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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 16  |  Issue : 2  |  Page : 401-403

Human leukocyte antigen and periodontal diseases


Department of Periodontics, Sharad Pawar Dental College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (M), Wardha, Maharashtra, India

Date of Submission09-Apr-2020
Date of Decision22-Nov-2020
Date of Acceptance15-Jan-2021
Date of Web Publication18-Oct-2021

Correspondence Address:
Dr. Khushboo Durge
Department of Periodontics, Sharad Pawar Dental College, Sawangi, Wardha, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdmimsu.jdmimsu_101_20

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  Abstract 


It is well recognized that plaque microbiota alone cannot account for periodontal tissue destruction, as some individuals are relatively at a higher risk for tissue destruction than others. Probably, some host factors have a role to play in this field. It is well documented that the human leukocyte antigens (HLA) system is a complex genetic polymorphic system in man. HLA have been considered a candidate of genetic risk markers for aggressive periodontitis (AP). The HLA play an important role in immune responsiveness and may be involved in antigen recognition of periodontal pathogens. These cell surface molecules have a key role in antigen presentation and activation of T-cells. The polymorphisms of HLA can directly affect the binding capability of antigen peptides and thus affect the antigen-specific T-cell response. Hence, these polymorphisms could represent an important susceptibility or resistance factor to periodontitis.

Keywords: Aggressive periodontitis, chronic periodontitis, human leukocyte antigen-genotypes, human leukocyte antigen-serotypes, human leukocytes antigens


How to cite this article:
Durge K, Baliga V, Dhadse P, Agrawal D, Sethiya K, Nibudey A. Human leukocyte antigen and periodontal diseases. J Datta Meghe Inst Med Sci Univ 2021;16:401-3

How to cite this URL:
Durge K, Baliga V, Dhadse P, Agrawal D, Sethiya K, Nibudey A. Human leukocyte antigen and periodontal diseases. J Datta Meghe Inst Med Sci Univ [serial online] 2021 [cited 2021 Nov 28];16:401-3. Available from: http://www.journaldmims.com/text.asp?2021/16/2/401/328441




  Introduction Top


Human periodontitis is a multifactorial disease, consist of a varied group of infectious diseases characterized by the complex host-microorganism infections in periodontium. Periodontal disease may differ regarding bacterial etiology, host response, and disease progression. These evidences suggest that underlying host susceptibility factors play an important role in disease progression. Immunogenic mechanisms determine individual host susceptibility, which results in the progression of periodontitis. Due to the presence of numerous genetic factors, the importance of various human leukocyte antigen (HLA) markers have been investigated in many studies. It has been evaluated to determine individual susceptibility factors in aggressive forms of periodontitis and adult periodontitis. HLA are present on the surface of leukocytes and set of genes coding them are called as HLA complex. The HLA complex genes are present on the short arm of chromosome 6. Recognition of antigen peptides and their presentation to T-cells is important for an immune response toward periodontal pathogens. Because of the presence of antigen and activity of T-cell is prevented by the major histocompatibility complex (MHC). MHC in humans is known as HLA.

Therefore the purpose of the review is to illustrate the role of HLA in periodontal disease and also to clarify how the diversity of HLA types affects periodontal disease.


  Types of Human Leukocyte Antigen Top


  • Class I-HLA (A, B, C), generally for cellular immune response
  • Class II– HLA D, DR, DQ, DP, needed to mount a humoral immune response
  • Class III– activate complement system.



  Mechanism of Action Top


HLA have been known as “antigens for tissue adaptation,” means they play a role in the immune reaction. They work by presenting foreign or nonself-antigens to immune cells such as helper T-cells. After nonspecific defense by neutrophils, the bacteria are phagocytized and digested by monocytes/macrophages, and presented to helper T-cells. This binding capability depends on the amino acid sequence of the variable domains of the HLA molecule, which is specific to the HLA type. After this event, helper T-cells are activated and mediate the further steps in the immune reaction. Therefore, the HLA molecule has an important role in initiating specific immune responses in infectious diseases.


  Human Leukocyte Antigens Serotypes Associated with Periodontal Diseases Top


Since Terasaki et al.[1] established the HLA serotyping method in 1975 on the association of HLA serotypes with periodontal diseases. Most of these studies dealt with the HLA class I molecule, which is involved in cellular immunity. Some studies found no obvious correlation between any HLA types and periodontal disease.


  Aggressive Periodontitis Top


Terasaki et al. 1975[1] and Kaslick et al. 1980[2] in their study evaluated the decrease number of HLA-A2 in juvenile periodontitis patients. Tiwari and Terasaki et al. 1985,[3] analyzed the juvenile periodontitis, and stated that only B15 was responsible. Klouda et al. 1986,[4] examined 44 patients and observed that there was an increased in frequency of HLA-A9 in rapidly progressive patients. Katz et al. 1987[5] reported the role of DR4 with rapidly progressive periodontitis in Jewish population subjects. The authors concluded that 80% of the patients were effective for HLA-DR4 compared to the control group. Shapira et al. 1994[6] observed A9 and B15 were associated with generalized early-onset periodontitis, but not with localized type of disease. Firatli et al. 1996[7] found HLAs A24, A9 and DR4 were associated with Juvenile and rapidly progressive periodontitis.


  Chronic Periodontitis Top


Goteiner and Goldman 1984[8] observed decreased frequency of HLA-B5 in chronic adult periodontitis. Also found that there is an increased frequency of HLA-A9,-B15 and-A29 (A19) and a decreased occurrence of HLA-A2, A3 and-B5 in chronic periodontitis.


  Human Leukocyte Antigens Genotypes Associated with Periodontal Diseases Top


Since serological HLA types include many subtypes, it may have been difficult to isolate specific serotypes. To distinguish the differences precisely, HLA typing is now performed at the gene level. Several researchers have tried to find links between HLA genotypes and periodontal diseases. Overall, however, there are few reports describing this correlation, suggesting the difficulty involved in that type of study with the technology available.


  Genotyping not Specific to Human Leukocyte Antigens Type Top


There has been one attempt to find a genotype not directly specific to HLA types. An atypical restriction fragment length polymorphism (RFLP) pattern was found in the HLA-DQBl gene that encodes the highly polymorphic β-chain of the HLA-DQ molecule Takashiba et al. 1999.[9] The genomic DNA is digested with the restriction enzyme, and DNA fragment is detected by Southern hybridization with the cDNA probe. An uncommon pattern with DNA fragments was found by RFLP analysis of DNA isolated from periodontitis patients which was confirmed by nucleotide sequencing. This atypical site was found in EOP patients than adult periodontitis (AP) patients or in healthy controls.


  Genotyping Specific to Human Leukocyte Antigens Type Top


For HLA type-specific genotyping is the group-specific polymerase chain reaction (PCR)-RFLP method established by Ota et al.[10] After gene amplification of the polymorphic region in the second exon of HLA-DRBl,-DQAl and-DQBl by PCR, the amplified DNA fragment was digested with group-specific restriction enzymes. Studies by Ohyama et al. 1996[11] showed that the HLA-DRB1 * 14O1 and * I501, HLA-DQA*0101, and HLA-DQB1*O5O3 and * 0602 genotypes were detected in EOP patients with elevated relative risk). However, none of the genotypes associated significantly with the disease in this study. In another study, Bonfil et al.[12] observed DRB1 * 0401, *0404, *0405 and * 0408 in severe forms of periodontal disease and in rapidly progressive periodontitis by PCR-allele-specific oligonucleotide method in a case-control study.

Recently, studies have been carried out to determine the function of HLA genotypes associated with periodontal disease in diabetic patients and indirectly evaluated immune reactions to the HLA types isolated. The direct immunological functions such as T cell proliferation specific to HLA types were also investigated (Ohyama et al. 1996).[13],[14],[15],[16],[17],[18]


  Summary Top


Research in HLA genetics has improved remarkably in recent years to contribute to the diagnosis of susceptibility to aggressive forms of periodontitis and to our understanding of its role in pathogenesis. Host antigens homologous to the T cell epitopes of antigenic proteins of periodontal bacteria and antigens of other periodontal bacteria should be studied further.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Terasaki PI, Kaslick RS, West TL, Chasens AI. Low HL-A2 frequency and periodontitis. Tissue Antigens 1975;5:286-8.  Back to cited text no. 1
    
2.
Kaslick RS, West TL, Chasens AI. Association between ABO blood groups, HL-A antigens and periodontal diseases in young adults: A follow-up study. J Periodontol 1980;51:339-42.  Back to cited text no. 2
    
3.
Tiwari JL, Terasaki P. HLA and disease assoeiations. New York: Springer Verlag; 1985.  Back to cited text no. 3
    
4.
Klouda PT, Porter SR, Scully C, Corbin SA, Bradley BA, Smith R. Association between HLA-A9 and rapidly progressive periodontitis. Tissue Antigens 1986;28:146-9.  Back to cited text no. 4
    
5.
Katz J, Goultschin J, Benoliel R, Brautbar H. Human leukocyte antigen (HLA) DR4: Positive association with rapidly progressive Periodontitis. Periodontol 1987;58:607-10.  Back to cited text no. 5
    
6.
Shapira L, Eizenberg S, Sela MN, Soskolne A, Brauthar H. HLA A9 and B15 are associated with the generalized form, but not the localized form of early onset periodontal diseases. J Periodontol 1994;65:219-23.  Back to cited text no. 6
    
7.
Firatli E, Kantarci A, Cebeci I, Tanyeri H, Sonmez G, Carin M, et al. Association between HLA antigens and early onset periodontitis. J Clin Periodontol 1996;23:563-6.  Back to cited text no. 7
    
8.
Goteiner D, Goldman MJ. Human lymphoyte antigen haplotype and resistence to periodontitis. J Periodontol 1984;55:155-8.  Back to cited text no. 8
    
9.
Takashiba S, Ohyama H, Oyaizu K, Kogoe-Kato N, Murayama Y. HLA genetics for diagnosis of susceptibility to earlv-on.set periodontitis. J Periodont Res 1999:34: 374-8.  Back to cited text no. 9
    
10.
Ota M, Seki T, Fukushima H, Tsuji K, Inoko H. HLA-DRB1 genotyping by modified PCR-RFLP method combined with group-specific primers. Tissue Antigens 1992;39:187-202.  Back to cited text no. 10
    
11.
Ohyama H, Takashiba S, Oyaizu K, Nagai A, Naruse T, Inoko H, et al. HLA class II genotypes associated with early-onset periodontitis: DQB1 molecule primarily confers susceptibility to the disease. J Periodontol 1996;67:888-94.  Back to cited text no. 11
    
12.
Bonfil JJ, Dillier FL, Mercier P, Reviron D, Foti B, Sambuc R, et al. A “case control” study on the role of HLA DR4 in severe periodontitis and rapidly progressive periodontitis. J Clin Periodontol 1999;26:77-84.  Back to cited text no. 12
    
13.
Ohyama H, Takashiba S, Oyaizu K, Nagai A, Naruse T, Inoko H, et al. HLA Class II genotypes associated with early-onset periodontitis: DQB1 molecule primarily confers susceptibility to the disease. J Periodontol 1996;9:888-94.  Back to cited text no. 13
    
14.
Clinical Periodontology: Newman, Carranza, Klokkevold and Takei. 10th ed. St. Louis, Mo. : Saunders Elsevier, 2006.  Back to cited text no. 14
    
15.
Ananthnarayan R, Panikar CJ. Text of Microbiology. 7th ed. Universities Pr; 2005.  Back to cited text no. 15
    
16.
Blumberg RS, Wal YV, Claypool S, Corazza N, Dickinson B, Nieuwenhuis E, et al. “The multiple roles of major histocompatibility complex class-I-like molecules in mucosal immune function.” Acta Odontol 2001;59:139-44.  Back to cited text no. 16
    
17.
Han DC, Huang G, Lin LM, Warner NA, Gim JS, Jewett A. “Expression of MHC Class II, CD70, CD80, CD86 and pro-inflammatory cytokines is differentially regulated in oral epithelial cells following bacterial challenge. Oral Microbiol immunol 2003;18:350-8.  Back to cited text no. 17
    
18.
Machulla HK, Stein J, Gautsch A, Langner J, Schaller HG, Reichert S. “HLA-A, B, Cw, DRB1, DRB3/4/5, DQB1 in German patients suffering from rapidly progressive periodontitis (RPP) and adult periodontitis (AP). J Clin Periodontol 2002;29:573-9.  Back to cited text no. 18
    




 

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  In this article
Abstract
Introduction
Types of Human L...
Mechanism of Action
Human Leukocyte ...
Aggressive Perio...
Chronic Periodon...
Human Leukocyte ...
Genotyping not S...
Genotyping Speci...
Summary
References

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