyzed separately and found not to have linkage to this region. Our results support the presence of the SLEB2 locus at 2q37.

Base Sequence↗

[Myalgia and high sedimentation rate in adults].

The polymyalgic syndrome may be the presenting clinical feature for several diseases such as polymyalgia rheumatica, temporal arteritis, malignancy, rheumatoid arthritis, virus infections, connective tissue diseases, and myositis. In this review we present the various diagnostic options seen from a rheumatological point of view, with emphasis on polymyalgia rheumatica, temporal arteritis and the paraneoplastic syndrome. We are of the opinion that polymyalgia rheumatica is overdiagnosed in general practice, and steroid treatment may delay diagnosis and treatment of other differential diagnosis presenting as the polymyalgic syndrome. Several recently published Norwegian epidemiological studies offer new information on various aspects of the polymyalgic syndrome, which will be discussed.

Adult↗

[Rheumatological manifestations in HIV infections].

BACKGROUND: The recognised clinical spectrum of disease associated with HIV infection is rapidly expanding and now includes a variety of rheumatological manifestations. MATERIAL AND METHODS: In this review of the literature of the last 15 years, we present the most common rheumatic manifestations described in association with HIV infection. RESULTS: Manifestations include a wide array of articular syndromes and autoimmune manifestations such as Reiter's syndrome, psoriatic arthritis, HIV associated arthritis and septic arthritis. Autoimmune diseases associated with HIV infection include a Sjögren-like syndrome, myopathies and systemic vasculitis. INTERPRETATION: Rheumatological manifestations of HIV infection may present earlier than clinical signs of the infection itself. Steroid and cytostatic treatment of rheumatic diseases may worsen the HIV disease.

AIDS-Related Opportunistic Infections↗

[Symptoms in women with Sjogren's syndrome].

More knowledge about symptom experience is needed for diagnosing Sjögren's disease at an early stage of disease development. We have performed a qualitative study based on group interview with eight women with Sjögren's disease. The women presented with several different symptoms. They all described weariness, fatigue, sicca symptoms, various pains, hypersensitivity and organ manifestations in the same manner. Some of the symptoms had a dramatic impact on their life activities. The study revealed new descriptions of previously known symptoms and descriptions of previously unfamiliar symptoms. The results of the study may supplement the existing criteria of Sjögren's disease and provide new hypotheses about pathogenetic mechanisms related to chest pain, abdominal pain and facial pain in patients with Sjögren's disease.

Activities of Daily Living↗

[Heredity and immunology in Sjogren's syndrome].

BACKGROUND: Over the next 3-5 years, the rapid progress in genomic research will enable the discovery of many genes associated with the more common diseases. An example of such a common disease is the rheumatic disorder Sjögren's syndrome, an autoimmune disease. A more precise genetic explanation of the mechanism leading to Sjögren's syndrome remains to be given. MATERIAL AND METHODS: One way of investigating the disease related genes in such complex polygenic diseases is to perform linkage studies in families with two or more affected. Another possibility is to conduct association studies on trios (parents and affected child), case control studies, or other experimental designs. In association studies one is testing if an allele is significantly elevated among patients compared to controls, while in linkage analyses one finds subchromosomal regions that are significantly more often inherited by patients than by healthy family members. RESULTS: The most well defined genetic association in Sjögren's syndrome is currently related to different HLA alleles and their association with anti-Ro/SSA and anti-La/SSB autoantibodies. Additional genetic studies focusing on non-HLA regions are under way. INTERPRETATION: Increased genetic knowledge would allow optimisation of the diagnostic criteria as well as development of new and more effective treatment for Sjögren's syndrome, which causes substantial suffering for a large group of patients.

Autoimmune Diseases↗

Evaluation of diagnostic tests for antinuclear antibodies in rheumatological practice.

To investigate and compare the accuracy and usefulness of diagnostic tests for antinuclear antibodies (ANA) a cross-sectional study of sera derived from patients admitted to the Department of Rheumatology was tested for the presence of ANA using either indirect immunofluorescence on HEp-2 cells, indirect immunoperoxidase techniques on HEp-2 cells and mouse kidney, or two commercial enzyme-linked immunosorbent assays (ELISA). The diagnostic sensitivity and predictive values of the tests were calculated and compared. The accuracy of tests was compared using receiver-operating characteristics (ROC) methodology. All ANA-positive sera were further analysed for the presence of antibodies against extractable nuclear antigens (anti-ENA) and anti-DNA. A moderate to good agreement was found between tests, with kappa ranging from 0.469 to 0.659. Highest sensitivity for systemic lupus erythematosus (SLE; 93.3%) and primary Sjögren's syndrome (SS; 70%) was found using immunofluorescence on HEp-2 cells. Immunofluorescence on HEp-2 cells performed statistically better than the other tests in predicting SLE but not SS. All tests except mouse kidney showed good and comparable performance in detecting sera with anti-ENA and anti-DNA. At the given cut-off values indirect immunofluorescence on HEp-2 cells performed best. All assays except mouse kidney showed performance characteristics sufficient for use in routine analysis of ANA.

Animals↗

Current concepts on diagnosis, autoantibodies and therapy in Sjögren's syndrome.

Sjögren's syndrome is a chronic autoimmune and rheumatic disorder. Most patients have mild to moderate complaints and this may explain the great discrepancy in prevalence found in population studies compared to studies performed in the clinic. However, there is no straightforward and simple diagnostic test for Sjögren's syndrome, although several classification criteria have been designed. Initiatives have been taken to propose a new set of classification criteria in a joint effort by research groups in Europe and USA. A large number of autoantibodies have been reported in Sjögren's syndrome where, in some cases, the antibodies are correlated with the extent and severity of disease. The finding of serum autoantibodies directed against the muscarinic M3 receptor is an important advance in understanding the pathogenesis of not only the impaired glandular function but also associated features of autonomic dysfunction in some patients. The treatment of primary Sjögren's syndrome is still mainly symptomatic.

Autoantibodies↗

Anti-cardiolipin autoantibodies and pulmonary embolism. A case for a common cause.

A patient with primary Sjögren's syndrome developed pulmonary embolism following infection with influenza A virus. IgM anti-cardiolipin autoantibodies (aCL) evolved two weeks after hospitalisation, synchronously with antibodies against influenza A. IgG aCL developed three weeks after hospitalization, peaked during the recovery period, and gradually declined to undetectable levels 12 months after admission. Antibodies against beta2 glycoprotein I were not detected. Our results assign a high likelihood to the hypothesis that influenza A virus caused the patient's thromboembolic disease as well as development of aCL. aCL may have contributed to tissue pathology by forming immune-complexes with cardiolipin and rheumatoid factor.

Adult↗

Renal involvement in primary Sjögren's syndrome.

Renal involvement was evaluated in 62 patients with primary Sjögren's syndrome, classified according to criteria proposed by The European Classification Criteria Group. Urine concentration capacity was tested using intranasal 1-desamino-8-D-arginine-vasopressin. For patients with urine pH>5.5 without metabolic acidosis (n=28), an acidification test with ammonium chloride was performed. Urinary citrate, albumin, NAG, ALP and beta2-microglobulin were measured and creatinine clearance was calculated. Maximum urine concentration capacity and creatinine clearance were reduced in 13 (21%). Albumin excretion was >30 microg/min in only one patient (1.6%). Seven patients (11.3%) had complete or incomplete distal renal tubular acidosis (dRTA), four had reduced creatinine clearance and five had reduced maximum urine concentration capacity. The ratio of citrate/creatinine in spot urine was below the 2.5 percentile in all patients with complete or incomplete dRTA. The prevalence of dRTA was lower than in previous studies. There were also few patients with signs of glomerular disease (1.6%). The use of citrate:creatinine ratio in spot urine can be a helpful method in identifying patients with complete or incomplete dRTA.

Acetylglucosaminidase↗

A longitudinal study of human cytomegalovirus serology and viruria fails to detect active viral infection in 20 systemic lupus erythematosus patients.

In this study, we investigated whether active human cytomegalovirus infection could be detected in 20 systemic lupus erythematosus (SLE) patients over a one-year observation period by polymerase chain reaction on serial urine specimens and by monitoring of IgG and IgM HCMV-specific antibody profiles in serial serum samples. Of 788 urine samples analysed for the presence of human cytomegalovirus DNA, only 2 specimens (0.25%) collected from two different patients contained genuine human cytomegalovirus sequences as determined by polymerase chain reaction and subsequent sequencing of the PCR products. These two patients had one positive sample out of 36 samples or 40 samples, respectively. Nineteen of the patients (95%) possessed IgG antibodies against human cytomegalovirus, while 9 (45%) produced IgM antibodies. However, none of the patients showed signs of an active virus infection as judged by the stable anti-HCMV IgG or IgM antibody levels during the observation period, nor was any correlation between disease activity and HCMV serology/viruria observed. Of single serum samples of 26 age- and sex-matched blood donors, 21 (81%) were HCMV IgG positive and 1 (3.8%) was IgM seropositive. In conclusion, our data fail to establish an active human cytomegalovirus infection in SLE patients.

Adult↗

Monozygotic twins with primary Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease mainly characterized by dry mouth and dry eyes due to an inflammatory process in the exocrine glands. We describe a pair of Caucasian monozygotic twin sisters and their mother, all having primary SS. The twins had very similar clinical presentation and almost identical serological data, and histological examination of lower labial salivary glands gave a focus score of 3 in both twins. We also present their family medical history, which shows aggregation of immunological disorders among family members, although the twins and their mother were the only individuals with primary SS.

Adult↗