Frequency of neoplasia in systemic lupus erythematosus and rheumatoid arthritis

A patient population admitted to the hospital for either SLE or RA was surveyed for the subsequent development of neoplasms. The frequency of neoplasm in SLE patients appeared to be exaggerated, whereas the frequency of subsequent neoplasm in rheumatoid patients was unexpectedly low. A paucity of nephritis in the SLE group was noted. Further reports are encouraged so that the magnitude of the risk of malignancy developing with immunosuppressive therapy can be more precisely ascertained.     

The level of serum thymic activity in patients with rheumatoid arthritis and systemic lupus erythematosus

Thymic serum activity (TSA) has been studied in 52 healthy subjects, 48 rheumatoid arthritis patients and 17 sufferers with systemic lupus erythematosus aged from 18 to 70. TSA was compared in patients under and over 40 years. In those under 40 TSA appeared significantly inhibited, while in older subjects it did not differ from age-matched control. No correlations were reported between TSA levels and clinical characteristics. Changes in TSA levels may be related both to low content of thymic hormones and formation of inactive complexes from thymic mediators with inhibitors.     

Reduction of pleural fluid complement activity in patients with systemic lupus erythematosus and rheumatoid arthritis

In this paper the author gives a survey and a classification of 642 cases of narcolepsy and hypersomnia which he himself studied in the course of 26 years. 368 cases were classified as narcolepsy, 274 as hypersomnia. The author further classifies narcolepsies according to their etiology, clinical form and pathophysiological mechanisms of origin. Hypersomnias are divided by the author into the symptomatic and the functional groups. According to the author it is useful to distinguish "short cycle hypersomnia", i.e. those with short duration of sleep attacks (hours) and intervals, from "long cycle hypersomnia", i.e. those with long attacks (days or weeks) and intervals. The author goes on to describe different forms of symptomatic and functional hypersomnias, such as idiopathic hypersomnia, neurotic hypersomnia, the Pickwickian syndrome" and its variants as well as different varieties of periodic long cycle hypersomnias. Finally the author makes a brief mention of the syndrome of insufficiency of wakefulness.     

Anti-DNA, anti-deoxyribonucleoprotein and rheumatoid factor measured by ELISA in patients with systemic lupus erythematosus, Sj?gren's syndrome and rheumatoid arthritis

Serum concentrations of anti-DNA and anti-deoxyribonucleoprotein (NP) antibodies were measured in parallel by standardized ELISA methods with a polyvalent anti-immunoglobulin conjugate in patients with systemic lupus erythematosus (SLE), Sj?gren's syndrome (SS) and rheumatoid arthritis (RA). High levels of these antibodies predominated in systemic lupus erythematosus. While an appreciable incidence of antibodies also occurred in SS and RA, they were mostly at lower levels. By using heavy chain-specific anti-immunoglobulin conjugates, IgG antibodies to both DNA and NP were found in SLE more frequently and at higher levels than were IgM antibodies. In contrast, IgM antibodies to DNA and NP predominated in SS and RA. The immunoglobulin class of the anti-DNA and anti-NP responses in a given SLE patient were not infrequently different. For example, a patient might show a very high IgG but low IgM anti-DNA value, with the reverse being true for anti-NP. IgG anti-DNA antibodies were significantly associated with depressions of C3. During changes in SLE serology, normalization of DNA binding by Farr radioimmunoassay and/or complement was most frequently associated with normalization of the IgG anti-DNA antibody concentrations. In patients simultaneously possessing elevated levels of anti-DNA, anti-NP and rheumatoid factor (RF), absorption with aggregated human IgG usually decreased only the RF activity. In some, however, such absorption decreased all three antibody values simultaneously. The latter findings support observations that some RF possess antinuclear properties.     

Amidolytic and peptidolytic activities of immunoglobulin G present in sera from patients with rheumatoid arthritis, Sjogren''s syndrome and systemic lupus erythematosus

The galactosemias are a series of three inborn errors of metabolism caused by deficiency of any one of the three human galactose-metabolic enzymes: galactokinase (GALK), galactose-1-phosphate uridyl transferase (GALT), and UDP-galactose 4' epimerase (GALE). We report here the characterization of the entire coding sequence of the GALE gene and screening for mutations in epimerase-deficient individuals. The human GALE gene is about 4 kb in size and is divided into 11 exons on chromosome band 1p36. We have identified five mutations in the GALE gene of epimerase-deficient galactosemia patients. The patients were either homozygotes or compound heterozygotes for mutations. These results confirm that epimerase-deficiency galactosemia is the result of missense mutations in the GALE gene and indicate that the disease is characterized by extensive allelic heterogeneity.     

Lupus anticoagulants in patients with systemic lupus erythematosus

Lupus anticoagulants (LA) and anticardiolipin antibodies (aCL) are known as thrombosis-related antiphospholipid antibodies. LA is not as well characterized as aCL, and the relation between LA and aCL is not clarified. Since standardized method for the detection of LA has not been established, we measured LA activities in outpatients with SLE by using two different methods (KCT and dRVVT), and analyzed the characteristics of LA in SLE. LA was detected in 29.8% of all samples (14.3% in both methods, 15.5% in one method). IgG-aCL and IgM-aCL was detected in 38% and 20%, respectively, of all LA positive samples. Though a good correlation was observed between LA activities and IgG-aCL levels, a considerable number of LA positive samples were negative for aCL. This indicated the presence of factors with LA activity other than aCL. On the contrary there was also a high percentage of LA negative samples with positive aCL (42.4% in IgG-aCL, 47.4% in IgM-aCL), suggesting the presence of aCL with poor or low LA activity. These findings showed the heterogeneity of antiphospholipid antibodies both in LA and in aCL. The platelet function tests showed increased platelet adhesiveness and normal platelet aggregation in LA positive patients with SLE even in the inactive phase. The serum levels of factors such as protein C, protein S, antithrombin III and thrombomodulin were within normal range. Clinical features such as hemolytic anemia, thrombosis and abortion were more frequently observed in LA positive population than in LA negative population. The clinical features tend to be different between patients with dRVVT-LA and those with KCT-LA, though not significant. Because of the heterogeneity in LA, a combination of more than two different methods including dRVVT was recommended for the detection and the evaluation of LA.     

Absence of correlation between interleukin 6 and C-reactive protein blood levels in systemic lupus erythematosus compared with rheumatoid arthritis

To investigate if the low C-reactive protein (CRP) response frequently observed in systemic lupus erythematosus (SLE) is related to an impaired expression of interleukin 6 (IL-6), considered its main inducer, we studied serum IL-6 and CRP levels in 37 patients with SLE and 22 with rheumatoid arthritis (RA). Results show that in contrast to CRP, IL-6 levels are significantly higher in SLE than in RA. A linear regression analysis shows a positive correlation between levels of these 2 molecules in RA but not in SLE. Similarly, levels of fibrinogen, another acute phase protein mainly induced by IL-6, did not correlate with IL-6 in SLE. Our results suggest an impairment of part of the acute phase response to IL-6 that might play a role in the pathogenesis of SLE.     

Tuberculosis among Filipino patients with systemic lupus erythematosus

A retrospective review of the clinical records of 54 patients with systemic lupus erythematosus (SLE) and documented tuberculosis (TB) infection seen at the University of Santo Tomas Hospital was accomplished. There were 53 women and one man, with a mean age of 32.2 +/- 10 years and a total of 57 TB occurrences. Pulmonary involvement was recorded in 42 (74%): upper lungfield in 25, mid to lower lungfield in 7, and miliary pattern or diffuse infiltrates in 10. TB arthritis was noted in 8, osteomyelitis in 4, and soft tissue abscesses in 4. Central nervous system involvement consisted of brain abscesses (tuberculomas) in two and meningitis in one. Two patients each had TB lymphadenitis, genitourinary TB, ileocecal TB, and TB peritonitis. Hepatobiliary and cutaneous TB occurred in one patient each. Eight of 10 patients with disseminated or miliary TB died primarily of respiratory failure; six of these eight patients also had some form of extrapulmonary involvement. Using the Wilcoxon rank-sum test, there were significant differences in the mean SLE Disease Activity Index (SLEDAI) and Severity of Disease Index (SDI) scores between those with limited TB (SLEDAI 24 +/- 7 SD; SDI 19 +/- 18 SD) versus those with extensive TB (SLEDAI 41 +/- 16 SD; SDI 36 +/- 21 SD), P < .05. There was no significant difference in the average daily prednisone dose (mg) between those with limited TB (25 +/- 17 SD) versus those with extensive TB (31 +/- 16 SD). The contributory role of tuberculous infection in the morbidity and mortality of patients with SLE must be emphasized, especially in areas endemic for TB.     

Increased risk of malignancy in patients with systemic lupus erythematosus

BACKGROUND: Systemic lupus erythematosus is a chronic, multisystem, autoimmune disorder that primarily affects women. Morbidity and mortality have improved for lupus patients during the last 15 years. An increased risk of malignancy in patients with lupus has been shown in some, but not all studies. The purpose of this study was to ascertain cancer risk in lupus patients by linking two disease registries. METHODS: Participants in the Chicago Lupus Cohort included 616 women with lupus who were residents of Cook County, Illinois. They were seen during 1985-1995 at 4 University, inner city, and suburban inpatient and outpatient clinics in Chicago. Malignancies occurring in these subjects during the study interval, 1985-1995, were identified from the Illinois State Cancer Registry by matching name, birthdate, and social security number. Standardized incidence ratios (SIRs) were estimated for all malignancies in this cohort of lupus patients using age, gender, and all race or race-stratified specific cancer incidence data from Cook County, Illinois. RESULTS: The registry linkage study with the Illinois State Cancer Registry documented that 30 women with lupus had a malignancy. The expected number of malignancies for women in the lupus cohort was 15.0. There were 8 cases of breast cancer and 4 each of lung and cervical cancer. In the remaining 14 women, 12 different types of cancers were noted. The SIR and 95% confidence interval (CI) for malignancy for all women with lupus in the study were 2.0 (1.4, 2.9) and lung cancer was the only individual cancer increased in all women--SIR and 95% CI were 3.1 (1.3, 7.9). In the analysis stratified by race, the risk of malignancy (SIR and 95% CI) was increased in Caucasian women, 2.3 (1.4, 3.9). Breast cancer was the only individual cancer increased in Caucasian women with lupus with an SIR and 95% CI of 2.9 (1.4, 6.4). CONCLUSIONS: Lupus patients have an increased risk of malignancy. Breast, lung, and gynecological malignancies were the most common malignancies observed in the cohort and breast cancer was significantly increased in Caucasian women.     

The genetics of human systemic lupus erythematosus

The present study, using confocal laser scanning microscopy and immunoelectron microscopy, examined the intracellular localization of tyrosine-phosphorylated proteins in cultured mouse dorsal root ganglion neurons with special reference to their growth cones. The growth cone is the specialized structure formed at the growing tip of the axon; characteristically highly motile with filopodia on the surface, it is responsible for the extension and guidance of the neurites to the appropriate targets during nerve regeneration. It has been suggested that protein-tyrosine phosphorylation plays an important role in the intracellular signal transduction that regulates the extension and motility of growth cones. By fluorescence immunocytochemistry, phosphotyrosine immunoreactivity was found in the growth cones and neurites. Some of the filopodia exhibited strong immunoreactivity at their tips. By immunoelectron microscopy, a large number of immunogold particles (gold particles conjugated to the secondary antibody) were seen to be distributed in the cytoplasm and some were observed on the plasma membrane in the growth cones, whereas in the neurites the density of immunogold particles was the same in the axoplasm as on the plasma membranes. These findings suggest that in the growth cones phosphotyrosines might mainly be involved in intracellular signaling for maintaining their high motility whereas in the neurites they might mostly be associated with the receptor proteins at the plasma membrane for adhesion as well as for growth of neurites. Thus, tyrosine phosphorylation might contribute to different functions for growth cones and neurites.     

Autoantibodies to human recombinant erythropoietin in patients with systemic lupus erythematosus: correlation with anemia

OBJECTIVE: To investigate the existence of circulating autoantibodies to erythropoietin (EPO) in sera from patients with systemic lupus erythematosus (SLE), and to correlate their presence with anemia and clinical activity. METHODS: Ninety-two consecutive patients with SLE, 80 patients with rheumatoid arthritis, and 42 normal individuals were studied. The patients with SLE were categorized into 3 groups according to hemoglobin (Hgb) level: group A (45 patients with Hgb > 12 gm/dl), group B (26 patients with Hgb 10.1-12 gm/dl), and group C (21 patients with Hgb < or = 10 gm/dl). In all patients with SLE, the disease activity was evaluated using the European Consensus Lupus Activity Measurement scale. Antibodies to EPO were detected using an enzyme-linked immunosorbent assay and purified recombinant human EPO as antigen. The specificity of the method was evaluated with homologous and cross-reactive inhibition assays. RESULTS: Antibodies to EPO were found in 15.2% of the SLE patient sera. The distribution of these antibodies among the 3 groups of SLE patients was as follows: 8.8% (4 of 45) from group A, 15.4% (4 of 26) from group B, and 28.6% (6 of 21) from group C. The prevalence of antibodies to EPO in patients with severe anemia (group C) was statistically significantly higher compared with patients without anemia (chi(2) = 4.31, P < 0.05). Patients with antibodies to EPO had higher disease activity scores (P < 0.005) and lower levels of the C4 component of complement (P < 0.05) compared with patients without antibodies to EPO. CONCLUSION: In this study, the presence of antibodies to EPO in the sera of SLE patients is demonstrated for the first time. The presence of these antibodies is associated with severe anemia and active disease.     

Hyperprolactinemia in males with systemic lupus erythematosus

Alanine dehydrogenase [EC 1. 4. 1. 1] was purified to homogeneity from a crude extract of Enterobacter aerogenes ICR 0220. The enzyme had a molecular mass of about 245 kDa and consisted of six identical subunits. The enzyme showed maximal activity at about pH 10.9 for the deamination of L-alanine and at about pH 8.7 for the amination of pyruvate. The enzyme required NAD+ as a coenzyme. Analogs of NAD+, deamino-NAD+ and nicotinamide guanine dinucleotide served as coenzymes. Initial-velocity and product inhibition studies suggested that the deamination of L-alanine proceeded through a sequential ordered binary-ternary mechanism. NAD+ bound first to the enzyme, followed by L-alanine, and the products were released in the order of ammonia, pyruvate, and NADH. The Km were 0.47 mM for L-alanine, 0.16 mM for NAD+, 0.22 mM for pyruvate, 0.067 mM for NADH, and 66.7 mM for ammonia. The Km for L-alanine was the smallest in the alanine dehydrogenases studied so far. The enzyme gene was cloned into Escherichia coli JM109 cells and the nucleotides were sequenced. The deduced amino acid sequence was very similar to that of the alanine dehydrogenase from Bacillus subtilis. However, the Enterobacter enzyme has no cysteine residue. In this respect, the Enterobacter enzyme is different from other alanine dehydrogenases.     

Development of pathogenic anti-DNA antibodies in patients with systemic lupus erythematosus

The anti-DNA response is a hallmark of systemic lupus erythematosus (SLE). The precise mechanisms leading to anti-DNA antibody (Ab) production remain to be studied. Nonetheless, it is becoming clear that anti-DNA Abs cause inflammatory lesions not only via deposition of circulating immune complexes (IC) consisting of anti-DNA Ab and antigens (Ags), but also via in situ IC formation by cationic anti-DNA Abs. It is intriguing that cationic anti-DNA Abs are encoded by a unique germline Vkappa gene, A30, which encodes an extraordinary cationic light chain, whereas somatic mutations did not induce a cationic shift of electrical charge in human lupus nephritis, suggesting that the usage of a specific germline gene may confer the cationic charge (or pathogenicity) on anti-DNA Abs and that somatic mutations induce the affinity maturation of Abs. Whether cationic anti-DNA Abs will develop depends at least partly on the presence or absence of the germline A30 gene, since patients who lack this gene in the germline Vkappa repertoire did not develop severe lupus nephritis. Receptor editing, a mechanism for changing the affinity of the B cell Ag receptor [surface immunoglobulin (Ig) receptor] to avoid self-reactivity actually seems defective in patients with SLE because normal B cells edited the A30 gene, whereas SLE B cells express A30 mRNA. Thus, along with the importance of somatic mutations, polymorphisms of Ig Vkappa locus, and genetic predisposition, the failure of receptor editing may contribute to the development of pathogenic anti-DNA responses in humans.     

Tyrosine phosphorylation in peripheral lymphocytes from patients with systemic lupus erythematosus

A comparative study of tyrosine phosphorylation was performed on peripheral blood lymphocytes from systemic lupus erythematosus (SLE) patients and from healthy donors. Freshly isolated SLE lymphocytes presented an elevated tyrosine phosphorylation level when compared to healthy donors lymphocytes (p = 0.005). Among all phosphorylated proteins, those called p120, p110, p80 and p55-p60 were more phosphorylated. The level of tyrosine phosphorylation of p120 and p110 proteins discriminated significantly (p = 0.0048, respectively, p = 0.02) between SLE patients and healthy donors. Lymphocytes form SLE patients and healthy donors were then stimulated by cross-linking T cell antigens (CD3, CD4, CD8) to further distinguish the signal transduction between normal and pathologic lymphocytes. No statistical differences in the tyrosine phosphorylation pattern, following CD4 or CD8 cross-linking, were observed between SLE patients and healthy donors lymphocytes. CD3 cross-linking induced an effect on tyrosine phosphorylation different in SLE patients versus healthy donors lymphocytes. Thus, the lymphocytes of SLE patients were refractile in anti-CD3 stimulation in comparison with the healthy donors lymphocytes. Chi-square analysis demonstrated that a significantly larger number of healthy donors responded to anti-CD3 stimulation compared to SLE patients (p = 0.03). The high frequency of tyrosine phosphorylation of p110 and p80 proteins, following CD3 stimulation, in normal versus SLE lymphocytes, suggested that these proteins could be involved in abnormal signal transduction in SLE cells.     

Decreased bone mineral density in premenopausal patients with systemic lupus erythematosus

To study bone mineral density (BMD) in premenopausal adult female patients with systemic lupus erythematosus (SLE) and its relation with clinical parameters, 56 SLE patients (mean age 31 years, mean disease duration 6.3 years) and 15 normal controls were studied. BMD at the lumbar vertebrae (L2-L4) was measured by dual energy X-ray absorptiometry (DEXA). Classification of BMD was made according to the WHO criteria in 1994. Correlation between BMD and clinical parameters was calculated. It was found BMD in the SLE patients (0.942 +/- 0.136 g/cm2) was lower than in the control group (1.055 +/- 0.080 g/cm2) (P < 0.01). According to the WHO criteria, 17 patients (30%) had normal BMD, 22 patients (40%) had osteopenia and 17 patients (30%) had osteoporosis. BMD was inversely correlated with disease duration in SLE patients (p < 0.005). The minimal disease duration for a female SLE patient to develop osteopenia was 3.5 years. In conclusion, SLE patients have lower lumbar BMD than normal controls. SLE patients with longer disease duration have lower BMD. In order to achieve early prevention of osteoporosis, we suggest that female SLE patients with disease duration for more than 3.5 years should take a BMD examination.     

Soluble tumor necrosis factor receptors in patients with systemic lupus erythematosus

OBJECTIVE: To study the variations of type II soluble receptors for tumor necrosis factor (sR-TNF) in patients with systemic lupus erythematosus and investigate their use in the clinical setting. PATIENTS AND METHODS: Twenty-six patients with systemic lupus were followed for a mean 3 years. sR-TNF and other immunological parameters (C reactive protein, anti-DNA antibodies, C3 and C4 complement fractions, soluble receptors for interleukin 2) were measured in sera at different points of the disease course. The systemic lupus activity measure (SLAM) was determined at each point, and confronted with the biology results. The study was cross sectional for the group and longitudinal for the patients. RESULTS: sR-TNF was the immunological parameter which correlated best with SLAM. It also correlated with sedimentation rate, C reactive protein, thrombopenia, anemia, creatinine level, anti-DNA antibodies and sR-IL2. The longitudinal study pointed out however that this finding is not consistent for each patient. CONCLUSION: A rise in sR-TNF related to systemic lupus activity but is of limited practical interest for individual patient follow-up.