Antibodies In Systemic Lupus Erythematosus Patients Research Articles

Spectrum of autoantibodies for gastrointestinal autoimmune diseases in systemic lupus erythematosus patients

Organ-specific autoimmune diseases may appear in patients with systemic lupus erythematosus (SLE). Gastrointestinal symptoms are well documented in SLE and may be similar to those related to autoimmune gastrointestinal diseases. Our aim was to search for gastrointestinal organ-specific autoantibodies in 194 patients with systemic lupus and 103 healthy controls from Southern Brazil. Methods Anti-endomysium antibodies (IgA-EmA), anti-gastric parietal cells (GPC) antibodies, anti-smooth muscle antibodies (ASMA), anti-mitochondrial antibodies (AMA) and anti-LKM-1 (liver-kidney microsomal) were searched for using indirect immunofluorescence in the sera of patients and controls. The total positivity of antibodies in SLE patients was 14.4% (28/194) and differed significantly from healthy individuals (0.97%; p<0.001). IgA-EmA was more common in lupus patients than in controls (11/194; p=0.009), and one of these patients had dermatitis herpetiformis. Clinical association revealed that IgA-EmA was more common in SLE patients with discoid lesions. The frequency of anti-GPC (p=0.10), ASMA (p=0.16) and AMA (p=0.55) did not differ significantly between groups. No patient presented LKM-1 autoantibodies. One patient presenting anti-GPC was diagnosed with atrophic gastritis and pernicious anemia. Only IgA-EmA was significantly associated with lupus and with the presence of discoid lesions. Until now, no obvious association with celiac disease has been found.

Expression level of the growth factor progranulin is related with development of systemic lupus erythematosus

BackgroundThis study is to investigate the expression of progranulin (PGRN) in systemic lupus erythematosus (SLE) patients and the effect of glucocorticoid (GC) treatment on its expression.MethodsThirty newly diagnosed severe SLE patients and 30 healthy subjects were enrolled in this study. The serum levels of PGRN and the inflammatory factors of SLE were detected by ELISA and the mRNA expression of these proteins were detected by real-time PCR.ResultsThe serum levels of PGRN, IL-6, PR3, TNFR, TNF-α and anti-dsDNA antibody in SLE patients were increased significantly compared with healthy controls (P < 0.05). The relative expression of PGRN mRNA was increased by 4.88-fold in pre-treatment SLE patients compared with controls (P < 0.05). After prednisone treatment, the serum levels of PGRN decreased significantly, and the relative expression of PGRN mRNA was decreased by 1.34-fold compared with the untreated controls (P < 0.01). Moreover, Serum concentration of PGRN was correlated with serum levels of IL-6, TNF-α, TNFR and anti-dsDNA antibody in both pre-treatment and post-treatment SLE patients.ConclusionsPGRN is up-regulated in the SLE patients and is correlated with pro-inflammatory cytokines and anti-dsDNA antibody. Glucocorticoids can down-regulate the expression of PGRN in SLE patients.Virtual slideshttp://www.diagnosticpathology.diagnomx.eu/vs/1562484036905973

Specificity of anti-SSB as a diagnostic marker for the classification of systemic lupus erythematosus

The aim of the present study was to investigate the sensitivity and specificity of anti-Sjögren’s syndrome type B (SSB) antibodies for diagnosing systemic lupus erythematosus (SLE) and to understand the correlation between anti-SSB antibodies and the clinical manifestations of SLE. A line immunoassay (LIA) was used to detect the presence of serum anti-SSB antibodies in SLE patients. The clinical manifestations of the patients were recorded to enable their correlation with the serum anti-SSB antibodies to be analyzed. In 25.7% of the 74 SLE patients, the serum was positive for anti-SSB antibodies, whereas only 3.3% of the 30 control cases were positive. The specificity of anti-SSB antibodies for detecting SLE was 96.7%. In anti-SSB antibody-positive SLE patients, the incidence of cheek erythema, alopecia, serositis, secondary Sjögren’s syndrome (sSS), leukocytopenia, elevated immunoglobulin (Ig)G and positive presence of anti-Sjögren’s syndrome type A (SSA)60 or anti-SSA52 antibodies was higher than in the anti-SSB antibody-negative group (P<0.05). Anti-SSB antibodies are important for the diagnosis of SLE and are associated with cheek erythema, alopecia, serositis, sSS, leukocytopenia, the elevation of IgG and positive presence of anti-SSA60 or anti-SSA52 antibodies.

Serum antibodies against the 70k polypeptides of the U1 ribonucleoprotein complex are associated with psychiatric syndromes in systemic lupus erythematosus: a retrospective study

Objectives: We assessed the association between serum autoantibodies against the 70-kDa polypeptide of the U1-ribonucleoprotein (RNP) complex (U1-70k) and the central nervous system (CNS) syndromes in systemic lupus erythematosus (SLE) patients.Methods: We studied 106 hospitalized patients with active SLE, comparing those with (n = 32) and without (n = 74) CNS syndromes. CNS syndromes were further classified into neurologic (n = 21) and psychiatric (n = 15) disorders. Immunoglobulin G (IgG) anti-U1-70k antibodies were measured by enzyme-linked immunosorbent assay (ELISA) using recombinant antigens. IgG antibodies against whole U1-RNP were measured using commercial ELISA kits.Results: Although there was no significant difference in the levels of serum anti-U1-70k antibodies in SLE patients with or without CNS syndromes (p = 0.83), the levels were significantly elevated in SLE patients compared with patients without psychiatric syndromes (p = 0.030). In contrast, no significant difference was observed in the levels of serum anti-U1-RNP antibodies in SLE patients with or without psychiatric syndromes (p = 0.555).Conclusions: These results indicate that serum anti-U1-70k antibodies are associated with psychiatric syndromes in SLE but that they are not associated with CNS syndromes as a whole or with neurologic syndromes. The anti-U1-70k antibodies might be involved in the pathological mechanisms of psychiatric syndromes in SLE.

Anti-cyclic citrullinated peptide antibodies in systemic lupus erythematosus patients with articular involvement: a predictive marker for erosive disease?

A small number of systemic lupus erythematosus (SLE) patients develop an erosive disease. Some studies have suggested an association between anti-cyclic citrullinated (anti-CCP) antibodies and this pattern of arthritis, but their exact significance in SLE patients remains unclear. The aim of this study was to evaluate the prevalence of anti-CCP antibodies in SLE patients with different subsets of articular disease. Among 521 SLE patients followed in this center from 1976 to 2011, those with articular involvement (n=298) were selected to take part in the study. We searched for anti-CCP2 IgG antibodies in 198 patients using a commercial enzyme linked immunosorbent assay (Immunoscan RA, Eurodiagnostica). In 174 patients the results for rheumatoid factor (RF) by nephelometry were retrospectively collected. C reactive protein (CRP) was obtained from clinical records. Patients were classified into 3 groups: erosive, non-erosive deforming, non-erosive non-deforming arthritis. Results of the different tests were compared among the groups. P&lt;0.05 was considered statistically significant. Anti-CCP antibodies were significantly associated with erosive disease. We also found that RF positivity and increased CRP were more frequent in erosive arthritis and erosive or non-deforming arthritis, respectively, than in non-erosive non-deforming arthritis. This study supports the evidence that anti-CCP antibodies could be a useful marker of erosive disease in SLE patients. Increase in RF and CRP could be an additional means of identifying lupus patients with arthritis at risk of a worse prognosis.

Anti-erythropoietin receptor antibodies in systemic lupus erythematosus patients with anemia

Anemia is a common hematologic abnormality in systemic lupus erythematosus (SLE). An inadequate erythropoietin (EPO) response in SLE patients with anemia has been described that may be due to the presence of antibodies to EPO in SLE patients. However, whether anemia in patients with SLE is related to antibodies to EPO receptor (EPOR) has not yet been investigated. We enlisted 169 consecutive patients with SLE and 45 normal individuals to investigate the existence and importance of circulating autoantibodies to EPOR in sera from patients with SLE. In all patients with SLE, the disease activity was evaluated by using the SLE disease activity index SLEDAI. Anti-EPOR antibodies were detected by using an enzyme-linked immunosorbent assay (ELISA). A higher frequency of anti-EPOR antibodies was observed in SLE patients than in healthy controls (18.3% vs 2.2%, p = 0.007). Moreover, anti-EPOR antibodies were detected in 22 of 69 (31.9%) SLE patients with anemia and in only nine of 100 (9.0%, p < 0.001) in those without. Furthermore, the patients with anti-EPOR antibodies exhibited more severe anemia and often presented as microcytic anemia (p = 0.001). Finally, anti-EPOR antibodies seemed more likely to occur in patients with rash (p = 0.008), lower levels of C(3) component (p = 0.01), higher titer of anti-dsDNA antibodies (p < 0.001) and higher disease activity scores (p = 0.024). The results of this study suggest that anti-EPOR antibodies might play a vital role in SLE patients developing anemia because of the higher incidence of antibodies to EPOR found in SLE patients with anemia. Thus, there might be clinical value in detecting anti-EPOR antibodies in SLE patients with anemia. Therefore, the pathologic role of the antibodies in inducing anemia needs to be established in future studies.

Jaccoud’s arthropathy: proper classification criteria and treatment are still needed

A deforming arthropathy was first described in patients with rheumatic fever (RF) by Francois-Sigismond Jaccoud more than a century ago [1], and it has been widely known in the literature as Jaccoud’s arthropathy (JA). Presently, the majority of the cases of JA are seen in systemic lupus erythematosus (SLE) [2]. Either in RF or in lupus, its prevalence is around 5 %. Such arthropathy has also been described in other connective tissue diseases, neoplasias and infections [3]. JA is characterized clinically by ‘‘reversible’’ joint deformities such as swan neck, thumb subluxation, ulnar deviation and ‘‘boutonniere.’’ However, the term ‘‘reversible’’ seems to be inappropriate because once the deformity is installed it lasts forever. Likewise, although the ‘‘reducible’’ nature of the arthropathy is demonstrated in the majority of the cases, sometimes the longstanding process of fibrosis in soft tissues of the joints can lead to a limitation of their mobility, making the diagnosis of JA still more difficult. Although mainly observed in hands, JA has also been seen in other sites such as feet, knees and shoulders [4]. The classical imaging feature of JA is the absence of articular erosions on a plain radiograph. The mechanisms responsible for the development of JA are not entirely known, but it is recognized that the deformities are a result of soft tissue abnormalities including laxity of ligaments and joint capsule and secondary deviation of the tendon from its axis with the contribution of muscular imbalance. Synovitis may contribute to the process, but it is not as aggressive as in rheumatoid arthritis (RA). Some studies have suggested an association of JA with hypermobility syndrome, and others have attempted to establish an association with different antibodies in SLE patients, but their findings did not lead to any definite conclusion. A limitation on the study of JA is the lack of definite diagnostic or classification criteria. Previous attempts to classify JA were made based on the presence of ‘‘reversible deformities’’ and absence of erosions on X-rays and rheumatoid factor negativity [5] or as ‘‘any deviation of the metacarpus finger axes assessed by a goniometer’’ [6]. Spronk et al. [7] developed a diagnostic ‘‘index’’ which allowed for the presence of different deformities and attributing JA a score of over five points. None of these sets of criteria has been universally accepted. Furthermore, to make the definition of JA more complicated, it has also been observed in individuals without any associated disease, a form referred to as ‘‘idiopathic’’ or in the elderly population as ‘‘senescent’’ [8, 9]. In fact, it is not rare to find typical ‘‘swan neck’’ deformity in normal population as an individual phenotypical feature. Sometimes, other members of the same family may have such deformities. In these cases generally, there is no other type of joint deformity. Thus, we understand the definition of JA is more appropriate if the criteria below are fulfilled:

Serum IgG levels demonstrate seasonal change in connective tissue diseases: a large-scale, 4-year analysis in Japanese

Hypergammaglobulinemia is often found in patients with autoimmune diseases, such as systemic lupus erythematosus (SLE), and its level may correlate with disease activity. However, it is unclear whether immunoglobulin G (IgG) displays seasonal changes. We analyzed the seasonal change in serum IgG by assessing 450 patients with connective tissue disease. The serum IgG levels in summer were compared with those in winter from 2006 to 2009. Independent samples from 355 patients were analyzed to confirm results in the first set. The differences in the IgG levels between the two seasons were analyzed in each disease and compared with disease activity. 488 patients without connective tissue disease were analyzed as reference instead of healthy people as control. We found that connective tissue disease patients tended to show higher levels of serum IgG in summer than in winter every year from 2006 to 2009, whereas patients without connective tissue disease did not demonstrate such a tendency. We observed this seasonal tendency in each disease. Seasonal changes weakly correlated with those of anti-DNA antibody in SLE patients and those of disease activity score in rheumatoid arthritis (RA) patients. Serum IgG levels of patients with connective tissue diseases display seasonal variations. Biological and clinical significance of these variations should be elucidated.

Serum antibodies against the 70k polypeptides of the U1 ribonucleoprotein complex are associated with psychiatric syndromes in systemic lupus erythematosus: a retrospective study

We assessed the association between serum autoantibodies against the 70-kDa polypeptide of the U1-ribonucleoprotein (RNP) complex (U1-70k) and the central nervous system (CNS) syndromes in systemic lupus erythematosus (SLE) patients. We studied 106 hospitalized patients with active SLE, comparing those with (n=32) and without (n=74) CNS syndromes. CNS syndromes were further classified into neurologic (n=21) and psychiatric (n=15) disorders. Immunoglobulin G (IgG) anti-U1-70k antibodies were measured by enzyme-linked immunosorbent assay (ELISA) using recombinant antigens. IgG antibodies against whole U1-RNP were measured using commercial ELISA kits. Although there was no significant difference in the levels of serum anti-U1-70k antibodies in SLE patients with or without CNS syndromes (p=0.83), the levels were significantly elevated in SLE patients compared with patients without psychiatric syndromes (p=0.030). In contrast, no significant difference was observed in the levels of serum anti-U1-RNP antibodies in SLE patients with or without psychiatric syndromes (p=0.555). These results indicate that serum anti-U1-70k antibodies are associated with psychiatric syndromes in SLE but that they are not associated with CNS syndromes as a whole or with neurologic syndromes. The anti-U1-70k antibodies might be involved in the pathological mechanisms of psychiatric syndromes in SLE.

Anti-C1q antibodies and their association with complement components in Indian systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease, characterized by immune complex formation and systemic inflammation. Complement components such as C1q and mannose-binding lectin (MBL) play an important role in the clearance of immune complexes. Anti-C1q antibodies are associated with lupus nephritis and reduced levels of the complement components. The objective of this study was to detect anti-C1q antibodies in SLE patients and to evaluate their association with the complement components. Sixty SLE patients were included, of whom 75% had lupus nephritis (LN) and 25% were without renal manifestations (non-LN). The disease activity was assessed at the time of evaluation by the systemic lupus erythematosus disease activity index (SLEDAI). Anti-C1q antibodies, circulating immune complexes, and serum MBL levels were detected by enzyme-linked immunosorbent assay. The anti-C1q antibody prevalence was 58.3%. The LN patients showed 60% anti-C1q positivity with a higher percentage in membranoproliferative glomerulonephritis patients (51.9%). Anti-dsDNA positivity was slightly higher among the anti-C1q positives than in the anti-C1q negatives (65.7% vs. 60%). A higher percentage of reduced C3 and C4 levels was noted among the anti-C1q positives. The LN patients showed a higher percentage of low MBL levels among anti-C1q negatives than in the anti-C1q positives (61.1% vs. 55.6%). Non-LN patients showed a higher percentage of low MBL levels among anti-C1q positives than among anti-C1q negatives (87.5% vs. 57.1%). Anti-C1q antibodies were found in both LN and non-LN patients, but there was no correlation with the clinical severity of the disease.

Serum IgG levels demonstrate seasonal change in connective tissue diseases: a large-scale, 4-year analysis in Japanese

Hypergammaglobulinemia is often found in patients with autoimmune diseases, such as systemic lupus erythematosus (SLE), and its level may correlate with disease activity. However, it is unclear whether immunoglobulin G (IgG) displays seasonal changes. We analyzed the seasonal change in serum IgG by assessing 450 patients with connective tissue disease. The serum IgG levels in summer were compared with those in winter from 2006 to 2009. Independent samples from 355 patients were analyzed to confirm results in the first set. The differences in the IgG levels between the two seasons were analyzed in each disease and compared with disease activity. 488 patients without connective tissue disease were analyzed as reference instead of healthy people as control. We found that connective tissue disease patients tended to show higher levels of serum IgG in summer than in winter every year from 2006 to 2009, whereas patients without connective tissue disease did not demonstrate such a tendency. We observed this seasonal tendency in each disease. Seasonal changes weakly correlated with those of anti-DNA antibody in SLE patients and those of disease activity score in rheumatoid arthritis (RA) patients. Serum IgG levels of patients with connective tissue diseases display seasonal variations. Biological and clinical significance of these variations should be elucidated.

Chorea in Systemic Lupus Erythematosus

Chorea is recognized as one of the neurologic manifestations of systemic lupus erythematosus (SLE). Most reports show an association between chorea and antiphospholipid (aPL) antibodies in SLE patients. The objective of this study was to describe the association of aPL antibodies with lupus chorea and its possible role in the pathogenesis of chorea. We made a retrospective review of all cases of lupus chorea between 1989 and 2007 in a tertiary care center in Mexico City. We found 7 episodes of chorea in 5 patients with SLE. In 2 patients (3 episodes), chorea was associated with cerebral ischemia; one of these cases had positive anticardiolipin (aCL) immunoglobulin G (IgG) antibodies, whereas the other was diagnosed as having vascular lipohyalinosis as the probable cause of cerebral ischemia. In 3 patients (4 episodes), an immune-mediated mechanism was suspected; these cases had negative aPL at the onset of chorea, but IgM aCL antibodies became positive later. In most episodes, chorea seems to be immunologically mediated and was associated with a later appearance of IgM aCL antibodies. Chorea in patients with lupus may also be caused by cerebral ischemia, and in some cases, it may be associated with IgG aCL antibodies.

Screening, identification and significance of the phage-display random 7 amino acid peptide specific to the sera of patients with systemic lupus erythematosus

Objective To screen and identify the phage-display random 7 amino acid peptide specific to the systemic lupus erythematosus(SLE) and analyze its practical significance. Methods Using the phage random 7 peptide library screening, the SLE specific phage clones are obtained after binding with the mixture of sera from 30 SLE patients and 30 normal controls as ligand respectively. Then the Dot-ELISA is used to identify the SLE specific phage clones reactive to sera of the SLE patients and normal controls individually. Finally the identified phage-display random 7 amino acid peptides are sequenced and it's homology with the antigenic epitope of human being and other are also analyzed. Results Total 12 of the phage-display random 7 amino acid peptide are obtained by phage peptide library screening and the Dot-ELISA identification. Sequence analysis shows that the identified phage-display random 7 amino acid peptide epitope have homology with E. coli, Salmonella and human immunodeficiency virus, but not with that of human being. Conclusion SLE-specific peptides screened by phage random peptide library maybe used to diagnosis the SLE. Meanwhile, the antibodies in SLE patients which are combined with the Pathogen epitope, suggest that SLE maybe relate to pathogen infection. Key words: Phage peptide library; Systemic lupus erythematosus; Sera

全身性エリテマトーデスとプロテオミクスを用いた自己抗原の解析

Analysis of autoantibodies/antigens has very important impact for investigation of the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent progress has enabled us to detect and analyze the autoantibodies/antigens easily by using a proteomics approach. By proteomics, we can directly detect proteins as gene products as well as their alterations by post-translational modification and internal abscission which are characteristically observed in proteins. For example, we pick up autoantigens of interest as spots through combination of two-dimensional electrophoresis and western blot, and identify them by analysis using mass spectrometry. These methods allow us to use clinical specimens, including various tissues as a source of autoantigens. In this review, we introduce application of proteomics approach to autoimmune diseases, referring to our study of the autoantigens detected by anti-neuronal antibodies in SLE patients with central nervous system involvement.

A study of immune responses to myelin and cardiolipin in patients with systemic lupus erythematosus (SLE)

Sera from 39 patients with SLE, 20 patients with cerebrovascular disease with no evidence of SLE, and 20 normal controls were tested for antibodies to cardiolipin (CL), brain total upper (UPG) and lower phase (LPG) glycolipids, myelin basic protein (MBP), myelin, and single strand DNA (ssDNA) by ELISA. Binding to the glycolipids and MBP was negative or negligible in all the groups, but significant binding was observed against CL, myelin and ssDNA in some of the SLE patients. Many sera from SLE patients with cerebral disorders and high CL binding also demonstrated high binding to myelin. These sera also labelled cell surface antigens on neonatal mouse neurons and astrocytes by immunofluorescence in tissue culture. A correlation was found to exist between anti-CL and antimyelin antibodies in SLE patients with cerebral lesions, but not between anti-ssDNA and anti-CL antibodies. As much as 80-90% of the specific activity of these antibodies could be absorbed out by the relevant antigens but only partially by the other antigens. In the control groups binding was low and no specific absorption could be demonstrated.

Association of FOXJ1 polymorphisms with systemic lupus erythematosus and rheumatoid arthritis in Korean population

The forkhead-box J1 (FOXJ1) transcription factor could suppress a spontaneous activation of T cells and B cells through an induction of IkappaBbeta that results in repression of NF-kappaB activity. In Foxj1 deficiency mice, systemic autoimmune inflammation is quite common symptom. Therefore, deregulated Foxj1 is supposed to be associated with autoimmune diseases and/or other inflammatory diseases. Previously, we identified that polymorphisms of human FOXJ1 gene (g.??460C>T, g.1805G>T and g.3375G>C) are associated with allergic rhinitis in a Korean population. In present study, we compared the genotype and allele frequencies of these SNPs between healthy controls and systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) patients. We also investigated the relationships between each genotype and the expression levels of anti- nuclear antibodies in SLE patients, and rheumatoid factor and anti-cyclic citrullinated peptide in RA patients. The frequencies of haplotypes constructed by these FOXJ1 SNPs were compared between controls and SLE (or RA) patients. The results of genotype and allele analysis showed that the prevalence of polymorphism g.3375G>C was associated with the susceptibility of SLE (P = 0.0072 and 0.0042, respectively). But no significant association was found with RA. In the haplotype analysis, however, the main CGG showed a weak association between controls and RA patients (P = 0.048).

Prevalence of depressive and anxiety disorders in systemic lupus erythematosus and their association with anti-ribosomal P antibodies

Objective To estimate the prevalence of psychiatric disorders in patients with systemic lupus erythematosus (SLE) and explore their association with anti-ribosomal P (anti-P) antibodies. Methods Seventy-one consecutive female SLE patients without neurological manifestations were evaluated for psychiatric disorders using the Structured Clinical Interview for DSM-IV (SCID). Anti-P antibodies were measured by enzyme-linked immunosorbent assay (ELISA)/immunoblot analysis. Results The mean age of subjects was 34.8 years (SD: 10.1 years), and the mean duration of SLE was 9.8 years (SD: 6.5 years). The 30-day prevalences of psychiatric disorders were: mood disorders 26.8%, anxiety disorders 46.5%, adjustment disorders 8.4%, alcohol abuse 1.4%, and somatoform disorder 1.4%. The lifetime prevalences of psychiatric disorders were: mood disorders 69%, anxiety disorders 52.1%, alcohol abuse 1.4%, and somatoform disorder 1.4%. Subjects with and without psychiatric manifestations did not differ regarding SLE clinical and laboratorial parameters including presence or absence of anti-P antibodies (23.1% vs. 20%, respectively, p = 1.0), disease activity, as measured by the Systemic Lupus Erythematosus Disease activity Index (4.08 ± 5.7 vs. 4.95 ± 6.3 respectively, p = 0.60) and cumulated damage, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (0.7 ± 2.3 vs. 0.3 ± 0.7 respectively, p = 0.33). Conclusions Mood and anxiety disorders are the most frequently observed psychiatric disorders in female SLE patients without concomitant neurological manifestations. These mild/moderate forms of psychiatric disorders are not associated with anti-P antibodies in SLE patients. Our findings reinforce the importance of systematic psychiatric evaluation for these patients in order to provide adequate and comprehensive care.

Gonad evaluation in male systemic lupus erythematosus

To assess gonad function in male patients with systemic lupus erythematosus (SLE). Thirty-five consecutive male patients with SLE according to the criteria of the American College of Rheumatology were prospectively evaluated for demographic and clinical features as well as previous and current treatment. Patients underwent urologic evaluation and testicular Doppler ultrasound. We obtained a hormone profile and performed a semen analysis including morphology and testing for the presence of antisperm antibodies. Patients were compared with 35 age-matched healthy controls. Compared with controls, SLE patients had lower median testicular volumes in both testes, a lower median total sperm count, and a lower median total motile sperm count. The mean sperm volume and percentage of normally formed sperm were lower in SLE patients than in controls. Since all SLE patients had semen alterations, they were further subdivided into 2 groups according to the severity of these abnormalities (group 1, with teratozoospermia [n = 18], and group 2, with azoospermia or teratozoospermia in combination with oligozoospermia and/or asthenozoospermia [n = 17]). The frequency of treatment with intravenous cyclophosphamide (IV CYC) after the first ejaculation was higher in group 2 than in group 1. The median testicular volumes measured by ultrasound in both testicles were lower in group 2 than in group 1. Follicle-stimulating hormone levels were higher in group 2 than in group 1. The overall frequency of antisperm antibodies in SLE patients was 40%. The apparent higher frequency of antisperm antibodies in group 1 than in group 2 did not reach significance. SLE patients have a high frequency of sperm abnormalities associated with reduced testicular volume. Postpubertal IV CYC treatment was the major factor in potential permanent damage to the testes.

Évaluation du kit Diasorin Liaison ® dsDNA pour la détection des anticorps anti-DNA natif

Screening and quantification of anti dsDNA antibodies are useful for positive diagnosis and follow-up of Systemic Lupus Erythematosus (SLE). Various assays exist based on different techniques which can influence the results. This study evaluated the specificity and the sentitivity of the Liaison ® dsDNA Diasorin assay for the detection of anti dsDNA antibodies. We compared the results with those obtained with ELIA ® dsDNA Pharmacia routinely used in our laboratory. The study has involved the sera of 153 systemic lupus erythematosus and 78 controls. The control group included 54 other autoimmune diseases and 24 patients without autoimmune markers. Liaison ® dsDNA ( Pharmacia) assay offers a sensitivity of 91,5% and a specificity > 99%. Correlation with the ELIA ® dsDNA assay is 0,68. The automated Liaison ® dsDNA Diasorin assay demonstrates its value for the detection and quantification of anti dsDNA antibodies in SLE patients.

Cross‐reactivity of human lupus anti‐DNA antibodies with α‐actinin and nephritogenic potential

Cross-reactivity with kidney antigens is believed to be a critical determinant in the renal pathogenicity of anti-double-stranded DNA (anti-dsDNA) antibodies. Murine nephritogenic anti-dsDNA antibodies have been shown to cross-react with alpha-actinin, and anti-alpha-actinin antibodies have been found to be deposited in the kidneys of lupus mice with active nephritis. Furthermore, in humans with systemic lupus erythematosus (SLE), it has been found that a greater proportion of polyclonal IgG anti-dsDNA antibodies from patients with renal involvement bind to alpha-actinin than do those from patients without renal disease. We undertook this study to substantiate a direct link between cross-reactive anti-dsDNA/anti-alpha-actinin antibodies and the pathogenesis of lupus nephritis in humans. A panel of 10 anti-dsDNA and/or anti-alpha-actinin antibodies was generated by Epstein-Barr virus transformation of lymphocytes from patients with SLE and was extensively characterized. Antibody binding was studied by enzyme-linked immunosorbent assay and Western blotting. Antibody potential for pathogenicity was assessed by measuring binding to isolated glomeruli and mesangial cells and by evaluation of histologic features of the kidney following injection in vivo. All anti-dsDNA antibodies isolated also bound alpha-actinin. Cross-reactive antibodies bound to mesangial cells and to isolated glomeruli ex vivo. Binding to glomeruli was not inhibited by DNase treatment, but could be abrogated by alpha-actinin. Furthermore, histopathologic abnormalities seen in mice injected intraperitoneally with a cross-reactive cell line included fusion of podocyte foot processes and subepithelial and subendothelial deposition. These studies provide strong support for the hypothesis that alpha-actinin is a major cross-reactive target for anti-dsDNA antibodies in SLE patients. Cross-reactive anti-dsDNA/anti-alpha-actinin antibodies from SLE patients are pathogenic and may contribute to the kidney lesions in lupus nephritis.