Autoantibody Profile In Patients Research Articles

Characterization of Clinicopathological Features and Autoantibody Profiles in Patients with Cutaneous Lupus Erythematous: A Single-Center Retrospective Study.

Cutaneous lupus erythematosus (CLE) is an autoimmune condition characterized by a wide range of clinical manifestations and limited treatment options. There is little research on the impact of commonly used diagnostic tests including antinuclear antibodies (ANA) and extractable nuclear antigens (ENA) on disease course or responsiveness to treatment. This single-center retrospective cohort study aims to address this gap by characterizing clinicopathological characteristics, patient demographics, and treatment response among patients with CLE. The study included patients with a diagnosis of CLE based on the International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes evaluated in the outpatient clinics of the Department of Dermatology at Michigan Medicine between 1 January 2012 and 31 December 2022. Chart review was conducted to collect patient and clinical data including CLE subtype, patient demographics, disease course, presence of SLE, ANA and ENA results, and CLE treatments and response. 390 patients with CLE were included, 86% (n = 334) of whom had biopsy-proven CLE. Most patients were female (77%), non-Hispanic (97%), and Caucasian (58%). Of all patients, 35% (n = 138) were ANA negative. The most common CLE treatments were antimalarials (86%, n = 336), topical steroids (85%, n = 331), systemic steroids (42%, n = 164), and mycophenolate mofetil (30%, n = 119). Treatment response was determined by clinician documentation and ranged from stabilization of disease to complete remission. Treatments with the highest CLE response rates included systemic steroids (84%, n = 138), antimalarials (63%, n = 212), belimumab (54%, n = 29), and topical steroids (50%, n = 165). Factors associated with lower response rates to antimalarials using chi-squared tests included anti-double stranded (ds) DNA (n = 54, 57% response among anti-dsDNA+ versus n = 165, 74% response among anti-dsDNA-), anti-Smith (n = 33, 54% versus n = 82, 72%), anti-RNP (n = 48, 56% versus n = 67, 73%), anti-SmRNP (n = 44, 54% versus n = 171, 74%), anti-chromatin (n = 33, 50% versus n = 179, 74%), SLE (n = 81, 57% versus n = 143, 79%), and ACLE subtype (n = 28, 58% versus n = 195, 71%). When controlling for demographics, CLE subtype, and presence of SLE using a logistic regression, factors associated with lower antimalarial response rates included anti-dsDNA (OR 0.5), anti-Smith (OR 0.5), and anti-chromatin (OR 0.6) CONCLUSION: Our results suggest that numerous patient characteristics, namely the presence of ACLE, SLE, and its most commonly implicated autoantibodies (i.e., anti-dsDNA and anti-Smith), are associated with lower response rates to first-line therapies, including topical steroids and antimalarials.

Autoantibody Profiling Using Human Autoantigen Protein Array and AlphaScreen.

Autoantibodies that recognize self-antigens are believed to have a close relationship with diseases such as autoimmune diseases, cancer, and lifestyle diseases. Analysis of autoantibodies is essential for investigating pathology mechanisms, diagnosis, and therapeutics of these diseases. We developed an autoantibody profiling assay using a cell-free synthesized protein array and high-throughput screening technology. Our assay system can sensitively detect interaction between recombinant antigen protein and autoantibody and efficiently analyze autoantibody profiling in patients' sera.

Synthetic Nucleic Acid Antigens in Localized Scleroderma.

We investigated the impact of synthetic nucleic acid antigens on the autoantibody profiles in patients with localized scleroderma, an autoimmune skin disease. Anti-DNA antibodies, including double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA), are common among autoimmune diseases, such as systemic lupus erythematosus and localized scleroderma. Based on recent studies, we hypothesized that the sequence of nucleic acid antigens has an impact on the autoimmune reactions in localized scleroderma. To test our hypothesis, we synthesized a panel of DNA and RNA antigens and used them for autoantibody profiling of 70 children with localized scleroderma compared with the healthy controls and patients with pediatric systemic lupus erythematosus (as a disease control). Among the tested antigens, dsD4, which contains the sequence of the human oncogene BRAF, showed a particularly strong presence in localized scleroderma but not systemic lupus erythematosus. Disease activity in patients was significantly associated with dsD4 autoantibody levels. We confirmed this result in vivo by using a bleomycin-induced mouse model of localized scleroderma. When administered intraperitoneally, dsD4 promoted an active polyclonal response in the mouse model. Our study highlights sequence specificity for nucleic acid antigens in localized scleroderma that could potentially lead to developing novel early-stage diagnostic tools.

Late Onset Systemic Lupus Erythematosus - Clinical and Autoantibody Profile and its Comparison with Young Onset Systemic Lupus Erythematosus.

The aim of the study was to determine the clinical features & autoantibody profile of patients having late onset Systemic Lupus Erythematosus (SLE) and to compare with young onset SLE due to its scarce data from India. All patients who fulfilled the 1997 ACR criteria for SLE were included. Late onset patients were >50 years of age and young onset were <50 years >18 years at the time of first SLE-related symptom. Clinical, laboratory, and autoantibody (ENA 25 & APLA) profiles were compared between the two groups using descriptive statistics and chi square test. Of the 305 patients, 69 had late onset (75.4% females). Mean age was 59.42±6.7 years (Late onset lupus) and 33.13±8.44 years (young onset lupus). The most common symptom was arthritis (60%) followed by oral ulceration (50%), fever (43%), and serositis (37.68%). Most common antibody was SSA/Ro60 (50%) and anti-SSA/Ro52 (46%). Interstitial lung disease (ILD) (14.5%), pancytopenia (13%) and diffuse alveolar haemorrhage (4.3%) were more frequent in late onset group. Statistically significant differences were found between two groups in terms of photosensitivity (p=0.009), malar rash (p=0.005), excessive hair loss (p=0.0006), Raynaud's phenomenon (p=0.001), lymphadenopathy (p=0.01), nephritis (p=0.0007), ILD (p=0.01), anti-dsDNA (p=0.005), anti-nucleosome (p=0.01), anti-Sm (p=0.007), Ribosomes P0 (p=0.0004). This study suggests that late onset SLE has distinct clinical and serological manifestations when compared with young onset SLE patients.

Extended autoantibody panel in Turkish patients with early-stage systemic sclerosis: Coexpressions and their influences on clinical phenotypes.

To investigate the frequency and clinical relevance of an extended autoantibody profile in patients with systemic sclerosis(SSc). In this cross-sectional study, serum from 100 consecutive patients was subjected to indirect immunofluorescence (IIF)(HEp-20-10/primate liver mosaic) and Systemic Sclerosis Profile by EUROIMMUNto evaluate anti-nuclear antibodies(ANA) and autoantibodies against 13 different autoantibodies in patients with SSc less than 3 years. Ninety-three of 100 patients were positive for ANA byIIF. Fifty-three patients showed single positivity, 26 anti-topoisomerase antibodies (anti-Scl70 ab), 16 anticentromere antibodies (ACAs), six anti-RNA polymerase III antibodies (anti-RNAPIII ab), one anti-Ku antibody, one anti-PM/Scl100 antibody, two anti-PM/Scl75 antibodies, one anti-Ro52 antibody, whereas 32 patients had multiple autoantibody positivities. Among classic SSc-specific autoantibodies, anti-Scl70 and anti-RNAPIII abs showed the highest cooccurrence (n = 4). One patient was simultaneously positive for anti-RNAPIII ab and ACA, and one was positive for ACA and anti-Scl70 ab. The clinical features were not statistically different between single and multiple autoantibody-positivity for classic SSc-specific autoantibodies (ACA, anti-Scl70 ab, and anti-RNAPIII ab), except for digital ulcer in the multiantibody positive ACA group (p = .019). Based on our results, coexpression of autoantibodies is not uncommon in SSc patients. Although autoantibodies specific to SSc in early disease show generally known clinical features, it remains to be investigated how the coexpression of autoantibodies will affect clinical presentation.

Is Every Thyroid Antibody a Bad Sign?: The Complex Relationship of Antithyroid Antibodies and Obsessive-compulsive Symptoms.

: Several immunological factors are emphasized in the etiology of autoimmune thyroid diseases and obsessivecompulsive disorder. Obsessive-compulsive symptoms (OCS) are commonly seen in patients with autoimmune thyroid diseases. This study aims to evaluate the relationship between OCS and antithyroid antibodies. : The study included 145 patients with Hashimoto thyroiditis or Graves' disease and 42 healthy controls. Thyroid function tests and serum thyroid autobody levels (anti-thyroglobulin [TG], anti-thyroid peroxidase [TPO], and anti-thyroid stimulating hormone [TSH]) of the patients were measured. The socio-demographic data and OCS of the participants were evaluated with Dimensional OCS (DOCS). : DOCS scores were higher in patients than in the control group. There was not found a significant relationship between free T3, free T4, and TSH levels and DOCS scores. Anti-TG positivity in females was associated with lower DOCS scores. Anti-TPO positivity in males had a positive correlation with DOCS scores. There was no correlation between sex and the presence of anti-TSH in terms of OCS severity. Univariate analysis found the highest OCS scores in anti-TPO positive, anti-TG, and anti-TSH negative patients. The group with the lowest OCS scores was found to be anti-TG positive, anti-TPO, and anti-TSH negative patients. : OCS severity could be affected by different thyroid autoantibody profiles in patients with autoimmune thyroid diseases. While anti-TG serves a protective role against OCS in females, the presence of anti-TPO may worsen the OCS in men. Additionally, the co-existence of different antithyroid antibodies may affect the severity of OCS differently according to sex.

Baseline autoantibody profiling in patients with NSCLC with pre-existing autoimmune diseases or who had received prior anti-PD-1 therapy before enrolling in the TAIL study.

2512 Background: Patients (pts) with pre-existing autoimmune diseases (AID) and prior immune checkpoint inhibitor (ICI) experience were historically excluded from studies with ICIs. Moreover, about 50% pts with pre-existing autoimmunity have a flare up when given ICI therapies (1). In this post-hoc exploratory analysis, we characterized the baseline autoantibody (AAb) profiles and evaluated its correlation with efficacy and safety outcomes in NSCLC pts with either pre-existing AID or who had prior ICI therapy and received atezolizumab in the TAIL study (2). Methods: Plasma samples were obtained from 57 NSCLC pts prior to receiving atezolizumab (TAIL study, NCT03285763). AAb testing was performed using tailored immuno-oncology bead-based antigen arrays comprising 1,340 tumor, AID and immune pathway antigens (3, 4). The cohort includes 39 pts with prior ICI therapy or prior AID (experimental group) and 18 pts without prior ICI therapy or AID (control group). Differences in IgG AAbs were compared between the experimental and control group in pts with or w/o irAE and overall survival (OS) longer or shorter than 11.1 months (median OS in overall population in TAIL). Furthermore, the AAb profiles of a subgroup of pts with therapeutic benefit (OS ≥ 11.1 months) and no or low grade irAEs (standard toxicity grade ≤ 2) were analyzed. Statistical analysis included 2-way permutation-based ANOVA (factors: outcome, study group) and Significance Analysis of Microarrays (SAM). Results: While pre-treatment AAbs were detected in the overall cohort, significant differences in AAb were observed between the experimental and control group at baseline, which were associated with OS and irAEs. In experimental group pts, pre-existing AAbs to AQP4 and NCOA1 predicted the development of irAEs. Differences were also observed in AAbs predicting longer OS. AAbs to CENPT were specifically identified in pts in the experimental group with longer OS, whereas AAbs to SOX5 were elevated in pts of the control group with longer OS. In the subgroup of pts with therapeutic benefit and no or low risk of irAE, AAbs to IL6, CENPT and the cancer testis antigens NY-ESO-2 and MAGEB2 were elevated in the experimental group. Conclusions: This AAb analysis provides important preliminary data in helping to understand the drivers of clinical outcomes with ICIs in pts with pre-existing AID and prior ICI therapy. The findings seem biologically plausible as some of the identified antigens refer to the breach of tolerance to classical AAb targets e.g. CENPT, AQP4 and to an immune response to classic tumor antigens e.g. NY-ESO-2 and MAGEB2. Further validation of the AAb profiling approach is warranted to shed insights on potential therapeutically actionable antigens and generate data orthogonal to efforts to identify biomarkers that are predictive of efficacy and safety outcomes with ICI therapies.

Serum Autoantibodies in Patients with Dry and Wet Age-Related Macular Degeneration

To assess the serum autoantibody profile in patients with dry and exudative age-related macular degeneration compared with healthy volunteers to detect potential biomarkers, e.g., markers for progression of the disease. IgG Immunoreactivities were compared in patients suffering from dry age-related macular degeneration (AMD) (n = 20), patients with treatment-naive exudative AMD (n = 29) and healthy volunteers (n = 21). Serum was analysed by customized antigen microarrays containing 61 antigens. The statistical analysis was performed by univariate and multivariate analysis of variance, predictive data-mining methods and artificial neuronal networks were used to detect specific autoantibody patterns. The immunoreactivities of dry and wet AMD patients were significantly different from each other and from controls. One of the most prominently changed reactivity was against alpha-synuclein (p ≤ 0.0034), which is known from other neurodegenerative diseases. Furthermore, reactivities against glyceraldehyde-3-phosphat-dehydrogenase (p ≤ 0.031) and Annexin V (p ≤ 0.034), which performs a major role in apoptotic processes, were significantly changed. Some immunoreacitvities were antithetic regulated in wet and dry-AMD, such as Vesicle transport-related protein (VTI-B). Comparison of autoantibody profiles in patients with dry and wet AMD revealed significantly altered immunoreactivities against proteins particularly found in immunological diseases, further neurodegenerative, apoptotic and autoimmune markers could be observed. A validation study has to explore if these antibody pattern can help to understand the underlying differences in pathogenesis, evaluate their prognostic value and if those could be possibly useful as additional therapeutic targets.

Autoantibody profiles in patients with immune checkpoint inhibitor-induced neurological immune related adverse events.

Neurological immune-related adverse events (irAE-n) are severe and potentially fatal toxicities of immune checkpoint inhibitors (ICI). To date, the clinical significance of neuronal autoantibodies in irAE-n is poorly understood. Here, we characterize neuronal autoantibody profiles in patients with irAE-n and compare these with ICI-treated cancer patients without irAE-n. In this cohort study (DRKS00012668), we consecutively collected clinical data and serum samples of 29 cancer patients with irAE-n (n = 2 pre-ICI, n = 29 post-ICI) and 44 cancer control patients without irAE-n (n = 44 pre- and post-ICI). Using indirect immunofluorescence and immunoblot assays, serum samples were tested for a large panel of neuromuscular and brain-reactive autoantibodies. IrAE-n patients and controls received ICI treatment targeting programmed death protein (PD-)1 (61% and 62%), programmed death ligand (PD-L)1 (18% and 33%) or PD-1 and cytotoxic T-lymphocyte-associated protein (CTLA-)4 (21% and 5%). Most common malignancies were melanoma (both 55%) and lung cancer (11% and 14%). IrAE-n affected the peripheral nervous system (59%), the central nervous system (21%), or both (21%). Prevalence of neuromuscular autoantibodies was 63% in irAE-n patients, which was higher compared to ICI-treated cancer patients without irAE-n (7%, p <.0001). Brain-reactive autoantibodies targeting surface (anti-GABABR, -NMDAR, -myelin), intracellular (anti-GFAP, -Zic4, -septin complex), or unknown antigens were detected in 13 irAE-n patients (45%). In contrast, only 9 of 44 controls (20%) presented brain-reactive autoantibodies before ICI administration. However, seven controls developed de novo brain-reactive autoantibodies after ICI initiation, therefore, prevalence of brain-reactive autoantibodies was comparable between ICI-treated patients with and without irAE-n (p = .36). While there was no clear association between specific brain-reactive autoantibodies and clinical presentation, presence of at least one of six selected neuromuscular autoantibodies (anti-titin, anti-skeletal muscle, anti-heart muscle, anti-LRP4, anti-RyR, anti-AchR) had a sensitivity of 80% (95% CI 0.52-0.96) and a specificity of 88% (95% CI 0.76-0.95) for the diagnosis of myositis, myocarditis, or myasthenia gravis. Neuromuscular autoantibodies may serve as a feasible marker to diagnose and potentially predict life-threatening ICI-induced neuromuscular disease. However, brain-reactive autoantibodies are common in both ICI-treated patients with and without irAE-n, hence, their pathogenic significance remains unclear.

Autoantibody screening of plasma and peritoneal fluid of patients with endometriosis.

Are there specific autoantibody profiles in patients with endometriosis that are different from those in controls? This study did not reveal a significantly higher prevalence of autoantibodies in the studied groups of patients. Various inflammatory factors are postulated to be involved in the pathomechanisms of endometriosis, and a potential link exists with autoimmune diseases, which may also play an important role. As the diagnosis of endometriosis remains invasive, it can only be confirmed using laparoscopy with histopathological examination of tissues. Numerous studies have focused on identifying useful biomarkers to confirm the disease, but without unequivocal effects. Autoantibodies are promising molecules that serve as potential prognostic factors. A multicentre, cross-sectional study was conducted over 18 months (between 2018 and 2019), at eight Departments of Obstetrics and Gynaecology in several cities across Poland on 137 patients undergoing laparoscopic examination for the diagnosis of endometriosis. During laparoscopy, we obtained plasma samples from 137 patients and peritoneal fluid (PF) samples from 98 patients. Patients with autoimmune diseases were excluded from the study. Autoantibody profiling was performed using HuProt v3.1 human proteome microarrays. We observed no significant differences in the expression of autoantibodies in the plasma or PF between the endometriosis and control groups. The study revealed that in the PF of women with Stage II endometriosis, compared with other stages, there were significantly higher reactivity signals for ANAPC15 and GABPB1 (adj. P < 0.016 and adj. P < 0.026, respectively; logFC > 1 in both cases). Comparison of the luteal and follicular phases in endometriosis patients revealed that levels of NEIL1 (adj. P < 0.029), MAGEB4 (adj. P < 0.029), and TNIP2 (adj. P < 0.042) autoantibody signals were significantly higher in the luteal phase than in the follicular phase in PF samples of patients with endometriosis. No differences were observed between the two phases of the cycle in plasma or between women with endometriosis and controls. Clustering of PF and plasma samples did not reveal unique autoantibody profiles for endometriosis; however, comparison of PF and plasma in the same patient showed a high degree of concordance. Although this study was performed using the highest-throughput protein array available, it does not cover the entire human proteome and cannot be used to study potentially promising post-translational modifications. Autoantibody levels depend on numerous factors, such as infections; therefore the autoantibody tests should be repeated for more objective results. Although endometriosis has been linked to different autoimmune diseases, it is unlikely that autoimmune responses mediated by specific autoantibodies play a pivotal role in the pathogenesis of this inflammatory disease. Our study shows that in searching for biomarkers of endometriosis, it may be more efficient to use higher-throughput proteomic microarrays, which may allow the detection of potentially new biomarkers. Only research on such a scale, and possibly with different technologies, can help discover biomarkers that will change the method of endometriosis diagnosis. This study was funded by a grant from the Polish Ministry of Health (grant no. 6/6/4/1/NPZ/2017/1210/1352). It was also funded by the Estonian Research Council (grant PRG1076) and the Horizon 2020 Innovation Grant (ERIN; grant no. EU952516), Enterprise Estonia (grant no. EU48695), and MSCA-RISE-2020 project TRENDO (grant no. 101008193). The authors declare that there is no conflict of interest. N/A.

Diagnostic accuracy and predictive value of autoantibody profiles in patients with systemic sclerosis: a single-center study.

To determine diagnostic accuracy and evaluate the predictive value of autoantibody profiles in patients with systemic sclerosis (SSc). A total of 140 patients with SSc (125 female, mean age 54.2 ± 14.2years) were analyzed by a multiplex line immunoassay (Euroimmun) for autoantibodies against 12 SSc-related antigens. Associations between the presence of the autoantibodies and demographic clinical manifestations of patients with SSc were investigated. The sensitivity and specificity of this assay were as follows: 32.9% and 99.4% for anti-Scl-70, 29.3% and 88.9% for anti-CENP A, 28.6% and 87.8% for anti-CENP B, 7.1% and 97.8% for anti-RP11, 5.7% and 100% for anti-RP155, 2.9% and 99.4% for anti-NOR 90, 2.9% and 98.9% for anti-Th/To, 1.4% and 96.7% for anti-PM-Scl-100, 5.0% and 98.3% for anti-PM-Scl-75, and 2.9% and 97.2% for anti-Ku, respectively. Anti-Scl-70 was significantly associated with sine scleroderma (P = 0.003), digital ulcers (P = 0.047), and Raynaud's phenomenon as the first clinical manifestation of onset (P = 0.017). SSc-ILD was more common in patients with anti-Scl-70 (P = 0.029) and less frequent in patients with anti-CENP A (P < 0.001) and anti-CENP B (P < 0.001). There was a significant association between PAH with anti-CENP A (P = 0.008) and anti-CENP B (P = 0.025). Renal involvement was significantly related to anti-NOR90 (P = 0.026) and anti-Th/To (P = 0.026). This study confirmed the important role of autoantibodies in accurately diagnosing SSc. The autoimmune profile of patients with SSc was related to specific disease manifestations. Key Points • Autoantibody profiles were useful for diagnosing SSc and predicting clinical features of patients.

Autoantibodies in lupus nephritis useful in distinguishing proliferative nephritis from membranous nephritis.

This study was conducted to determine autoantibodies associated with lupus nephritis, especially those useful in diagnosing proliferative and membranous nephritis. 106 patients with lupus nephritis and 63 patients with SLE but no nephritis were enrolled. 55 patients were selected from the lupus nephritis group and were divided into two groups: proliferative nephritis patients (n=36) and membranous nephritis patients (n=19). The autoantibody profiles of patients' sera were evaluated using the EUROLINE ANA profile 3 (IgG) kit. A higher positivity rate of anti-dsDNA antibody and anti-histone antibody were seen in lupus nephritis patients compared to non-renal SLE patients. In comparing between proliferative and membranous nephritis, positivity of anti-nucleosome antibody was higher in proliferative nephritis compared to membranous nephritis, although it was not statistically significant. However, anti-nucleosome antibody-positive patients with lupus nephritis had higher prevalence of hematuria and pyuria, which are strong indications of proliferative nephritis. Also, a significantly higher positivity rate of anti-RNP70 antibody was seen in membranous nephritis compared to proliferative nephritis. Our results showed anti-nucleosome antibody and anti-RNP70 antibodies may be predictive non-histological factors for discriminating between proliferative and membranous lupus nephritis.

Performance of indirect immunofluorescence test and immunoblot tests in the evaluation of antinuclear and antimitochondrial antibodies.

Antinuclear antibodies (ANA) and antimitochondrial antibodies (AMA) have essential markers for the diagnosis of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). These autoantibodies are detecting different laboratory methods. In this study, we studied the diagnostic performance of used methods in detecting ANA and AMA. The autoantibody profiles of patients with AIH and PBC groups were analyzed with the indirect immunofluorescence test (IIF) and liver-specific antigens containing immunoblot test (IB). There were 45 (87%) women in the study group and 8 (53%) women in the control group. The mean age of the patients was 50.5 ± 14.21 years old. The serum ALT and AST levels were higher in AIH, and ALP, GGT, and Ig M were higher in PBC. IIF test results among AIH/PBC groups; there was no difference in overall ANA positivity (p: 0.078). AMA was negative in all patients with AIH but positive in 83.3% of patients with PBC. IB test results among AIH/PBC groups; antibodies against PDGH, LKM-1, and Scl-70 were not observed in any patient with AIH/PBC. Except for M2 (p: 0.001) and M23E (p: 0.007) antibodies, there was no significant difference in antibodies between groups. Out of five PBC patients with negative AMA by IIF method, one was positive for AMA-M2, two were positive anti-gp210, and three were positive anti-M2-3E, but anti-sp100 was negative in all of them by the IB. AIH/PBC has complex associations with different autoantibodies, and some of these antibodies are not readily detected by the IIF test. IB assays with a wide variety of liver-specific antigens may be helpful in the diagnosis (especially in patients with AMA negative PBC) and follow-up in AIH/PBC patients.

Autoantibodies are present in the bronchoalveolar lavage but not circulation in patients with fibrotic interstitial lung disease.

BackgroundFibrotic interstitial lung disease (fILD) has previously been associated with the presence of autoantibody. While studies have focused on systemic autoimmunity, the role of local autoantibodies in the airways remains unknown. We therefore extensively characterised the airway and peripheral autoantibody profiles in patients with fILD, and assessed association with disease severity and outcome.MethodsBronchoalveolar lavage (BAL) fluid was collected from a cohort of fILD patients and total BAL antibody concentrations were quantified. An autoantigen microarray was used to measure IgG and IgA autoantibodies against 122 autoantigens in BAL from 40 idiopathic pulmonary fibrosis (IPF), 20 chronic hypersensitivity pneumonitis (CHP), 20 connective tissue disease-associated ILD (CTD-ILD) patients and 20 controls.ResultsA subset of patients with fILD but not healthy controls had a local autoimmune signature in their BAL that was not present systemically, regardless of disease. The proportion of patients with IPF with a local autoantibody signature was comparable to that of CTD-ILD, which has a known autoimmune pathology, identifying a potentially novel subset of patients. The presence of an airway autoimmune signature was not associated with reduced survival probability or changes in lung function in the cohort as a whole. Patients with IPF had increased BAL total IgA and IgG1 while subjects with CHP had increased BAL IgA, IgG1 and IgG4. In patients with CHP, increased BAL total IgA was associated with reduced survival probability.ConclusionAirway autoantibodies that are not present systemically identify a group of patients with fILD and the mechanisms by which these autoantibodies contribute to disease requires further investigation.

Anti-ADAMTS13 autoantibody profiling in patients with immune-mediated thrombotic thrombocytopenic purpura

AbstractAnti-A Disintegrin and Metalloproteinase with a ThromboSpondin type 1 motif, member 13 (ADAMTS13) autoantibodies cause a severe ADAMTS13 deficiency in immune-mediated thrombotic thrombocytopenic purpura (iTTP). ADAMTS13 consists of a metalloprotease (M), a disintegrin-like (D) domain, 8 thrombospondin type 1 repeats (T1-T8), a cysteine-rich (C), a spacer (S), and 2 CUB domains (CUB1-2). We recently developed a high-throughput epitope mapping assay based on small, nonoverlapping ADAMTS13 fragments (M, DT, CS, T2-T5, T6-T8, CUB1-2). With this assay, we performed a comprehensive epitope mapping using 131 acute-phase samples and for the first time a large group of remission samples (n = 50). Next, samples were stratified according to their immunoprofiles, a field that is largely unexplored in iTTP. Three dominant immunoprofiles were found in acute-phase samples: profile 1: only anti-CS autoantibodies (26.7%); profile 2: both anti-CS and anti-CUB1-2 autoantibodies (12.2%); and profile 3: anti-DT, anti-CS, anti-T2-T5, anti-T6-T8, and anti-CUB1-2 autoantibodies (8.4%). Interestingly, profile 1 was the only dominant immunoprofile in remission samples (52.0%). Clinical data were available for a relatively small number of patients with acute iTTP (>68), and no correlation was found between immunoprofiles and disease severity. Nevertheless, profile 1 was linked with younger and anti-T2-T5 autoantibodies with older age and the absence of anti-CUB1-2 autoantibodies with cerebral involvement. In conclusion, identifying acute phase and remission immunoprofiles in iTTP revealed that anti-CS autoantibodies seem to persist or reappear during remission providing further support for the clinical development of a targeted anti-CS autoantibody therapy. A large cohort study with acute iTTP samples will validate possible links between immunoprofiles or anti-domain autoantibodies and clinical data.

Autoantibody profiles in patients' sera associated with distribution patterns of dermatomyositis skin symptoms

To the Editor: Myositis-specific autoantibodies (MSAs) were recently reported to be associated with distinctive clinical features of dermatomyositis (DM). For example, anti–transcriptional intermediary factor 1 (TIF1) γ antibody positivity is highly associated with malignancy, and serum anti-MDA5 antibody is a known marker of rapidly progressive interstitial lung disease (ILD).1 To decide treatment approaches for patients with DM, identifying serum MSAs or myositis-associated autoantibodies (MAAs) is quite important, although convenient kits for measuring many kinds of MSAs/MAAs are not always available.

Comprehensive exploratory autoantibody profiling in patients with early rheumatoid arthritis treated with methotrexate or tocilizumab.

BackgroundWe sought to identify immunoglobin G autoantibodies predictive of early treatment response to methotrexate, the recommended first-line therapy for patients with newly diagnosed rheumatoid arthritis, and to the interleukin-6 receptor inhibitor biologic tocilizumab, initiated as the first disease-modifying anti-rheumatic drug.Materials and methodsIn baseline sera of a subset of patients with newly diagnosed rheumatoid arthritis in the U-Act-Early study, selected based on specific responder/non-responder criteria using the Disease Activity Score assessing 28 joints (DAS28) within the first 20 weeks, we measured immunoglobin G antibody reactivity against 463 protein antigens and performed supervised cluster analysis to identify predictive autoantibodies for treatment response. The analysis subset comprised 56 patients in the methotrexate arm (22 responders, 34 non-responders) and 50 patients in the tocilizumab arm (34 responders, 16 non-responders). For comparison, these analyses were also performed in 50 age- and gender-matched healthy controls.ResultsIncreased reactivity in responders versus non-responders was found in the methotrexate arm against two antigens—DOT1-like histone lysine methyltransferase (p = 0.009) and tropomyosin (p = 0.003)—and in the tocilizumab arm against one antigen—neuro-oncological ventral antigen 2 (p = 0.039). Decreased reactivity was detected against two antigens in the methotrexate arm—G1 to S phase transition 2 (p = 0.023) and the zinc finger protein ZPR1 (p = 0.021). Reactivity against the identified antigens was not statistically significant in either treatment arm for patients with rheumatoid factor–positive versus–negative or anti-cyclic citrullinated test–positive versus test–negative rheumatoid arthritis (p ≥ 0.06).ConclusionsComprehensive profiling of baseline sera revealed several novel immunoglobin G autoantibodies associated with early treatment response to methotrexate and to tocilizumab in disease-modifying anti-rheumatic drug-naive patients with rheumatoid arthritis. These findings could eventually yield clinically relevant predictive markers, if corroborated in different patient cohorts, and may facilitate future benefit in personalised healthcare.

Pathogenesis of degenerative dementia: Emerging role for inflammation

AbstractBackgroundRecent evidence proposes a role for immune‐mediated mechanisms in pathogenesis of neurodegenerative dementias. Contribution of inflammatory processes to the progression of neurodegeneration has also been hypothesized. While deposition of various proteins is recognised as the pathological hallmark for the neurodegenerative dementias, Alzheimer’s disease (AD) and Frontotemporal dementia (FTD), the role of inflammation secondary to immune dysregulation in neurodegeneration remains to be determined. In this study, we aimed to investigate the profile of autoantibodies in patients diagnosed to have neurodegenerative dementia and compare the association between the different subtypes.MethodWe performed immunological screening in a large cohort of neurodegenerative dementias. Diagnosis was based on standard criteria, on review of clinical, MR imaging and laboratory features. Dementia types comprised of Alzheimer’s disease (AD), Frontotemporal dementia (FTD), and Dementia with Lewy Bodies (DLB). The immunological screening consisted of antinuclear antibody (ANA) profile, paraneoplastic and autoimmune encephalitis profile.ResultOf 274 consecutive patients with degenerative dementia evaluated in the Cognitive Disorders Clinic (AD = 62, FTD = 202, DLB = 10), autoantibody profile was done in 174(63.5%). ANA profile was positive in 18.3%, paraneoplastic panel in 8.3% and autoimmune panel in 2.1% of patients. We observed a significantly higher frequency of immunopositivity in patients with FTD (34.4%) compared to AD(10.4%) and DLBD(14.2%). The range of antibodies detected included antibodies against anti‐Ro 52(SS‐A), anti‐La(SS‐B), PM‐Scl, centromere protein B(CENP‐B), dsDNA, histones and ribosomal P‐proteins in the ANA profile; anti‐Hu, anti‐Ri, anti‐Yo, anti‐CV‐2, PNMA2 (Ma2/Ta), Anti‐amphiphysin, Anti‐ SOX1, anti‐glial nuclear antibody(AGNA), anti‐Tr, Anti‐GAD65, anti‐Zic4, anti‐titin and anti‐recoverin in paraneoplastic and in the autoimmune profile autoantibodies present were N‐methyl‐D‐asparate(NMDA), alpha‐amino‐3‐hydroxy‐5 methyl‐4‐isoxazoleproprionic acid (AMPA), Leucine rich glioma‐inactivated protein‐1(LGI1), Contactin‐associated protein‐2(CASPR2), and GABAB receptor antibody. There were no significant systemic complaints in majority of patients, and no difference was observed in the mean age, gender and duration of illness between immune‐positive and immune‐negative patients.ConclusionOur findings further substantiate the emerging role for neuroinflammation secondary to immune dysregulation, in patients with classical neurodegenerative dementias. Establishing the profile of specific autoantibodies that occur in association with dementia subtypes, especially FTD, may aid in understanding mechanisms that underlie role of autoimmunity in neurodegenerative dementias, with therapeutic implications.

Interstitial Pneumonia with Autoimmune Features – An Observational Study in a Tertiary Care Institute from South India

Background: Often, patients with idiopathic interstitial pneumonia (IIP) have certain specific clinical features to suggest an autoimmune disease but do not justify the current rheumatologic classification systems to fit into a diagnosis of connective tissue disease (CTD)-associated IIP. There is a great paucity of clinical, serological, and radiological data of these patients from India. Aim: The aim was to study the clinicoradiological and autoantibody profile in patients with interstitial pneumonia with autoimmune features (IPAF). Methodology: It was a prospective, observational study conducted in a tertiary care center between December 2015 and December 2016. A total of 30 patients who satisfied the criteria for IPAF according to the American Thoracic Society/European Respiratory Society research were included in the study. Results: All 30 patients satisfied IPAF criteria, but they did not meet the immunological criteria for CTD. Majority of them were female (86.67%) and nonsmokers. The mean age was 52.5 ± 14.5 years. The most common clinical symptom was inflammatory arthritis in 20 (66.67%) patients, followed by Raynaud's phenomenon in 5 (16%) patients. Nonspecific interstitial pneumonia was the most common radiological pattern seen in 20 (66.67%) patients, while antinuclear antibody (1:320) was the most common autoantibody positive in 18 (60.0%) patients, followed by rheumatoid arthritis factor in 15 (50%) patients. Conclusions: High female predominance along with distinct imaging, histologic and serological characteristic features are seen in patients with IPAF as compared to those with IIP. Further studies in patients with IPAF are needed to understand the natural history and its management.

Evaluation of Auto-antibody Profiles in Patients with Tuberculosis

Background: Tuberculosis remains a major public health problem internationally, causing 9.6 million new cases and 1.5 million deaths worldwide, Tuberculosis (TB) has become one of the most important diseases in the past two decades. It leads to organ dysfunction, mortality and various clinical manifestations. Previous studies have shown that sera from patients with active TB may contain autoantibodies that are unique in autoimmune diseases. Objective: To detect the prevalence of wide array of autoantibodies in sera of patients with tuberculosis compared with healthy control subject. Patients and Methods: A consecutive patients with recently diagnosed pulmonary and extra pulmonary {axial & peripheral joints TB} , mean age 36.2 years . 41 males and 21 females . the autoantibodies are R.F lgM, ANA , anti cls DNA. P-ANCA , ACL, ENA,SSA, SSB . RNP SM SCL70}. Results: Mean duration of symptoms 15.69 & 15.70(SD) months . 82% had fever , 39.3% had cough and hemoptysis . 27% had arthralgia and myalgia , 31.1% are diabetic and 24% are smoker serum level above the upeer normal limits were found in 25.7% of patients with RF ,ANA was 8.8% , 20% , 6.3% in pulmonary , peripheral , axial TB respectively , P-ANCA 10% , 6.3% & for anti DNA was 5% , 10% ,7 6.3% for pulmonary , peripheral & axial :ACL was 33.3 , 12.5 pulmonary , axial TB,ENA was {SCL70 3.2% , SM 3.2% , RNP3.2%, SSA 8.1% SSB 6.5%}. Conclusion: R F: Rheumatoid Factor--Anti ds DNA: Anti-deoxyribonucleic acid (double strand).-ACL: Anti cardiolipin Antibody.-ANCA: Anti neutrophil cytoplasmic Antibody.-ANA: Anti nuclear Antibody.-ENA: Extractable Nuclear Antigen. S: Significant. N-S: Not Significant.Pul: Pulmonary.TB: Tuberculosis .AFB:Acidfastbacilli.