Antibodies In Connective Tissue Diseases Research Articles

Clinical Significance of Different Profiles of anti-Ro Antibodies in Connective Tissue Diseases.

Anti-Ro60 and anti-Ro52 antibodies are associated with different connective tissue diseases (CTDs). However, the clinical significance of anti-Ro antibodies is not always consistent among different global regions. The aim of this study was to investigate the clinical characteristics of patients with anti-Ro antibodies. A total of 1596 inpatients with anti-Ro antibodies were included in the study. Demographic, clinical, and serological data were compared between individuals with different profiles of anti-Ro antibodies: patients with anti-Ro52 antibodies alone, patients with anti-Ro60 antibodies alone, and patients with combined anti-Ro52 and anti-Ro60 antibodies. Of the 1596 patients, 1362 (85.3%) were female, the mean age was 45.5 years, and systemic lupus erythematosus (SLE) (46.0%) and Sjogren's syndrome (SS) (19.0%) were the most common CTD diagnoses. Among the patients with anti-Ro52 antibodies alone, idiopathic inflammatory myopathy (18.8%) and SLE (17.6%) were the most common CTD diagnoses. The coexistent autoantibodies of this group were significantly lower compared with those of the other two groups, while the presence of anti-Jo1 antibodies were significantly higher compared with those of the other two groups (3.7% vs. 0.6% vs. 1.9%, p = 0.029). In addition, the patients with isolated anti-Ro52 antibodies were more likely to suffer from interstitial lung disease (35.5% vs. 11.3% vs. 13.7%, p < 10-4) and pulmonary arterial hypertension (10.1% vs. 5.3% vs. 3.6%, p = 0.001) compared with the other two groups of patients. Compared with patients with isolated anti-Ro52 or anti-Ro60 antibodies, the patients with combined anti-Ro52 and anti-Ro60 antibodies were more likely to suffer from xerophthalmia and xerostomia. Furthermore, hypocomplementemia, hyperglobulinemia, and proteinuria were particularly prevalent in patients with anti-Ro60 antibodies. Different profiles of anti-Ro antibodies were significantly associated with clinical phenotypic features in CTDs, indicating the potential diagnostic and prognostic value of these antibodies in clinical practice.

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study.

ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. Worse baseline PF could be related to the absence of extra-thoracic symptoms and "classic" antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study

Background and objectivesILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. MethodsMulticentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. ResultsWe included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. ConclusionsWorse baseline PF could be related to the absence of extra-thoracic symptoms and “classic” antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.

Clinical significance of anti-Ro52 (TRIM21) antibodies in adult patients with connective tissue diseases

ObjectivesClinical significance of anti-Ro52 antibodies in connective tissue diseases (CTD) is controversial. Anti-Ro52 antibodies might be associated with a more severe CTD phenotype, especially interstitial lung disease (ILD). The aims of this study were to evaluate ILD prevalence and severity, the prevalence of micro- or macroangiopathy and CTD-associated cancers in CTD with anti-Ro52 antibodies. MethodsCTD patients with anti-Ro52 antibody screening by immunoblot at diagnosis were enrolled. Two groups were retrospectively formed according to the presence of anti-Ro52 antibodies with an unbiased 1:1 matching on CTD types. Unsupervised multiple correspondence analysis and hierarchical clustering analysis were used to aggregate anti-Ro52 positive patients in subgroups. Results408 CTD patients were included. Anti-Ro52 antibodies were detected in 33 % of CTD patients. Anti-Ro52 antibodies were associated with ILD at CTD diagnosis (47.8% vs. 23.0%, OR 3.3 95% IC 1.4 to 8.0, p = 0.008), even after adjusting for the presence of anti-Ro60 antibodies, especially in patients with antisynthetase syndrome, primary Sjögren syndrome and systemic sclerosis. Micro- or macroangiopathy was more frequent in anti-Ro52 positive CTD patients (18.6% vs. 9.7%, p = 0.02) and CTD patients with anti-Ro52 antibodies experienced more frequent relapses and required more immunosuppressive drugs. Clusters 4 and 5 identified anti-Ro52 positive CTD patients with severe ILD and with clinical features of systemic sclerosis or antisynthetase syndrome respectively. ConclusionsWe found that anti-Ro52 antibodies were independently associated with ILD in CTD patients irrespective of CTD type. Anti-Ro52 antibodies could be associated with severity and a more relapsing disease course in CTD patients.

Anti-endothelial cell antibodies in connective tissue diseases associated with pulmonary arterial hypertension.

To investigate the prevalence of anti-endothelial cell antibodies (AECA) in connective tissue diseases (CTD) associated with pulmonary arterial hypertension (PAH) and to corroborate the pathologic function of AECA in PAH-associated CTDs. AECA were detected by cellular enzyme-linked immunosorbent assay (ELISA) in sera of 19 PAH-associated CTD patients, 22 CTD patients without PAH involvement, and 20 age- and sex-matched healthy individuals as controls. Using IgG purified from the sera of AECA-positive, AECA-negative, and healthy subjects, the effects of AECA on the expression of ICAM-1 and the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) in cultured endothelial cells were also evaluated. A total of 12 of the 19 (63.2%) CTD patients with PAH, 9 of the 22 (40.9%) CTD patients without PAH, and 1 of the 20 (5%) healthy controls were positive for AECA, which were calculated as ELISA ratio (ER) values. ER values in PAH-associated CTD patients were significantly higher than those with CTD without PAH (3.68±2.05 versus 1.67±1.07, P<0.001). IgG purified from AECA-positive sera induced a significantly increased level of ICAM-1 expression after 48 h incubation (795.2±32.5 pg/mL) compared with AECA-negative or healthy control IgG (231.5±27.1 and 192.8±33.4 pg/mL, respectively; P<0.001). In addition, RANTES production by cultured human pulmonary arterial endothelial cells (HPAECs) increased in both a time- and concentration-dependent manner in response to incubation with purified AECA-positive IgG. AECA could be involved in CTD and might participate in the pathogenesis of PAH-associated CTD.

Detection of serum anti-B/B' UsnRNP antibodies in patients with connective tissue diseases by immunoblotting

To investigate the reliability of the immunoblot method in the detection of serum immunoreactivity towards the B/B' polypeptides of U small nuclear ribonucleoproteins (UsnRNP) and to assess the significance of these antibodies in connective tissue disease (CTD) patients. We tested the sera of 348 patients with CTD (101 SLE, 51 systemic sclerosis, 53 primary Sjögren's syndrome, 27 poly/dermatomyositis, 15 rheumatoid arthritis and 101 overlap CTD), of 31 matched healthy subjects and 13 patients with primary Epstein-Barr virus (EBV) infection with high titre of IgG anti-EBV antibodies. IgG anti-UsnRNP antibodies were determined by immunoblotting on nuclear extract from Raji cells (an EBV-immortalised human B lymphoid cell line) and Jurkat cells (a human T lymphoid cell line). Anti-dsDNA antibodies were detected by indirect immunofluorescence on Crithidia luciliae and anti-ENA by counterimmunoelectrophoresis. Anti-dsDNA activity and avidity were measured in SLE sera by ELISA with Scatchard analysis. Results were statistically analysed by chi-square and Mann-Whitney tests. A high frequency of anti-B/B' antibodies was found in the sera of CTD patients, confined to SLE (54.4%) and overlap CTD with SLE features (55,2%). Anti-B/B' immune reactivity was closely associated with other anti-UsnRNP specificities, gel precipitating anti-nRNP and anti-P antibodies. Nine out of 15 (60%) anti-B/B' positive/anti-ENA negative lupus sera on Raji blots were confirmed to be positive also on Jurkat blots. The sera from patients with EBV infection provided, on Raji blots, completely different band patterns from those obtained with auto-immune sera. CONCLUSIONS. The Sm B/B' proteins are the predominant or, at least, the most frequently targeted antigens of the UsnRNP auto-immune response in SLE and "lupus-like" overlap CTD. Moreover, anti-B/B' is diagnostically specific for CTD with SLE features. Immunoblotting on human B lymphoid cells is a reliable method, in terms of sensitivity and specificity, for the detection of anti-Sm B/B' antibodies.

Induction of Endothelial Cell Apoptosis by Anti-alpha-enolase Antibody

To assess the prevalence of anti-alpha-enolase antibody in systemic autoimmune diseases in Chinese patients and its role in endothelial cell apoptosis. The reactivity of anti-alpha-enolase antibody in a variety of autoimmune disorders in Chinese patients was evaluated by dot blot assay. Endothelial cell apoptosis was investigated by in vitro incubation of endothelial cells with IgG purified from anti-alpha-enolase antibody-positive sera, with or without pre-incubation with recombinant alpha-enolase. Anti-alpha-enolase antibody was prevalent in different systemic autoimmune diseases with relatively high reactivity in Chinese patients. In vitro incubation of endothelial cells with IgG containing anti-alpha-enolase antibody induced apoptosis in a time- and dose-dependent manner. Apoptosis was partly inhibited by pre-incubation of the endothelial cells with recombinant alpha-enolase. Our data suggest that alpha-enolase is a common auto-antigen recognized by anti-endothelial cell antibodies in connective tissue disease. Interaction between alpha-enolase and its autoantibody plays a role in endothelial cell apoptosis. Changes other than cell killing may contribute to the pathogenesis of endothelial damage and microvascular lesions.

Diagnostic accuracy of the FIDIS multiplex fluorescent microsphere immunodetection system for anti-extractable nuclear antigen (ENA) antibodies in connective tissue diseases

Anti-extractable nuclear antigen antibodies (ENA) are markers of connective tissue diseases (CTDs). We compared FIDIS reagents in the multiplex fluorescent microsphere immunodetection system to INNO-LIA and immunodiffusion for 174 antinuclear antibody-positive patients, 102 with well-defined CTDs and 72 disease controls. No significant differences were found in sensitivity or specificity between FIDIS and immunodiffusion, or between FIDIS and INNO-LIA for all anti-ENA in all CTD patients; nor were any differences found for individual anti-ENAs within distinct CTDs. The FIDIS sensitivity was 41% (anti-SSA) and 17% (anti-SSB) in lupus erythematosus (LE) or primary Sjögren's syndrome; 5% (anti-ribosome and anti-Sm) in LE; 17% (anti-RNP) in LE or mixed CTD; 21% (anti-Scl70) in systemic sclerosis; and 61% (anti-centromere) in limited systemic sclerosis. The specificity reached 88%-100%. Receiver operating characteristic curve areas did not differ between FIDIS and INNO-LIA. Agreement ranged from 91% (anti-SSB) to 99% (anti-Jo1) between FIDIS and INNO-LIA, and from 95% (anti-Scl70) to 100% (anti-Sm) between FIDIS and immunodiffusion. Samples scored positive with all techniques in 83% (anti-centromere), 70% (anti-RNP), 67% (anti-Jo1), 60% (anti-SSA), 40% (anti-SSB), 33% (anti-ribosome), 25% (anti-Sm) and 13% (anti-Scl70) of cases. The diagnostic performance of FIDIS anti-ENA reagents is comparable to immunodiffusion and INNO-LIA.

Abnormalities of Serum Antielastin Antibodies in Connective Tissue Diseases

Background Antibodies (Abs) to α-elastin (elastin breakdown product) and tropoelastin (elastin precursor) are found in the serum of all human subjects and correlate with their respective serum peptide levels; however, peptide levels vary with age and some disease states. This study was undertaken to determine if serum elastin Abs, peptides, and elastin metabolism were altered in autoimmune diseases by detecting a changing ratio of serum anti-α: tropoelastin Ab levels. Methods Serum from patients with a variety of connective tissue diseases, including 28 with systemic lupus erythematosus (SLE), 24 with scleroderma, 18 with rheumatoid arthritis (RA), 10 with polymyositis, and 39 with vasculitis, was compared with serum from 19 age-matched healthy subjects for levels of antitropoelastin and anti-α-elastin Abs. Results We found an increase in IgG anti-α-elastin and a decrease in antitropoelastin Abs in the sera of patients with scleroderma ( p &lt; .02 and .00005) and SLE ( p &lt; .006 and .011). There was also a marked increase in anti-α-elastin Abs in patients with polyarteritis nodosa ( p &lt; .0005) and decreases in antitropoelastin Abs in patients with RA ( p &lt; .05), polymyositis ( p &lt; .01), and a variety of other vasculidities ( p &lt; .0003). Conclusions Abnormal variations in elastin metabolism may be detected in several connective tissue diseases by measuring ratios of a- and tropoelastin IgG Abs as markers of elastin degradation and synthesis.

Abnormalities of Serum Antielastin Antibodies in Connective Tissue Diseases

Abnormalities of Serum Antielastin Antibodies in Connective Tissue Diseases

Abnormalities of Serum Antielastin Antibodies in Connective Tissue Diseases

BackgroundAntibodies (Abs) to α-elastin (elastin breakdown product) and tropoelastin (elastin precursor) are found in the serum of all human subjects and correlate with their respective serum peptide levels; however, peptide...

Abnormalities of Serum Antielastin Antibodies in Connective Tissue Diseases

Abnormalities of Serum Antielastin Antibodies in Connective Tissue Diseases

Analysis of anti-U1 RNA antibodies in patients with connective tissue disease. Association with HLA and clinical manifestations of disease.

To determine the prevalence of anti-U1 RNA antibodies in connective tissue disease (CTD) patients and evaluate immunogenetic and clinical features of patients possessing these antibodies. RNA immunoprecipitation was used to analyze patient and healthy control sera for the presence of anti-R1 RNA antibodies. Enzyme-linked immunosorbent assay and immunoblotting were used to determine small nuclear RNP (snRNP) polypeptide antibodies. HLA polymorphisms were determined by microcytotoxicity and DNA typing. Anti-U1 RNA IgM and IgG antibodies were found in 60% of anti-RNP positive patients. All of the anti-U1 RNA positive patients had anti-70K, and most had anti-A, (U1)snRNP polypeptide antibodies. HLA-DR2/DR4, as well as Raynaud's phenomenon and synovitis, were significantly increased in the anti-U1 RNA positive group. The presence of anti-U1 RNA antibodies correlates with anti-70K and anti-A polypeptide antibodies. In addition, the anti-U1 RNA positive CTD patient group is immunogenetically and clinically distinctive from the anti-U1 RNA negative patient group.

Frequency and clinical associations of anti-chromo antibodies in connective tissue disease.

To assess the frequency and clinical associations of anti-chromo antibodies in connective tissue disease and to study their relationship to anti-centromere autoreactivity. Anti-chromo and anti-centromere antibodies (ACA) were measured by immunoblotting in 50 patients with systemic sclerosis (SSc) and 58 connective tissue disease controls. Common epitopes on centromere and chromo antigens were sought using affinity-purified antibodies from immunoblots. Anti-chromo antibodies were detected in three of 32 sera with ACA and no controls. The three patients with anti-chromo antibodies had limited cutaneous SSc, and two had erosive arthritis. No cross-reactivity between chromo or centromere-related proteins was demonstrated. Anti-chromo antibodies form a rare autoantibody specificity that may identify an overlap group of patients with SSc and arthritis. Chromo and centromere antigens are associated but immunologically distinct autoimmune targets. Whether they localise to the same chromosomal site remains unknown.

Anti-Ku antibodies in connective tissue diseases: Report of three cases

Three patients are described with clinical features of connective tissue diseases, namely, dermatomyositis, progressive systemic scleroderma, and systemic lupus erythematosus. In two patients the symptoms of disease overlapped. The rare anti-Ku antibody was found in all of them. Anti-Ku antibody characterizes those patients with polymyositis-scleroderma overlap syndromes who have a good prognosis. One of our patients, who also had severe anti-Sm-positive systemic lupus erythematosus, seems to be an exception.

The clinical relevance of antinuclear antibodies in connective tissue diseases.

Detection of antinuclear antibodies (ANA) is of growing relevance in the management of connective tissue diseases (CTD). ANA are useful diagnostic tools, since most CTD have a peculiar ANA profile, characterized either by restricted specificities, abnormally high titers, or both. Furthermore, the study of the intimate structure and function of nuclear antigens, and of their corresponding antibodies may provide important insights to understand both origin and pathogenesis of CTD. Finally, the more or less close association of ANA levels and/or specificity with certain signs or symptoms of CTD is of increasing help to the clinician in the correct monitoring and management of CTD.

Connective Tissue Disease Antibodies and Pregnancy

Half a century ago, the first hint that there might be such a subject as reproductive immunology came with Hench’s observation of the frequent improvement of rheumatoid arthritis (RA) in pregnancy, which led to discovery of cortisone and corticosteroid therapy. Twenty years later when organ transplant was being pioneered, the discipline developed as a recognizable entity, and it did so particularly in relation to the immunologic problem of the fetus as a graft. It was observed in women with connective tissue diseases (CTDs) that although antibodies such as lupus erythematosus (LE) factor and antinuclear factor crossed the placenta to their children, these did not produce any obvious disease. Consequently, CTDs were virtually ignored in the early years of reproductive immunology. In this period, however, pregnancy observations led to major advances in the elucidation of the mechanisms of a number of single-system autoimmune diseases, notably myasthenia gravis, thrombocytopenic purpura, and thyroid diseases.1

Anti-double-stranded RNA antibodies in connective tissue disease

Sera from patients with systemic lupus erythematosus (SLE) contain antibodies to a number of nucleic acids. Antibodies to double stranded DNA have been found in patients with SLE, and their titer are generally associated with the disease activity. In this study, the sera from patients with SLE and other rheumatic disorders were examined for antibodies to double-stranded RNA in the major immunoglobulin classes by solid-phase radioimmunoassay employing polystyrene tubes coated with poly-L-lysine. The technique provided high specificity for the antibody to double stranded RNA. The anti-RNA antibodies were found not only in the sera of patients with SLE, but also from patients with other related diseases though less frequently.

Serum antibodies in connective tissue diseases

Serum antibodies in connective tissue diseases

膠原病における抗リボゾーム抗体の検索

膠原病における抗リボゾーム抗体の検索