Clinical Significance Of Autoantibodies Research Articles

Prevalence and clinical value of autoantibodies directed against lysobisphosphatidic acid in antiphospholipid syndrome.

To assess the prevalence and clinical significance of autoantibodies against lysobisphophatidic acid (aLBPA) in patients with antiphospholipid syndrome (APS). We conducted a retrospective analysis involving 91 patients with persistent conventional antiphospholipid antibodies (aPL): 60 patients with at least one clinical event of APS (symptomatic group) and 31 without (asymptomatic group), as well as 33 aPL-negative controls. Detection of aLBPA in serum samples was performed using an enzyme-linked immunosorbent assay (ELISA) specifically designed for this study. The prevalence of aLBPA is significantly higher in patients with persistent aPL than that of the control group (p< 0.0001). Among patients with persistent aPL, our findings reveal a significantly higher prevalence of aLBPA in asymptomatic patients compared with their symptomatic counterparts (p= 0.027). Notably, patients positive for IgG aPL alone demonstrated a greater likelihood of presenting clinical events suggestive of APS. The combined assay of aLBPA and conventional aPL could be used to stratify patients with persistent aPL. This combined approach could serve as a valuable tool in the management of this complex autoimmune disease, particularly in guiding decisions regarding the initiation of primary thromboprophylaxis in asymptomatic patients with persistent aPL.

Autoantibody against aquaporin-5 may be a new diagnostic biomarker for primary Sjögren’s syndrome

The study aims to assess the diagnostic and clinical significance of autoantibodies against aquaporin-1 (anti-AQP1) and aquaporin-5 (anti-AQP5) in primary Sjögren’s syndrome (pSS). A total of 163 participants were categorized into three groups: pSS group, other connective tissue diseases (CTD) group, and healthy control (HC) group. The levels of anti-AQP1 and anti-AQP5 autoantibodies in serum were determined using enzyme-linked immunosorbent assay (ELISA), and clinical data from patients were collected for statistical analysis. Our results showed that the level of anti-AQP1 in the pSS group was higher than in the HC group (P < 0.05), and no significant difference was observed between the pSS group and the CTD group (P > 0.05). ROC showed that the anti-AQP1 had no diagnostic value for pSS (P > 0.05). The anti-AQP5 level of 39 healthy adults was all below the cut-off value (14.10 ng/ml) (P < 0.05). The level of anti-AQP5 in the pSS group was higher than the CTD group (P < 0.05), the AUC was 0.86 (95% CI 0.80–0.93), with a sensitivity of 0.95 (95% CI 0.87–0.99) and a specificity of 0.70 (95% CI 0.58–0.84). No correlation was found between anti-AQP5 levels and the EULAR primary Sjögren’s syndrome disease activity index score, anti-SSA, anti-SSB, antinuclear antibodies, rheumatoid factor, anti-ds-DNA, salivary gland flow rate, complement 3, and lymphocyte count in pSS samples (P > 0.05), respectively. Therefore, the elevated anti-AQP5 may emerge as a novel diagnostic biomarker for pSS patients due to high sensitivity and specificity.Key Points• The elevated anti-AQP5 may emerge as a novel diagnostic biomarker for pSS patients due to high sensitivity and specificity.

The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS.

Rheumatoid factor is associated with severe COVID-19.

Coronavirus disease 2019 (COVID-19) has been proposed as triggering autoimmunity. The aim of this study was to evaluate the presence and clinical significance of autoantibodies in patients with COVID-19. We retrospectively collected data from 245 patients who were hospitalized for COVID-19. All patients were tested for the presence of antinuclear antibody (ANA), rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), and anti-cytoplasmic neutrophil antibody (ANCA). Risk factors for death and critical COVID-19, defined as the need for invasive mechanical ventilation or extracorporeal membrane oxygenation, were analyzed. Ninety (36.7%) patients tested positive for ANA, and 51 (20.8%) patients tested positive for RF. Three patients each (1.2%) tested positive for ACPA and ANCA. RF-positive patients had higher rates of invasive mechanical ventilation and death than RF-negative patients (70.6% vs 28.4%, P < 0.001 and 45.1% vs 18.6%, P < 0.001, respectively). Underlying lung disease, kidney disease, heart disease, quick COVID severity index (qCSI), and lactate dehydrogenase (LDH) were associated with in-hospital death. RF (odds ratio [OR] 7.31, 95% CI 2.50-21.37, P < 0.001), qCSI (OR 1.42, 95% CI 1.19-1.69, P < 0.001), and LDH (OR 1.004, 95% CI 1.002-1.005, P < 0.001) were associated with critical COVID-19. Combination of RF, qCSI, and LDH showed good prognostic value (area under the curve=0.903, P < 0.001) for critical COVID-19. ANA and RF were frequently detected in COVID-19 patients. RF could be a risk factor for critical COVID-19. The results of this study suggest immune dysfunction contributes to the complications of COVID-19.

Myositis autoantibodies in Iranian myositis patients: assessment the frequency and clinical relevancy.

Dermatomyositis (DM) and polymyositis (PM) are known as two major types of idiopathic inflammatory myopathies (IMMs). During the past years, growing data strongly suggest the clinical significance of myositis-associated autoantibodies (MAAs) and myositis-specific autoantibodies (MSAs). The present study aimed to determine the profile of MSAs and MAAs, subsequently to address the clinical significance of these autoantibodies in Iranian myositis patients. In this cross-sectional study, 28 DM and 24 PM patients were entered. Demographic and clinical characteristics were collected by direct examination and patients' medical record. The existence of MSAs and MAAs was assessed by indirect immunofluorescence then using immunoblotting (FA 1510-1005-1, DL 1530-1601-4 G; Euroimmun, Germany). Data were analyzed using the SPSS software (v22; SPSS Inc. Chicago, IL, USA). The mean age of the patients was 46.18 ± 12.95years and male/female ratio was 28.8/71.2. Autoantibodies were positive in 63.46% of myositis patients. Interestingly, anti-TIF1γ and anti-PL7 were significantly associated with malignancy (P < 0.001, P = 0.008; respectively). The existence of autoantibody and anti-Jo1 had significant relation with interstitial lung disease (ILD) (P = 0.034, P = 0.006; respectively). Joint involvements including arthritis and arthralgia were significantly associated with anti-Ro52 and anti-Jo1 (P = 0.04, P = 0.02; respectively). Taken together, it can be concluded that certain myositis autoantibodies present clinical significance which is in line with the literature. The use of these autoantibodies as biomarkers by line blotting along with indirect immunofluorescence facilitates diagnosis of inflammatory myopathies and makes it more accurate as well as better management of myositis patients if used based on a science-based manner. Key Points • Identification of MSAs and MAAs facilitates the diagnosis of inflammatory myopathies and provides better myositis patient's management if used according to a science-based manner. • Anti-rod and ring antibody was detected in a patient with ovarian cancer-induced dermatomyositis. • Malignancy and ILD are integrated parts of myositis which can be associated with MSAs and MAAs.

Prevalence and Clinical Significance of Autoantibodies in Children with Overweight and Obesity with Nonalcoholic Fatty Liver Disease

To evaluate the prevalence and clinical significance of autoantibodies in children with overweight and obesity with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) compared with those with autoimmune liver disease (ALD). This was a retrospective, cross-sectional study of children with a biopsy-proven diagnosis of NAFL, NASH, autoimmune hepatitis (AIH), or primary sclerosing cholangitis (PSC) and a body mass index (BMI) >85th percentile treated between 2007 and2016. A total of 181 patients were identified, including 31 (17%) with NAFL, 121 (67%) with NASH, 12 (6.6%) with ALD (AIH, PSC, or overlap), and 17 (9.4%) with combined ALD and NAFLD. Antinuclear antibody (ANA), anti-actin antibody, and anti-liver kidney microsomal (LKM) antibody were positive in 16.1%, 13.8%, and 0%, respectively, of the patients with NAFL and in 32.8%, 15.5%, and 0%, respectively, of those with NASH. Total immunoglobulin G (IgG) was elevated in 27.3% of the patients with NAFL and in 47.7% of those with NASH, but in 100% of those with ALD. The positive predictive value of LKM was 100% for ALD but only 29% for ANA and 46% for anti-actin antibody. False-positive rates of autoantibodies were higher in pediatric patients with overweight and obesity with NAFLD compared with the general adult population. Positive LKM had the highest specificity and positive predictive value, and elevated IgG level had the highest sensitivity for ALD. The presence of autoantibodies does not signal more severe NAFLD in children. BMI >98th percentile seems to be an important breakpoint above which ALD is less likely.

Clinical significance of autoantibodies in the assessment and treatment of idiopathic membranous nephropathy.

The present study aimed to explore the correlation between the dynamic serum levels of phospholipase A2 receptor (PLA2R), aldose reductase (AR) and superoxide dismutase 2(SOD2) antibodies with disease activity and treatment response in patients with idiopathic membranous nephropathy (IMN). The present study included 56 patients with IMN who were diagnosed through a renal biopsy and presenting with nephrotic syndrome. The patients were divided into two treatment groups: One treated with cyclophosphamide (CTX) and one with tacrolimus (FK506). Serum was collected prior to treatment, and at 1, 3, 6, 9 and 12 months after the start of the 12-month-long therapy. Samples were tested by ELISA to measure anti-PLA2R, anti-AR and anti-SOD2 antibody titers. In addition, urinary protein excretion, serum albumin (Alb) and other blood biochemical indexes were measured. Theanti-PLA2R antibody positivity rate was 71.43% in the patients prior to treatment. After 12 months of treatment, proteinuria and PLA2R antibody levels were decreased, whereas serum Alb was increased. There was no significant difference of remission rates between the CTX and FK506 groups. In conclusion, the results of the present study indicate that the anti-PLA2R antibody level is correlated with the severity of IMN, whereas anti-AR and anti-SOD2 antibody levels are not. In addition, there was no significant difference between the CTX and FK506 groups in regards to the remission rates of patients with IMN.

Mo1493 - Prevalence and Clinical Significance of Auto-Antibodies in Overweight and Obese Children with Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

Mo1493 - Prevalence and Clinical Significance of Auto-Antibodies in Overweight and Obese Children with Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

Clinical significance of autoantibodies in dermatomyositis and systemic sclerosis

Autoimmune connective tissue diseases, including dermatomyositis and systemic sclerosis, have a heterogeneous clinical presentation and prognosis; moreover, their clinical features are often incomplete and overlap with other rheumatic disorders, which can make diagnosis and prognostic stratification challenging. Specific autoantibodies have been associated with certain clinical findings as well as prognostic implications, and many new associations have been made over the last decade. Although patient populations manifest considerable heterogeneity, autoantibodies can be used to help predict clinical features, prognosis, and response to therapy. In this review, the clinical and prognostic implications associated with disease-specific autoantibodies in dermatomyositis and scleroderma are summarized with an emphasis on how the clinician can use this information for patient care.

Autoantibodies to Thrombopoietin and the Thrombopoietin Receptor in Patients with Immune Thrombocytopenia

Background: Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by autoantibodies against platelet glycoproteins (GP). These autoantibodies are detected in only 40-60% of ITP patients even when sensitive techniques are used. Our understanding of the mechanisms of ITP is limited by the variability in clinical presentation, varied differences in treatment responses and the lack of reliable biomarkers. Several studies have exploited the possibilities of other immune-mediated mechanisms to account for low platelet counts in the absence of detectable antibodies. Thus, we hypothesized that other autoantibodies that target antigens involved in the platelet lifecycle can be important in ITP, such as thrombopoietin (TPO) and the thrombopoietin receptor (cMpl). The objective of this study was to evaluate the frequency and clinical significance of autoantibodies against TPO and cMpl in patients with ITP compared to patients with other thrombocytopenic disorders and healthy controls.Methods: We tested well-defined adult ITP patients with a platelet count less than 100 x109/L and ITP patients in remission (platelets > 100,000) all of whom had not received any immune-modulating treatments in the previous 3 months. We also tested patients with other immune-mediated platelet disorders, non-immune thrombocytopenia and healthy controls. Patients with immune-mediated platelet disorders had anti-phospholipid syndrome (APS); heparin induced thrombocytopenia (HIT); or thrombotic thrombocytopenic purpura (TTP). Patients with non-immune thrombocytopenia had hypersplenism with documented splenic enlargement; familial thrombocytopenia; or myelodysplastic syndrome. Samples were tested for circulating antibodies against TPO or cMpl using newly developed enzyme immunoassays (EIAs) and for antibodies against platelet glycoproteins (GPIIb/IIIa and GPIb/IX) using the antigen capture assay.Results: Among patients with active ITP, 36/42 (86%) had antibodies to TPO or c-Mpl: 4/42 (10%) had anti-TPO autoantibodies only and 5/42 (12%) had anti-cMpl autoantibodies only and 15/42 (36%) had both. Among patients with ITP in remission, 8/15 (53%) had autoantibodies to TPO or cMpl. Autoantibodies were not detected in healthy controls; however, all patients with non-immune thrombocytopenia had circulating autoantibodies to TPO or c-Mpl (10/10, 100%): 1/10 (10%) had anti-TPO autoantibodies only and 1/10 (10%) had anti-cMpl autoantibodies only and 8/10 (80%) had both. We also found antibodies against TPO and cMpl in patients with other immune-mediated platelet disorders. Among HIT patients (n=26), 73% had antibodies to TPO and 50% had antibodies to cMpl; among TTP patients (n=16), 31% had antibodies to TPO and 13% had antibodies to cMpl; and among APS patients (n=17), 29% had antibodies to TPO and 47% had antibodies to cMpl. Platelet bound antibodies to GPIIb/IIIa, GPIb/IX or both were detected in 18/42 (43%) active ITP samples; 6/15 (40%) remission ITP samples; and 2/10 (20%) patients with thrombocytopenia from non-immune causes. ITP patients with anti-TPO or anti-cMpl antibodies required fewer ITP therapies before remission was achieved compared with patients who had anti-GP autoantibodies.Conclusions: Testing the entire panel of autoantibodies that included anti-TPO, anti-cMpl and anti-GP, we were able to identify all patients with active ITP; however, we could not distinguish between patients with ITP and other thrombocytopenic syndromes. DisclosuresArnold:Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; UCB: Consultancy; Amgen: Consultancy, Research Funding.

The dynamic and clinical significance of autoantibodies and immunoglobulins in liver transplant recipients.

Little is known about autoantibody pattern in liver transplantation (LT). The aim of the study was to examine autoantibodies (AAB) and immunoglobulins in patients with end-stage liver disease before and after LT. Patients with LT who underwent post-LT biopsies between 10/2008 and 8/2011 were enrolled. AAB were assessed at the time of LT and liver biopsy. Demographics, serum immunoglobulins, AAB, and liver histology (explant, post-LT biopsies) were analyzed. Two hundred and twenty patients (M/F 143/77; age at LT 54 (19-73)) were included; AAB and immunoglobulins were evaluated in 76 patients. Length of follow-up from LT was 285 (30-1462) days. Sixty-one percent of patients had hepatitis C (HCV); 83% developed recurrent HCV. A significant decrease in IgG, IgA, IgM (p < 0.001 each), anticardiolipin antibodies IgG and IgM (p = 0.02), and beta-2 microglobulin (p = 0.004) was observed post-LT. HCV patients had higher IgG (p = 0.005), rheumatoid factor (p = 0.044) before LT; elevated IgM was associated with increased inflammation in the explant (p = 0.007). Lower IgG levels and antismooth muscle antibodies were present before LT in a higher percentage in patients who would develop recurrent HCV (p = 0.004, p = 0.077, respectively). In conclusion, AAB change significantly after LT and have a different pattern in HCV. Some immunological markers are associated with HCV recurrence and advanced inflammation on explant.

Molecular diagnosis of collagen vascular diseases and vasculitides

Collagen vascular diseases and vasculitides comprise various diseases, which may affect virtually every organ system. Therefore, their diagnosis and management is often an interdisciplinary challenge. Because of the heterogeneous symptoms, these diseases have significant overlap, which interferes with the clinical diagnosis and may require additional investigation. Therefore, a rational and comprehensive diagnostic work-up should be performed at the initial presentation before initiation of therapy. The detection of antinuclear (ANA) or anticell antibodies by indirect immunofluorescence microscopy on Hep2 cells is used to screen for autoantibodies in collagen vascular diseases. The molecular specificity of autoantibodies should be further characterized using immunoassays with recombinant or purified protein. When systemic autoimmune disease is suspected, the function of the frequently affected organs should be evaluated. The immunopathological findings should always be interpreted in the context of clinical, histological, and imaging data. The detection of autoantibodies is helpful for the initial diagnosis, provides prognostic information, may indicate involvement of organs or systems and some parameters may also be used for disease monitoring. The clinical significance of autoantibodies is emphasized by the fact that their detection constitutes diagnostic criteria for most collagen vascular diseases and several vasculitides. The screening for ANCA may be performed using immunoassays with recombinant myeloperoxidase and proteinase 3 or by indirect immunofluorescence microscopy on granulocytes. In this article, the current diagnostic tools and their relevance for the diagnosis and monitoring of systemic autoimmune diseases with primary skin involvement are reviewed.

The Spectrum and Clinical Significance of Autoantibodies in Rheumatoid Arthritis.

In the late 19th century, early 20th, the main known rheumatic diseases were Gout, deforming arthritis (osteoarthritis), acute rheumatism (rheumatic fever), and chronic rheumatism [rheumatoid arthritis (RA)]. There was uncertainty whether acute and chronic rheumatisms were separate diseases or a single entity with heterogeneous manifestations according to the influence of age, heredity, and environment. At the turn of the last century, the possibility of a bacterial etiology of both diseases began to be considered (1). In this scenario, the demonstration of circulating factors interacting with self-structures, later recognized as autoantibodies, contributed substantially to the establishment of the concept of autoimmunity and autoimmune diseases.

Autoantibodies in systemic sclerosis

Systemic sclerosis (SSc) is a rare connective tissue disorder, which leads to progressive fibrosis of many organs. Its course is characterized by the presence of two classical autoantibodies: anti-topoisomerase I (ATA, Scl-70) and anti-centromere (ACA). In recent years, the presence of antibodies against a wider range of antigens was demonstrated, namely: RNA polymerase III, fibrillarin, NOR90, Th/To, PM-Scl-100, PM-Scl-75, Ku, PDGFR, but their clinical significance is relatively little known and until recently the methods of their assessment were available only in specialized laboratories. More and more reports in the literature indicate existence of links between the presence of selected autoantibodies with clinical correlations i.e. anti-RNA polymerase III with scleroderma renal crisis or anti-Ku and myositis, arthritis and joint contractures. The importance of autoantibodies in the diagnostic process was underlined by their inclusion into the new ACR/EULAR 2013 classification criteria for systemic sclerosis. This work reviews the current knowledge on the clinical significance of autoantibodies in systemic sclerosis.

The Clinical Significance of Autoantibodies in Hepatitis C Patients Submitted to Interferon Treatment

Hepatitis C virus is associated with several immune-mediated phenomena, presented usually as extra-hepatic hepatitis C manifestations. A predisposition to autoimmunity associated with the presence of baseline autoantibodies has been demonstrated in interferon mediated autoimmune diseases. We report a male patient, 34 years old, with genotype 1, chronic hepatitis C (hepatitis C viremia 1.432.463UI/mL) and family history of psoriasis. He had high levels of transaminases and immunology showed positive antinuclear antibodies (1/320) and anti-smooth-muscle antibodies, with elevated immunoglobulin G (1740mg/dL). Liver biopsy revealed a F1/2 Metavir score, histologic activity index of 3 and mild piecemeal necrosis. Antiviral treatment was started with peg-interferon α2a 180mcg plus ribavirin 1200mg, and the patient had rapid virologic response, normalization of transaminases, negativation of antinuclear antibodies positivity and decrease of immunoglobulin levels. However, at week 22, he developed psoriatic-like eczema and arthritis with functional limitation. Due to suspicion of latent psoriatic arthritis not previously diagnosed, he was started on methotrexate 10mg/weekly with improvement of psoriatic plaques, arthritis and functional limitation. Patient achieved sustained virologic response, with normal transaminases and no significant changes in immunology. Post-treatment median hepatic elastography was 3.6kPa. Autoimmunity in hepatitis C infection is not limited to surrogate autoantibody seropositivity, but may embrace the full spectrum of autoimmune disorders.

Clinical significance of autoantibodies in primary biliary cirrhosis.

Antimitochondrial, anti-gp210, anti-sp100, and anticentromere antibodies are specifically detected in primary biliary cirrhosis (PBC). In clinical practice, they are useful for the diagnosis of PBC or for evaluating disease severity, clinical phenotype, and long-term outcome. In the typical or classical form of PBC which shows slow progressive loss of small bile ducts with a parallel increase in liver fibrosis, anti-gp210 antibodies are a strong risk factor for progression to jaundice and hepatic failure, whereas the presence of anticentromere antibodies is a risk factor for progression to cirrhosis and portal hypertension. Of note, the autoimmune repertoire, which is established during the early stage of the disease process, can influence the clinical phenotype and the long-term prognosis of PBC. Because the natural course of PBC is being altered by treatment with ursodeoxycholic acid, the clinical significance of these PBC-specific autoantibodies awaits re-evaluation in various ethnicities.

Clinical significance of autoantibodies directed against nuclear and cytoplasmic antigens in autoimmune liver disease

Previous research carried out in the area of autoimmune liver disease and autoantibody specificity has not been conclusive, and correlation between the two in most situations remains unclear. This study aims to facilitate a consensus on these autoantibodies in an unselected patient population and their relationship to autoimmune liver disease (AILD). The study detected two autoantibodies that show reasonable specificity for primary biliary cirrhosis (PBC), anti-sp100 and anti-gp210, and it may be clinically useful to report any antimitochondrial antibody (AMA) detected, as this may be a sign of very early PBC. The inter-methodological differences in assays available for detection of the autoantibodies were also noted. Care must be taken when selecting methods to detect these autoantibodies.

Prevalence and clinical significance of autoantibodies in 144 adult patients with cystic fibrosis

Prevalence and clinical significance of autoantibodies in 144 adult patients with cystic fibrosis

Prevalence and clinical significance of auto-antibodies in adults with cystic fibrosis

The aim of this study was to determine the prevalence of different auto-antibodies in adult, French cystic fibrosis (CF) patients and to look for a correlation between autoimmunity, patient characteristics and survival. The sera of 144 patients were screened for a wide range of antibodies. Clinical, biological and bacteriological characteristics and the cystic fibrosis transmembrane conductance regulator genotype were recorded and progression of lung disease was examined. 113 (78.5%) patients displayed one or several auto-antibodies, predominantly immunoglobulin (Ig)A anti-Saccharomyces cerevisiae antibodies (ASCA; 43.7%) and antineutrophil cytoplasmic antibodies (ANCA; 40%), of which 59% showed bactericidal/permeability-increasing protein (BPI) specificity. The presence of BPI-ANCA was associated with the number of antibiotic courses, low body mass index, Pseudomonas aeruginosa colonisation, the presence of resistant P. aeruginosa, low forced expiratory volume in 1 s, CF-related liver disease, hypergammaglobulinaemia, male sex and inflammatory syndrome. The presence of ASCA-IgA was correlated with male sex and hypergammaglobulinaemia. 41 patients presented with chronic respiratory failure and/or requested lung transplantation or died during follow-up. These events were more frequent in patients with BPI-ANCA or ASCA-IgA. These findings confirm the high frequency of auto-antibodies in CF, particularly BPI-ANCA and ASCA-IgA, and the link between BPI-ANCA, severity of lung disease and CF prognosis.

Clinical significance of autoantibodies to inner ear antigens in sera of patients with systemic diseases

Clinical significance of autoantibodies to inner ear antigens in sera of patients with systemic diseases