Autoantibody diagnostics in clinical practice

doi:10.1016/j.autrev.2011.05.014

Autoimmunity Reviews

Volume 11, Issue 3, January 2012, Pages 207-211

https://doi.org/10.1016/j.autrev.2011.05.014 Get rights and content

Abstract

Disease associated autoantibodies (AAB) are important biomarkers not only to confirm the diagnosis of the respective systemic autoimmune disease but also to diagnose the disease at very early stages (mono- or oligosymptomatic manifestations) or to diagnose the respective disease without the typical clinical manifestations (atypical forms). A confirmation of the diagnosis in early stages is required, if patients should benefit from early therapeutic intervention. Furthermore, AAB determinations are used for prognostic purposes and for monitoring of disease activity or response to therapy. For the advancement of autoantibody diagnostics in clinical practice the following aspects have to be considered: (i) The search for novel clinically relevant AAB and the identification of autoantigenic targets of AAB broadened the spectrum of autoimmune diagnostics and permit the diagnosis of former idiopathic diseases. (ii) To obtain steady diagnostic variables of clinically relevant AAB, the evaluation studies have to be standardized. (iii) Several special features and novel developments of autoantibody diagnostics make correct interpretation of antibody test results increasingly difficult. (iv) Beside standardization of AAB detection methods and quality management efforts the improvement of autoantibody diagnostics depends on further development of diagnostic algorithms including cost-effective multiparametric analyses.

Introduction

The determination of disease associated autoantibodies (AAB) is very helpful in diagnostics, prognostics, and, in some cases, monitoring of autoimmune diseases (AID). With the growing medical and economical impact of AID and the continuous improvement of treatment possibilities through targeted therapies, the acceptance and relevance of autoantibody diagnostics increases. However, there is a gap between the practical options and the requirements for high quality and cost-efficient serological diagnostics of AID. The reasons for this are manifold and comprise: (a) methodical problems due to the heterogeneity of AAB, inadequate standardization of autoimmune diagnostics, local working conditions and traditions, (b) marginal commercial interests in the development of assays for the detection of rare AAB, (c) cost constraints by medical insurers, (d) limited knowledge and/or little acceptance regarding the relevance of AAB, especially among general practitioners, (e) inability to correctly interpret the results of certain assays, (e) missing cost-effective multiparametric assays of high quality, and (f) no or unsatisfactory standardization of evaluation studies. Due to several unique features, the AAB diagnostics cannot be compared with other laboratory diagnostics in terms of automation, quality assessment, and standardization as well as in terms of interpretation and consequences of the results. Furthermore, there are no “golden standards” for the determination of most, if not all, of the clinically relevant AAB.

Section snippets

Special features of autoantibody diagnostics

Several features of AAB diagnostics are more or less different from other laboratory diagnostics such as the biological heterogeneity of autoantibody responses, the broad spectrum of autoantigenic targets even in one defined disease entity, the highly inverse relationship between diagnostic sensitivity and specificity, various factors influencing the expression of autoantibodies, disrupting factors influencing the measurement of autoantibodies, the pre-symptomatic occurrence of autoantibodies,

Significance of autoantibodies in clinical practice

Regardless of the pathological role, AAB are used as serological markers if a significant association between their expression (production) and a defined disease and/or special disease features (course, organ manifestations, activity, response to therapy) exists. The traditional role of AAB diagnostics is the discrimination of an autoimmune disease from non-autoimmune disorders. Because many AAB specificities are detectable at early disease stages, their determination is very helpful to make a

Search for novel clinically relevant autoantibodies

The identification of autoantigenic targets of AAB as well as the discovery of novel AAB may not only lead to the improvement of the serological diagnostics of AID but also to define former “idiopathic” diseases as novel autoimmune entities. Recently, the major zymogen granule membrane glycoprotein 2 (GP2) has been identified as the main target antigen of pancreatic AAB in sera of patients with Crohn's disease [13]. The quantification of GP2 AAB could significantly improve the serological

Conclusion

The importance of AAB determinations, especially for the early diagnosis of AID, increases continuously. To fulfill the requirements of the growing relevance of AAB diagnostics, standardized procedures must be established including disease-targeted stepwise multiparametric testing. The challenges for optimized AAB diagnostics require cooperation and coordination between manufactures, clinical laboratories and physicians as well as expert committees and networks (Table 1).

Disclosure statement

Dirk Roggenbuck is a shareholder of GA Generic Assays GmbH and Medipan GmbH. Both companies are diagnostic manufacturers. The remaining authors declare that they have no competing financial interests.

Take-home messages

•
The importance of AAB determinations, especially for the early diagnosis of AID, increases continuously.
•
The identification of novel clinically relevant AAB broadened the spectrum of autoimmune diagnostics and permits the diagnosis of former idiopathic diseases.
•
The introduction of novel autoantibody markers, the possibilities of autoantibody profiling and methodological aspects make correct interpretation of antibody test results increasingly difficult.
•
To meet the requirements of a growing

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Rapid advances in diagnostic technologies used to detect autoantibodies have made it challenging for clinicians and even the most modern laboratory to keep abreast of the constantly evolving diagnostic assays and revised diagnostic algorithms. Autoantibody testing has traditionally served the realm of diagnostic medicine, but along with genomics, transcriptomics, proteomics, and metabolomics, it is achieving importance in precision medicine, case finding, and disease prevention. The effective use and interpretation of autoantibody testing is dependent upon keep abreast of new autoantibodies and emerging diagnostic technologies that have an impact on diagnostic and clinical care pathways. Despite the best efforts of educators, clinicians, diagnosticians, regulators, and manufacturers, false-positive and false-negative autoantibody test results remain an issue. While major gaps of standardized assay performance and autoantibody nomenclature are being addressed, there are still significant gaps in our understanding of the origin and roles of autoantibodies.
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Their profiling for the serology of IBD, including the novel autoAbs to GP2 and CUZD1, could offer an exciting diagnostic opportunity for the stratification of patients with IBD. Indeed, the usefulness of autoAb profiling has been widely accepted for the diagnosis of other autoimmune disorders such as rheumatic diseases [135–138]. Since the discovery of PAbs as CD-specific markers, several serological studies have been conducted to determine the associated staining patterns of pancreatic tissues (detected by IFA) in clinically defined CD phenotypes.
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A novel enzyme-linked immunosorbent assay (ELISA) employing purified rabbit ASGPR was used to detect ASGPR Abs in patients with ALD and controls. ASGPR Ab was determined in sera from 172 patients with AIH type 1, AIH type 2 (n = 42), primary biliary cirrhosis (PBC) (n = 113), cryptogenic liver disease (n = 30), toxic liver disease (n = 11), primary sclerosing cholangitis (PSC) (n = 27), HCV infection (n = 25), non-alcoholic steatohepatitis (n = 43) and 100 blood donors. ASGPR Ab positivity was compared with AIH-related Abs (ANA, ASMA, Abs to LKM-1, LC-1, and SLA/LP) in patients with AIH.
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View full text

ReviewAutoantibody diagnostics in clinical practice

Abstract

Introduction

Section snippets

Special features of autoantibody diagnostics

Significance of autoantibodies in clinical practice

Search for novel clinically relevant autoantibodies

Conclusion

Disclosure statement

Take-home messages

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Review
Autoantibody diagnostics in clinical practice