Immunophenotyping Peripheral Blood Lymphocyte (TBNK) and beyond in Severe Periodontitis Reveals Immunodeficiency
Abstract:
Bacterial biofilms and host
immune responses combine intricately to cause periodontitis, a chronic
inflammatory disease that gradually destroys periodontal tissues. Here, notable
changes in the subsets of lymphocytes were observed. The patient had increased
counts of central memory T-helper cells and different B cell subsets, but
significantly lower levels of both total T and B lymphocytes, with a drop in
CD4+ T cells. This pattern points to a potential immunodeficiency that may
worsen periodontitis by compromising the control of inflammation. A
dysregulated immune response is additionally indicated by elevated pre- and
post-germinal center B cell counts and naïve cytotoxic T cell counts, which may
offset decreased T cell-mediated immunity. This study uses
immunophenotyping by flow cytometry to obtain the patient's immunological
profile and tried to find out any possible underlying immune dysfunctions in
the context of severe recurrent periodontitis. The results underscore the
plausible contribution of immunological dysfunction to the endurance and
intensity of periodontitis and stress the necessity of tailored immunotherapies
for enhanced management of persistent cases. The study's shortcomings, despite
the thorough immunophenotyping, are that it only focused on one patient, who
might not be a representative sample of the broader population, and it lacked
longitudinal data to evaluate changes over time. The comprehensive
immunological analysis that flows cytometry offers is where the strengths are.
More extensive cohorts should be used in future studies to examine the
effectiveness of immunomodulatory treatments in improving treatment outcomes
for patients with severe periodontitis.
References:
[1].
Slots, J., 2017, Periodontitis: facts, fallacies, and the
future. Periodontology, 75(1), 7-23.
[2].
Papapanou, P.N, Sanz, M, Buduneli, N, Dietrich, T, Feres, M,
Fine, D.H, Flemmig, T.F, Garcia, R, Giannobile, W.V, Graziani, F, Greenwell, H,
2018, Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop
on the Classification of Periodontal and Peri‐Implant Diseases and Conditions. Journal of Periodontology, 89, S173-S182.
[3].
Page, R.C, Offenbacher, S, Schroeder, H.E, Seymour, G.J,
Kornman, K.S, 1997, Advances in the pathogenesis of periodontitis: summary of
developments, clinical implications, and future directions. Periodontology, 14(1), 216-248.
[4].
Brunsvold, M.A, 2005, Pathologic tooth migration. Journal of Periodontology, 76(6), 859-866.
[5].
Richards, D, 2014, Review finds that severe periodontitis
affects 11% of the world population. Evidence-Based Dentistry, 15(3),70-71.
[6].
Kassebaum, N.J, Bernabé, E, Dahiya, M, Bhandari, B, Murray,
C.J.L, Marcenes, W, 2014, Global burden of severe periodontitis in 1990-2010: a
systematic review and meta-regression. Journal of Dental Research, 93(11),1045-1053.
[7].
Frencken, J.E, Sharma, P, Stenhouse, L, Green, D, Laverty, D,
Dietrich, T, 2017, Global epidemiology of dental caries and severe
periodontitis–a comprehensive review. Journal of Clinical Periodontology, 44, S94-S105.
[8].
Borges, T.D.F, Regalo, S.C, Taba Jr, M, Siéssere, S,
Mestriner Jr, W, Semprini, M, 2013, Changes in masticatory performance and
quality of life in individuals with chronic periodontitis. Journal of Periodontology, 84(3), 325-331.
[9].
Graziani, F, Music, L, Bozic, D, Tsakos, G, 2019, Is
periodontitis and its treatment capable of changing the quality of life of a
patient? British Dental Journal, 227(7), 621-625.
[10]. Hajishengallis, G, Darveau, R.P, Curtis, M.A,
2012, The keystone-pathogen hypothesis. Nature Reviews Microbiology, 10(10), 717-725.
[11]. Bergström, J, 2004, Tobacco smoking and chronic
destructive periodontal disease. Odontology, 92, 1-8.
[12]. Shi, B, Chang, M, Martin, J, Mitreva, M, Lux,
R, Klokkevold, P, Sodergren, E, Weinstock, G.M, Haake, S.K, Li, H, 2015,
Dynamic changes in the subgingival microbiome and their potential for diagnosis
and prognosis of periodontitis. MBio, 6(1), 10-1128.
[13]. McKinnon, K.M, 2018, Flow cytometry: an
overview. Current Protocols in Immunology, 120(1), 1-11.
[14]. Pitoiset, F, Barbié, M, Monneret, G, Braudeau,
C, Pochard, P, Pellegrin, I, Trauet, J, Labalette, M, Klatzmann, D, Rosenzwajg,
M, 2018, A standardized flow cytometry procedure for the monitoring of
regulatory T cells in clinical trials. Cytometry Part B: Clinical Cytometry, 94(5), 777-782.
[15]. Maecker, H.T, McCoy Jr, J.P, 2010, A model for
harmonizing flow cytometry in clinical trials. Nature Immunology, 11(11), 975-978.
[16]. Jahan-Tigh, R.R, Ryan, C, Obermoser, G,
Schwarzenberger, K, 2012, Flow cytometry. The Journal of Investigative Dermatology, 132(10), e1.
[17]. Pockley, A.G, Foulds, G.A, Oughton, J.A,
Kerkvliet, N.I, Multhoff, G, 2015, Immune cell phenotyping using flow
cytometry. Current Protocols in Toxicology, 66(1),18-8.
[18]. Buduneli, N, Bıçakçı, N, Keskinogˇlu, A, 2001,
Flow‐cytometric analysis of lymphocyte subsets and
mCD14 expression in patients with various periodontitis categories. Journal of Clinical Periodontology, 28(5),419-424.
[19]. Radhakrishnan, S., Varghese, S.S., Rajasekar,
A. and Venugopalan, S., 2023. Comparative Analysis of Occlusal Force
Distribution Using T-Scan in Chronic Periodontitis Patients before and after
Periodontal Therapy: A Randomized Controlled Trial. World, 14(11), p.948.
[20]. Kannan, B. and Arumugam, P., 2023. The
implication of mitochondrial DNA mutation and dysfunction in periodontal
diseases. Journal of Indian Society of Periodontology, 27(2), pp.126-130.
[21]. Rajasekar, A. and Ganapathy, D., 2023.
Effectiveness of nonsurgical periodontal therapy on salivary visfatin: a
clinical and biochemical analysis. World J Dentistry, 14, p.75.
[22]. Rajasekar, A., 2023. Correlation of salivary
visfatin levels in obese and NON-OBESE population with periodontal
status. Journal of oral biology and craniofacial research, 13(1), pp.67-70.
[23]. Renu, K., Gopalakrishnan, A.V. and Madhyastha,
H., 2024. Is periodontitis triggering an inflammatory response in the liver,
and does this reaction entail oxidative stress?. Odontology, pp.1-14.
[24]. Aarthi, L., Renu, K., Priya, V.V., Gayathri, R.
and Kavitha, S., Molecular Docking Analysis of Epigallocatechin 3-Gallate
[EGCG] on Fatty Acids and Carnitine Transporters Family. DOI: 10.21522/TIJPH.2013.SE.24.01.Art010
[25]. Hirshasri, A.G., Renu, K., Priya, V.V.,
Gayathri, R. and Kavitha, S., The Effect of Aspalathin on SMAD2, SMAD3, TGF-β-A
Major Contributor of Inflammation–An In-silico Approach.
DOI:
10.21522/TIJPH.2013.SE.24.01.Art009
[26]. Juvairiya Fathima, A., Renu, K., Priya, V.V.,
Gayathri, R. and Kavitha, S., Determining the Role of Caffeic Acid on Lipogenic
Regulators: An In-Silico Approach. DOI: 10.21522/TIJPH.2013.SE.24.01.Art012
[27]. Naiff, P. F, Ferraz, R, Cunha, C. F, Orlandi,
P. P, Boechat, A. L, Bertho, A. L, Dos-Santos, M. C, 2014, Immunophenotyping in
saliva as an alternative approach for evaluation of immunopathogenesis in
chronic periodontitis. Journal of Periodontology, 85(5), e111–e120.
[28]. Afar, B, Engel, D, Clark, E. A, 1992, Activated
lymphocyte subsets in adult periodontitis. Journal of Periodontal Research, 27(2), 126–133.
[29]. Zafiropoulos, G. G, Flores-de-Jacoby, L,
Schoop, B, Havemann, K, Heymanns, J, 1990, Flow-cytometric analysis of
lymphocyte subsets in patients with advanced periodontitis. Journal of Clinical Periodontology, 17(9), 636–641.
[30]. Walker, C.B, 1996, The acquisition of
antibiotic resistance in the periodontal microflora. Periodontology, 10(1),79-88.
[31]. Balaji, S, Cholan, P. K, Victor, D. J, 2021, An
emphasis of T-cell subsets as regulators of periodontal health and
disease. Journal of Clinical and Translational Research, 7(5), 648–656.
[32]. Cardoso, E.M, Arosa, F.A, 2017, CD8+ T cells in
chronic periodontitis: Roles and rules. Frontiers in Immunology, 8, 145.
[33]. Demoersman, J, Pochard, P, Framery, C, Simon,
Q, Boisramé, S, Soueidan, A, Pers, J.O, 2018, B cell subset distribution is
altered in patients with severe periodontitis. PLoS One, 13(2), e0192986.
[34]. Rajasekaran, K., Renu, K., Sankaran, K.,
Veeraraghavan, V.P., Rengasamy, G., Ronsivalle, V., Cicciù, M. and Minervini,
G., Determination of red blood cell parameters for signs of iron deficiency
anemia in patients with oral diseases. Minerva dental and oral science. DOI: 10.23736/S2724-6329.24.04907-6.
[35]. Sundaravadivelu, I., Renu, K., Kavitha, S.,
Priya, V.V., Gayathri, R., Ronsivalle, V., Cicciù, M. and Minervini, G., 2024.
Elucidating hematological profile and electrolyte balance in oral cancer
patients. Minerva Dental and Oral Science. doi: 10.23736/S2724-6329.24.04902-7.
[36]. Gonzales, J.R, 2015, T‐and B‐cell subsets in periodontitis. Periodontology, 69(1), 181-200.
[37]. Mahanonda, R, Champaiboon, C, Subbalekha, K,
Sa-Ard-Iam, N, Rattanathammatada, W, Thawanaphong, S, Rerkyen, P, Yoshimura, F,
Nagano, K, Lang, N.P, Pichyangkul, S., 2016, Human memory B cells in healthy
gingiva, gingivitis, and periodontitis. The Journal of Immunology, 197(3), 715-725.
[38]. Rajendran, P., Renu, K., Abdallah, B.M., Ali,
E.M., Veeraraghavan, V.P., Sivalingam, K., Rustagi, Y., Abdelsalam, S.A.,
Ibrahim, R.I.H. and Al-Ramadan, S.Y., 2024. Nimbolide: promising agent for
prevention and treatment of chronic diseases (recent update). Food & Nutrition Research, 68. DOI:10.29219/fnr.v68.9650
[39]. Renu, K., 2024. A molecular viewpoint of the intricate
relationships among HNSCC, HPV infections, and the oral microbiota
dysbiosis. Journal of Stomatology, Oral and Maxillofacial Surgery,
p.102134.
[40]. Rajendran, P., Renu, K., Ali, E.M., Genena,
M.A.M., Veeraraghavan, V., Sekar, R., Sekar, A.K., Tejavat, S., Barik, P. and
Abdallah, B.M., 2024. Promising and challenging phytochemicals targeting LC3
mediated autophagy signaling in cancer therapy. Immunity, Inflammation and Disease, 12(10), p.e70041. doi: 10.1002/iid3.70041.
[41]. Manchery,
N., John, J., Nagappan, N., Subbiah, G.K. and Premnath, P., 2019.
Remineralization potential of dentifrice containing nanohydroxyapatite on
artificial carious lesions of enamel: A comparative: in vitro: study. Dental
research journal, 16(5), pp.310-317.
[42]. Kavarthapu,
A. and Malaiappan, S., 2019. Comparative evaluation of demineralized bone
matrix and type II collagen membrane versus eggshell powder as a graft material
and membrane in rat model. Indian Journal of Dental Research, 30(6),
pp.877-880.
[43]. Kaarthikeyan,
G., Jayakumar, N.D. and Sivakumar, D., 2019. Comparative Evaluation of Bone
Formation between PRF and Blood Clot Alone as the Sole Sinus-Filling Material
in Maxillary Sinus Augmentation with the Implant as a Tent Pole: A Randomized
Split-Mouth Study. Journal of long-term effects of medical implants, 29(2).
[44]. Ginesin, O, Mayer, Y, Gabay, E, Rotenberg, D, Machtei, E. E, Coyac, B. R, Bar-On, Y, Zigdon-Giladi, H, 2023, Revealing leukocyte populations in human peri-implantitis and periodontitis using flow cytometry. Clinical Oral Investigations, 27(9), 5499–5508.