Although, the association between celiac disease (CD) and selective immunoglobulin A deficiency (SIgAD) has been known for more than fifty years, the procedures for diagnosing and monitoring patients ...with both conditions are still far from definitive. When serological markers were introduced as pre-bioptic investigations, it was immediately clear that searching for specific IgA antibodies without checking total serum IgA could lead to a failure in diagnosing IgA-deficient CD patients, while specific IgG antibodies could be useful as additional tests, because they are frequently found in the serum of affected patients. Nonetheless, until recently the diagnosis of CD in IgA-deficient patients was based on the few, fragmentary and often contradictory data available in literature. The introduction of the
European Society for Pediatric Gastroenterology, Hepatology and Nutrition
(ESPGHAN) guidelines in 2012 provided the current criteria for diagnosing CD in IgA-deficient patients, although some issues remained open, such as the selection of patients who should undergo specific IgG antibody testing and the choice of the most reliable IgG-based test for both diagnosis and follow-up. A real-life study recently assessed the impact of the 2012 ESPGHAN guidelines in diagnosing and monitoring CD in SIgAD patients, highlighting several pitfalls that can lead to operational uncertainties and difficulties in patient management. In the present report, the evolution of diagnostic tools and criteria for CD in SIgAD patients has been critically assessed, both strengths and open issues have been highlighted, and future perspectives for improving the current diagnostic protocols have been suggested.
Abstract
Objectives
Anti-parietal cell antibodies (APCA) are a serologic marker of autoimmune gastritis. Their prevalence in healthy individuals is not well defined.
Methods
We evaluated APCA ...prevalence in 515 healthy blood-donors by rat/primate tissue indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and immunoblot.
Results
Fifty-three of 515 (10.3%) subjects were positive for APCA by at least one method: 18 only by ELISA, 10 by rodent tissue IIF, and one by primate tissue IIF; 18 were positive by ELISA and primate tissue IIF, and one by ELISA and rodent tissue IIF. Two were positive by both IIF methods, and three were triple positive. APCA positivity was confirmed by immunoblot in 100% of ELISA positive, in 95.8% of positive primate tissue IIF, and in 50% of positive rat tissue IIF.
Conclusions
A great discrepancy in APCA prevalence detected by different methods in this cohort was apparent. Thus, the results on APCA prevalence in healthy individuals are likely method-dependent.
Abstract Background Evidence of a relationship between stressful life events and the onset of autoimmune diseases is not univocal and there are no meta-analyses in the literature on the question. Aim ...To look for differences in the number and type of stressful life events in the premorbid period between patients with autoimmune diseases and healthy subjects. Method Review of the literature in PubMed and Scopus (January 1963–May 2015). Inclusion criteria We included retrospective case–control studies that compared patients diagnosed with autoimmune disorders and controls regarding the incidence of stressful events occurring before diagnosis, and investigated said events with validated questionnaires. Effect-size indexes By random effect meta-analysis, two independent researchers calculated effect-size indexes as the difference between the means of the clinical groups and the control group in relation to the combined standard deviation. Results The database searches produced 2490 articles, 14 of which were selected (3201 patients). Analysis showed a moderate but significant mean effect-size index d = 0.63, p < 0.01, suggesting that autoimmune disorders are effectively associated with major stressful events in the premorbid period. The relationship between stressful events and autoimmune disease was weaker in studies with a high proportion of female subjects β = − 0.004, p < 0.01 and stronger in studies that considered a longer interval between stressors and onset of disease β = 0.16, p < 0.01. Conclusions The results of this meta-analysis suggest that stressors may play an important role in the etiopathogenesis of autoimmune disorders. Only prospective studies can provide more certain inference about the causality of this relationship.
In recent years, there has been a profound change in autoimmune diagnostics. From long, tiring and inaccurate manual methods, the art of diagnostics has turned to modern, rapid and automated ...technology. New antibody tests have been developed, and almost all autoimmune diseases now have some specific diagnostic markers. The current need to make the most of available economic and human resources has led to the production of diagnostic algorithms and guidelines designated for optimal strategic use of the tests and to increase the diagnostic appropriateness. An important role in this scenario was assumed by the laboratory autoimmunologist, whose task is not only to govern the analytical phase, but also to help clinicians in correctly choosing the most suitable test for each clinical situation and provide consultancy support. In this review, we summarize recent advances in technology, describe the diagnostic strategies and highlight the current role of the laboratory autoimmunologist in the clinical governance of autoimmune diagnostics.
Detection of antinuclear antibodies (ANA) by indirect immunofluorescence assay using HEp-2 cells (HEp-2 IFA) is used to screen for various autoimmune diseases. HEp-2 IFA suffers from variability, ...which hampers harmonization.
A questionnaire was developed to collect information on HEp-2 IFA methodology, computer-assisted diagnosis (CAD) systems, training, inter-observer variability, quality assessment, reagent lot change control, and method verification. The questionnaire was distributed to laboratories by Sciensano (Belgium), national EASI groups (Italy, Croatia, Portugal, Estonia, Greece) and ICAP (worldwide). Answers were obtained by 414 laboratories. The results were analysed in the framework of the recent EFLM/EASI/ICAP ANA recommendations (companion paper).
Laboratories used either HEp-2, HEp-2000, or HEp-20-10 cells and most laboratories (80%) applied the same screening dilution for children and adults. The conjugate used varied between laboratories IgG-specific (in 57% of laboratories) vs. polyvalent. Sixty-nine percent of CAD users reviewed the automatic nuclear pattern and 53% of CAD users did not fully exploit the fluorescence intensity for quality assurance. Internal quality control was performed by 96% of the laboratories, in 52% of the laboratories only with strongly positive samples. Interobserver variation was controlled by 79% of the laboratories. Limited lot-to-lot evaluation was performed by 68% of the laboratories. Method verification was done by 80% of the respondents.
Even though many laboratories embrace high-quality HEp-2 IFA, substantial differences in how HEp-2 IFA is performed and controlled remain. Acting according to the EFLM/EASI/ICAP ANA recommendations can improve the global performance and quality of HEp-2 IFA and nurture harmonization.
Autoantibodies to nuclear and cytoplasmic antigens are commonly detected by indirect immunofluorescence (IIF) on HEp-2 cells, and three major staining patterns (nuclear, cytoplasmic, and mitotic) are ...distinguished. Here, we report an atypical cytoplasmic pattern, not described so far, observed in the serum of a patient with a controversial diagnosis of systemic lupus erythematosus (SLE). Moreover, for the first time, we have revealed the presence of autoantibodies against the microtubule-associated light-chain 3 (LC3) protein, which plays a key role in the autophagic process. The target antigen has been identified in IIF by means of a competition test using purified anti-LC3 antibodies on HEp-2 cells, and confirmed by Western blot analysis using cellular or recombinant LC3 as antigen, immunoreacted with the patient's serum. The identification of this atypical pattern and the related autoantibody-antigen system sheds new light on autophagy, which is increasingly considered to be involved in the etiopathogenesis of autoimmune disorders, and could contribute to select more personalized therapies.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
ObjectiveThe first biomarker associated with the rheumatoid arthritis is rheumatoid factor (RF) and since the earliest reports a role has been proposed in the diagnosis and in the prediction of ...clinical features and outcome. The study of RF isotypes has further attempted to improve diagnostic accuracy and identify specific subgroups of patients. The main objective of this study is to provide an analysis of the literature on the role of RF isotypes in the diagnosis and prognosis of rheumatoid arthritis (RA).MethodsWe performed a systematic literature review and meta-analysis on the role of RF isotypes in RA (only in English, from PubMed, search terms: “rheumatoid factor isotypes”, “diagnosis”, “prognosis” and “rheumatoid arthritis”, last search 31 July 2022, two independent assessment of quality and biases, results included in tables and in the meta-analysis).ResultsThirty-six articles were examined (7517 patients). Testing all RF isotypes with latex test or nephelometry allows for the highest sensitivity (68.6%, 95% CI 66.2% to 71.0%); nonetheless, the determination of IgA isotype provides the highest specificity (91.4%, 95% CI 90.8% to 92.0%) and the highest positive likelihood ratio (7.7, 95% CI 5.7 to 10.4). When testing IgM isotype the highest diagnostic OR (21.7, 95% CI 16.1 to 29.3) is reached. When analysing anti-citrullinated protein antibodies, RF isotype determination increases diagnostic accuracy. On the other hand, these do not provide relevant prognostic information, as results are conflicting.ConclusionsTesting RF allows the highest sensitivity, while IgA isotype the highest specificity and positive likelihood ratio for RA diagnosis. On the other hand, determination of RF isotypes dose not allow prognostic information, as data are limited and heterogeneous.
Pernicious anemia (PA) is a megaloblastic anemia consisting of hematological, gastric and immunological alterations. The immunopathogenesis of PA is sustained by both autoantibodies (e.g. intrinsic ...factor (IFA) antibodies and anti parietal cell (PCA) antibodies and autoreactive T cells specific for IFA and the parietal cell proton pump ATPase. Iron deficient anemia (IDA) is a microcytic anemia and represents the most common cause of anemia worldwide. Our work aimed to investigate serum levels of several interleukins (IL) of the IL-20 cytokine subfamily in patients with PA, with IDA and in healthy subjects (HC). We compared serum levels of IL-19, IL-20, IL-26, IL-28A and IL-29 in 43 patients with PA and autoimmune gastritis, in 20 patients with IDA and no autoimmune gastritis, and in 47 HC. Furthermore, we analyzed the IL-19 cytokine production by gastric lamina propria mononuclear cells (LPMC) in eight patients with PA and four HC. We found that patients with PA have significantly higher serum levels of IL-19 (163.68 ± 75.96 pg/ml) than patients with IDA (35.49 ± 40.97 pg/ml; p<0.001) and healthy subjects (55.68 ± 36.75 pg/ml; p<0.001). Gastric LPMC from all PA patients were able to produce significantly higher levels of IL-19 (420.67 ± 68.14 pg/ml) than HC (53.69 ± 10.92 pg/ml) (
<0.01). Altogether, our results indicate that IL-19 serum levels are significantly increased in patients with PA but not with IDA and that IL-19 is produced
in the stomach of PA patients. These data open a new perspective on PA pathogenesis and suggest that IL-19 may represent a novel important tool for the management of patients with PA.
In patients affected by connective tissue diseases (CTDs), the identification of wide autoantibody profiles may prove useful in early diagnosis, in the evaluation of prognosis (risk stratification), ...and in predicting response to therapy. The aim of the present study was to evaluate the utility of multiparametric autoantibody analysis performed by a new fully automated particle-based multi-analyte technology (PMAT) digital system in a large multicenter cohort of CTD patients and controls.
Serum samples from 787 patients with CTD (166 systemic lupus erythematosus; 133 systemic sclerosis; 279 Sjögren's syndrome; 106 idiopathic inflammatory myopathies; 103 undifferentiated CTD), 339 patients with other disorders (disease controls) (118 infectious diseases, 110 organ-specific autoimmune diseases, 111 other rheumatic diseases), and 121 healthy subjects were collected in 13 rheumatologic centers of the FIRMA group. Sera were analyzed with the Aptiva-PMAT instrument (Inova Diagnostics) for a panel of 29 autoantibodies.
Multiparametric logistic regression showed that enlarged antibody profiles have a higher diagnostic efficiency than that of individual antibodies or of antibodies that constitute classification criteria for a given disease and that probability of disease increases with multiple positive autoantibodies.
This is the first study that analyzes the clinical and diagnostic impact of autoantibody profiling in CTD. The results obtained with the new Aptiva-PMAT method may open interesting perspectives in the diagnosis and sub-classification of patients with autoimmune rheumatic diseases.
Human gastric autoimmunity autoimmune gastritis (AIG) is characterized by inflammation of the gastric mucosa and parietal cell loss. The gastric parietal cell proton pump H
+
/K
+
-adenosine ...triphosphatase (H
+
/K
+
-ATPase) is the major autoantigen in AIG. Our work aimed to investigate the gastric H
+
/K
+
-ATPase-specific T helper 17 (Th17) responses in AIG and serum interleukin (IL)-17 cytokine subfamily in AIG patients, in healthy subjects healthy controls (HCs), and in patients with iron deficiency anemia (IDA) without AIG. We analyzed the activation of gastric lamina propria mononuclear cells (LPMCs) by H
+
/K
+
-ATPase and the IL-17A and IL-17F cytokine production in eight patients with AIG and four HCs. Furthermore, we compared serum levels of IL-17A, IL-17F, IL-21, IL-17E, IL-22, and IL-23 in 43 AIG patients, in 47 HCs, and in 20 IDA patients without AIG. Gastric LPMCs from all AIG patients, but not those from HCs, were activated by H
+
/K
+
-ATPase and were able to proliferate and produce high levels of IL-17A and IL-17F. AIG patients have significantly higher serum IL-17A, IL-17F, IL-21, and IL-17E (393.3 ± 410.02 pg/ml, 394.0 ± 378.03 pg/ml, 300.46 ± 303.45 pg/ml, 34.92 ± 32.56 pg/ml, respectively) than those in HCs (222.99 ± 361.24 pg/ml, 217.49 ± 312.1 pg/ml, 147.43 ± 259.17 pg/ml, 8.69 ± 8.98 pg/ml, respectively) and those in IDA patients without AIG (58.06 ± 107.49 pg/ml, 74.26 ± 178.50 pg/ml, 96.86 ± 177.46 pg/ml, 10.64 ± 17.70 pg/ml, respectively). Altogether, our results indicate that IL-17A and IL-17F are produced
in vivo
in the stomach of AIG patients following activation with H
+
/K
+
-ATPase and that serum IL-17A, IL-17F, IL-21, and IL-17E levels are significantly elevated in AIG patients but not in patients without AIG. These data suggest a Th17 signature in AIG and that IL-17A, IL-17F, IL-21, and IL-17E may represent a relevant tool for AIG management.
PDF
