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Objective: To study the outcome of pregnancy in patients with primary Sjögren's syndrome (pSS)., Methods: A questionnaire covering demographic data and the outcome of pregnancies was answered by 58 patients with pSS and 157 controls. For 36 patients and 93 controls, we analyzed detailed data about pregnancy, birth, and status of the newborn from the Medical Birth Registry of Norway (MFR) for birth order one, 2, and 3. Thirty-two of 36 patients registered in MFR were diagnosed with pSS after the last birth., Results: Pregnancy outcomes were not different in patients compared to controls. Two patients (3.4%) reported giving birth to a child with congenital heart block., Conclusion: PSS had no impact on pregnancy outcome before disease onset. The most important condition associated with pSS in anti-SSA positive mothers was congenital heart block in the offspring.

Objective: To study which clinical and immunological factors may be associated with low salivary and lacrimal flow in patients with primary Sjögren's syndrome (SS). Are the lacrimal and salivary flows influenced by age of the patient, age at diagnosis, disease duration, or findings in the biopsies of the minor salivary glands, or are immunological factors of importance for reduced flow rates?, Methods: In total 72 patients (mean age 57 yrs and disease duration 13.5 yrs) with primary SS diagnosed according to the European classification criteria were evaluated objectively by serological testing and by measures of exocrine gland function, such as unstimulated whole saliva collection (UWSC) and by Schirmer I test., Results: Salivary flow (UWSC) in 72 patients with primary SS correlated to the presence of antinuclear antibodies (ANA) (r = -0.32, p = 0.006) and to anti-SSA/SSB (r = -0.31, p = 0.010). No such correlation was seen for the lacrimal flow, and there was no mutual correlation between lacrimal and salivary flow. UWSC was significantly lower in patients with anti-SSA versus those without anti-SSA (1.63 ml vs 2.63 ml; p < 0.007), while such a significant difference was not observed in the presence versus absence of anti-SSB. The salivary and lacrimal flow was not significantly affected by age of the patient, and did not correlate to age at diagnosis, sex, disease duration, rheumatoid factor finding, or findings in minor salivary gland biopsies., Conclusion: Salivary flow in patients with primary SS was negatively correlated with immunological factors such as ANA and anti-SSA/SSB, in contrast to low lacrimal flow, where no such correlation was seen. There was no association of lacrimal and salivary flow with age of patient, age at diagnosis, disease duration, and findings in minor salivary gland biopsies. The results indicate that reduced salivary flow is closely associated with immunological factors, and is not associated with the age of the patient or infiltration of lymphocytes in salivary glands.

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.

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.

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.

Objective: To assess the prevalence of hyperprolactinemia in 55 patients with primary Sjögren's syndrome (SS), and its clinical significance., Methods: Concentrations of serum prolactin (PRL) were determined in 55 consecutive patients with primary SS and 110 controls by a fluoroimmunometric assay in a prospective case-control design., Results: The 55 patients with primary SS had higher serum PRL than 110 matching controls (271.5 vs 205.9 mIU/l; p < 0.02), and this difference was most evident in patients diagnosed before the age of 45 years (374.8 vs 245.5 mIU/l; p < 0.05), a patient population characterized by active immunological disease. Serum PRL did not correlate to disease duration, serum immunoglobulin, autoantibodies, or focus score in biopsies from minor salivary glands, but did correlate to score for internal organ disease (r = 0.33, p < 0.05). Two patients were diagnosed as having primary SS 12 years after hyperprolactinemia was first detected, and both patients had aggressive primary SS as indicated by extraglandular manifestations. One of the patients developed primary SS after being treated with bromocriptine, an inhibitor of PRL synthesis, for 12 years., Conclusion: Patients with primary SS have moderately increased levels of serum PRL, especially evident in patients diagnosed at a young age with active immunological disease. Serum PRL is correlated to index for internal organ disease, and primary SS may be preceded by hyperprolactinemia for many years.

Objective: To investigate whether diagnostic tests for primary Sjögren's syndrome (pSS) are reproducible when repeated after one year (reliability). To evaluate whether the sensitivity of the diagnostic tests increases with repeated testing., Methods: A structured interview investigating the subjective sensation of dry eyes and dry mouth, and the diagnostic tests Schirmer I, unstimulated whole saliva collection (UWSC), serological tests for antinuclear antibodies (ANA), for anti-Ro/SSA and anti-La/SSB antibodies as well as Waaler's test for rheumatoid factor, were performed twice with a one year interval in 66 patients with pSS. Reliability was given as the percentage of positive tests remaining positive at the second examination, while sensitivity was given as the percentage of patients with positive tests., Results: Highest reliability was obtained for the sensation of dry mouth (98.2%) and sensation of dry eyes (96.4%), and anti-SSA/SSB antibodies (93.3%). Lowest reliability was obtained for rheumatoid factor at cutoff titer 1:32 (70.6%) and positive Schirmer I in one eye (77.4%). The reliability for ANA was 80% at cutoff titer 1:32, and increased to 93.3% at cutoff titer 1:128. UWSC had a reliability of 84.2%. The pooled sensitivity for all the tests increased significantly (p < 0.05) compared to the examination, which had the lowest sensitivity., Conclusion: The diagnostic tests for pSS are generally highly reliable when performed twice with a one year interval. The gain in sensitivity by repeating the tests is limited, being most marked for Schirmer I.

Objective: To investigate if the plasma level of the granulocyte protein calprotectin is a useful indicator of severity of arthritis in patients with inflammatory rheumatic diseases, and to analyze which factors contribute to the raised plasma calprotectin levels., Methods: Plasma calprotectin levels were measured by ELISA: In a cross sectional study of 154 patients with various inflammatory rheumatic diseases, calprotectin levels were correlated with laboratory and clinical variables., Results: The plasma levels of calprotectin and C-reactive protein (CRP) correlated significantly with the clinical evaluation of swollen joints (r = 0.51, p < or = 0.01 and r = 0.29, p < or = 0.01, respectively). Calprotectin levels, but not CRP levels or erythrocyte sedimentation rate, were significantly lower in patients with no swollen joints than in patients with one or more swollen joints (2613.6 micrograms/l vs 6287.0 micrograms/l, p < 0.001). A significant correlation between calprotectin and number of neutrophils was demonstrated (r = 0.43, p < or = 0.01), indicating that circulating neutrophils contribute to plasma calprotectin levels., Conclusion: The plasma calprotectin level may be a useful indicator of arthritis in inflammatory rheumatic diseases.

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.

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).

During a 6-month period, 100 patients with systemic lupus erythematosus (SLE) were consecutively studied for the presence of antithyroid antibodies and thyroid disease. Overall, the prevalence of antithyroid antibodies was similar in patients with SLE (21%) and controls (16%). However, antithyroglobulin antibodies were found in 11% of patients with SLE and only 2% of controls (p = 0.009). The levels of antimicrosomal antibodies were also different (median levels: SLE = 400; controls = 100) but this difference did not reach statistical significance. We found a significant correlation between thyroid stimulating hormone (TSH) levels and the levels of both the antithyroglobulin dilutions (p less than 0.05) and the antimicrosomal dilutions (p less than 0.05). This was not seen in the controls. A higher frequency of clinical thyroid disease was seen in patients with SLE with thyroid antibodies (5/21; 3 hypothyroid, 2 hyperthyroid) than in those without these antibodies (1/79; p = 0.001). Levels of antithyroid antibodies correlated with clinical or subclinical (marked by elevations of TSH) thyroid disease. Patients with SLE with these antibodies were significantly older (mean age 47.5 +/- 13 years) than those without antithyroid antibodies (mean age 37.5 +/- 12 years; p less than 0.001). Antithyroid antibodies define a subset of older patients with SLE with increased prevalence of both clinical and subclinical thyroid disease.