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Diagnostics
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Biomarkers for Immune-Mediated Diseases
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Biomarkers for Immune-Mediated Diseases

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 24849

Special Issue Editor

Prof. Dr. Marcos Lõpez-Hoyos

E-Mail Website
Guest Editor
Immunology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, Facultad de Medicina, Universidad Cantabria, Santander, Spain
Interests: autoimmunity; solid organ transplantation; autoantibodies; anti-HLA antibodies; flow cytometry; immunological biomarkers

Special Issue Information

Dear Colleagues,

The term immune-mediated inflammatory disease (IMID) encompasses a heterogeneous group of chronic inflammatory-based diseases that are characterized by (1) an inappropriate and dysregulation of the immune response with the production of pro-inflammatory cytokines, (2) a chronic inflammatory damage whose phenotype depends on the affected organ, (3) shared susceptibility genes and risk factors that can justify the co-occurrence of several IMIDs in the same individual and the familial aggregation of multiple IMIDs, (4) comorbidities and common effects generated by a chronic inflammatory state, and (5) a common response to pharmacological agents with common therapeutic targets within the inflammatory pathway. These are responsible for direct tissue damage in different organs, but in the case of IMID, they are also directly related to the comorbidities that IMIDs share, including a clear increase in cardiovascular morbidity and mortality, obesity, metabolic syndrome, non-alcoholic steatohepatitis, chronic renal disease, and others. There is a clear need for biomarkers for prediction, diagnosis, management, and prognosis in the different aspects of IMID, as well as to differentiate between different manifestations of these related diseases.

This Special Issue is aimed at collecting recent evidence from basic and translational research on the possible biomarkers of clinical utility in the study of IMIDs. Special attention will be paid to the use of biomarkers as potential companion diagnostics in IMIDs in which therapeutic intervention in the immune response is essential at every stage of the disease.

Prof. Dr. Marcos Lõpez-Hoyos
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Immune-mediated inflammatory disease
  • Biomarker
  • Companion diagnostics
  • Cytokines
  • Immunoregulation
  • Complement
  • Autoantibodies
  • Innate immunity
  • Adaptive immunity
  • Multiplexing
  • Immunophenotype
  • Mass cytometry
  • ELISPOT
  • Single-cell RNA

Published Papers (8 papers)

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Research

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17 pages, 2759 KiB  
Article
Specific Combinations of Inflammatory, Angiogenesis and Vascular Integrity Biomarkers Are Associated with Clinical Severity, Coma and Mortality in Beninese Children with Plasmodium Falciparum Malaria
by Bernard Tornyigah, Samuel Odarkwei Blankson, Rafiou Adamou, Azizath Moussiliou, Lauriane Rietmeyer, Patrick Tettey, Liliane Dikroh, Bernard Addo, Helena Lamptey, Maroufou J. Alao, Annick Amoussou, Caroline Padounou, Christian Roussilhon, Sylvie Pons, Benedicta Ayiedu Mensah, Nicaise Tuikue Ndam and Rachida Tahar
Diagnostics 2022, 12(2), 524; https://doi.org/10.3390/diagnostics12020524 - 18 Feb 2022
Cited by 2 | Viewed by 1928
Abstract
Malaria-related deaths could be prevented if powerful diagnostic and reliable prognostic biomarkers were available to allow rapid prediction of the clinical severity allowing adequate treatment. Using quantitative ELISA, we assessed the plasma concentrations of Procalcitonin, Pentraxine-3, Ang-2, sTie-2, suPAR, sEPCR and sICAM-1 in [...] Read more.
Malaria-related deaths could be prevented if powerful diagnostic and reliable prognostic biomarkers were available to allow rapid prediction of the clinical severity allowing adequate treatment. Using quantitative ELISA, we assessed the plasma concentrations of Procalcitonin, Pentraxine-3, Ang-2, sTie-2, suPAR, sEPCR and sICAM-1 in a cohort of Beninese children with malaria to investigate their potential association with clinical manifestations of malaria. We found that all molecules showed higher levels in children with severe or cerebral malaria compared to those with uncomplicated malaria (p-value < 0.005). Plasma concentrations of Pentraxine-3, Procalcitonin, Ang-2 and the soluble receptors were significantly higher in children with coma as defined by a Blantyre Coma Score < 3 (p < 0.001 for Pentraxine-3, suPAR, and sTie-2, p = 0.004 for PCT, p = 0.005 for sICAM-1, p = 0.04 for Ang-2). Moreover, except for the PCT level, the concentrations of Pentraxine-3, suPAR, sEPCR, sICAM-1, sTie-2 and Ang-2 were higher among children who died from severe malaria compared to those who survived (p = 0.037, p = 0.035, p < 0.0001, p= 0.0008, p = 0.01 and p = 0.02, respectively). These findings indicate the ability of these molecules to accurately discriminate among clinical manifestations of malaria, thus, they might be potentially useful for the early prognostic of severe and fatal malaria, and to improve management of severe cases. Full article
(This article belongs to the Special Issue Biomarkers for Immune-Mediated Diseases)
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10 pages, 1724 KiB  
Article
Clues to Disease Activity in Juvenile Dermatomyositis: Neopterin and Other Biomarkers
by Amer Khojah, Gabrielle Morgan and Lauren M. Pachman
Diagnostics 2022, 12(1), 8; https://doi.org/10.3390/diagnostics12010008 - 21 Dec 2021
Cited by 10 | Viewed by 2590
Abstract
Easily accessible biomarkers are urgently needed to evaluate immune activation in Juvenile Dermatomyositis (JDM). The goal of this retrospective study is to define immunological and clinical differences between untreated JDM patients with either normal or elevated (>10 mmol/L) levels of neopterin, a biomarker [...] Read more.
Easily accessible biomarkers are urgently needed to evaluate immune activation in Juvenile Dermatomyositis (JDM). The goal of this retrospective study is to define immunological and clinical differences between untreated JDM patients with either normal or elevated (>10 mmol/L) levels of neopterin, a biomarker of macrophage activation. We included all JDM with neopterin data obtained before initiating medical therapy. We assessed T, B, NK cell populations, muscle enzymes, and disease activity scores for skin (sDAS), muscle (mDAS), total (tDAS), the duration of untreated disease, disease course, and myositis-specific antibody (MSA). Seventy-nine percent of 139 untreated JDM patients had elevated serum neopterin. The group with elevated neopterin had significantly more active disease: tDAS 11.9 vs. 8.1 (p < 0.0001), mDAS 5.8 vs. 3.1 (p < 0.0001), sDAS 6.1 vs. 4.9 (p = 0.0002), aldolase 24.0 vs. 7.6 U/L (p < 0.0001), von Willebrand factor antigen (p < 0.0001), and ESR 19.8 vs. 11.5 mm/hr (p = 0.01). The flow cytometry documented both reduced T cells (1494 vs. 2278/mm3, p = 0.008) and NK cells (145 vs. 240/mm3, p = 0.003). TNFα-308AA/AG polymorphism was more common in children with elevated neopterin than TNFα-308GG (p 0.05). We conclude that the availability of neopterin data will contribute to the rapid assessment of untreated JDM disease activity. Full article
(This article belongs to the Special Issue Biomarkers for Immune-Mediated Diseases)
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14 pages, 2917 KiB  
Article
Profiling of Myositis Specific Antibodies and Composite Scores as an Aid in the Differential Diagnosis of Autoimmune Myopathies
by Michael Mahler, Kishore Malyavantham, Andrea Seaman, Chelsea Bentow, Ariadna Anunciacion-Llunell, María Teresa Sanz-Martínez, Laura Viñas-Gimenez and Albert Selva-O’Callaghan
Diagnostics 2021, 11(12), 2246; https://doi.org/10.3390/diagnostics11122246 - 30 Nov 2021
Cited by 10 | Viewed by 2553
Abstract
(1) Background: Myositis specific antibodies (MSA) represent important diagnostic and stratification tools in idiopathic inflammatory myositis (IIM) patients. Here we aimed to evaluate the clinical performance of MSA profiled by a novel particle based multi-analyte technology (PMAT) in IIM and subsets thereof. (2) [...] Read more.
(1) Background: Myositis specific antibodies (MSA) represent important diagnostic and stratification tools in idiopathic inflammatory myositis (IIM) patients. Here we aimed to evaluate the clinical performance of MSA profiled by a novel particle based multi-analyte technology (PMAT) in IIM and subsets thereof. (2) Methods: 264 IIM patients and 200 controls were tested for MSA using PMAT (Inova Diagnostics, research use only). Diagnostic performance was analyzed and composite scores were generated. (3) Results: The sensitivity/specificity of the individual MSA were: 19.7%/100% (Jo-1), 7.2%/100.0% (Mi-2), 3.0%/99.0% (NXP2), 3.8%/100.0% (SAE), 2.7%/100.0% (PL-7), 1.9%/99.5 (PL-12), 1.1%/100.0% (EJ), 15.5%/99.5% (TIF1γ), 8.3%/98.5% (MDA5), 6.1%/99.0% (HMGCR) and 1.9%/98.5% (SRP). Of all IIM patients, 180/264 tested positive for at least one of the MSAs. In the individual control group, 12/200 (6.0%) tested positive for at least one MSA, most of which had levels close to the cut-off (except one SRP and one PL-12). Only 6/264 (2.3%) IIM patients were positive for more than one antibody (MDA5/HMGCR, EJ/PL-7, 2 x MDA5/TIF1γ, EJ/SAE, SAE/TIF1γ). The overall sensitivity was 68.2% paired with a specificity of 94.0%, leading to an odds ratio of 33.8. The composite scores showed good discrimination between subgroups (e.g., anti-synthetase syndrome). (4) Conclusion: MSA, especially when combined in composite scores (here measured by PMAT), provide value in stratification of patients with IIM. Full article
(This article belongs to the Special Issue Biomarkers for Immune-Mediated Diseases)
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Review

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12 pages, 2211 KiB  
Review
The Past, Present, and Future in Antinuclear Antibodies (ANA)
by Juan Irure-Ventura and Marcos López-Hoyos
Diagnostics 2022, 12(3), 647; https://doi.org/10.3390/diagnostics12030647 - 07 Mar 2022
Cited by 16 | Viewed by 8380
Abstract
Autoantibodies are a hallmark of autoimmunity and, specifically, antinuclear antibodies (ANAs) are the most relevant autoantibodies present in systemic autoimmune rheumatic diseases (SARDs). Over the years, different methods from LE cell to HEp-2 indirect immunofluorescence (IIF), solid-phase assays (SPAs), and finally multianalyte technologies [...] Read more.
Autoantibodies are a hallmark of autoimmunity and, specifically, antinuclear antibodies (ANAs) are the most relevant autoantibodies present in systemic autoimmune rheumatic diseases (SARDs). Over the years, different methods from LE cell to HEp-2 indirect immunofluorescence (IIF), solid-phase assays (SPAs), and finally multianalyte technologies have been developed to study ANA-associated SARDs. All of them provide complementary information that is important to provide the most clinically valuable information. The identification of new biomarkers together with multianalyte platforms will help close the so-called “seronegative gap” and to correctly classify and diagnose patients with SARDs. Finally, artificial intelligence and machine learning is an area still to be exploited but in a next future will help to extract patterns within patient data, and exploit these patterns to predict patient outcomes for improved clinical management. Full article
(This article belongs to the Special Issue Biomarkers for Immune-Mediated Diseases)
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15 pages, 343 KiB  
Review
Diagnostic Value of Interferon-Gamma Release Assays for Tuberculosis in the Immunocompromised Population
by Ying Yang, Hong-Jiao Wang, Wei-Lin Hu, Guan-Nan Bai and Chun-Zhen Hua
Diagnostics 2022, 12(2), 453; https://doi.org/10.3390/diagnostics12020453 - 10 Feb 2022
Cited by 8 | Viewed by 2660
Abstract
Interferon-gamma release assays (IGRAs) are widely used in the diagnosis of Mycobacterium tuberculosis (M. tuberculosis) infection by detecting interferon-γ released by previously sensitized T-cells in-vitro. Currently, there are two assays based on either enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunospot (ELISPOT) [...] Read more.
Interferon-gamma release assays (IGRAs) are widely used in the diagnosis of Mycobacterium tuberculosis (M. tuberculosis) infection by detecting interferon-γ released by previously sensitized T-cells in-vitro. Currently, there are two assays based on either enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunospot (ELISPOT) technology, with several generations of products available. The diagnostic value of IGRAs in the immunocompromised population is significantly different from that in the immunocompetent population because their results are strongly affected by the host immune function. Both physiological and pathological factors can lead to an immunocompromised situation. We summarized the diagnostic value and clinical recommendations of IGRAs for different immunocompromised populations, including peoplewith physiological factors (pregnant and puerperal women, children, and older people), as well as people with pathological factors (solid organ transplantation recipients, combination with human immunodeficiency virus infection, diabetes mellitus, end-stage renal disease, end-stage liver disease, and chronic immune-mediated inflammatory diseases). Though the performance of IGRAs is not perfect and often requires a combination with other diagnostic strategies, it still has some value in the immunocompromised population. Hopefully, the newly developed IGRAs could better target this population. Full article
(This article belongs to the Special Issue Biomarkers for Immune-Mediated Diseases)

Other

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9 pages, 1421 KiB  
Brief Report
Anti-Carbamylated Protein (Anti-CarP) Antibodies in Patients Evaluated for Suspected Rheumatoid Arthritis
by Vincent Ricchiuti, Kelly Y. Chun, Jane M. Yang, Mary Ann Aure, Luis Gomez, Gary L. Norman and Michael Mahler
Diagnostics 2022, 12(7), 1661; https://doi.org/10.3390/diagnostics12071661 - 08 Jul 2022
Cited by 3 | Viewed by 1898
Abstract
(1) Background: Anti-carbamylated protein (CarP) antibodies have been studied as novel markers to aid in the diagnosis and prognosis of rheumatoid arthritis. (2) Methods: A total of 265 samples were included in the evaluation, for which 98 had results for anti-cyclic citrullinated peptide [...] Read more.
(1) Background: Anti-carbamylated protein (CarP) antibodies have been studied as novel markers to aid in the diagnosis and prognosis of rheumatoid arthritis. (2) Methods: A total of 265 samples were included in the evaluation, for which 98 had results for anti-cyclic citrullinated peptide (CCP), 86 for rheumatoid factor (RF), and 212 for 14-3-3 eta protein. Anti-CarP antibodies were measured using a fetal calf serum-based single-step assay (research use only, Inova Diagnostics, San Diego, CA). (3) Results: Anti-CarP antibodies were significantly higher and more frequent in anti-CCP3.1+ (p = 0.0025), RF+ (p = 0.0043) and 14-3-3 eta+ (p = 0.028) samples compared to the negative counterpart group. In addition, isolated anti-CarP positivity occurred in samples negative for anti-CCP3.1, RF, or 14-3-3 eta. When anti-CarP antibodies were compared to each of the RF, anti-CCP3.1, and 14-3-3 eta by receiver operating characteristic (ROC) analyses, the area under the curve (AUC) values of 0.71 (RF), 0.68 (anti-CCP3.1), and 0.59 (14-3-3 eta), respectively, demonstrated a moderate correlation. Using an UpSet plot, we determined that 10.6% of the samples with available results for anti-CCP3.1, RF, and anti-CarP showed triple positivity. (4) Conclusions: Anti-carbamylated protein (anti-CarP) antibodies can be detected in anti-CCP, RF and 14-3-3 eta-positive and -negative patients, potentially identifying specific subsets of patients. Full article
(This article belongs to the Special Issue Biomarkers for Immune-Mediated Diseases)
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10 pages, 1072 KiB  
Brief Report
Circulating Calprotectin as a Predictive and Severity Biomarker in Patients with COVID-19
by Gary L. Norman, Sherwin A. Navaz, Yogendra Kanthi, Roger Albesa, Michael Mahler, Jason S. Knight and Yu Zuo
Diagnostics 2022, 12(6), 1324; https://doi.org/10.3390/diagnostics12061324 - 27 May 2022
Cited by 8 | Viewed by 1806
Abstract
Background: New tools for the assessment and prediction of the severity of hospitalized COVID-19 patients can help direct limited resources to patients with the greatest need. Circulating levels of calprotectin (S100A8/S100A9) reflect inflammatory activity in multiple conditions, and have been described as being [...] Read more.
Background: New tools for the assessment and prediction of the severity of hospitalized COVID-19 patients can help direct limited resources to patients with the greatest need. Circulating levels of calprotectin (S100A8/S100A9) reflect inflammatory activity in multiple conditions, and have been described as being elevated in COVID-19 patients, but their measurement is not routinely utilized. The aim of our study was to assess the practical and predictive value of measuring circulating calprotectin levels in patients at admission and during their hospitalization. Methods: Circulating calprotectin levels were measured in 157 hospitalized patients with COVID-19 using an automated quantitative chemiluminescent assay. Results: Circulating calprotectin levels were strongly correlated with changing respiratory supplementation needs of patients. The overall trajectory of circulating calprotectin levels generally correlated with patient improvement or deterioration. Conclusions: Routine measurement of circulating calprotectin levels may offer a valuable tool to assess and monitor hospitalized patients with COVID-19, as well as other acute inflammatory conditions. Full article
(This article belongs to the Special Issue Biomarkers for Immune-Mediated Diseases)
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6 pages, 1086 KiB  
Brief Report
Growth Differentiation Factor 15 (GDF-15): A Novel Biomarker Associated with Poorer Respiratory Function in COVID-19
by Leticia Alserawan, Patricia Peñacoba, Sandra Elizabet Orozco Echevarría, Diego Castillo, Esther Ortiz, Laura Martínez-Martínez, Esther Moga Naranjo, Pere Domingo, Ivan Castellví, Cándido Juárez and Anaís Mariscal
Diagnostics 2021, 11(11), 1998; https://doi.org/10.3390/diagnostics11111998 - 27 Oct 2021
Cited by 16 | Viewed by 1877
Abstract
It is essential to find new biomarkers for severity stratification of patients with coronavirus disease (COVID-19). Growth differentiation factor 15 (GDF-15) is upregulated in pathological conditions that involve inflammation and/or oxidative stress. We determined circulating levels of GDF-15 and correlated them with clinical [...] Read more.
It is essential to find new biomarkers for severity stratification of patients with coronavirus disease (COVID-19). Growth differentiation factor 15 (GDF-15) is upregulated in pathological conditions that involve inflammation and/or oxidative stress. We determined circulating levels of GDF-15 and correlated them with clinical and laboratory parameters reflecting severity in 84 patients with COVID-19, finding that GDF-15 levels were higher in both patients than in 20 healthy controls and were higher in patients with poorer respiratory function. GDF-15 levels also correlated with interleukin-6, C-reactive protein, ferritin and D-dimer levels and with neutrophilia and lymphopenia. Of all the analysed biomarkers, GDF-15 showed the best area under the receiver operating characteristics curve in identifying patients with poor respiratory function. In conclusion, our data support GDF-15 as a biomarker associated with pulmonary impairment in COVID-19 and so can potentially be useful in stratifying COVID-19 cases by severity. Full article
(This article belongs to the Special Issue Biomarkers for Immune-Mediated Diseases)
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