Immunological Disorders: Gradations and the Current Approach in Laboratory Diagnostics
Abstract
:1. Introduction
2. Local Immune Response and Its Interaction with Systemic Defense Processes
3. Systemic Inflammatory Response
4. Three Main Types of Innate and Adaptive Cell-Mediated Effector Immunity
4.1. Immunopathological Syndromes Associated with the First Type of Cellular Immune Response
4.2. Cellular-Effector Deficiency
- Frequent acute respiratory viral infections (more than 4 times a year);
- All types of warts, acute condylomas mediated by human papillomavirus, and molluscum contagiosum;
- Clinically evident infections caused by the Herpesviridae group (recurrent course of herpes types 1 and 2, type 3 (herpes zoster), cytomegalovirus infection, and diseases caused by Epstein–Barr virus (virus type 4) or by the viruses of viral hepatitis (B, C, D, F, and G);
- Viral enteritis;
- Recurrent childhood infections and/or infections that develop after vaccination (in children over 7 years of age and adults);
- Fungal infections (candidiasis and other mycoses of the skin, nails, and mucous membranes (thrush); trichophytosis; and visceral mycoses;
- All types of tumor processes.
4.3. Cell-Mediated Damage (Delayed-Type Hypersensitivity)
4.4. Immunopathological Syndromes Associated with the Second Type of Cellular Immune Response
4.5. Hypersensitivity of the Immediate Type
5. Immunopathological Syndromes Associated with the Third Type of Cellular Immune Response
5.1. Macrophage–Phagocyte Deficiency Syndrome
5.2. Autoinflammatory Syndromes
6. Immunopathological Syndromes, Associated with Disorders of the Humoral Link of the Immune Response
6.1. Humoral-Effector Immunodeficiency (That Is, Insufficiency of Antibody Formation and/or Antibody-Dependent Complement Functions) Is Suspected If the Patient Has Certain Symptoms
- Bacterial infections of the upper respiratory tract and ENT organs (more than 3–4 times a year with a protracted course, with residual phenomena in the form of subfebrile, asthenia, or long-lasting sore throat);
- Bacterial infections of the lungs (chronic bronchitis with or without bronchospasm, pneumonia of various etiologies);
- Bacterial infections of the skin and subcutaneous tissue (furunculosis, abscesses, phlegmons, and recurrent paraproctitis);
- Infectious–inflammatory diseases of the genitourinary system (cystitis, pyelonephritis, adnexitis, etc.);
- Other bacterial infections (meningoencephalitis, arthritis, and septicemia);
- Diseases of the digestive tract caused by bacteria (stomatitis, periodontitis, gastritis, gastroduodenitis, peptic ulcer, colitis, enterocolitis, cholecystitis, and peritonitis), or various kinds of dysbacteriosis.
6.2. Antibody-Dependent Cytotoxic Syndrome
- ADCC of various K cells (see above);
- Complement activation;
- Opsonizing effect and antibody-dependent phagocytosis by professional phagocytes.
7. Multifactorial Immunopathological Syndromes
7.1. Syndrome of Pathogenic Effects of Immune Complexes
7.2. Regeneration Fibrosis
7.3. Syndrome of Immune Regulatory Deficiency
7.4. Autoimmune Neurological Disorders
8. Laboratory Diagnosis of Immune Disorders
8.1. Assessment of Cellular Immunity Indicators
8.2. Assessment of Indicators of Humoral Immunity
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Nautiyal, G.; Sharma, I.; Pandey, P.; Sharma, S.K. Autoimmune Diseases: Recent Insights on Epidemiology, Pathogenesis, and Prevalence Rate. In Artificial Intelligence and Autoimmune Diseases. Studies in Computational Intelligence; Raza, K., Singh, S., Eds.; Springer: Singapore, 2024; Volume 1133. [Google Scholar] [CrossRef]
- Borisov, A.G. Clinical characterization of functional disorders affecting immune system. Med. Immunol. 2013, 15, 45–50. (In Russian) [Google Scholar] [CrossRef]
- Sasikala, K.; Kumari, M.R. An account on promising alternative system of medicine to boost immunity. Plant Sci. Today 2022, 9 (Suppl. S2), 47–50. [Google Scholar] [CrossRef]
- Okada, H.; Kuhn, C.; Feillet, H.; Bach, J.F. The ’hygiene hypothesis’ for autoimmune and allergic diseases: An update. Clin. Exp. Immunol. 2010, 160, 1–9. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Cooper, G.S.; Bynum, M.L.; Somers, E.C. Recent insights in the epidemiology of autoimmune diseases: Improved prevalence estimates and understanding of clustering of diseases. J. Autoimmun. 2009, 33, 197–207. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Somers, E.C.; Thomas, S.L.; Smeeth, L.; Hall, A.J. Autoimmune diseases co-occurring within individuals and within families: A systematic review. Epidemiology 2006, 17, 202–217. [Google Scholar] [CrossRef] [PubMed]
- Pizano, J.M.; Williamson, C.B.; Dolan, K.E.; Gossard, C.M.; Burns, C.M.; Gasta, M.G.; Finley, H.J.; Parker, E.C.; Lipski, E.A. Probiotics and Disease: A Comprehensive Summary-Part 7, Immune Disorders. Integr. Med. 2017, 16, 46–57. [Google Scholar] [PubMed] [PubMed Central]
- Churilov, L.P.; Vasiliev, A.G. Pathophysiology of the Immune System; Foliant: St. Petersburg, Russia, 2014; Volume 664, p. 9. [Google Scholar]
- Marshall, J.S.; Warrington, R.; Watson, W.; Kim, H.L. An introduction to immunology and immunopathology. Allergy Asthma Clin. Immunol. 2018, 14 (Suppl. S2), 49. [Google Scholar] [CrossRef]
- Cárdenas-Roldán, J.; Rojas-Villarraga, A.; Anaya, J.M. How do autoimmune diseases cluster in families? A systematic review and meta-analysis. BMC Med. 2013, 11, 73. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Gottlieb, S. Early exposure to cows’ milk raises risk of diabetes in high risk children. BMJ 2000, 321, 1040. [Google Scholar] [PubMed Central]
- Churilov, L.P. General Pathophysiology with the Basics of Immunopathology, 5th ed.; Medizdat-SPb: St. Petersburg, Russia, 2020; p. 656. [Google Scholar]
- Kasparov, E.V.; Savchenko, A.A.; Kudlay, D.A.; Kudryavtsev, I.V.; Golovkin, A.S.; Tikhonova, E.P.; Borisov, A.G. Clinical immunology. In Rehabilitation of the Immune System; Verso: Krasnoyarsk, Russia, 2022; p. 194. [Google Scholar]
- Tikhonova, E.P.; Savchenko, A.A.; Elistratova, T.A.; Kasparov, E.V.; Kudlay, D.A.; Kuzmina TYu Kasparova, I.E.; Kudryavtsev, I.V.; Kalinina, Y.u.S.; Borisov, A.G. Immunorehabilitation of Patients with COVID-19; AS-KIT: Krasnoyarsk, Russia, 2023; p. 112. [Google Scholar]
- Reddy, H.; Javvaji, C.K.; Malali, S.; Kumar, S.; Acharya, S.; Toshniwal, S. Navigating the Cytokine Storm: A Comprehensive Review of Chemokines and Cytokines in Sepsis. Cureus 2024, 16, e54275. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Li, T.; Wang, D.; Wei, H.; Xu, X. Cytokine storm and translating IL-6 biology into effective treatments for COVID-19. Front. Med. 2023, 17, 1080–1095. [Google Scholar] [CrossRef] [PubMed]
- Ryabkova, V.A.; Churilov, L.P.; Shoenfeld, Y. Influenza infection, SARS, MERS and COVID-19: Cytokine storm–The common denominator and the lessons to be learned. Clin. Immunol. 2021, 223, 108652. [Google Scholar] [CrossRef] [PubMed]
- Tripp, B.; Shortlidge, E.E. A Framework to Guide Undergraduate Education in Interdisciplinary Science. CBE Life Sci. Educ. 2019, 18, es3. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Hunter, J.A. A Treatise on the Blood, Inflammation, and Gunshot Wounds; Nicol Publ.: London, UK, 1794. [Google Scholar]
- Barsukov, A.V.; Seidova, A.Y.; Shcherbakova, K.A.; Black, M.S.; Korovin, A.E.; Churilov, L.P.; Tovpeko, D.V. Systemic Action of Inflammatory Mediators in Patients with Essential Hypertension and Diastolic Chronic Heart Failure: A Clinical Pathophysiological Study. Pathophysiology 2020, 27, 30–43. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Hawker, F. Endocrine changes in the critically ill. Br. J. Hosp. Med. 1988, 39, 278–280, 282–284, 286 passim. [Google Scholar]
- Labori, A. Regulation of metabolic processes. M Med. 1970, 384. [Google Scholar]
- Churilov, L.P.; Utekhin, V.I. The metabolic logistics of stress, diabetes mellitus and works by Bernardo Alberto Houssay. Pediatrician 2015, 6, 104–111. [Google Scholar] [CrossRef]
- Churilov, L.P. On the system approach in general pathology: Necessity and principles of pathoinformatics//bulletin of the Saint Petersburg State University. Medicine 2009. Available online: https://cyberleninka.ru/article/n/o-sistemnom-podhode-v-obschey-patologii-neobhodimost-i-printsipy-patoinformatiki (accessed on 20 January 2025).
- Cerra, F.B. Hypermetabolism, organ failure, and metabolic support. Surgery 1987, 101, 1–14. [Google Scholar]
- Laurent, P.E. Induction et régulation de la réaction inflammatoire systémique. Ann Biol Clin 1988, 46, 329–335. [Google Scholar]
- Bone, R.C. Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome. JAMA 1992, 268, 3452–3455. [Google Scholar] [CrossRef]
- Bone, R.C.; Balk, R.A.; Cerra, F.B.; Dellinger, R.P.; Fein, A.M.; Knaus, W.A.; Schein, R.M.H.; Sibbald, W.J. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992, 101, 1644–1655. [Google Scholar] [CrossRef] [PubMed]
- Kaplan, M.A.; Lebretti, A. The role of C-reactive protein in allergic inflammation; relationship between the acute phase response and the antibody titer. J. Allergy 1956, 27, 450–460. [Google Scholar] [CrossRef]
- Hietbrink, F.; Koenderman, L.; Rijkers, G.; Leenen, L. Trauma: The role of the innate immune system. World J. Emerg. Surg. 2006, 1, 15. [Google Scholar] [CrossRef]
- Moore, F.A.; Sauaia, A.; Moore, E.E.; Haenel, J.B.; Burch, J.M.; Lezotte, D.C. Postinjury multiple organ failure: A bimodal phenomenon. J. Trauma 1996, 40, 501–510, discussion 510–512. [Google Scholar] [CrossRef] [PubMed]
- Humanenko, E.K.; Khromov, A.A.; Churilov, L.P.; Rud, A.A.; Suprun, A.Y. Shock, systemic inflammatory response, multiple organ dysfunction and sepsis are the main links in the pathogenesis of traumatic disease in polytrauma. In the collection: The Indelible Tablets: Sepsis et cetera. In Collection of Materials of the Conference of the Association of General Surgeons Dedicated to the Anniversary of the Department of General Surgery of ASMU; Digital Printing: Yaroslavl, Russia, 2020; pp. 74–78. [Google Scholar]
- Cedzyński, M.; Świerzko, A.S. Collectins and ficolins in neonatal health and disease. Front. Immunol. 2023, 14, 1328658. [Google Scholar] [CrossRef] [PubMed]
- Zur Stadt, U.; Beutel, K.; Kolberg, S.; Schneppenheim, R.; Kabisch, H.; Janka, G.; Hennies, H.C. Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: Molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Hum. Mutat. 2006, 27, 62–68. [Google Scholar] [CrossRef]
- Chousterman, B.G.; Swirski, F.K.; Weber, G.F. Cytokine storm and sepsis disease pathogenesis. Semin. Immunopathol. 2017, 39, 517–528. [Google Scholar] [CrossRef]
- Tisoncik, J.R.; Korth, M.J.; Simmons, C.P.; Farrar, J.; Martin, T.R.; Katze, M.G. Into the eye of the cytokine storm. Microbiol. Mol. Biol. Rev. 2012, 76, 16–32. [Google Scholar] [CrossRef]
- Rosário, C.; Zandman-Goddard, G.; Meyron-Holtz, E.G.; D’Cruz, D.P.; Shoenfeld, Y. The hyperferritinemic syndrome: Macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med. 2013, 11, 185. [Google Scholar] [CrossRef]
- Cauwels, A.; Rogge, E.; Vandendriessche, B.; Shiva, S.; Brouckaert, P. Extracellular ATP drives systemic inflammation, tissue damage and mortality. Cell Death Dis. 2014, 5, e1102. [Google Scholar] [CrossRef]
- Kubyshkin, A.; Ivanovna, F.I. Fomochkina Irina Ivanovna Pathogenetic Relationship of Systemic Inflammatory Reaction Syndrome and Shock. Bull. St. Petersburg State Univ. Med. 2011. Available online: https://cyberleninka.ru/article/n/patogeneticheskaya-vzaimosvyaz-sindroma-sistemnoy-vospalitelnoy-reaktsii-i-shoka (accessed on 23 November 2011).
- Teijaro, J.R. Cytokine storms in infectious diseases. Semin Immunopathol. 2017, 39, 501–503. [Google Scholar] [CrossRef] [PubMed]
- Santacroce, L.; Topi, S.; Charitos, I.A.; Lovero, R.; Luperto, P.; Palmirotta, R.; Jirillo, E. Current Views about the Inflammatory Damage Triggered by Bacterial Superantigens and Experimental Attempts to Neutralize Superantigen-Mediated Toxic Effects with Natural and Biological Products. Pathophysiology 2024, 31, 18–31. [Google Scholar] [CrossRef] [PubMed]
- Annunziato, F.; Romagnani, C.; Romagnani, S. The 3 major types of innate and adaptive cell-mediated effector immunity. J. Allergy Clin. Immunol. 2015, 135, 626–635. [Google Scholar] [CrossRef] [PubMed]
- Carter, S.J.; Tattersall, R.S.; Ramanan, A.V. Macrophage activation syndrome in adults: Recent advances in pathophysiology, diagnosis and treatment. Rheumatol. Oxf. Engl. 2019, 58, 5–17. [Google Scholar] [CrossRef]
- Korsunsky, I.A.; Kudlay, D.A.; Prodeus, A.P.; Shcherbina, A.Y.; Rumyantsev, A.G. Neonatal screening for primary immunodeficiency states and T/B-cell lymphopenia as a basis for the formation of risk groups of children with congenital pathologies. Paediatrics 2020, 99, 8–15. [Google Scholar] [CrossRef]
- Abbas, A.; Lichtman, A.H.; Pillai, S. Cellular and Molecular Immunology, 10th ed.; Elsevier: Philadelphia, PA, USA, 2022. [Google Scholar]
- Singer, M.; Deutschman, C.S.; Seymour, C.W.; Shankar-Hari, M.; Annane, D.; Bauer, M.; Bellomo, R.; Bernard, G.R.; Chiche, J.D.; Coopersmith, C.M.; et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016, 315, 801–810. [Google Scholar] [CrossRef]
- Pandya, S.; Thakur, A.; Saxena, S.; Jassal, N.; Patel, C.; Modi, K.; Shah, P.; Joshi, R.; Gonge, S.; Kadam, K.; et al. A Study of the Recent Trends of Immunology: Key Challenges, Domains, Applications, Datasets, and Future Directions. Sensors 2021, 21, 7786. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Han, Y.; Jia, Q.; Jahani, P.S.; Hurrell, B.P.; Pan, C.; Huang, P.; Gukasyan, J.; Woodward, N.C.; Eskin, E.; Gilliland, F.D.; et al. Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma. Nat. Commun. 2020, 11, 1776. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Coombs, R.R.A.; Gell, P.G.H. Classification of allergic reactions responsible for drug hypersensitivity reactions. In Clinical Aspects of Immunology; Coombs, R.R.A., Gell, P.G.H., Eds.; Davis Publ.: Philadelphia, PA, USA, 1968; pp. 575–596. [Google Scholar]
- Jutel, M.; Agache, I.; Zemelka-Wiacek, M.; Akdis, M.; Chivato, T.; Del Giacco, S.; Gajdanowicz, P.; Gracia, I.E.; Klimek, L.; Lauerma, A.; et al. Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper. Allergy 2023, 78, 2851–2874. [Google Scholar] [CrossRef]
- Ebo, D.G.; Beyens, M.; Heremans, K.; van der Poorten, M.M.; Van Gasse, A.L.; Mertens, C.; Houdt, M.V.; Sabato, V.; Elst, J. Recent Knowledge and Insights on the Mechanisms of Immediate Hypersensitivity and Anaphylaxis: IgE/FcεRI- and Non-IgE/FcεRI-Dependent Anaphylaxis. Curr. Pharm. Des. 2023, 29, 178–184. [Google Scholar] [CrossRef] [PubMed]
- Doña, I.; Torres, M.J.; Celik, G.; Phillips, E.; Tanno, L.K.; Castells, M. Changing patterns in the epidemiology of drug allergy. Allergy 2024, 79, 613–628. [Google Scholar] [CrossRef] [PubMed]
- Colloca, L.; Ludman, T.; Bouhassira, D.; Baron, R.; Dickenson, A.H.; Yarnitsky, D.; Freeman, R.; Truini, A.; Attal, N.; Finnerup, N.; et al. Neuropathic pain. Nat. Rev. Dis. Primers 2017, 3, 17002. [Google Scholar] [CrossRef] [PubMed]
- Cazzato, D.; Lauria, G. Small fiber neuropathy. Curr. Opin. Neurol. 2017, 30, 490–499. [Google Scholar] [CrossRef] [PubMed]
- Chiang, M.-C.; Tseng, M.-T.; Pan, C.-L.; Chao, C.-C.; Hsie, S.-T. Progress in the treatment of small fiber peripheral neuropathy. Expert Rev. Neurother. 2015, 15, 305–313. [Google Scholar] [CrossRef]
- Gibbons, C.H. Small Fiber Neuropathies. Continuum 2014, 20, 1398–1412. [Google Scholar] [CrossRef]
- Hovaguimian, A.; Gibbons, C.H. Diagnosis and Treatment of Pain in Small Fiber Neuropathy. Curr. Pain Headache Rep. 2011, 15, 193–200. [Google Scholar] [CrossRef]
- Brouwer, B.A.; Bakkers, M.; Hoeijmakers, J.G.J.; Faber, C.J.; Merkies, I.S.J. Improving assessment in small fiber neuropathy. J. Peripher. Nerv. Syst. 2015, 20, 333–340. [Google Scholar] [CrossRef]
- Sene, D. Small fiber neuropathy: Diagnosis, causes and treatment. Jt. Bone Spine 2018, 85, 553–559. [Google Scholar] [CrossRef]
- Sweiss, N.J.; Patterson, K.; Sawaqed, R.; Jabbar, U.; Korsten, P.; Hogarth, K.; Baughman, R.P. Rheumatologic Manifestations of Sarcoidosis. Semin. Respir. Crit. Care Med. 2010, 31, 463–473. [Google Scholar] [CrossRef]
- Tavee, O.J.; Stern, B.J. Neurosarcoidosis. Continuum 2014, 20, 545–559. [Google Scholar]
- Hoitsma, E.; de Vries, J.; Drent, M. The small fiber neuropathy screening list: Construction and cross-validation in sarcoidosis. Respir. Med. 2010, 105, 95–100. [Google Scholar] [CrossRef]
- Kumar, P.; Rajasekaran, K.; Palmer, J.M.; Thakar, M.S.; Malarkannan, S. IL-22: An Evolutionary Missing-Link Authenticating the Role of the Immune System in Tissue Regeneration. J. Cancer 2013, 4, 57–65. [Google Scholar] [CrossRef] [PubMed]
- Cardoneanu, A.; Rezus, I.I.; Burlui, A.M.; Richter, P.; Bratoiu, I.; Mihai, I.R.; Macovei, L.A.; Rezus, E. Autoimmunity and Autoinflammation: Relapsing Polychondritis and VEXAS Syndrome Challenge. Int. J. Mol. Sci. 2024, 25, 2261. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Shinwari, K.; Bolkov, M.; Tuzankina, I.A.; Chereshnev, V.A. Newborn Screening through TREC, TREC/KREC System for Primary Immunodeficiency with limitation of TREC/KREC. Comprehensive Review. Antiinflamm. Antiallergy Agents Med. Chem. 2021, 20, 132–149. [Google Scholar] [CrossRef] [PubMed]
- Zaichik, A.; Churilov, L.P.; Utekhin, V.J. Autoimmune regulation of genetically determined cell functions in health and disease. Pathophysiology 2008, 15, 191–207. [Google Scholar] [CrossRef]
- Rojas, M.; Restrepo-Jiménez, P.; Monsalve, D.M.; Pacheco, Y.; Acosta-Ampudia, Y.; Ramírez-Santana, C.; Anaya, J.M. Molecular mimicry and autoimmunity. J. Autoimmun. 2018, 95, 100–123. [Google Scholar] [CrossRef] [PubMed]
- Sunderkötter, C.; Golle, L.; Pillebout, E.; Michl, C. Pathophysiology and clinical manifestations of immune complex vasculitides. Front. Med. 2023, 10, 1103065. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Churilov, L.P.; Fedotkina, T.V.; Schoenfeld, I. Autoimmune and infectious inflammation as a link in atherogenesis in experiment and clinic. Health Is Basis Hum. Potential Probl. Solut. 2022, 17, 720–735. [Google Scholar]
- Zaichik ASh Churilov, L.P. Mechanisms of Development of Diseases and Syndromes, 2nd ed.; expanded and revised; ELBI-SPb: St. Petersburg, Russia, 2005; p. 508. [Google Scholar]
- Londeree, W.; Davis, K.; Helman, D.; Abadie, J. Bodily fluid analysis of non-serum samples using point-of-care testing with iSTAT and Piccolo analyzers versus a fixed hospital chemistry analytical platform. Hawaii J. Med. Public Health 2014, 73 (Suppl. S1), 3–8. [Google Scholar] [PubMed] [PubMed Central]
- Savchenko, A.A.; Borisov, A.G.; Cherdantsev, D.V.; Pervova, O.V.; Kudryavtsev, I.V.; Beleniuk, V.D. Features of the T-lymphocyte Phenotype in the Dynamics of the Postoperative Period in Patients with Peritonitis Depending on the Outcome of the Disease. Infect. Immun. 2019. Available online: https://cyberleninka.ru/article/n/osobennosti-fenotipa-t-limfotsitov-v-dinamike-posleoperatsionnogo-perioda-u-bolnyh-peritonitom-v-zavisimosti-ot-ishoda-zabolevaniya (accessed on 15 March 2019).
- Kudryavtsev, I.V.; Borisov, A.G.; Volkov, A.E.; Savchenko, A.A.; Serebryakova, M.K.; Polevschikov, A.V. CD56 and CD57 expression by distinct populations of human cytotoxic T lymphocytes. Pac. Med. J. 2015, 30–35. (In Russian) [Google Scholar]
- Eggenhuizen, P.J.; Ooi, J.D. The Influence of Cross-Reactive T Cells in COVID-19. Biomedicines 2024, 12, 564. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Jiang, H.; Jiang, J. Balancing act: The complex role of NK cells in immune regulation. Front. Immunol. 2023, 14, 1275028. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Kudryavtsev, I.V.; Borisov, A.G.; Vasilyeva, E.V.; Krobinets, I.I.; Savchenko, A.A.; Serebriakova, M.K.; Totolian Areg, A. Phenotypic characterisation of peripheral blood cytotoxic t lymphocytes: Regulatory and effector molecules. Med. Immunol. 2018, 20, 227–240. (In Russian) [Google Scholar] [CrossRef]
- Wu, S.S.; Lin, O.S.; Chen, Y.Y.; Hwang, K.L.; Soon, M.S.; Keeffe, E.B. Ascitic fluid carcinoembryonic antigen and alkaline phosphatase levels for the differentiation of primary from secondary bacterial peritonitis with intestinal perforation. J. Hepatol. 2001, 34, 215–221. [Google Scholar] [CrossRef] [PubMed]
- Thome, S.; Begandt, D.; Pick, R.; Salvermoser, M.; Walzog, B. Intracellular β2 integrin (CD11/CD18) interacting partners in neutrophil trafficking. Eur. J. Clin Investig. 2018, 48 (Suppl. S2), e12966. [Google Scholar] [CrossRef] [PubMed]
- Gonzalez, J.C.; Chakraborty, S.; Thulin, N.K.; Wang, T.T. Heterogeneity in IgG-CD16 signaling in infectious disease outcomes. Immunol. Rev. 2022, 309, 64–74. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Engeroff, P.; Vogel, M. The role of CD23 in the regulation of allergic responses. Allergy 2021, 76, 1981–1989. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Peng, Y.; Tao, Y.; Zhang, Y.; Wang, J.; Yang, J.; Wang, Y. CD25: A potential tumor therapeutic target. Int. J. Cancer 2023, 152, 1290–1303. [Google Scholar] [CrossRef] [PubMed]
- Burke, K.P.; Chaudhri, A.; Freeman, G.J.; Sharpe, A.H. The B7:CD28 family and friends: Unraveling coinhibitory interactions. Immunity 2024, 57, 223–244. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Bisht, K.; Fukao, T.; Chiron, M.; Richardson, P.; Atanackovic, D.; Chini, E.; Chng, W.J.; Van De Velde, H.; Malavasi, F. Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma. Cancer Med. 2023, 12, 20332–20352. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Kudryavtsev, I.V.; Borisov, A.G.; Krobinets, I.I.; Savchenko, A.A.; Serebryakova, M.K. MULTICOLOR FLOW CYTOMETRIC ANALYSIS OF CYTOTOXIC T CELL SUBSETS. Med. Immunol. 2015, 17, 525–538. (In Russian) [Google Scholar] [CrossRef]
- Patnaik, R.; Azim, A.; Agarwal, V. Neutrophil CD64 a Diagnostic and Prognostic Marker of Sepsis in Adult Critically Ill Patients: A Brief Review. Indian J. Crit. Care Med. 2020, 24, 1242–1250. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Joshi, I.; Carney, W.P.; Rock, E.P. Utility of monocyte HLA-DR and rationale for therapeutic GM-CSF in sepsis immunoparalysis. Front. Immunol. 2023, 14, 1130214. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Aravindhan, V.; Yuvaraj, S. Immune-endocrine network in diabetes-tuberculosis nexus: Does latent tuberculosis infection confer protection against meta-inflammation and insulin resistance? Front. Endocrinol. 2024, 15, 1303338. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Lee, Y.E.; Lee, S.H.; Kim, W.U. Cytokines, Vascular Endothelial Growth Factors, and PlGF in Autoimmunity: Insights From Rheumatoid Arthritis to Multiple Sclerosis. Immune Netw. 2024, 24, e10. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Khadzhieva, M.B.; Kalinina, E.V.; Larin, S.S.; Sviridova, D.A.; Gracheva, A.S.; Chursinova, J.V.; Stepanov, V.A.; Redkin, I.V.; Avdeikina, L.S.; Rumyantsev, A.G.; et al. TREC/KREC Levels in Young COVID-19 Patients. Diagnostics 2021, 11, 1486. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Korsunskiy, I.; Blyuss, O.; Gordukova, M.; Davydova, N.; Zaikin, A.; Zinovieva, N.; Zimin, S.; Molchanov, R.; Salpagarova, A.; Eremeeva, A.; et al. Expanding TREC and KREC Utility in Primary Immunodeficiency Diseases Diagnosis. Front. Immunol. 2020, 11, 320. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Savchenko, A.A.; Tikhonova, E.; Kudryavtsev, I.; Kudlay, D.; Korsunsky, I.; Beleniuk, V.; Borisov, A. TREC/KREC Levels and T and B Lymphocyte Subpopulations in COVID-19 Patients at Differ-ent Stages of the Disease. Viruses 2022, 14, 646. [Google Scholar] [CrossRef]
- Chen, L.Y.C. IgG4-related disease for the hematologist. Hematol. Am. Soc. Hematol. Educ. Program. 2024, 2024, 594–603. [Google Scholar] [CrossRef]
- Jia, X.; Yu, L. Understanding Islet Autoantibodies in Prediction of Type 1 Diabetes. J. Endocr. Soc. 2024, 8, bvad160. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Steiner, G.; Toes, R.E.M. Autoantibodies in rheumatoid arthritis-rheumatoid factor, anticitrullinated protein antibodies and beyond. Curr. Opin. Rheumatol. 2024, 36, 217–224. [Google Scholar] [CrossRef] [PubMed]
- Pashnina, I.A.; Krivolapova, I.M.; Fedotkina, T.V.; Ryabkova, V.A.; Chereshneva, M.V.; Churilov, L.P.; Chereshnev, V.A. Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease. Antibodies 2021, 10, 9. [Google Scholar] [CrossRef] [PubMed]
- Ragusa, F.; Fallahi, P.; Elia, G.; Gonnella, D.; Paparo, S.R.; Giusti, C.; Churilov, L.P.; Ferrari, S.M.; Antonelli, A. Hashimotos’ thyroiditis: Epidemiology, pathogenesis, clinic and therapy. Best Pract. Res Clin. Endocrinol. Metab. 2019, 33, 101367. [Google Scholar] [CrossRef]
- Oh, S.J.; LaGanke, C.; Powers, R.; Wolfe, G.I.; Quinton, R.A.; Burns, D.K. Multifocal motor sensory demyelinating neuropathy: Inflammatory demyelinating polyradiculoneuropathy. Neurology 2005, 65, 1639–1642. [Google Scholar] [CrossRef] [PubMed]
- Cheremokhin, D.A.; Shinwari Kh Deryabina, S.S.; Bolkov, M.A.; Tuzankina, I.A.; Kudlay, D.A. Analysis of the TREC and KREC levels in the dried blood spots of healthy newborns with different gestational ages and weights. Acta Naturae 2022, 14, 101–108. [Google Scholar] [CrossRef]
Indication | Values | |
---|---|---|
Body temperature | ≥38 °C | or ≤36 °C |
Heart rate | ≥90/min (tachycardia) | |
Respiratory rate | ≥20/min or blood carbon dioxide ≤ 32 mmHg | |
Clinical blood analysis | Leukocytosis > 12 × 109/L or young forms of granulocytes more than 10% | or leucopenia <4 × 109/L |
Symptoms | Indicator |
---|---|
Fever | Maximum rise in body temperature > 38.5 °C or ≤36 °C (hypothermia) |
Tachycardia | ≥90/min |
Respiratory failure | Dyspnea ≥ 20/min, blood carbon dioxide ≤ 32 mmHg, or saturation less than 95% |
Hepatomegaly/splenomegaly | Liver and/or spleen palpated below the edge of the costal arch |
Leukocytosis | >12 × 109/L |
Cytopenia with involvement of more than 2 cell sprouts | Hb < 90 g/L, neutrophils < 1 × 109/L |
Lymphocytopenia | Platelets < 100 × 109/L |
NK cells, CTL | Less than 1.0 × 109/L |
Cytokines IL-6, IL-1β, TNF, IFNγ | Elevated |
Level of soluble IL-2 (CD25) | >2400 units/mL |
IFNγ-induced chemokine CXCL9 | Elevated |
C-reactive protein | More than 5 μg/L |
Serum ferritin | >500 µg/L |
LDH, AST, ALT | Elevated, associated with tissue lesions |
Hemostasis | Fibrinogen < 1.5 g/L, D-dimer > 243 ng/mL |
Hypertriglyceridemia | Fasting triglycerides > 3.0 mmol/L or >3 standard deviations above age-appropriate levels |
Procalcitonin | Above 2.0 ng/mL |
Hemophagocytosis | In bone marrow, spleen, or lymph node biopsies |
Immunological Receptors | Functions |
---|---|
CD5 | CD5 is an adhesion molecule that regulates cell activation. It is detected on T-lymphocytes, thymocytes, and B1-clone of B cells. |
CD11b | CD11b belongs to the most important integrins for cell migration that determine the activity of phagocytosis, cell cytotoxicity, chemotaxis, and cellular activation of T effectors, NK cells, macrophages, and granulocytes [5,67]. |
CD16 | CD16 is a receptor of the Fc-fragment of IgG, it mediates phagocytosis and antibody-dependent cellular cytotoxicity, its activation increases the cytotoxicity of NK cells, and it stimulates the secretion of IFN and TNF-α [5,77,78,79]. |
CD23 | CD23 is expressed on activated B cells, macrophages, thymic epithelial cells, eosinophils, and platelets. It is also an indicator of B-cell activity [5,80]. |
CD25 | CD25 is the α-chain of IL-2 receptor. It is expressed on different types of peripheral blood cells: CD4+-, CD8+-, NK-lymphocytes, NKT cells, B-lymphocytes, and monocytes. Marker of early activation of T-lymphocytes. An increase in their number, as well as in the total population of CD25-positive lymphocytes, may indicate an inflammatory process of any nature (infectious and autoimmune) [5,81]. |
CD27 | CD27 is an additional marker of B2-lymphocytes and indicates the transition of B-lymphocytes from naive cells to memory cells. |
CD28 | CD28 is expressed on most activated T-lymphocytes, naive T cells and memory T cells. It is required as a costimulatory factor for induction of immune response (cell proliferation and activation) [5,82,83]. |
CD38 | CD38, cyclic ADP-ribosylhydrolase, located on the surface of lymphocytes, provides adhesion and signal transduction; it is also a marker of cell activation (metabolic marker). It is decreased in HIV infection, leukemia, myeloma, co-lead tumors, and type II diabetes mellitus [5,82]. |
CD50 | CD50 is an intercellular adhesion molecule (ICAM-3), in addition to being a potent signaling molecule. Present on all leukocytes, endothelial, and dendritic cells. Provides costimulatory signals for T cells and regulates cell adhesion by interacting with integrins. It has been shown to decrease the number of CD50+ cells in tumor diseases [5,81]. |
CD57 | CD57 is expressed on subpopulations of 15–20% of peripheral blood mononuclear cells, and in 60% of NK- and T cells. Elevated values are found in cancer patients, post-transplant patients, patients with HIV, and patients with rheumatoid arthritis and Felty’s syndrome. The decrease is pathognomonic for chronic Lyme disease [4,84]. |
CD62L | CD62L is a member of the family of cell adhesion molecules (L-selectin) located on the cell surface of leukocytes (T and NK cells, monocytes, and granulocytes); it provides translocation of leukocytes from the blood to the lymphoid tissue, where they interact with antigen [4,85]. |
CD64 | CD64 is a mediator of antibody-dependent cellular cytotoxicity (functional marker). |
CD158a | CD158a is an important functional marker of NK activity. |
HLA-DR | HLA-DR is expressed by various cells of peripheral blood. It is detected on all B-lymphocytes and monocytes, and on activated T-lymphocytes (marker of late activation), but it also plays an important part in monocytes functions. The level of HLA-DR-receptor expression on monocytes less than 50% is an unfavorable pathognomonic sign of severe bacterial infection (sepsis, peritonitis) [4,86]. |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Starshinova, A.A.; Savchenko, A.A.; Borisov, A.; Kudryavtsev, I.; Rubinstein, A.; Dovgalyuk, I.; Kulpina, A.; Churilov, L.P.; Sobolevskaia, P.; Fedotkina, T.; et al. Immunological Disorders: Gradations and the Current Approach in Laboratory Diagnostics. Pathophysiology 2025, 32, 17. https://doi.org/10.3390/pathophysiology32020017
Starshinova AA, Savchenko AA, Borisov A, Kudryavtsev I, Rubinstein A, Dovgalyuk I, Kulpina A, Churilov LP, Sobolevskaia P, Fedotkina T, et al. Immunological Disorders: Gradations and the Current Approach in Laboratory Diagnostics. Pathophysiology. 2025; 32(2):17. https://doi.org/10.3390/pathophysiology32020017
Chicago/Turabian StyleStarshinova, Anna A., Andrey An. Savchenko, Alexander Borisov, Igor Kudryavtsev, Artem Rubinstein, Irina Dovgalyuk, Anastasia Kulpina, Leonid P. Churilov, Polina Sobolevskaia, Tamara Fedotkina, and et al. 2025. "Immunological Disorders: Gradations and the Current Approach in Laboratory Diagnostics" Pathophysiology 32, no. 2: 17. https://doi.org/10.3390/pathophysiology32020017
APA StyleStarshinova, A. A., Savchenko, A. A., Borisov, A., Kudryavtsev, I., Rubinstein, A., Dovgalyuk, I., Kulpina, A., Churilov, L. P., Sobolevskaia, P., Fedotkina, T., Kudlay, D., & Shlyakhto, E. V. (2025). Immunological Disorders: Gradations and the Current Approach in Laboratory Diagnostics. Pathophysiology, 32(2), 17. https://doi.org/10.3390/pathophysiology32020017