IgA rheumatoid factor in primary Sjogren's syndrome.

OBJECTIVE: To assess the serum level of immunoglobulin A rheumatoid factor (IgA-RF) in patients with primary Sjogren's syndrome (pSS) and study the association with immunological and clinical factors. METHODS: Sera from 97 pSS patients diagnosed according to the preliminary European criteria and 100 controls were analysed for IgA-RF in a cross-sectional study design. RESULTS: IgA-RF was detected in serum of 25.8% of the pSS patients and in 1% of the controls. In patients with positive vs. negative IgA-RF, the focus scores in biopsy of the minor salivary glands were 4.41 and 1.43 (p<0.0001), respectively. There was a correlation between positive IgA-RF and positive antinuclear antibodies (ANA) (r = 0.263, p<0.009), IgM-RF (r = 0.70, p<0.0001), anti-SSA/SSB (r = 0.73, p<0.0001), and a high serum level of IgG (r = 0.59, p<0.0001). The presence of renal disease was higher in IgA-RF-positive vs. negative pSS patients (20.0% vs. 5.6%, p = 0.047). The serum level of the hormone prolactin (PRL) correlated to the serum level of IgA-RF (r = 0.31, p = 0.026). CONCLUSIONS: The presence of IgA-RF in patients with pSS is closely associated with the presence of autoantibodies, and with focus scoring in biopsies of the salivary glands. IgA-RF is associated with renal disease in pSS but we found no correlation to other extraglandular manifestations.

Experimental expression in mice and spontaneous expression in human SLE of polyomavirus T-antigen. A molecular basis for induction of antibodies to DNA and eukaryotic transcription factors.

We have previously demonstrated that experimental expression of the polyomavirus transcription factor T-antigen has the potential to induce anti-DNA antibodies in mice. Two sets of independent evidences are presented here that demonstrate a biological relevance for this model. First, we describe results demonstrating that mice inoculated with T-antigen-expressing plasmids produced antibodies, not only to T-antigen and DNA, but also to the DNA-binding eukaryotic transcription factors TATA-binding protein (TBP), and to the cAMP-response-element-binding protein (CREB). Secondly, we investigated whether polyomavirus reactivation occurs in SLE patients, and whether antibodies to T-antigen, DNA, and to TBP and CREB are linked to such events. Both within and among these SLE patients, frequent polyomavirus reactivations were observed that could not be explained by certain rearrangements of the noncoding control regions, nor by corticosteroid treatment. Linked to these events, antibodies to T-antigen, DNA, TBP, and CREB were detected, identical to what we observed in mice. Antibodies recognizing double-stranded DNA were confined to patients with frequent polyomavirus reactivations. The results described here indicate that cognate interaction of B cells recognizing DNA or DNA-associated proteins and T cells recognizing T antigen had taken place as a consequence of complex formation between T ag and DNA in vivo in the context of polyomavirus reactivations.

A study of the arthritis pattern in primary Sjögren's syndrome.

OBJECTIVE: To study the frequency and pattern of arthritis in primary Sjögren's syndrome (pSS), and its association with clinical and immunological factors. METHODS: 102 patients with pSS diagnosed according to the preliminary European Classification Criteria were examined yearly for 4.5 years in a prospective study design. Arthralgia and arthritis were registered during the 459 patient-years observation period. RESULTS: Arthralgia was reported by 75 patients (73.5%) and arthritis was demonstrated in 18 patients (17.6%) during the observation period. The most commonly affected joints were ancles (n = 7), MCP joints (n = 6), shoulders (n = 6), MTP joints (n = 6) and wrists (n = 5). Symmetrical bilateral arthritis were most commonly observed in ancles (4 patients) and wrists, shoulders and MTP joints. Five patients had longstanding arthritis observed at more than one clinical examination, and one developed seronegative rheumatoid arthritis. Arthralgia/arthritis was not correlated to any clinical or immunological factors, and usually ESR and CRP were normal when arthritis was observed. CONCLUSION: Arthritis in pSS is usually mild, resolving, and unrelated to other clinical and immunological factors. A typical pattern is uni- and bilateral arthritis in the ankles, but joints in hands, feet and shoulders may also be affected.

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.

Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1,000 patients. European Working Party on Systemic Lupus Erythematosus.

In the present study we assessed the frequency and characteristics of the main causes of morbidity and mortality in SLE during a 5-year period and analyzed the prognostic significance for morbidity and mortality of the main immunologic parameters used in clinical practice. We started in 1990 a multicenter study of 1,000 patients from 7 European countries. All had medical histories documented and underwent medical interview and routine general physical examination when entered in the study, and all were followed prospectively by the same physicians during the ensuing 5 years (1990-1995). Four hundred thirteen patients (41.3%) presented 1 or more episodes of arthritis, 264 (26.4%) had malar rash, 222 (22.2%) active nephropathy, 139 (13.9%) fever, 136 (13.6%) neurologic involvement, 132 (13.2%) Raynaud phenomenon, 129 (12.9%) serositis (pleuritis and/or pericarditis), 95 (9.5%) thrombocytopenia, and 72 (7.2%) thrombosis. Two hundred seventy patients (27%) presented infections, 113 (11.3%) hypertension, 75 (7.5%) osteoporosis, and 59 (5.9%) cytopenia due to immunosuppressive agents. Sixteen patients (1.6%) developed malignancies, with the most frequent primary localizations the uterus and the breast. Several immunologic parameters (anti-dsDNA or antiphospholipid antibodies) were found to have a predictive value for the development of SLE manifestations during the period of the study. Forty-five patients (4.5%) died; the most frequent causes of death were divided similarly among active SLE (28.9%), infections (28.9%), and thromboses (26.7%). A survival probability of 95% at 5 years was found. A lower survival probability (92%) was detected in those patients who presented at the beginning of the study with nephropathy.

Lack of association between anticardiolipin antibodies and migraine in systemic lupus erythematosus.

We carried out a prospective study of the prevalence and characteristics of anticardiolipin antibodies (aCL) and migraine on 103 consecutive patients with systemic lupus erythematosus (SLE) derived from three European referral university centers. We also included a control group of 58 patients with migraine not associated with SLE. We interviewed all patients using a data collection form designed to provide a complete record of the clinical characteristics of headache. Fifty-four (52%) patients with SLE suffered recurrent headache. We diagnosed migraine in 32 patients, tension headache in 21, and cluster headache in one. Thirty (29%) patients with SLE had aCL. Migraine was present in five patients with aCL and in 27 patients without aCL (17% versus 37%, p = 0.07). No migraine control patient had aCL. Our study highlights the frequency of headache in SLE, but does not support an association between the presence of aCL and migraine in this disease.

Effects of calprotectin in avridine-induced arthritis.

Plasma levels of calprotectin correlate with disease activity and clinical assessments of arthritis in various rheumatic diseases, and high levels have been demonstrated in the synovial fluid of patients with rheumatoid arthritis. However, the role of calprotectin in rheumatic inflammation is unclear. The purpose of the present study was to investigate potential intra-articular effects of calprotectin. Calprotectin was injected into joints of healthy male Lewis rats and into joints of rats in the latency period before onset of avridine-induced arthritis. In addition, a group of animals had IgG antibodies to rat calprotectin injected into joints before onset of avridine-induced arthritis. Injection of 0.2 or 10 micrograms calprotectin into the ankles of healthy male Lewis rats resulted in histologically minor and reversible inflammatory changes, but without any circulating antibodies to calprotectin. Furthermore, animals with 40 micrograms calprotectin injected into ankles before the expected onset of avridine-induced arthritis had lower scores for cellular infiltration than were seen in control joints. This difference did not quite reach statistical significance in the two-sided test used. However, the induced arthritis increased in joints injected with IgG antibodies to calprotectin. These findings may indicate that increased local concentrations of calprotectin are partially protective against avridine-induced arthritis. In contrast, reduced local concentrations appear to exacerbate the severity of arthritis. Calprotectin may thus be involved in the regulation of inflammatory processes in joints.

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.

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.

Incidence of thromboembolic events in patients with primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a connective tissue disease with symptoms and serological findings often overlapping with systemic lupus erythematosus (SLE) (1). Thromboembolic events are common in SLE but not in pSS (2)(3). However, case reports have described pSS patients who developed fulminant multiorgan disease due to thrombotic diathesis 4, and we have presented a case with acute catastrophic anti-phospholipid syndrome (APS) in a pSS patient (5). In this study we wanted to examine the incidence of thromboembolic episodes and relate these to the presence of autoantibodies and coagulation abnormalities in 90 pSS patients during a 4.6-year follow-up.

Estimation of the prevalence of primary Sjögren's syndrome in two age-different community-based populations using two sets of classification criteria: the Hordaland Health Study.

OBJECTIVE: To estimate the point prevalence of primary Sjögren's syndrome (pSS) in two populations, aged 40-44 and 71-74 years, using two sets of classification criteria. METHODS: The participating individuals were recruited from the Hordaland Health Study (HUSK) conducted during 1997-99. A total of 18 592 individuals born 1953-57 and 3346 individuals born 1925-27 were sent a questionnaire covering various health-related questions, including four questions about sicca symptoms. Among those answering positive to at least one of the four questions, 99 and 90 individuals born 1953-57 and 1925-27, respectively, were examined further. For diagnosis of pSS two classifications were used, the preliminary European criteria from 1993, and the revised European criteria from 1996. RESULTS: By using the two classification criteria from 1993 and 1996, the point prevalences were 0.44% [95% confidence interval (CI) 0.34-0.57] and 0.22% (95% CI 0.15-0.32), respectively, for the population group born 1953-57. The corresponding estimates were 3.39% (95% CI 2.77-4.14) and 1.40% (95% CI 1.02-1.92) for the population born 1925-27. CONCLUSION: The point prevalence of pSS was approximately seven times higher in the elderly population aged 71-74 years compared to individuals aged 40-44 years, regardless of the classification criteria used.

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.

[Systemic lupus erythematosus and pregnancy]. / Systemisk lupus erythematosus og graviditet.

In patients with systemic lupus erythematosus in remission pregnancy has a good prognosis for mother and foetus. Pregnancy does not have a negative effect on systemic lupus erythematosus in remission, either in the short or the long term. Immuno-regulatory drugs should not be withdrawn before or after start of pregnancy, and flares during pregnancy can be treated with steroids and/or azathioprine. The risk of flare is very high in the puerperium, and can be prevented by steroids. All patients are at high risk of losing the foetus, particularly patients with antiphospholipid antibodies. Patients at high risk should be given low doses of aspirin (80 mg daily) from the first day of pregnancy. Neonatal lupus and congenital heart block are rare, and are associated with the presence of anti-SSA and anti-SSB antibodies in the maternal blood.

Isoenzymes of N-acetyl-beta-D-glucosaminidase in kidney cortex and urine of normal and nephritic rats.

Induction of acute Heyman nephritis in rats gave a significant increase in the urinary excretion of protein (p less than 0.001) and N-acetyl-beta-D-glucosaminidase (NAG; p less than 0.01) 14 days after injection of antibody. The isoelectric points (IP) of NAG were studied by chromatofocusing of the urine, serum and various lysosomal populations purified from kidney cortex homogenates of normal and nephritic rats. The chromatofocusing profiles for serum NAG (IP = 5.8) were totally different from the patterns found in normal and nephritic urines. The acidic IPs of NAG in normal urine (IP = 5.0) were changed into slightly more basic values in nephritic urine (IP = 5.15). Similar changes were also demonstrated in normal urine after acidification and prolonged incubation. The chromatofocusing profile obtained for NAG in the large, dense lysosomes was almost identical to the pattern observed in nephritic urine and demonstrated IPs for NAG in a slightly more basic pH area than observed for small and medium-sized lysosomes. The difference in IP in normal and nephritic urines may therefore be due to an increased autolytic degradation of NAG or excretion of the enzyme from different populations of lysosomes.

[Low back pain and instability of the pelvic ring]. / Lave ryggsmerter og instabilitet i bekkenringen.

Low back pain is a major cause of disability, and a large percentage of patients with low back pain have no identifiable pathology. In this review of the literature low back pain is considered from the point of view of dysfunction of the pelvic joints. The reliability of the commonly used tests, signs and procedures are considered. Inflammatory causes such as ankylosing spondylitis are well documented to cause low back pain, but mechanical factors apart from intervertebral disc protrusion are largely speculative.

[Early diagnosis of systemic lupus erythematosus. A challenge for clinicians of different specialties]. / Tidlig diagnostikk av systemisk lupus erythematosus. En utfordring for klinikere i mange spesialiteter.

This paper presents some of the results from a ten year prospective study (Eurolupus) analyzing the main clinical and immunological manifestations in 1,000 patients with systemic lupus erythematosus (SLE). The time lag from the first symptoms to diagnosis was much longer in patients from Norway compared with patients from Europe in general (6.6 years versus two years respectively). In order to improve the early diagnosis of SLE, the authors focus on early clinical symptoms and signs.

[Polymyalgia rheumatica and temporal arteritis. New aspects of diagnosis, treatment, prognosis and risk of cancer]. / Polymyalgia rheumatica og arteritis temporalis. Nyere synspunkter på diagnostikk, behandling, prognose og risiko for cancer.

The incidence of polymyalgia rheumatica and temporal arteritis is increasing, mainly in elderly people. The risk of cancer during a lifetime is high in patients with positive biopsy of the temporal artery, but polymyalgia rheumatica and temporal arteritis are not to be considered as paraneoplastic syndromes. Temporal arteritis can appear in patients under treatment for polymyalgia rheumatica, and polymyalgia rheumatica can be accompanied by arthritis. Various new aspects of diagnoses and treatment are discussed.

[Rheumatological manifestations in HIV infections]. / Revmatiske manifestasjoner ved HIV-infeksjon.

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.

Measurement of adenosine 3':5'-cyclic monophosphate by competitive binding to salt-dissociated protein kinase.

An assay for cyclic AMP is described which takes advantage of the high affinity of the dissociated receptor moiety of cyclic AMP-dependent protein kinase I for the nucleotide. The kinase is kept dissociated by salt (800 mM-NaCl/30mM-EDTA). In the presence of a simply prepared heat-stable protein fraction the binding reagent is stable for the time needed to reach equilibrium of binding. A simple procedure [precipitation with poly-(ethylene glycol) followed by DEAE-cellulose chromatography] is described for the separation of protein kinase I from other binding proteins for cyclic AMP in rabbit skeletal muscle. The sensitivity, precision, reproducibility and specificity of the assay compared favourably with those of other cyclic AMP assays. The main advantage of the present assay is its resistance towards non-specific interference from a number of salts, tissue-culture media and substances found in crude tissue extracts. The reliability of cyclic AMP measurement directly in crude tissue extracts was ensured by removal of the assayable cyclic AMP with cyclic nucleotide phosphodiesterase digestion or adsorption with antibody against cyclic AMP, by comparison with measurement in tissue extracts purified by chromatography on QAE-Sephadex or sequentially on Dowex 50, and aluminium oxide as well as by dilution and recovery experiments.