its a journal club with aim of describing association between first degree relatives of Rheumatoid arthritis and periodontitis using ACPA

2. Periodontal Status Correlates With
Anti-citrullinated Protein Antibodies In First
Degree Relatives Of Individuals With
Rheumatoid Arthritis
PRESENTED BY :- DR K. ABHILASHA
MODERATED BY :- DR FOUZIA TARANNUM
DEPARTMENT OF PERIODONTICS
M. R. AMBEDKAR DENTAL COLLEGE & HOSPITAL, BENGALURU

3. PRESENTATION LAYOUT
 HISTORICAL BACKDROP
 PERIODONTITIS
 ASSOCIATION WITH SYSTEMIC
DISEASE
 RHEUMATOID ARTHRITIS (RA)
WHAT IS RA?
PERIODONTAL CO-RELATION
RELATED STUDIES
ARTICLE
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSION
 CLINICAL RELEVANCE
 REFERENCES

4. HISTORICAL BACKDROP
• Hippocrates (460-370BC) – noted a case of rheumatism cured after infected
tooth extraction.
• Benjamin Rush (1745-1813) – recognized relation of oral infection to
general health.
• W. D. Miller (1853-1907) – proposed oral infections as the cause of many
diseases.

5. HISTORICAL BACKDROP
• G.V.Black – important part of dental profession in preserving general
health.
• Frank Billings, Edward C. Rosenow, Charles H. Mayo – interested in the
same concept.
• William Hunter (1861-1937) – indicated dentistry as a cause of what he
called “oral sepsis” – that caused rheumatic & other chronic diseases.

6. PERIODONTITIS
• Periodontitis (PD) is a chronic inflammatory disease where resident cells and
preformed mediators induce leukocyte infiltration and progressive destruction
of the tooth supporting tissues as a result of interaction between bacterial
products, cell populations, and mediators in disease-susceptible individuals.
• Results in irreversible attachment loss, bone destruction and tooth loss
eventually.
• The primary aetiology of PD is the dental biofilm (Löe et al.,1965) while the
host inflammatory response causes the resulting tissue damage (Bartold et al.,
2013).

7. PERIODONTITIS
• Periodontitis differs from many other types of infections since it is not caused
by a single bacterium but by a group of bacteria.
• Although more than 500 different types of bacteria have been isolated from the
oral cavity, Actinobacillus actinomycetemcomitans and Porphyromonas
gingivalis have been considered the major pathogenic species in destructive
periodontal disease.
• Other subgingival species involved include Prevotella intermedia, Tanerella
forsythus, Fusobacterium nucleatum, Campylobacter rectus, Eikenella corrodens,
Treponema denticola, Peptostreptococcus and some other species.

9. ASSOCIATION WITH SYSTEMIC DIESEASE
• There is a substantial microbial and inflammatory burden associated with human
periodontal disease, and considerable evidence is accumulating that this systemic
burden may contribute to specific systemic diseases and conditions.
• The concept that oral diseases and systemic diseases influence each other goes back
to the theory of focal infection.
• In 1891, Miller published his theory regarding focal infection in which he indicated that
microorganisms and their products are able to access parts of the body that are
adjacent to or distant from the mouth.

10. ASSOCIATION WITH SYSTEMIC DIESEASE
• In recent years, the concept of focal infection has changed and now mostly
relies on the correlation between chronic periodontitis and systemic diseases.
• At present, it is generally known that a patient’s oral status is connected with
their systemic health, as poor oral health may cause serious underlying diseases
concomitantly and may predispose patients to developing other systemic
diseases.

11. ASSOCIATION WITH SYSTEMIC DIESEASE
Oral-hematogenous spread of periodontal pathogens and
direct effects to target organs.
Transtracheal spread of periodontal pathogens and direct
effects to target organs.
Oral-hematogenous spread of cytokines and antibodies with
effects at distant organs
The mechanisms by which periodontal infections may influence systemic health
have been described as follows:

12. NEWMAN AND
CARRANZA’S, CLINICAL
PERIODONTOLOGY, 13TH
ED

13. RHEUMATOID ARTHRITIS
• Rheumatoid arthritis (RA) is a chronic inflammatory disorder of autoimmune origin that
may affect many tissues and organs but principally attacks the joints, producing a
nonsuppurative proliferative and inflammatory synovitis.
• The current understanding of RA pathogenesis postulates that the activity of
peptidil arginine deiminase (PAD), an enzyme that transforms arginine into
citrulline, which causes a post-translational modification in structural proteins.
• In addition, the formation of anti-citrullinated protein antibodies (ACPA) and
rheumatoid factor (RF) is almost unique to this disease, these antibodies being
a marker of aggressive RA.

14. RHEUMATOID ARTHRITIS
DNA Template
Transcription
Nucleus;
RNA Polymerase
RNA
Translation
Cytoplasm
AMINO ACIDS
MATURE PROTEIN PRODUCTS
Post-translational
modification
Enzymatic
ARGININE
PEPTIDYLARGININE
DEIMINASE
CITRULLINE

37. Newer assays detect non-cyclic citrullinated peptides; the term anti-citrullinated peptide antibody (ACPA)
has thus replaced anti-cyclic citrullinated peptide (anti-CCP) antibody.

38. RHEUMATOID ARTHRITIS
• CLINICAL FEATURES:-
• The incidence of RA increases between 25 and 55 years of age, MORE IN FEMALES
AS compared to male.
• The presenting symptoms of joint pain in RA typically result from inflammation of
the joints, tendons, and bursae.
• Extra-articular manifestations may develop during the clinical course of RA in up
to 40% of patients, even prior to the onset of arthritis.

39. HARRISON’S PRINCIPLES
OF INTERNAL MEDICINE
20TH EDITION

40. Correlation Between Rheumatoid Arthritis And Periodontitis
• There is evidence that periodontitis and RA share genetic risk factors such as the HLA-DRB1
allele of the MHC class II molecules.
• Similarly, environmental risk factors, such as smoking, socioeconomic status and obesity, may
influence both diseases.
• In addition to that Porphyromonas gingivalis, a Gram-negative, anaerobic bacterium, by
releasing a specific deaminase is able to induce protein citrullination, which stimulate ACPA
formation in RA patients.
• In severe periodontitis, the chronic exposure of citrullinated proteins and the subsequent
development of autoantibodies explain the reported association between periodontitis and
RA.

41. Possible Mechanisms Of The Relationship Between Rheumatoid Arthritis And Periodonti

42. RELATED STUDIES
2013

43. 2014

44. 2016
CONCLUSION

45. 2019

47. AIM OF THE STUDY
To Evaluate Periodontal Status In First-
degree Relatives Of Patients With
Rheumatoid Arthritis (FDR-RA) And Detect
Correlation With Presence Of Anti-
citrullinated Protein Antibodies (ACPA)

48. INTRODUCTION

55. MATERIALS AND METHODS
STUDY DESIGN
• This is a nested case-control study within a larger cohort of individuals
at risk for RA.
• The Ethical Committee on human clinical research of the
Canton of Geneva approved the project (CER 08-102).
• Participants were contacted by phone and informed verbally
and in writing about the study, and all provided written
informed consent prior to dental examination.

56. MATERIALS AND METHODS
• The SCERRN-RA study is a prospective cohort of FDR-RA, comprising subjects
without a diagnosis of RA at enrolment.
• Cases were defined by the presence of systemic autoimmunity associated with
RA, defined by ACPA+, which was operationally characterized by a positive
result to any of the anti-cyclic citrullinated peptide antibodies tests (anti-CCP
2.0, 3.0 or 3.1) performed at any time during follow-up.
• Auto-antibodies were measured using the following commercially available
ELISA kits: anti-CCP 2, anti-CCP3 or anti-CCP 3.1
STUDY POPULATION

57. MATERIALS AND METHODS
• . ACPA positivity was defined according to the manufactures’ cut-off values
(anti-CCP2 >25 U/mL, anti-CCP 3 and 3.1 >20 U/mL).
• Controls were defined as individuals without any autoantibody positivity.
• Individuals with complete clinical information and available ACPA status
were included.

58. 52 ACPA+ were contacted
34 agreed for dental examination
18 refused to participate CASES
(32 females and 2 males, aged 22 to 81 years; mean age: 56.5 + 14.4 years
65 ACPA- were recruited
(61 females and 4 males, aged 24 to 83 years; mean age: 56.3 + 12.1 years)
NONE
CONTROLS

59. MATERIALS AND METHODS
• The following information was retrieved from the medical and dental
history:
age,
gender,
comorbidities,
general medication,
 shared epitope (SE),
 smoking (former, light (<10/d) or heavy (>10/d) smoker),
oral hygiene habits
CLINICAL EXAMINATION

60. MATERIALS AND METHODS
• A full-mouth examination at six sites on each tooth was performed by calibrated
periodontist.
• The following clinical parameters were recorded:
• Gingival Index (GI) (Löe and Silness 1963),
• Plaque Index (PI) (Löe and Silness 1963),
• Probing depth (PD) using a manual probe,
• Bleeding On probing (BOP) recorded as present or absent within 30 seconds,
• Recession (Rec) as the vertical distance between the cement-enamel junction and the
gingival margin,
• Furcation involvement and
• Tooth mobility.
CLINICAL EXAMINATION

61. MATERIALS AND METHODS
• Periodontitis was classified as:-
• Mild periodontitis one or more teeth with interproximal sites showing >4 mm CAL and
>4 mm PD;
• Moderate periodontitis  as two or more non-adjacent teeth with interproximal sites
showing >5 mm CAL and > 4 mm PD;
• Severe periodontitis,  as two or more non-adjacent teeth with interproximal sites
showing > 6 mm CAL and > 4 mm PD.
• Diagnosis of gingivitis was given when the BOP score was > 10% and the PD <3 mm.
• Healthy periodontal status was attributed when the BOP score was less than 10%.
CLINICAL EXAMINATION

62. MATERIALS AND METHODS
• ACPA+ and ACPA- participants were described using frequencies and percentages
for categorical variables and mean and standard deviations for continuous
variables.
• Two groups were compared using conditional logistic regression.
• Further the independent associations of periodontal status with clinical variables
using mixed effects logistic regression to account for the matched structure of the
data were examined.
• All analyses were conducted using R v3.5.1 with a significance threshold set at
p<0.05.
STATISTICAL ANALYSIS

63. RESULTS

64. RESULTS
TABLE 1 continued

65. RESULTS

66. RESULTS

67. RESULTS

68. RESULTS

69. DISCUSSION

77. CONCLUSION
• In conclusion, they found a high prevalence of periodontitis in ACPA+ FDR-RA as
compared to ACPA- subjects from the same cohort, strengthening the hypothesis
that periodontitis may be a major risk factor in the development of RA.
• The study suggests that specific guidelines should be given to both medical and
dental health practitioners to decrease the risk for developing periodontitis in this
population.
• Longitudinal studies are needed to further elucidate the impact of such preventive
interventions on subsequent RA development and to establish the predictive value
of the periodontal status on the risk of developing RA.

78. CLINICAL RELEVANCE
• Scientific rationale for the study
• A relationship between periodontitis and rheumatoid arthritis has been established. Several years
before the clinical manifestations of rheumatoid arthritis (RA), anti-citrullinated protein antibodies
(ACPAs) are present in the serum of subjects who are at risk of RA on the basis of genetic and
environmental factors. The role of these autoantibodies in the link between periodontitis and RA
development is still unclear.
• Principal findings
• Higher prevalence and severity of periodontitis and poorer periodontal conditions were found in
ACPA positive compared to ACPA negative subjects.

79. CLINICAL RELEVANCE
Practical implications
• Dentists should incorporate the family history of RA into risk
assessment and treatment planning.
• Physicians need to be aware on the implication of periodontal
disease in RA development and recommend regular dental
assessments and early treatment of periodontal disease.

80. REFERENCES
• Text book of Periodontology, NEWMANN & CARANZZA, 13TH EDITION
• HARRISON’S Principles of Internal Medicine, 20TH EDITION
• Taylor GW. Periodontal health and systemic disorders. J Can Dent Assoc.
2002;68(3):188-92.
• Chiranjeevi T, Prasad OH, Prasad UV, Kumar AK, Chakravarthi VP, Rao PB, Sarma PV.
Identification of microbial pathogens in periodontal disease and diabetic patients of
south indian population. Bioinformation. 2014;10(4):241.
• Lee YH, Lew PH, Cheah CW, Rahman MT, Baharuddin NA, Vaithilingam RD. Potential
mechanisms linking periodontitis to rheumatoid arthritis. Journal of the International
Academy of Periodontology. 2019 Jul;21(3):99-110.

81. REFERENCES
• Igari K, Kudo T, Toyofuku T, Inoue Y, Iwai T. Association between periodontitis and
the development of systemic diseases. Oral Biol Dent. 2014;2(1):4.
• Kaur S, Bright R, Proudman SM, Bartold PM. Does periodontal treatment influence
clinical and biochemical measures for rheumatoid arthritis? A systematic review
and meta-analysis. InSeminars in arthritis and rheumatism 2014 Oct 1 (Vol. 44,
No. 2, pp. 113-122). WB Saunders.
• Araújo VM, Melo IM, Lima V. Relationship between periodontitis and rheumatoid
arthritis: review of the literature. Mediators of inflammation. 2015;2015.