Periodontal disease afflicts 20% of world population. This process usually occurs in the form of being lethargic and chronic, and consequently this disease is known as chronic process. All chronic diseases constantly cause activation of the immune system, and therefore the presentation of microbial peptides which are presented to lymphocytes by professional antigen presenting cells can present microbial peptides very similar to important structures of human economy causing autoimmune diseases, process known as molecular mimicry. Thus, the aim of this study was to verify the presence of molecular mimicry phenomenon between periodontopathogens and human proteins. Blasting microbes of Socransky periodontal complexes against human collagen were performed and then the proteins with similarities were modelled and were screened in the MHI binding virtual methods. The epitopes selected were produced and plasma of chronic periodontal volunteers was obtained and a dot immunobinding assay was performed. Hypothetical protein of
Since the publication of the subgingival plaque’s microbial complexes by Socransky, there has been more knowledge about the microorganisms which are linked directly to the evolution of the periodontal disease; and it has been possible to determine new therapies for its treatment [
These strict anaerobic bacteria have many factors of virulence that activate the immune system in such a way that the immune response causes the destruction of dental support tissues. Another interesting revision of Ximenes describes the complexes of the supragingival microflora, which demonstrates that there are few differences in comparison to the subgingival complexes [
The immune response against these microbial complexes has only one similarity: inflammation. As it is known, the subgingival plaque produces inflammation of the gingiva, but without the destruction of the dental support tissue. It is so that once eliminated the cause (that is to say) by removing the dental plaque, this inflammation disappears; but if the inflammation continues due to the dental plaque accumulation, it can cause the activation of the immune system both innate and adaptive, causing the resorption of the dental support. If this process is not stopped by periodontal therapies, it will eventually cause the exfoliation of the dental pieces [
The destruction process of dental support tissues is explained by the activation of the innate cells (neutrophils and macrophages) by the use of the TLRs, mainly the TLR4, to recognize the LPS of predominant gram-negative anaerobic microorganisms in the subgingival plaque and is going to promote the transcription of inflammatory cytosine via NF-kB. Thus, this inflammatory cytosine like TNF-
Concomitant to the innate immunology answer, the periodontal bacteria mobilize mechanisms of the adaptive immune response, being that the professional cells (macrophages and dendritic cells) of the innate immunity, at the moment of recognizing the microorganisms by means of the TLRs, and once engulfed, have the first stimulus for their maturation, and a second cytosine profile will determine the subsequent polarization and activation of the specific antigen lymphocytes via MHC II [
On the other hand, the presence of Th17 lymphocytes and the secretion of its cytosine IL-17 will increase the action of the cells of the innate immunity in response to the microorganisms. The rough nature of this answer is going to produce the destruction of the bone support. Nevertheless, the IL-17 also has been found in destroyed tissues by autoimmune diseases, like rheumatoid arthritis. Nevertheless, several authors suppose that when this cytosine appears in the injury, the destruction of the dental support can be maintained, by more periodontal therapies the guest receives, causing an autoimmune periodontitis [
Many studies relate autoimmune diseases like rheumatoid arthritis, coronary syndrome, and even erythematous lupus with the presence of periodontitis; this can prove that the phenomenon of molecular mimicry can take place in the oral cavity, being in the activation of the immune system able to destroy own tissues [
The immunological tolerance for T and B cells supposes many processes of education in which these cells are eliminated if they do not recognize in the first place the histocompatibility major complexes I and II and if they recognize own structures. Consequently, the molecular mimicry does not obey this process of education. It simply happens because some microorganism structure is similar to some component of the guest, causing an autoimmune disease. An example of this process occurs when an immune response against protein m of the
Another example in which this phenomenon occurs is in the pancreatic beta cells, due to the crossed answer by cells T associated with viral infections in diabetes type I [
The objective of this study was to verify the presence of the phenomenon of molecular mimicry between periodontal pathogens with human proteins.
The free BLAST program (
The MHCpred free program (
The program in real-time Swiss-Model (
Voluntary patients from the Dental Clinic of the Universidad Católica de Santa María with chronic periodontitis were selected. The chronic periodontitis was diagnosed following the periodontal classification of 1999 [
Eleven volunteers were selected and 20 mL of blood was extracted from each patient and then proceeded to obtain the plasma. The plasma obtained was carefully stored for its later use. Afterwards, the peptide in question was obtained from ByoSynthesis (Texas, USA) and later submitted to diva technique, described by Sumi et al. [
A microbial peptide could be found with the BLAST method with a similarity of more than 90% to human collagen. This difference only falls to the difference of 1 amino acid for a total epitope of 10 amino acids (Table
PubMed ref | Microorganism | Microbial peptide | Human collagen peptide |
---|---|---|---|
ZP_05918585.1 | | GAKG-DRGEKG | GAKG-ERGEKG |
Found peptide of 10 aa pertaining to
>gi|18780273|ref|NP_110447.2| collagen alpha-1(XXI) chain precursor [Homo sapiens] MAHYITFLCMVLVLLLQNSVLAEDGEVRSSCRTAPTDLVFILDGSYSVGPENFEIVKKWLVNITKN FDIGPKFIQVGVVQYSDYPVLEIPLGSYDSGEHLTAAVESILYLGGNTKTGKAIQFALDYLFAKSSR FLTKIAVVLTDGKSQDDVKDAAQAARDSKITLFAIGVGSETEDAELRAIANKPSSTYVFYVEDYIAI SKIREVMKQKLCEESVCPTRIPVAARDERGFDILLGLDVNKKVKKRIQLSPKKIKGYEVTSKVDLSE LTSNVFPEGLPPSYVFVSTQRFKVKKIWDLWRILTIDGRPQIAVTLNGVDKILLFTTTSVINGSQVVT FANPQVKTLFDEGWHQIRLLVTEQDVTLYIDDQQIENKPLHPVLGILINGQTQIGKYSGKEETVQFD VQKLRIYCDPEQNNRETACEIPGFNGECLNGPSDVGSTPAPCICPPGKPGLQGPKGDPGLPGNPGYP GQPGQDGKPGYQGIAGTPGVPGSPGIQGARGLPGYKGEPGRDGDKGDRGLPGFPGLHGMPGSKG EMGAKGDKGSPGFYGKKGAKGEKGNAGFPGLPGPAGEPGRHGKDGLMGSPGFKGEAGSPGAPG QDGTRGEPGIPGFPGNRGLMGQKGEIGPPGQQGKKGAPGMPGLMGSNGSPGQPGTPGSKGSKGEP GIQGMPGASGLKGEPGATGSPGEPGYMGLPGIQGKKGDKGNQGEKGIQGQKGENGRQGIPGQQGI QGHH QFIRQVCTDVIRAQLPVLLQSGRIRNCDHCLSQHGSPGIPGPPGPIGPEGPRGLPGLPGRDGVPGLVG VPGRPGVRGLKGLPGRNGEKGSQGFGYPGEQGPPGPPGPEGPPGISKEGPPGDPGLPGKDGDHGKP GIQGQPGPPGICDPSLCFSVIARRDPFRKGPNY
>gi|260912023|ref|ZP_05918585.1| conserved hypothetical protein [ MHHDIMNCNNNRGLTPLARKNYNEDFYVRLRLGTEGNHKPFPDGDFTVIFTSTGGGRYTCGCEN GALTNCKVNPDGTATCFIQGGNLEVGTLKAEVRIMQDDPNFPSGKRRDVLFPDGVIELVTGASSFD DVQMEVAMNYAIVSAYELAVKKGYQGTQEEFYATFSELTKTMNSTKETAKGLQTKLEEVTSKW ENLNTSITDKLSTIKDGKSAYELAKEHGFVGTAEEWLASLKGERGERGEQGVQGQKGEQGARGE QGLRGLQGEQGQKGDT HVWGEVAQLTLTLGAPMPNVVNEYAFEFQSPTTPTNLSVPSTLKWYNNYTPTIRAGKRYQASIVN DVIIMGEIEI
With the Swiss-Model and PyMOL programs, very similar structures were obtained (Figures
Alfa-1 collagen (a) and
These proteins own a structure of 3 helixes of similar characteristics.
The results showed a strong positive ligation (++) for 7 of the obtained samples of patients with chronic periodontitis, 3 of them had lighter positive feedback (+) and 1 of them did not obtain ligation (−) (Figure
It is observed that in 7 patients there is a strong ligation between the designed bacterial epitope and obtained antibodies of blood plasma.
The periodontal disease, whose etiology is clearly of microbial origin, activates the immune system in such a way that it produces chronic bone resorption leading up to the complete exfoliation of the affected dental pieces, if the aggressive agent is not removed. The activation of the immune system, by consequence, begins with the recognition of the microorganisms by the macrophages with an activation pathway of the TLR2 and TLR4, leading to the apparition of inflammatory cytosines with the consequent expression of RANKL for the osteoclasts activation and survival mechanisms [
The
The molecular mimicry, a theoretical possibility that sequences of epitopes of an organism are similar to some component of another microorganism, proves evident in a periodontal inflammation [
Our results confirm these two findings, besides describing the epitope that generates the molecular mimicry that is not yet described in scientific literature. This epitope by consequence belongs to a protein with unknown function, whose structure seems to be very similar to the human collagen. Besides being reactive for MHC II, the similar bacterial protein similarity with human collagen has been already reported previously and studied [
Future studies must be directed to discover the protein’s function in a matter of
With this result the existence of the molecular mimicry phenomenon in the periodontal disease can be suggested, almost in initial stages of the gingival inflammation, giving rise to autoimmune diseases that affect collagen, as a rheumatoid arthritis.
The author declared that there is no conflict of interests related to this study.
The present work was carried out with the research funds of the Vicerrectorado de Investigación de la Universidad Católica de Santa María de Arequipa, Peru.